Vaccines for Ever

Vaccine development potential
in the developing world

Eduardo R. Aycardi

Get the Book

This genuine history of vaccine development in countries on the verge of development reveals the limited capacity for scientific entrepreneurship in many world areas where political and economic factors impede moving forward. It is also quite disturbing to observe how various health entities in the governmental or business world look to the other side to assist the developing world to fabricate their products. Moreover, these same institutions make significant efforts mainly to aid countries to utilize vaccines from multinational commercial manufacturers. These notes are an outcry from many scientists in countries with low economic levels needing assistance to bring about their natural vaccine products.

— The Author

TO

the many people that have survived suffering and death due to the protection given by numerous vaccines developed by scientists in the last three centuries

Vaccines for Ever

Written by: Eduardo R. Aycardi

First edition: 2024

Book cover and layout design:

Guillermo E. Garcia A. and Camilo A. Garcia A.

Typefaces: Baskerville & Vremena Grotesk

This work is licensed under CC BY-NC-ND 4.0.
To view a copy of this license,
visit https://creativecommons.org/licenses/by-nc-nd/4.0/

Attribution, NonComercial, NoDerivatives.

ISBN: 978-628-01-5287-5

www.vaccinesforever.com

2024

Prologue

Writing meaningfully about vaccine development will require many pages and volumes of lengthy documents and books. Every vaccine developed to prevent the most common transmissible diseases that affect the human population has taken considerable effort from innumerable scientists, scholars, and professionals from many disciplines over prolonged periods. At least eighteen types of vaccines are commonly available to prevent the same kind of disease in different phases of human population growth.

It is common knowledge that the arduous production of vaccines to arrive at a marketable product requires considerable time and multiple investment costs. It is estimated that developing some of the most common vaccines, such as polio, tuberculosis, or mumps, took nearly twenty years before being approved. It is also common knowledge that the health divisions of government agencies in many countries have immense volumes of written requirements that new vaccines or new pharmaceuticals must meet before the issuance of a sales license.

The narrative of this book describes the history of the development of a new procedure to manufacture a rabies vaccine for human use, bearing in mind that the original rabies vaccine was developed by Louis Pasteur in 1885. Numerous variations in the manufacturing process have been generated in many countries around the world. The events described in this book account for the many vicissitudes that developing countries experience in developing new industrial, modern, and updated versions of the rabies vaccine for human use. Rabies still exists in many countries, and individuals are typically vaccinated after exposure to the disease. In essence, there is a present-day need for high-quality rabies vaccines for human use in different world areas.

The following pages describe the different approaches governments in developing countries employ for scientific research and health management. The narrative presents how a scientific research group tried to develop a new modern system for rabies vaccine production despite governments, political barriers, and opposition. It also appreciates the group leader’s goal, inspired by a private foundation program to teach developing countries how to produce modern vaccines for the population’s well-being and lessen the dependence on private multinational business companies. Whether the purpose was achieved would be decided by the reader.

Other facts analyzed in the book describe how enormous differences in cultural habits influence scientific research and health management issues. It is also interesting to see examples of how scientific development directly improves the prosperity and social status of companies, researchers, and their families. One of the essential features depicted in many of the country’s projects described in the book is related to the fact that political and personal obstacles directly and gravely influence scientific development worldwide. More recently, it appears that in several countries, vaccines and vaccinations are being utilized by politicians as a plan to denigrate against their use, in an effort to obtain more adepts and political influence, without consideration of the enormous benefits to human health and the millions of people that are still alive due to the protection afforded by many vaccines against major infectious diseases in the last century.

The chronicle includes illustrations of the enormous lack of managerial and financial deficiencies in countries on the verge of development. Another significant episode is related to the lack of private entrepreneurial investors in the field of vaccines in the developing world, as almost all production lies in the hands of government companies. The following pages clearly show the economic dependence and exploitation of the multinational pharmaceuticals that commercialize vaccines in the developing world and how, many times, those companies make numerous efforts to prevent the development of vaccines that could compete with their products.

The author decided not to release the real names of all the individuals mentioned in depicting the characters within the narrative in the chapters of the book. The real reason is to avoid any misunderstanding or direct criticism of the actions of every particular person, which could be interpreted as a direct denigration of their specific sociological culture. Similarly, the names of most countries and all companies mentioned in the book have been changed for the same reasons: to avoid attacking their cultural heritage. The name of China which is mentioned in a few chapters is one exemption to this. For the writer, the tremendous differences between Eastern and Western cultural practices and traditions cannot be hidden and, on the contrary, must be respected, and China is an excellent example of those discrepancies.

The book also describes the colossal differences in the approach and manner in which the vaccines utilized in the current COVID-19 pandemic compared to the regular methods outlined in the past for approving a vaccine for marketing. More striking is the lack of appropriate testing of undesirable reactions to some COVID-19 vaccines that the author has seen occur in vaccinated persons in several places around the globe. The justification for this lack of long-term testing is the determination to call the disease’s appearance a pandemic. Hence, vaccines were authorized only for emergency use during the pandemic. However, once the pandemic is declared over, there should be a decision to upgrade the approved vaccines rapidly to prevent local or systemic reactions in patients. Thus far, governments have not set a specific time for current pharmaceutical manufacturers to comply with the safety, security, and better protection of the current COVID-19 vaccines, especially those manufactured by genetic manipulations.

Some comments within the book pertain to the cost-effective advantages of manufacturing vaccines in developing countries. However, it should be kept in mind that any product, such as a vaccine, must be profitable to maintain its durability, survival, and, above all, superior quality. Importantly, local in-country vaccine production serves to avoid the profuse drainage of international currency that has to be spent buying vaccines at vast international prices to cover their needs. The book touches on the excessive dependence of the developing world on the large conglomerate of multinational pharmaceuticals that make huge profits from the sale of vaccines at outrageous prices.

Mention is made in a few pages on the need to dedicate more study and research to so-called zoonotic diseases. Innumerable diseases fit the pattern of transmissibility from animals to humans. Studies on this type of maladies go back several centuries, and many researchers and scholars have devoted their lives to studying them. We now have many vaccines to prevent zoonotic diseases or to diminish their ravages to health and survival. It is inadmissible to make allusions to zoonotic diseases without commenting on influenza, a viral infection that has been transmitted from birds to humans for centuries. The virus is carried by birds that seasonally migrate from all continents, and now people are used to seeing influenza appear year after year.

Vaccines to control the spread of the influenza virus and reduce its symptoms are prepared and officially approved every year due to the continuous mutation of the virus, taking into account that a new version of it is different from the one encountered in the previous year. Due to these variations, the influenza vaccine has limited protection against the virus. However, it is beneficial in reducing the severity of the symptoms. Considering that we know the rabies virus as much as the influenza virus, we should be able to reduce the approval time of rabies vaccines in cases of acute need, considering that rabies is always fatal in exposed, non-vaccinated subjects.

The rabies vaccine was developed due to the need to control the symptoms and death of persons bitten by carnivorous animals, which, in Asia are mainly wild, unvaccinated dogs. Seeing that in most places of the continent, dogs are not vaccinated due to cultural beliefs, the number of persons bitten by rabid animals is enormous. Hence, the market for the rabies vaccine is colossal. This opportunity is the moving objective for companies to set up vaccine production businesses. The idea is to create profitable enterprises, given the extensive business opportunities available. Very little, if any, consideration is given to the objective of saving human lives. In most places, it appears that profit is prioritized above mitigating human suffering. Are there any ethical considerations missing?

The intention of writing this book is not to discourage potential researchers who want to develop new vaccine methodologies or create new vaccine institutions. On the contrary, the primary purpose is to invoke awareness and understanding of the difficulties encountered by a group of scientists in developing new vaccine methodologies, which could help other researchers prepare as they anticipate, combat, and oppose the possible sources of conflict. A basic methodology mentioned in the book could also be applied to the manufacture of other viral vaccines of importance in many areas of the world. Hence, the field is broad, and there are many opportunities to use classical tissue culture, high density cell methodologies to produce safe, inactivated viral vaccines with minimal or no secondary reactions. Vaccines are here to stay forever.

Chapter One

1983-1985

It Can Be Done

It all started in dimmed light, in the spacious meeting rooms of a well-known multinational foundation interested in assisting countries on the verge of development. A high-ranking official from the foundation had proposed to the board that the health sciences division of the foundation initiate a long-term program to support the transfer of tissue culture-based vaccine production technology to selected large or medium-sized developing countries. The initial idea was to find the most modern vaccine technology available in a developed country and to teach other countries to master the production of such novel vaccines. One of the board members was very skeptical about the idea of transferring high technology to developing countries, even though the new vaccines would be used to prevent and cure deadly diseases that hampered the health status of the human population of developing countries in Latin America, Asia, and Africa.

Before this event, the World Health Organization (WHO) had cofounded a program for vaccine development in major infectious disease areas with the same foundation. The initial vaccines proposed for inclusion were those against rabies, dengue, Japanese encephalitis, and yellow fever, but later WHO decided to consult on the transfer of technology for rabies vaccine production and establish a group of experts chaired by the highest-ranking official of the foundation. The group of experts recommended using a strain of rabies virus known as tissue culture Pasteur virus, and the same group of experts also endorsed using Vero cells as the vehicle for the manufacture of human rabies vaccines in developing countries. The fact is that this cell line has been utilized for the manufacture of vaccines for a long time. Moreover, this cell strain has been extensively tested in laboratory animals to eliminate the possibility of reversion to pathogenicity, and numerous laboratories have found it safe. Site visits were planned for a few selected countries to choose one to participate in the technology transfer project with funds provided by the foundation.

The proposal for the technology transfer described rabies as causing countless human deaths worldwide and considered post-exposure treatments with tissue culture vaccines as only half of the need. Rabies is a viral zoonotic disease that is commonly fatal but preventable, and it can disseminate to people and pets bitten or scratched by a rabid animal. Rabies is a deadly virus spread to people from the saliva of infected animals. In the developing countries of Southeast Asia and Africa, stray dogs are the most likely to spread rabies to people. In Europe and North America, carnivores such as foxes, raccoons, and skunks are common reservoirs. In some areas of South America, vampire bats also carry the virus.

Rabies disease is estimated to cause 60,000 human deaths annually in approximately 150 countries, with 90% of cases occurring in Asia and Africa. Due to underreporting and unclear estimates, this number is probably higher. Once a person shows signs and symptoms of rabies, the disease nearly always causes death. For this reason, anyone at risk of contracting rabies should receive a rabies vaccination for protection.

The foundation’s board had concluded that most medium-sized developing nations should be able to acquire the capacity to produce inexpensive, safe, and efficient vaccines, which were needed to sustain preventive health programs and to gain effective control over the sale and distribution of biological products. The board members emphasized that this capacity implied mastery of large-scale tissue culture production techniques, especially viral vaccines. They also noted that safe and productive tissue culture-based vaccines manufactured in Europe or North America were too expensive to be widely used in developing countries to control the disease.

Preparing young talents in developing countries would empower such countries to acquire newer technologies to be transferred from well-known traditional reference research centers. Multinational pharmaceutical companies or corporations see no advantage in producing low-cost vaccines for developing nations, since it is not profitable for them. Moreover, they are not interested in developing countries learning about modern industrial and technological vaccine production, which would be unfavorable if the new vaccines had high technology and competitive quality.

Ryan, who had proposed the project to the foundation’s board of directors, was named as the head of the project; he was the highest-ranking health sciences official in the foundation. He contacted consultants and experts in the field of vaccinology from the rooster of scientists provided by the organization. He had to look for scientists with long-term experience in the essential microbiology, virology, and biotechnology of the vaccine against the rabies virus, the organism chosen to develop the first vaccine technology. Ryan and the WHO directorate had to set up a rabies vaccine group of experts to establish the principal technical guidelines for the execution of the project.

Ryan finally decided on a group of eight scientists who fit the conditions needed for the task of visiting countries and institutions to define the ones most suited to carry out the endeavor. The group met at the foundation headquarters and started to devise a program of work. They considered what to look for and ask during visits and how to report their findings. They wanted to be impartial and transparent, finally using their group’s conclusions from the written reports to make fair decisions. Members were asked to provide information on the standards for producing and controlling tissue cultures and viruses needed for human viral vaccines and quality control testing. They had to foresee how to apply the technology and devise means to train personnel to produce it. They also had to measure and assess the capabilities of the countries chosen to participate in a technology transfer project. They planned to select countries most severely affected by the disease and institutes with the best likelihood of succeeding in receiving a high-tech technology transfer.

Ryan was a man of few words; he wanted things to be solved immediately at the end of his talk. His personality was that of an international consultant ready to give lectures on how to save the world from malevolence. He was tall, looking at the rest of the world from above. Ryan had a triangular head, was almost half bald, and had big, curious eyes. His face appeared pale, and he acted very seriously all the time. He sometimes preached instead of listening, but above all, he was an executor—he knew how to get things done and would move people to work hard to avoid failure.

The group was divided into smaller teams that went to diverse places from north to south and from east to west, but only visited countries that, according to the foundation rules, could have at least a minimum development in the way of buildings with fair processes and reasonably trained technicians. This was difficult; every country they visited scarcely fit the criteria. Therefore, the consultants were unhappy, considering that most places and institutes visited needed to be fixed and could barely be adapted to receive a new, very sophisticated technology and processes probably not easily understood by deficiently trained technicians.

The reports received after eight months of work wholly deceived Ryan. Visiting some old vaccine production units was completely an ordeal for most consultants. Some local technicians were convinced that the foreigners, even though very respectable and consultants from a world-known foundation, would steal some of their precious technical know-how of the “old-fashion technology” they had. In other places, it was the opposite: the local technicians were utterly embarrassed and reluctant to allow foreigners to see inside the laboratories. They knew that they were inferior in quality, that they needed to be cleaner, and that there were other better methods, although the local administration and directors did not care at all. Moreover, internal and external government quality control was almost absent, and official government supervision looked away from these. Most people wanted things to stay as they had learned and how they had done them for many years and acted as if they did not need anything new.

Ryan almost gave up; he could not understand why the process could be so ineffectual. The entire outcome was mind-blowing. He asked himself, “Why could it be so hard to find a place to teach modern biotechnology despite having an approved grant and several top-notch scientists willing to assist?” At last, he thought of one more ace inside his sleeve. He asked Donald, his most interested and expert scientist, to go, among other places, to several government institutes in China, where the production of health-saving products was starting. Donald was working in a government quality control outfit, and he was a man of determination. His appearance was fascinating, and his stance was strange; he was short, with gray, curly hair, a head a little big for his body, and prominent eyes. His body was always straight, and his pace of short steps resembled how a Disney character with his name walked. Donald appeared to be very active and energetic, like an activist from a political party.

Donald was up and away, heading toward the world’s most populated continent. This trip would be his first time in Asia. He did not know what to expect and could not speak Mandarin, so he had to depend on a good English interpreter to ask the right questions and receive the answers he wanted. Upon arriving at the airport in China, Donald needed help understanding the signs in written Chinese, which had many unreadable characters. The first Chinese he met was his interpreter. Still, the English from the interpreter seemed to be somewhat sketchy, and Donald needed help understanding his words. Hence, he felt that he was in deep trouble, as he could barely comprehend that he would have to stay at a government hotel named “Shufen.” He did not enjoy his time at this hotel or at any Chinese hotel he later used, but he accepted the hospitality that the Chinese offered him.

Donald visited at least five factories, all owned by local government authorities or partly owned by the central government. Donald’s written report sadly advised against going to China to set up a development project. The conclusion was that the factories in China that he had seen were, in his words, “rather Spartan,” austere, and not hygienic. Personnel had minimal training in industrial vaccine production, old-fashioned equipment, antiquated production, and quality control procedures and processes, which were very difficult to upgrade. What confounded him the most was the insurmountable quality control technology and equipment deficiencies for adequate and accurate results.

He even noticed that the animal colonies for testing vaccine potency did not follow international safety and animal welfare regulations. He added that it would take at least twenty years or more to have some new developments in the way of better vaccine production companies in China. The final comment made by Donald was directed at the idea that until the government allowed some private companies to set up and establish new companies, the situation would remain the same. In his words, there was a need for private competition that would oblige government companies to modernize and acquire new technologies for their factories. The reports of other team members from several places in Asia and the Americas were somewhat disappointing.

Again, Ryan became impatient, as he could not understand why the production of vaccines was so old-fashioned in the developing world. However, after analyzing these outcomes, he concluded that this was precisely one of the reasons for the need for a technology transfer project financed by the foundation. Nevertheless, he remained bewildered, considering that none of the consultant reports could recommend at least one or two candidate countries. Ryan expected that the group of experts would have many choices to choose from, but that was not the case.

In considering a place to start a pilot plant for the technology transfer, the group found that several countries in the Americas had previously shut down their rabies vaccine production facilities. Ryan was puzzled, so he did a quick search and found that a multinational company offered, for free, a sizable amount of rabies vaccines to a certain country. At that time, the government had sufficient vaccines for the following two years, completely overturning its old-fashioned production facility. Although the multinational company did not supply more vaccines two years later, the country’s old vaccine factory was dismantled. After that, the government of another developing country started to import a considerable number of rabies vaccines for human use from international pharmaceuticals at astronomical prices.

Ryan even found another country with an ancient system to produce rabies vaccines for human and veterinary use, utilizing the old technology of suckling mouse brains. The building and facilities had not been modified or updated in the previous ten years. Under pressure from international health authorities, the central government was forced to discontinue the production of the vaccine for human use and only continued with vaccine production for veterinary use. Therefore, the human rabies vaccine had to be imported.

After a few months, Mathew, another team member, was summoned by Ryan and assigned to visit a country on the new continent. They both had heard of a government-owned institute manufacturing veterinary vaccines. The institute was in total production, and the industrial production and quality control technologies for various vaccines had previously been transferred from institutes of Italy, France, and England.

Mathew was the youngest member of the consultancy team. He was another character with peculiar qualities. As a university professor, he was interested in bridging relations and projects with universities in the tropics. Mathew was small, thin, and short. His head was narrow, with blond hair and green eyes, and he appeared much younger than he was. Mathew was pleasant and seemed like a local professor, due to his looks and height. He was more intelligent than the rest of the consultancy team and blended rapidly within the local community, even though he spoke the local language with some limitations. He owned and piloted a small plane that he used to fly through Central and South America.

As Mathew prepared himself for his visit, he found out that he had previously met the company’s general manager. Mathew had also been a consultant at a university in the same country, and that the general manager was, at that time, the dean of the veterinary school at that university. They had been in contact for some time before, so it was straightforward for Mathew to get along with the job, but he had a vague idea what he would find. He received a warm welcome from the company president and immediately attended the inspection visit to the production workshop.

Mathew was very pleased with what he saw. He had already visited several vaccine production facilities in Asia and other countries, but this company was somewhat different. People were very knowledgeable of the processes and had considerable experience, and the buildings were immaculately clean. The production of veterinary vaccines was of high quality, and there was some research on new methods and procedures. Mathew was impressed to see the output of a different veterinary vaccine on suspended cells in bioreactors of at least four hundred liters. Moreover, it was evident that most processes complied with good manufacturing practices in the industry. He congratulated the general manager and the professionals and told them his report would be highly favorable. He soon left the country and prepared a report for the foundation.

The vaccine project task force was again convened at the foundation headquarters and met for a few days, during which time they heard and discussed reports, including those from Mathew. The members ardently discussed some of the reports that did not recommend any project or country, and the group was somewhat disappointed with Ryan’s efforts, which lacked any significant progress. After listening to Mathew’s report, they completely changed their mood and finally concluded that the veterinary facility was probably the best place to start the project. According to the team, this institute was the ideal place to set up a pilot facility for training in the most modern technology for producing vaccines for human use. The fact that the central government was the majority shareholder of the institute allowed the foundation to grant the project to the institute, since foundations should not support lucrative private entities.

Other reasons for the selection were evident to them. The selected laboratory was already producing veterinary vaccines against diseases of bacterial and viral origin on a massive scale, and the underlying fermentation technology was their primary technical know-how. In the committee’s words, the laboratory was impressive in its scope, size, and cleanliness, with everyone busy, knowledgeable, and organized. Moreover, the technicians also showed keen interest in the new high-density cell culture technology transfer.

Compared to other laboratories in the country and elsewhere, this institute had the most exceptional promise for effective technology transfer, given its vast experience with tissue culture and fermentation technology, efficient and enthusiastic professional and technical staff, and a modern, clean physical plant. The task force concluded that producing one human tissue culture vaccine in a first-class laboratory that already produces numerous viral veterinary vaccines would make scientific and economic sense. They also emphasized that many of the techniques needed and several pieces of equipment and supplies were already at hand.

Another significant consideration in choosing the veterinary facility was that the company was already producing a vaccine to control rabies in the animal population. However, the manufacture of the vaccine was highly manual, with a significant quantity of roller bottles being handled for cell and viral growth. The veterinary facility already had significant technological input from a well-known rabies research organization in Europe. Moreover, the institute was forced to improve and augment its production technology due to the collapse of rabies vaccine production in the national institute laboratory. An endemic virus had decimated the government health mouse colony utilized to manufacture the rabies vaccine, and due to the lack of vaccine for persons bitten by rabid animals, several people died from rabies infections. Consequently, the government mandated the veterinary facility to increase the vaccine production for dogs. In essence, rabies disease was a significant health challenge for veterinary and health authorities in the country.

Rabies can be transmitted from dogs to people in cities and rural areas, and blood-sucking vats can also transmit rabies to persons and animals in tropical environments, especially cattle and horse populations. In this particular country, there was a need for the large-scale manufacture of high-quality vaccines for human and veterinary use. Any new technology can also be utilized for the industrial manufacture of other viral vaccines for human or veterinary use.

There was an obstacle: the project had to be accepted by local health authorities. They had to agree that a novel human vaccine would be produced in a veterinary manufacturing plant and not in their facilities, where other older regular bacterial vaccines were being manufactured. The common practice at that time was that buildings and constructions for veterinary products were separated from human manufacturing plants. The government health institute manufactured the rabies vaccine for human use using old suckling mouse brain technology. In this case, the veterinary biological products facility, Totem Inc., was the most modern, better equipped, and had better-trained personnel and much more extensive experience in advanced techniques. Several company technicians also had previous overseas training.

Totem Inc., a veterinary manufacturing plant, was currently the best in the country, and everyone agreed that it was the best in the region. Its general manager was Larry. He was a half-technical, half-politician who came from a well-endowed family from a productive cattle-grown country region. He was the best student in the capital in his graduating class, with a university degree in veterinary science. After graduation, he returned to his family farm. Following his father’s death, and after managing other businesses, he was convinced by some friends to enter politics, so he went back to the capital. With newly acquired political friends, he was soon named general manager of Totem Inc., the veterinary manufacturing plant in the capital. Larry was a visionary and a superb leader who converted into a businessman. He was also a problem solver who had already transformed the veterinary manufacturing plant from an old-fashioned outfit into a competitive modern production enterprise. Most areas of Totem Inc. had new equipment and trained personnel from new consultants from several countries in vaccine production and quality assurance capacities.

Larry was also a high-ability entrepreneur and organizer; he made the company appear in an advertisement in the “Cycling Tour de France,” which, at the time, was one of the most viewed sports broadcasts in the world. Larry had to use his abilities as a negotiator and politician to convince the physicians in the ministry of health that for the national interest, Totem Inc. was the best place to start the project. There were several series of meetings, discussions, negotiations, and transactions. Larry even invited scientists from the government to visit Totem Inc.’s facilities and personally observe the production process. The visitors were impressed but had difficulty understanding and accepting that a veterinary factory had much better facilities, equipment, and even technical personnel than they had in the ministry of health laboratories. Larry also sent some maintenance personnel to visit the government production facility and assisted in facilitating the operation of a bioreactor that no one had been able to repair. The whole ordeal of negotiations permitted the initiation of a warm, functional, and lasting relationship between the two institutes and their leaders.

To further improve the relations between the two institutes, Larry approved that two of his clinical veterinarians would collaborate with the health institute on technological matters relating to the institute’s animal colonies. The most important were those associated with handling the laboratory animals needed for quality control of the final vaccines, especially those for the potency test of the rabies vaccine. The veterinarians also assisted with improving the processes for producing very effective rabies immune serum in horses on one animal farm on the city’s outskirt. The serum was used to treat persons with highly acute disease due to bites from rabid animals.

On another occasion, Larry learned of the difficulty the government health sciences institute had with a viral vaccine for human immunization against tropical diseases. The vaccine passed all the internal physical and chemical tests, but mice injected to analyze the safety of the vaccine all died. Larry offered to bring a specialist from a university in North America who had been to Borazon City before, the site of Totem Inc., to solve similar problems with other avian veterinary vaccines. The government health institute director accepted the offer. The scientist completed two days of examining the vaccine from all kinds of parameters, using physical, biological, and chemical tests, and could not find anything wrong with the vaccine.

The scientist was puzzled but did not give up, so he asked for a sample from another older vaccine lot in the market that had passed all the quality tests. He used that vaccine sample to inject the same mice from the same source used for the previous tests he had done, and sure enough, the mice also died: eureka, something was wrong with the mouse colony. The visiting scientist examined the mouse colony in depth. After five more days, he discovered that the mouse colony had recently been infected with a virus that did not produce distinct signs or external symptoms but could develop a latent infection. He noted that he had seen many viruses in humans and animals with similar patterns, and that humans could be asymptomatic while harboring the disease-producing virus. Consequently, the mouse colony had to be replaced, and the vaccine passed all tests on a new mouse breed. The scientist received all kinds of gratitude from all concerned, considering that he had saved thousands of vaccine vials and a lot of money.

Regarding the approval of the move, the minister of health was not convinced at all and argued for some time against it. He was concerned about being brashly criticized by the medical community for not being allowed to get a foundation grant to a medical institute instead of a veterinary facility. However, after much analysis, he was convinced that the foundation would keep the decision; the board had already chosen the veterinary facility. There was no way to revoke the decision. Consequently, he eventually found some joint support and reluctantly admitted that the foundation-sponsored project could occur in the veterinary factory. He requested that in compensation, the foundation financially assist a new laboratory unit for quality control of biologicals on the health institute premises. He also required that Totem Inc. personnel teach some Ministry of Health technicians whatever was learned about production systems and quality control from the technology transfer project. As this was the mandate of the foundation’s board, Ryan and the foundation accepted it. So the project could now move on the right track.

The foundation selection committee also chose two other visited countries as follow-up countries in case the project could not be concluded at the veterinary facility. These two countries would act as the first recipients of the technology from the pilot plant that would be set up in Borazon City on the premises of Totem Inc. Therefore, the pilot plant would become a training facility for distributing the technology to other countries and institutes elsewhere.

The next step for Ryan and the foundation was to find who had the best technology to be transferred to the new, well-chosen recipient. He thought this search would be easy. After all, he finally found that many scientists around the globe had published plausible vaccine technologies. The inquiry started in North America, then Europe and Japan, until finally, Riley, an institute in Europe, was located. It was a government institute that produced vaccines for human use and researched manufacturing technologies. One of the scientists working there was Peter, a world-known researcher. He developed a technology that revolutionized the possibility of the large-scale manufacture of vaccines in reduced spaces and small volumes using a high concentration of various elements. He had reasonably described and published a cell culture system that would be a base for developing a fermentation production scheme that could compete with systems already in use by multinational biological producers.

Ryan traveled to Riley Inc. laboratories in Europe to visit the scientist. Peter’s laboratories were far from neat. The spaces were in complete disarray, and he would not allow any cleaning personnel to enter the rooms he was using to cultivate cells and operate the bioreactors. He designed and adapted the laboratories to the technology that had developed. He also designed the bioreactors, which were relatively small, workable, and ingenious. Peter was a one-of-a-kind scientist who was interested only in his laboratory, cells, and bioreactors.

When Ryan first entered the scientist’s laboratory, Peter did not pay much attention, thinking Ryan was just another seller trying to convince him to buy another chemical for his experiments. Later, Peter listened carefully, slightly interested in Ryan’s explanation of the project and the idea of transferring his technology to developing countries in Asia and the Americas. Then he started laughing, which made Ryan ask if he was deranged. Peter responded that transferring his technology to any “underdeveloped” country was almost impossible. Peter explained that his technology had many components that had taken him years to develop, which would pose great difficulties for technicians to master unless the recipients had considerable previous experience in handling cell cultures. He even argued that there was a lack of well-trained professionals with advanced knowledge of industrial vaccine manufacturing processes in the world’s developing areas.

Ryan calmly explained to Peter that a group of scientific experts had visited many laboratories and institutes in Asia and the Americas and that they had chosen a laboratory in the Americas that had considerable experience in tissue culture techniques. He also explained that this laboratory had already been selected as the technology recipient. Ryan went through many explanations to convince Peter that it was worth trying, but Peter was not entirely convinced. He eventually agreed to visit the company but stressed that if he found anything wrong, he would not accept the offer. He emphasized that he could not make miracles, but Ryan assured him that he would not regret going there to look. So Peter was reluctantly ready to go to Borazon City and Totem Inc.

Sometime later, Peter admitted that he had accepted the offer to enjoy the trip to the New World. It was going to be his first trip to the American continent, and he did not have any hope for the success of the project in a country under development. The objective was to produce the best vaccine at a reasonable profit and at a much lower market price than those available from multinationals so that people in developing nations could afford it. In his scientific publications, Peter described the preparation of vaccines in tissue culture as a “unit process” with specific cell and virus cultures, followed by concentration, inactivation, and purification of the viral harvest. The principal advantages of this cell culture vaccine, aside from the high-density cell concentration, were the innocuity achieved by the purification procedure and the absence of proteins in the final product, both of which ensured the absence of adverse reactions.

A significant advantage for Ryan was that Peter’s government-owned institute and its scientists had free hands and resources to operate, and there were no restrictions on the distribution of the research results. However, Peter was willing to try to transfer the entire system to a developing country. He would set up the pilot facility to demonstrate it and produce some vaccine lots for internal local analysis and for the government agency in charge of certifying new products.

The foundation’s board of directors had to assemble and study the proposal to finance Peter and his institute for this transfer. Ryan began introducing Peter’s accomplishments and work. Some board members interrupted the presentation and asked how this superb work had not previously transcended a large pharmaceutical conglomerate. However, another board member explained that Peter had already published the essential core of his findings in several international journals, although he had yet to scale it up to commercial industrial bioreactors. A board member also speculated that any multinational pharmaceutical company and its research teams and expert scientists could have designed a large bioreactor. Some companies had probably already integrated Peter’s primary findings and perhaps were no longer directly interested in his technology. At the end of the discussions, it was clear to all board members that the technology was excellent and could be scaled up to the industrial and commercial levels with an additional research effort financed by the foundation grant.

Finally, the board accepted the budget Ryan had prepared to start the project with the newly found Peter´s institute and the research scientist’s advanced technology for cultivating cells under high densities. The benefactor had to transfer a sizable contribution to Riley institute for their generosity in donating the technical know-how. The technology transfer would cover the technical know-how and expenses of project preparation, equipment, reagents, and Peter’s travel and work with the recipients in the New World. The project could start at the Totem Inc. veterinary facility in Borazon City.

Peter’s institute was responsible for preparing a complete description of the project, the technical elaboration of the construction plan for the pilot plant, and the identification and purchasing of the necessary equipment for production and quality control. Peter had to train staff in several technological fields and monitor visits to the recipient laboratory. The most critical tasks Peter’s institute had to accomplish were supplying the whole production and quality control procedures and providing the master and working cell and virus banks with standard reagents. He was also responsible for the quality control of the initial vaccine batches and the follow-up of the whole project for at least eighteen months to two years after the satisfactory functioning of the pilot plant.

Peter planned the trip to the New World, packed his baggage and papers, and took a plane to Borazon City alone. He remained somewhat skeptical of this trip. As this was his first trip to this region of the world, he was still unsure about what he would find. He was not convinced that his technology could readily take root in a new environment that needed many things. He was even more skeptical of the technical personnel and their technical know-how to master his highly sophisticated technological package. He prepared for the worst-case scenario.

David, a scientist from Totem Inc., met Peter at the airport. Peter encountered his first surprise, as he immediately found out that his counterpart spoke fluent English. Some of his anxiety was alleviated, as he immediately thought he had someone he could to talk to. Both men headed toward Peter’s hotel. Peter was a tall man with light blond hair. His face was reddish, donned with big black spectacles, and half covered by his thin hair in disarray. His eyes were also half-closed, and he always appeared smiling but seemed anxious and analytical. The following day, David came to pick him up and drive him to the institute. During the drive, Peter confessed to his host that he would rate the hotel five stars. He shared that he had previously thought that there were no five-star hotels in this part of the world and felt ashamed of his initial thoughts. He acknowledged that he was well cared for and felt almost at home.

When Peter arrived at the Totem Inc. manufacturing plant, he was immediately taken to the general manager’s office and welcomed there. He again was surprised to see that the offices were very modern, clean, neat, orderly, finely decorated with some famous local antique paintings, and very well designed. After the official exchanges of diplomatic words, Larry, the general manager, assured Peter that he would be supplied with all he needed for the project. He assured him that David would ensure he was well cared for. He then offered the visitor a native cup of tea, which Peter admired.

Peter was taken to the laboratory and introduced to Olga and Jesus, two vaccine scientists. Another surprise for him was that since he had never before worked with a woman laboratory researcher, he thought this field was more inclined toward men than women, so he immediately began to think, “This is not going to work at all.” He was then introduced to the rest of the staff and was shown all the equipment, supplies, and laboratory arrangements. Peter was pleased to see that the labs were well-equipped and well-kept. In one of the labs, he suddenly noticed an unusual medium-sized bottle with a gadget that he had designed and that appeared in one of his scientific publications. Again, he was not only surprised but was thrilled.

Peter could not understand how a country on the brink of development could have learned of his inventions and even had them working in one of their laboratories. He finally began to understand why this laboratory and its staff had been chosen to receive his vaccine technology. He became relieved, thinking that the project could be a success. At that moment, he did not see many obstacles in the way and realized why Ryan had praised the company and the staff.

Peter began working with Totem Inc. on the project. He made the first drafts of the design of a new area to house the pilot plant. Peter explained and delivered the significant components of a few documents and defined some specialized equipment and reagents needed. He also emphasized the need for local services and instructed local technicians on the essential elements of the technology. Peter also described the terms of reference and defined a schedule for the technology transfer program.

After four days of hard work, Peter had time to go sightseeing. David and Olga took him on a little cable car ride to a small mountain with fantastic city views. On top of the hill was a good restaurant, where they had a lovely meal. Peter was happy to taste a local dish made from red beans, pork scratchings, ground meat, fried eggs, and white rice. After a quick view and admiring the scenery of some old colonial buildings and churches in the city’s oldest section, they returned him to the hotel.

The next day, before leaving the country, Peter took extra time to talk to Larry, David, and the scientists in charge of vaccine production. He used a few words, but all of them were in appreciation of his satisfaction during his stay. He conveyed his feeling that the joint undertaking would succeed due to the readiness of most of the factors needed to develop the project. He confessed that the things he had found were much better than his initial thoughts but apologized for being so misinformed and incredulous.

Peter took a plane back to Riley in Europe to continue preparing for his new project. Upon arrival there he developed a floor plan with a layout with his team of engineers and technicians. The group also started working on the lists of equipment and supplies to be bought in Europe for the new pilot plant. Peter began to describe the technology to be transferred, design a process, choose equipment, set up production and quality control processes, and define a schedule for site control visits. Peter had a sizable budget from the foundation grant and could choose highly modern equipment and the best reagents. Some of the available machinery was even better than the one he had in his laboratory. He was, therefore, glad that the project would be the most advanced with this kind of support.

At Totem Inc., the recipient laboratory, workers had started preparing the pilot area where the project would be located. The walls and panels of an existing building had to be modified according to new international health regulations and recommendations for human vaccine production. The foundation provided the cost of the technology transfer and significant equipment and oversaw the training of the technicians. Still, the recipient company had to execute some remodeling, so there was a need for a budget for the task.

The technological transfer project was explained to the board of directors of Totem Inc. Some board members were reluctant to invest in setting up a pilot plant, which would also be used for training foreign personnel from other countries. They questioned how they could risk the presence of other technicians and health professionals inside the production areas where different products were manufactured. They were concerned that some of the private technical know-how could be stolen.

Other board members were reluctant to invest in technology to produce and commercialize a human-use vaccine. They felt that the company had been, from its inception, a producer of veterinary vaccines, and the company did not have any experience marketing any product for human use. Other board members stressed that the company needed to prepare for such a compromise. At the end of many discussions, the body of directors finally approved the budget. They concluded that procurement of the new technology justified the risk of losing some techniques that may be old-fashioned and that the marketing issue could be solved in the future.

The organization of the pilot plant at Totem Inc. continued. New essential basic equipment was ordered through the foundation’s financial assistance, and the remodeling of an old area was accomplished, which made all technicians in the vaccine production areas very proud. The company had to designate professionals and technicians who would be engaged in developing the pilot plant project. Some would have needed to be trained locally and in overseas laboratories with new procedures and equipment.

Larry had to ensure the project’s smooth development. He chose a well-trained and capable scientist to be in charge of the work, who happened to be a scientist he had hired a year earlier to head the research projects at Totem Inc. David, who had welcomed Peter, was later confirmed as the project leader.

David was a trained virologist with overseas graduate studies and vast experience in various local and international research institutes. He had a lot of laboratory and field research experience but limited hands-on experience in industrial vaccine production, so he would have to learn a lot while leading the project. David was a calm but steadfast leader who had already directed several successful research projects and was in charge of extensive groups of personnel in international institutes. Due to the time spent overseas, he had an excellent command of English, which was a plus for the smooth development of the technological transfer work.

Next, technicians for the laboratory work were selected. Everyone at Totem Inc. was interested in the opportunity, so the selection was severe, as most technicians felt this was a once-in-a-lifetime chance to be above others and be well-known and respected in the local scientific community. The final recipient team, which included three men and two women, was accepted with reservations. Among the many conditions, a good command of English as a second language was a premium in the ultimate selection. Another critical factor was previous experience in the work on cell cultures, handling bioreactors, and performing several quality control processes.

The initial people chosen were Jesus, Diego, Luis, Laura, and Olga, who will be later introduced in the narrative. Olga, a competent, intelligent, and dedicated woman, was named the team’s coleader. Whether she became a critical element in developing the whole process remains to be seen. She was the woman introduced to Peter during his first visit to Totem Inc., who was surprised to find a woman in vaccine production research and development.

Chapter Two

1985–1986

Unpredictable

Meanwhile, Peter, the transferor scientist, took a short, deserved vacation for the summer at a resort on the Greek islands. While vacationing, an unexpected event happened: he was found dead in his hotel room due to a fatal and massive brain stroke. He was only fifty-four years old. A stroke had ended his highly productive research and scientific life. Peter’s premature death caused a serious setback for the project. Everyone was shocked because the laboratory work had not even started, the foundation had already invested a lot of time and resources, and the man who had designed and tested the best possible source of technology was gone.

The people at Totem Inc. were disconcerted, especially David and Olga. They both felt that Peter and his technique were unique and valuable for the vaccine production development of many countries, and now he was inside a casket with all that knowledge. The technology transfer project had taken a new, unpredictable, hard-to-resolve road ahead. It took several months for the people involved in the project to realize what had finally happened.

After mourning Peter’s death, Ryan, the foundation’s benefactor, waited patiently for many months to resume the project with Peter’s colleagues at Riley Inc.. He had called the institute’s leaders several times to find out what was happening with Peter’s work, laboratory, and projects. Still, the answers always had many blank spaces, which Ryan felt were somewhat deceitful. Considerable time had passed, and there was no noise from the Old World, so Ryan contacted David, and both decided to visit together.

Ryan and David travel to Riley Inc. in the middle of Europe’s winter. The welcome was timid and not very warm, and Peter’s science colleagues were more patient, with apparent meager information about Peter’s technical know-how. The visitors, along with the local scientists, globally analyzed Peter’s laboratories and had difficulty locating a written trace, scheme, or clear diagram with essential detailed explanations of the technology that Peter had developed. They could see some bioreactors he had designed and some papers with many notes, but they could not find clear written standard procedures. What Peter had created had to become a scalable process for the industrial production of biologicals. Still, the visitors could not find a system description that could be given to other scientists to execute a scalable process with details of the technology and the procedures required to be included.

Peter had already published in international journals the basics of the new cell culture technology to produce, among other things, several vaccines for human use. Still, no one but him knew how to scale it to industrial production, much less how to do it on any scale and cheaply. The production facilities had to be small to reduce maintenance and installation costs, and the technology products had to be of high quality but at a modest fee for the patients. Ryan was dumbfounded. Riley Inc. had already been explicitly funded for this project. Many resources have been spent but precise, complete technology was not in sight. Ryan finally asked the director of Riley Inc. to designate a team that would go to Borazon City in the New World.

David, the scientist from the recipient country, lived in a sub-tropical country and was not used to the sudden cold in Europe. He waited patiently to pick up his luggage when he got off the plane, but after an hour of waiting, he was told that the bags had probably gone off track during a plane transfer. The officer told him that he did not have to worry and that the piece would be delivered the next day to his hotel. Unfortunately, he could not find his winter coat because he had placed it inside his luggage in Borazon City, since it was a little heavy to carry inside the plane. So David had to go out into the freezing temperatures without a coat. He decided he could catch a taxi and would be at the hotel in no time. The first taxi driver that stopped told him, “Look, your hotel is just across the park; you can even see it from here; it is only ten blocks away, and you can walk there,” and then he left. David did not give up; he stopped another taxi, but the answer was the same, and even the driver added a new sentence: “I cannot take you. It is too short a drive. Get out. I need another passenger.”

Here is a fellow who has no experience handling sub-freezing ambient temperatures. Even without a warm coat, he was told to walk through an open park without any other notion. David eventually started walking through the middle of the park, a vast open space. The air was very windy, with freezing temperatures and a low chilling factor. To top this off, he developed a cold overnight, yet another calamity for David and the meeting. Fortunately, one of Riley Inc.’s scientists had an effective recipe that, by the next day, started to relieve the uncomfortable symptoms of the cold.

Despite the substantial initial surprise of the lack of knowledge about Peter’s technology at Riley Inc., Ryan had to ask Peter’s colleagues to go and see what was being done at Borazon City. They were not entirely convinced, but in the end, they agreed to go. Consequentially, they traveled across the ocean and arrived in the New World. This time, just as with Peter, they were warmly welcomed and greeted as saviors. Like Peter, they thought that the local technical conditions were poor. They imagined to suggest a few improvements, and offered to later bring some of the equipment Peter had designed for adaptation to the local conditions. In their minds, the matter would be easily solved; however, they were in for a bit of surprise.

The next day, the visitors were taken for a visit to the factory and found that Totem Inc., the veterinary facility, had many more scale-up bioreactors and other processes that were much more prominent and modern than the ones they had at home. Although the institute lacked the high-density cell culture systems that Peter had designed, the scientists were very familiar with the technology he had developed. However, the fine details of the design and operation of the bioreactor, the type of cells, the growth media formulation, and many other elements for the industrial production of a rabies vaccine for human use were not available in Peter’s publications.

The two old-world visitors from Riley Inc. saw and examined the local preparations for setting up the pilot laboratory. They visited all areas and were particularly impressed with the laboratories for quality control and quality assurance. There were several conversations and talks among the parties from both institutes. They reviewed the lists of equipment, including the pieces Peter had prepared, and compared the costs of the apparatus with similar pieces that could be bought in North America. They found that every type of material that Peter chose appeared to be thirty or forty percent more expensive than their equivalents in North America.

It took a lot of wheeling and dealing to convince the visitors that buying all equipment and supplies in North America rather than Europe was more convenient. Moreover, most suppliers had direct distributors in the local country, and spare parts were more accessible. Plus, the equipment’s technology appeared to be more uncomplicated and more comfortable to run. The two scientists from Riley Inc. could have made a better impression on the group from Totem Inc. They appeared to have little command of industrial biotechnological processes, although they were more laboratory research-oriented. The most critical perception was that they needed a better grasp of Peter’s technical know-how and to be interested in the research work to scale it up. The whole situation again was mind-blowing.

Back in the laboratory, everyone was increasingly missing Peter’s legacy and felt sorry to sense that something was being lost. The technicians realized that Peter’s legacy transcended boundaries and thought he should be honored. Larry, the general manager, ordered a plaque in Peter’s honor. Two days later, in a very moving ceremony with the participation of the visitors, the plaque was unveiled in one of the vaccine production corridors, and Larry made a sentimental homage. The ambassador from Peter’s country was also invited to attend the ceremony. The two visitors from Riley Inc. and the ambassador were treated with considerable courtesy and were surprised by the significant appreciation given to Peter’s memory. Later, in private, Larry, David, and his scientists discussed the project’s status.

Beyond the general overview, nothing was revealed. No one at Riley Inc. knew precisely all the details of the technology Peter had developed. They needed to be more ready, interested, and capable of pursuing the technical know-how to transfer the technology and the innovations Peter had set out. Somebody needed to know how to answer this predicament. The group at Totem Inc. was very disappointed, since they needed accurate and complete feedback on Peter’s work, so they had to be very honest with the two scientists from Riley Inc. and tell them so. Disenchanted, the two scientists finally left Borazon City to return home to Riley Inc.. They felt the trip was a waste of time, because they learned nothing of significance about the project.

David needed to determine how to tell Ryan that the visit of the two scientists did not reveal any answers concerning the knowledge of the technology that Peter had developed. He decided to call Ryan and inform him about the outcome of the visit. Dumbfounded, the next day, Ryan got on the phone and talked to Riley Inc. managers and scientists. However, he received the same evading answers that David and the scientists had received at Borazon City. In need of a credible solution to this dilemma, the general manager of Riley Inc. confessed to Ryan that his scientists did not have the fine details of the design of the bioreactors, much less information about the operation of the technology. There were no specific details of the components of the formulation of the growth media for the cells and virus multiplication.

David could not believe that a developed country with numerous scientists, technicians, up-to-date equipment, modern reagents, and beautifully designed laboratories, and now, with additional funding from a world foundation, could not cope with the continuation of the work of one of their most illustrious researchers. The fact that the leaders of Riley Inc. were reluctant to reveal the status of Peter’s technology was mind-blowing.

Ryan was again furious. He had aggressively pressed for the project’s advancement through the foundation’s board of directors with many difficulties. Then, after three years and choosing probably the best transferor scientist and most appropriate receiving institute, Peter, the brain behind the vital technology, was gone. Moreover, an old-time, well-known, sufficiently advanced institute in a developed country with a financed project needed help with technological transfer. Critical parts of the knowledge and expertise were gone, laid inside a casket within Peter’s brain.

Ryan thought that the allowances given to Riley Inc. were hardly spent. Several minor pieces of equipment, supplies, and reagents had been ordered and were soon delivered. Still, Ryan had to find out how to recover the remaining money allocated to the institute, as those funds would need to be transferred somewhere to a new expert scientist or research institute to continue the development of the transfer project. Ryan called David and asked him to get an airline ticket to accompany him again to visit Riley Inc.. Unannounced, they both arrived there and were not greeted very warmly. Nonetheless, they informed the general manager of the institute that they would need to examine all accounts of the grant money given to Peter.

The institute manager reluctantly allowed Ryan and David to enter the accounting department and carefully inspect all papers, expenditures, and authorizations Peter had executed. Nothing was evident at all, and the effort was of no avail, since the grant money had been mixed with other technical projects. The head of the project, who could explain this undertaking, had passed away. Ryan and David felt saddened and completely frustrated. Ryan could not hold back, as he fervently complained to the Riley Inc. managers, who were still struggling to offer a solution. So Ryan and David had returned home, again empty-handed.

Meanwhile, Ryan felt intimidated, ashamed, and bashful to go to the foundation’s board of directors to tell them that the money had been spent and that the transferor scientists had passed away. Ryan’s report to the board of directors was received with dissatisfaction, and several members said they needed to know where the money went, whether everything was spent, and how. The foundation’s board of directors instructed Ryan to go there with the comptrollers from the foundation to see if they could find out what was going on. One more time, Ryan asked David to accompany him and the comptrollers to travel to Europe, visit Riley Inc., and make another effort to recover anything from the installment already made.

The group traveled to the Old World. The comptrollers took considerable time to examine everything available to them. They found that Peter had made many expenses in preparation for the technology transfer and was marked to be utilized for the project at Totem Inc. However, many were for other projects Peter was conducting at the institute, but according to the officials at Riley Inc., the money from the foundation grant was expended. The director of Riley Inc. expressed genuine apologies but explained that they could not return money that they did not have. Ryan, David, and the foundation comptrollers had reached their wits’ end and had no choice but to return home another time empty-handed.

So the foundation could not recover any grant money left over from its grantee, Riley Inc.. Three years and close to one million dollars have been spent, most of which were given to Peter’s institute to realize that the project and there was nothing to show for it. Ryan was occupied with what he should do next. Ryan spent a few months recovering from those technical, financial, and almost physical blows but encouraged himself and returned to the drawing board. He thought he had half of the starting point—at least an approved grantee ready to receive the technology. To resume, he contacted several university professors, as that he now had a better understanding of the vaccine technology business. He had discovered that several institutes and university researchers had pieces of vaccine technology components and knowledge similar to the technology developed by the deceased Peter. He felt that if he could find someone who could set these components together, a new vaccine system could materialize.

Ryan utilized the character of his beliefs and once again decided to ask the foundation’s board of directors for more funding to reopen and continue the transfer development project. He had to explain his new tactic to the foundation’s board to plan and handle the task. The battle was fierce this time, but Ryan tried to show board members that technology transfer was difficult, even within old technical institutes. Some of the board members again argued that new, very modern technology in many fields could not be transferred to developing countries, even emphasizing that technology in the biological field would be even more complex to share. It took a lot of convincing arguments from Ryan for the board to give it another try. For some board members, this started to become a challenge. Eventually, the board agreed to a new grant, primarily considering what had already been spent with minimal gain and with somewhat thin confidence but with an expectation of the best outcome.

Within himself, Ryan asked, “Why on earth am I in this, risking my position when probably nobody wants to share such specific knowledge? Is any institute or commercial company willing to share some modern vaccine production manufacturing technology in exchange for a grant?” He had to work hard to find answers. So he decided to conduct a comprehensive search again. As a man with unlimited personal resources and a researcher with several scientific publications on tropical diseases, he had many contacts in the medical and scientific community in many countries. He looked all over for a few months. Eventually, he located Roger, a well-respected cell scientist and university professor who had been in contact with Peter, the designer of the original technology. Roger also knew of Peter’s accomplishments, publications, and the heart of his discoveries for the laboratory’s high-density, large-scale growth of living cells.

Roger had a doctorate in cell biochemistry. He was a teacher and department head at a well-known university where several graduate students worked for him in areas very much related to the biochemistry of cells, investigating ways to control cancer cells to multiply in living organisms. Roger was willing to share some of his knowledge for a university grant and liked working overseas on development projects. By mere coincidence, Roger had patented a system for his university to grow cells in high densities, similar to the one described by Peter in his publications. However, Roger’s knowledge was only at the laboratory level rather than in a semi-continuous system for industrial production. Ryan also had concerns about getting a grant for a university, given the possibility that the university executives would later ask for royalties on any information Roger gave to a third party. Still, after considerable analysis, he dismissed the concern.

This time, Ryan was becoming convinced that he was on to a new start. This time, however, the process would be more complicated and lengthier, since the whole technological process had now to be assembled from pieces of knowledge spread through several places, different scientists, and several organizations. Roger was one of the scientists; however, he needed to gain experience scaling up methods for industrial manufacturing and the growth of highly infectious microorganisms, requiring superior, very sophisticated concealed units. Roger’s practical skills and unbeatable knowledge of biochemical cell metabolism and growth were limited to laboratory levels. He had also designed very small bioreactors capable of high cell densities; the only problem was that those bioreactors could maintain cell growth only in a batch system or single operation. They would need to be scaled up to the semi-continuous flow of nutrients and harvest for industrial use.

It was clear that one crucial factor was a bioreactor capable of scaling up to industrial levels. Ryan asked David if he would be willing to go to a few places where scientists claimed to have bioreactors for high-density cell cultures. David was more than happy to do. He was a travel addict and had already been involved in scientific projects and meetings in several countries in Europe and North America. Ryan gave David names and places he had found worth visiting and exploring. David immediately canceled some of his duties as a research manager at Totem Inc., purchased his airline tickets, and flew to see at least two European countries. In the first country he visited, he found an institute where a clever scientist showed him a nice bioreactor with a total capacity of ten liters, which he had designed. The scientist had some cells growing inside the vessel, and everything looked right. Still, when David asked for the concentration of cells within the bioreactor, the scientist explained that he only had approximately four million cells per cubic centimeter. David was quick to congratulate him for his superb design and respectable achievements.

Indeed, this laboratory was doing fascinating research on several aspects of cell multiplication, and David listened carefully to his host. After leaving the laboratory, David thought that although the bioreactor looked highly productive, there was no way that it could be used for the industrial production of vaccines, since it was only a batch system and the quantity of virus obtained in this system would not be enough to formulate many vaccine doses. By comparison, the original Peter’s bioreactor could handle approximately eight million cells per cubic centimeter. David then left for a visit to another laboratory after sincerely thanking his host for sharing the information.

David found another beautiful laboratory on a university campus and was directed to meet a research scientist who wanted to show one of his most valuable tools. The scientist explained his research on the cell behavior of cancer cells using a small bioreactor of his design. The apparatus was quite clever and worked to the complete satisfaction of the scientist. Instantly, David asked the scientist to assess whether his device could be scaled up to industrial size for vaccine production, and the answer was no; he did not think it could be possible. Once again, the scientist described his system as only a batch system. Even though David did not expect to find something beneficial, he was sorry to discover that most scientists did not worry or think about developing a scalable system for industrial vaccine production. As he took a plane to return to Borazon City the next day, he felt a bit down. He prepared and sent a written report to Ryan. The news did not entirely surprise Ryan, but he encouraged David to continue the search and that he should extend it next time to North America. He had to visit other places.

Four weeks later, David traveled to North America to look for a manufacturer that could design a device for cultivating high-density cells. With one connecting flight and a long travel time, he arrived at a small factory. After the formal introductions, he was taken to a shop that housed several types of equipment, probably for many different purposes. He was then shown a very peculiar device that, contrary to what he had seen in many places, was not a regular vessel. It was a medium-sized piece of stainless steel with hundreds of small tunnels that went from one side to the other. The manufacturer was growing cells inside the device, and the cells were growing on the inner surface of every tunnel, increasing the available surface for them to attach.

Even though it was a clever idea, there was no way it could be scaled up to the industrial production of vaccines. For culture large cell volumes, the device had to be several meters long, which would be inoperable, and to feed nutrients to the cells, a powerful pump would need to be attached. Due to the length of the tube, some cells would begin to detach, losing the capacity to produce the virus in industrial amounts. Although it may have had other applications in the research field, there were none for the development project. After congratulating the manufacturer of the industrial design, David left the premises to find another laboratory working on bioreactors capable of growing cells at high densities.

Ryan already had another laboratory for David’s visit. It was located in the western part of the country. The host was very graceful and said he was pleased to receive a visit from an ambassador from a well-known foundation. David had to explain that he was only a consultant for the foundation, interested in finding equipment to grow cells under high densities. He was then taken to a large laboratory, where many researchers were busy with many different kinds of equipment. The host showed him a ten-liter bioreactor equipped with a decanting system. During a media change, the old liquid media within the vessel was released to the outside while new media was fed into the vessel. The released old liquid media had to pass through a special filter to retain cells detached from the inside of the vessel.

The technician had to clean the filter, push the growth media back, and return the attached cells to the vessel. The inside of the vessel was like a system that David had seen in the previous visit, with many small tunnels on which the cells had grown. However, when David asked if the filter was partially plugged at some time, the answer was that the system was still under investigation. The technicians accepted that they still needed to solve the filter clogging, which hindered the continuous media perfusion. However, there was no constant high-density system, since the cells would not grow too high inside the vessel due to the plugging of the filter system. Even though this device was not yet workable at the industrial level, it was in the right direction. Once again, David had to return home, disillusioned after another unsuccessful trip but full of lessons and new knowledge. Once again, both Ryan and David had to return to the drawing board.

Ryan had to find someone with practical skills at the scale-up level of the industrial production of cells, which was only part of the knowledge lost when Peter suddenly died. Six months later, in his long quest, Ryan found a scientist couple with considerable expertise in cultivating microorganisms, especially for manufacturing large-scale antibiotics, and with a biochemical background. They had retired from large pharmaceutical multinational companies and were consulting for several private and government companies in several places worldwide. The couple also worked on development projects in some countries.

Since their retirement, the two scientists, Frank and his wife, Elsy, had been working together. They advised companies and groups on different processes and microorganisms without infringing privately owned technical know-how from the companies they had worked for. To add to the many coincidences within this technology transfer project, these scientists had been advising Totem Inc. periodically on several occasions in the previous two years, solving difficulties in the production of veterinary vaccines. They had assisted Totem Inc. in operating suspension cell cultures in large bioreactors of one thousand liters and in-process control of several biologicals. However, these bioreactors were only batch systems for different cells and viruses and were unsuitable for human vaccines. They told Ryan they were delighted to help and would be ready to join the effort in a few weeks.

Frank obtained a Ph.D. in biochemistry, devised the production of antibiotics in large vessels of more than twenty-five thousand liters for a multinational company, and coordinated research at a large pharmaceutical conglomerate. He was also involved in constructing good manufacturing practices for biologicals for the local government. Frank was a real scientist, a gentleman, and a very polite person. He was soft-spoken, had standard height, big light-green eyes behind massive spectacles, and had a light mustache and a pleasing posture. He was brilliant, always asked the most appropriate questions, and with the answers he very rapidly knew what was most likely happening in any industrial biotechnological laboratory procedure.

Elsy, Frank’s wife, had a doctorate in pharmaceutical chemistry and worked for several large industrial pharmaceutical companies, mostly researching new products. Recently, she dedicated most of her time to biological quality control and worked as a consultant with Frank. She always acted as the planner of the team and the writer of the reports. Elsy was also the public relations executive of the husband–wife team and had a very talented and profound observation gift. Elsy was charming and talkative and had grayish hair, brown eyes, and big spectacles. Her skin was smooth white, and she had a very candid expression. Elsy was an excellent teacher and student, and even learned many phrases in the local language to make herself understood.

Chapter Three

1986–1989

Something Missing

The equipment Peter had designed and utilized for his Riley Inc. assays needed massive scale-up expansion capabilities; something had to be done. Ryan had to find somebody using other equipment that could lead to the semi-industrial level. The project could initially produce small batches for internal tests and government analysis, leading to approval of the processes and testing of the final product when things went smoothly. This person, entity, or institute had to be willing to share knowledge in exchange for a grant and should not be a profitable or only commercial pharmaceutical entity, considering that no pharmaceutical company would share any scientific or industrial property knowledge.

Despite the difficulty of the search, Ryan refused to surrender. Meanwhile, Frank and Elsy, located an institute, Coloso Inc., somewhere in the developed world. It was partly owned by the government, which worked jointly with a commercial bioreactor manufacturer that had designed a device similar to the one Peter built. With his underlying technology, they could get high cell concentrations on a small scale. This institute was producing vaccines on a large scale using other different production methodologies and was researching new methods using high cell concentrations with bioreactors from commercial manufacturers of such devices.

Coloso Inc. had a large team of scientists with many specialties covering various vaccine production methodologies; however, the transferable cell culture technology needed a large-scale, high-density system. The technology transfer project also lacked the knowledge and expertise to handle and operate highly infectious microorganisms inside safety laboratories to prevent the escape of germs that could cause significant danger to the population. This last expertise, knowledge, and safety unit was available at the veterinary facility of Totem Inc. Thus, the fundamental core of Peter’s technical know-how could be assembled, scaled up, and transferred to Totem Inc. as the recipient company. With Frank, Elsy, Roger, the Coloso Inc. team, and David and Olga in the recipient company, Ryan was now pleased that he had probably gathered a knowledgeable group of people with a full range of scientific and practical expertise in vaccine production. Together, they would be capable of structuring a new project and introducing it to the recipient premises.

Ryan now had to go back to his foundation’s board of directors again since he had to propose another grant for Roger and Coloso Inc., so the new team could travel to Borazon City, examine what had been done, and submit a budget together with the Totem Inc.’s technical recipient team. Ryan was somehow losing convincing power with the directors, considering that he had appeared so many times before the board asking for money for the same project. This time, when one board member saw him entering the meeting room, he exclaimed, “Ryan, not again.”

It took several months for the foundation directors to re-examine the real prospects and feasibility of the success of the new arrangements. After one of the sessions, a board member challenged Ryan and told him that if this technology transfer was indeed achieved, he would ask for a medal from the foundation. It took several visits from some foundation’s board members to the Coloso Inc. outfit to insure they had what was needed to transfer a vaccine production methodology through Peter’s development path. The positive reports convinced the entire board, which was particularly impressed with Roger’s, Frank’s, and Elsy’s previous technical and scientific history, background, technological capacity, and ability to produce some goods from Coloso Inc.’s professional team.

Ryan was again given the go-ahead to continue the project’s development. The technology transfer project had miraculously survived another pertinacious obstacle and was financed again. This technological and development transfer was going to be a success. The whole world was in expectation. So this time, the grant news was published in some local papers in Coloso Inc.’s country. The headlines in the two newspapers were read, “Grant Will Help Develop Third-World Vaccine” and “New Program To Enable Vaccine Manufacture Abroad.” The comments regarding the news within the foundation emphasized that if this first technology transfer worked out at Totem Inc., other developing countries could send some technicians there to be trained in the new technologies. This was then made a requirement by the foundation to continue financing Roger and the Coloso Inc. team and, indirectly, Totem Inc. in the underdeveloped country. The newspapers reminded the readers that the idea of the foundation was to set up a pilot plant for technology teaching in other countries.

There were similar comments in the news, including “The agreement between the foundation, the university, and Coloso Inc. will expand and consolidate their applied research programs. The foundation’s support contributes to the WHO objectives to help the developing world achieve self-sufficiency in vaccine production since technology may ultimately reduce the cost per vaccine unit by one hundredfold.” The general comment was that Coloso Inc. was chosen for its expertise in producing vaccines and because it was not a private company for whom teaching developing countries how to make vaccines by themselves could be considered a conflict of interest.

Ryan sent a letter to Larry, Totem Inc.’s general manager, informing him about the news of the new arrangements for the methodology transfer and stating that the report from the foundation signaled a new era for developing transfer projects. According to Ryan, it was a rather unusual step to change the technology transfer institute for a project that was already five years old. Still, he emphasized that the newly found production methods would be simple, inexpensive, and eminently suitable to transfer to developing countries. Praise was given to Totem Inc.’s staff and scientists for their patience through the prolonged and challenging start-up phase. The reply from Larry of the Totem Inc. management stated that even though there had been a lot of frustration, they were delighted that a new technology package, especially suitable for developing countries, had been found, representing a breakthrough in industrial biological production.

Meanwhile, Frank and Elsy assisted Olga and Jesus in becoming familiar with Peter’s original technology. They knew that the research group at Totem Inc. had small glass jars that Peter had designed and could be used for a laboratory-scale mini-high-density production. These glass jars were already available from industrial and commercial scientific equipment and materials distributors. However, it was only a batch system that allowed technicians to learn the behavior of cells attached to tiny beads called micro-carriers. This was the original finding Peter had described in several scientific papers. His original idea was to attain at least a concentration of eight million cells per cubic centimeter. The manipulation of these small “bioreactors” by Olga and Jesus would be helpful for the work ahead with much larger industrial bioreactors.

Frank and Elsy were real globe trotters. Every place and country they had visited was another opportunity to get to know it by road and see the countryside. This time, they wanted to see a vast lake on top of the mountains in cool weather. However, the place was about a 5-hour drive from the city of Borazon on a winding and steep road. They asked Larry, Totem Inc.’s general manager, for a car, insisting on driving by themselves to the lake. There were a few bungalows at the place, and they could spend the night in one. Unfortunately, according to Larry, only one car was available that weekend; other vehicles had been taken to run some business errands. The available car was a manual drive, not an automatic transmission. But Frank did not care. He asked for the keys, and the couple left Borazon City for the trip. Elsy was a little worried because the vehicle was a tiny two-door Renault with manual shifts, and they would be driving on a steep road. Even Frank was not used to this type of landscape. The following day, they arrived back in Borazon and, smiling, told David they had a flat tire on the return trip, but a peasant farmer helped them change it. They were happy about the journey and did not feel remorse for the audacity.

Roger, the university professor, and John, the technical director of Coloso Inc., were ready to work with the foundation’s new team. John was a man in his late fifties, severe but with a good sense of humor. He was rather tall with an enormous body; his face was round with big black eyebrows, and he used spectacles that revealed his greenish eyes. He was a white-collar executive with vast technical knowledge but a little reserved, and he kept a little distance from the recipients of the technology. It was not easy to communicate with him; he always wanted to have the last word. John had difficulty placing himself on the side of the local technical personnel. Hence, he blamed the locals for any failure or lack of success in any trial. Sometimes, he appeared concealed, hiding inside his huge, awe-inspiring eyeglasses.

John’s associate and partner at Coloso Inc. was just the opposite personality. Jack had a very open character, was amusing, cheerful, and smiley, and had big, wide-open eyes that appeared to talk to you. His head looked like a well-known musician whose hair pointed straight at the ceiling. Jack was a completely open person. He was ready to do anything asked of him and with great satisfaction. Jack was probably in his late thirties and always happy. Even though he had great talent and technical know-how, working with him seemed more like a well-designed game with ups and downs but with the optimism that it was always moving forward. Jack was always making fun of the local technical assistants, referring to any professionals and members of the Coloso Inc. team as “doctors.” This was a typical local and usual way for subordinates to address anyone with more education and perhaps more status. There was, and probably exists up to the present time, a local saying, “Anybody can be a doctor, but very few are real gentlemen.”

A third member of the Coloso team was a lady. Mary was a tall woman with curious, inquisitive eyes and curly reddish hair, always dressed like an older woman, even though she was only in her late forties. She was talkative and prone to talking to other women about their personal lives. So in the first few days, Mary learned everything about the private lives of everyone in the company. As a microbiologist, she was bright, elegant, and passionate about perfection, which was very much needed for the quality control of all processes and products.

The first transferor team from Coloso Inc. was ready. The local recipient team from Totem Inc was assembled. Olga, the project co-leader, was a young microbiologist from a prestigious local university with limited practical industrial production experience. She was, however, a devoted reader of scientific journals. Olga did things by herself that she would later ask the assistant technicians to repeat the processes, in essence teaching them to use the techniques. Olga learned faster than other colleagues, had an excellent memory, and had the unique ability and talent to become a leader. Physically, she was attractive, with beautiful black eyes, black hair, and a forehead covered with hair. She was always very well-dressed, composed, and charming. Now, she was poised to prove that she had the talent of an industrial scientist.

Jesus was Olga’s production assistant and had particular expertise in the operation of the bioreactors. He was a graduate and trained biologist with many years of experience in the processes of large bioreactors to produce other vaccines at the veterinary company. He was an Afro-descendant and a self-made high-tech professional who always studied and observed others and learned by doing. He also had practical experience managing bioreactors and was always ready to assist with anything needed. He was a happy man and conveyed that feeling to others.

As a team, Olga and Jesus were ready to start the operation of the new pilot vaccine facility. A large area of the old production building was set aside in Totem Inc. to set up the pilot plant. New partitions, new services, new benches, modern tables, and brand-new equipment for production were installed. The refurbishment also included downstream and quality-control equipment, all donated by the foundation. Once again, the technicians and professionals from other areas in the building responsible for producing other biologicals and pharmaceuticals became very jealous of the brand-new vaccine pilot production area.

Few technicians had the chance to work inside this new area with modern equipment and the latest technology, and outsiders could see everything only through the glass windows. Later, this jealousy became an essential factor in the development and outcome of the methodology project. Olga and Jesus had to manage their relationships with the rest of the technicians and staff with caution and discretion to avoid more resentment.

Before starting the final installation of equipment and work inside the pilot plant, a recipient team had to visit Coloso Inc. to learn first-hand the operation of bioreactors, cell cultures, purification apparatus, and quality control of the first stages of the cell production cycles. Olga, Diego, Laura, Javier, and Luis were selected for the training trips. As it was the first time for some of them to travel outside the country, they had to get their passports and visas to travel overseas. They were enthusiastic, thrilled, and happy; it was summertime, so there was no need for formal office clothing. Each trainee had to work in separate laboratories with different Coloso Inc. scientists, learning different process phases. The training took approximately one month, and the group learned a lot and had a good time. They dedicated some time to sightseeing in the evening, but many clumsy things happened during this period.

Diego was the most undersized fellow in the group of trainees and was designed to work with the technician in charge of the purification of the harvests. One piece of equipment utilized for this task was chromatography glass columns of considerable height. Diego could not easily see what was going on inside the columns, and one time, he decided to get up on top of the side tables to look from above. Everyone inside the laboratory was amused to see a trainee standing on top of a working table.

As a well-trained runner, Diego had participated in marathon competitions, so he would go out early every morning for a short training run. One day, he was out of the hotel a little late and tried another route to get back. Of course, he became entirely lost. The rest of the group at the hotel could not wait for him, so they went to work and immediately advised John, who quickly sent a driver to look for him. After two hours and at least fifty blocks from the hotel, the driver found Diego sitting on a park bench where he was talking to a beautiful blonde young girl, using his meager English language but having plenty of fun. The girl appeared amazed of speaking to a handsome foreigner. Diego was not happy to return to the hotel to change his clothes and go to work. A sense of attraction between the sexes had probably broken the language barrier. Was this the only time they had met?

Back at Totem Inc., it took the assistance of Elsy and Frank to choose laboratory equipment, main furnishings, and sundries to furnish the new production unit. The pilot plant unit was designed using an existing building frame, with minor modifications to services, wall panels, insulation, roofing, and separate walk-in coolers and walk-in incubators. It took only eight months to install the laboratory wall panels and services. It was necessary, however, to design and build a unique air-handling unit with air conditioning. Therefore, the supply of sterile filtered air to the laboratory and filtered exhaust air was intended to avoid the escape of the virus to the surrounding areas. The pilot unit also had a walking-in two-door autoclave connected to the outside corridor and a continuous battery energy supply. At that time, this pilot plant unit was the best-designed and best-built research laboratory in the country to handle infectious materials.

Even though the equipment installation was cumbersome and took a lot of patience, it was much fun for the locals, who were intrigued by the many sophisticated pieces of equipment. Although they were difficult to operate, they were innovative, exciting, and showy. Some new equipment was also challenging to manage, even for the scientists transferring the technology. Most equipment represented a breakthrough, each in its field. Therefore, it took many months for local technicians to master the operation and maintenance of such excellent machinery. Moreover, a few installation problems were easy to solve, but others were more difficult to assemble and required much exploration time.

Power failure was frequent in Borazon City. A standby generator secured the new lab’s electricity supply and started when the power failed. However, the electric power in the pilot plant took two to five minutes to restore. With this arrangement, the micro-spheres and cells began to settle inside the bioreactors, and this electrical interruption greatly affected them. None of the scientists realized that this would dramatically alter the cell growth inside the bioreactor. Something had to be done. David asked the engineers to find a solution, and the chief engineer decided it was necessary to install one uninterrupted power supply. This powerful battery would respond immediately with an electrical supply to the pilot plant in case of local power failure, which solved the problem of the micro-spheres settling inside the bioreactors and crushing the cells.

Another critical factor in developing the vaccine project was obtaining unique cell seeds adapted to grow at high cell densities and a virus seed adapted to grow on such cells. The original Vero cell seed had to be officially ordered by Totem Inc. from a well-established and internationally accepted cell bank; however, after placing the order, the shipment took nearly five months to arrive at Totem Inc. Additionally, a special permit had to be obtained to be ready at local customs to avoid any delay upon arrival to prevent premature death of cells. The cells arrived frozen in a container at ultra-low temperatures in liquid nitrogen (-196 degrees Celsius). They were transferred to the pilot plant and kept in another specific container at the same temperatures and conditions. The technicians now had cells to work with, and they could start preparation of master and working Vero cell banks. However, both banks had to be submitted to quality control for a complete analysis before the start of the bioreactor cultures, so both processes took at least five more months.

The virus master seed was ordered from a research institute that had previously adapted the microorganism specifically to Vero cells. The viral seed shipment had to be approved by the government officials of the donor country. The virus pedigree, official source certifications, and its development’s natural history had to be presented to the recipient authorities for examination. The virus could be shipped after the recipient company completed a request specifying how it would be handled, by whom, and in what kind of laboratory building facilities. The specific training of the technicians was also needed, and more critically, a written agreement was required to refrain from handling or lending the microorganism to any other company or institute in the same country or overseas.

The country’s government officials harboring the virus thoroughly investigated the recipient company to ensure that the virus would be used only for research and vaccine production. They were serious about preventing any other use by any other company or country, including biological warfare. These requirements made the project unique and gave the institute and the people involved significant responsibility.

The virus master seed finally arrived at Totem Inc. almost six months after the request was made, and it had to have a special permit from the health authorities and customs to avoid delays upon arrival. The seed had to be transferred in individual containers at ultra-low temperatures of 70 degrees Celsius below zero in dry ice. With the cells and the virus, the team was ready to start the work. Olga and Jesus could now begin the preparation of cell banks to have seed materials for every bioreactor cycle that had to be made to standardize the cell production. They also had to prepare the virus banks. Even though both the cell seeds and virus seeds had previously been tested and validated at their source, they had to be locally certified; original specimens had to be propagated, tested for identity, specificity, and sterility from unknown germs, and determined the accurate concentration. Once Olga and Jesus developed, tested, and validated the cell and virus banks, they were ready to start cell cultures inside bioreactors. This certification and validation of cell and virus banks took approximately six months.

Ryan was on and off, visiting Totem Inc. technicians and overlooking the project’s development. However, some technicians at the company felt intimidated by Ryan due to his firmness, directness, and command. Locals were generally very polite and soft compared to international executives, but despite the differences in personalities within the project, there was some real progress in the group’s work. The development work moved softly for at least the next eighteen months, but new, unexpected events again affected the progress of the project.

Progress inside laboratories was quicker and more successful than expected. On the contrary, the equipment gadget that was supposed to keep the beads with cells attached and growing inside a small scale-up bioreactor made by Coloso Inc. technicians failed continuously. Many beads with attached cells escaped from the vessel, and the whole-cell culture batch was gradually lost. Microscopic beads and cell concentrations needed to be low for this device, which probably had been designed for smaller cell concentrations, lower than the ones devised initially by Peter. If the system could not hold an enormously high number of cells, no real scale-up would be achieved, and the final product would be costly without reaching the industrial or commercial levels. The cultures operated at Peter’s laboratory were in minimal volumes at the research laboratory level. The device that Coloso Inc. scientists prepared was also a research-type level.

Moreover, Peter’s and Coloso Inc.’s systems were only “batch systems,” consisting of the virus harvest of only the working capacity of the bioreactor. The volume was small, indeed, 3 to 5 liters. What was needed was a much bigger bioreactor and a continuous in-flow of cell culture media and an out-flow of the virus product. If beads with attached cells escaped from the bioreactor, in time, there would be no viable industrial product. David compared the cell concentrations obtained by Peter and Coloso Inc. with the needed ones. Both technologies had 4 to 8 million cell concentrations per cubic centimeter. The cell concentrations required for the industrial scale-up vaccine production were 8 to twelve million per cubic centimeter. Hence, there was some space to cover and the process had yet to reach the desired efficiency level.

Something had to be arranged to solve this lack of required productivity. This time, Coloso Inc.’s engineers proposed and built several new gadgets that they had designed to prevent the escape of beads from the bioreactor. A few of the modern devices were ingenious, but only some worked satisfactorily, and they eventually failed due to at least one or two factors. One gadget failed due to the plugging of a filter, which prevented the escape of beads from the bioreactor. This was similar to the companies David had visited several years before. They had precisely the same results. Another gadget failed because the beads with cells slowly and gradually went out from the top of the vessel. Something had to be done again to achieve the desired cell concentration for the project. Who could design a gadget that would fit the bioreactor vessel while preventing the escape of beads and cells from the bioreactor?

This time again, Frank and Elsy’s scientists were on their move at Ryan’s request. They contacted one factory that designed and built bioreactors and other biological equipment, hoping that they had similar gadgets in their bioreactors to keep beads inside the vessels. Such equipment would need to fit the new continuous flow technology. Again, only one batch system was found. Luckily, the company was willing to assist Ryan and the Coloso Inc. team in designing a piece that would do the job according to the needs of the new biotechnology. After conscientious considerations, Ryan decided that this job was for Roger and David, and he was willing to sponsor them to go to the bioreactor manufacturer, where they would have to work there with the company engineers until a new device was designed or reinvented.

Roger left a few commitments that he had at the university and met with David at the bioreactor company. They were joined by the factory engineers, who started a lengthy examination of the numerous connections and sensors that the bioreactors had inside and outside the vessel. They had to find a gadget that would allow continuous feeding of liquid nutrients to enter the container. Simultaneously, the same device had to let the old media and the liquid with the virus exit the vessel without permitting the beads with cells attached to escape the container. The group first tried to design a decanter to be installed inside the bioreactor, but that did not work. Roger, David, and the group experimented with different sizes and shapes of exhaust tubes fitted outside the bioreactor for approximately thirty or forty centimeters.

After exchanging different views, other mechanisms, and many working hours, they devised something else. They tried a wide tube with many thin plates inside, simulating a labyrinth. The used media, microscopic beads with the cells attached to them, had to go through the maze, and by controlling the speed of liquid flow to the outside, the beads, by gravity, had enough time to decant back into the bioreactor. Finally, a new decanting device was born. The engineers of the bioreactor manufacturer built a permanent piece, with a tube with stainless steel thin plates located inside a glass tube where the observer could view the decanting media and the beads with the cells as they pass through. They now had better control of the continuous flow system, preventing the beads with cells from escaping from the vessel. The new gadget was tested many times and worked satisfactorily. Cell growth of very high concentrations with a constant flow of nutrients was now possible. Another milestone was achieved for the vaccine technology transfer project, and the project seemed to have a new life.

The bioreactor company later patented the device and sold bioreactors with it all around the world. However, this time, it took advantage of a grant from a foundation and the work of two scientists sponsored by the same foundation to design and patent a new piece of their equipment. The device was sold in an open market to the benefit of many researchers and industrial producers around the globe. This new gadget made it possible to manufacture different kinds of products for the health sciences and nutritional products at a low cost.

The time came to use the new device at the Totem Inc. factory. So the Coloso Inc. team came to Borazon City for approximately half a month for the next ten months, hoping to complete the preparation of three pilot vaccine lots. The vaccine had to approve all internal quality control tests, and the official government control institute also had to study, test, and accept the vaccine’s final product. On several trips, university professor Roger occasionally joined the Coloso Inc. team in Borazon City. The group had to work long hours, seven days a week, with the transferor team to make substantial progress in the project. They all understood that the industrial production of vaccines required continuous non-stop monitoring, as cells and viruses were constantly growing. Living laboratory organisms do not distinguish between weekends, Sundays, and holidays. Therefore, the scientists had to be there in turns, day and night, adjusting the system to grow cells and control the virus production inside the bioreactors.

The Coloso Inc. team had young trainees as associates in its facilities. Larry, the Totem Inc. manager, was asked if he could bring along a bright young student fellow to learn some of the new and exciting things happening in the scale-up of high-density cell cultures. Nobody saw any obstacle, so a visit for eight weeks was agreed upon. Chris, the student, came in and started working inside the pilot plant, assisting the locals and learning simultaneously. Chris was a man in his early thirties, tall and thin, with a white face, flawless brown hair, and huge bright eyes. He always dressed casually, mostly in jeans and a blue sports jacket. His stance was challenging, and he appeared to be a spy—and most probably, he was one. He always smiled, asked questions, and was interested in everything. Chris had a little notebook on which he always wrote notes of everything in sight. He was probably of European descent, based on his English accent.

Since he was a member of the transferor party, nobody had held back any secret from Chris. He was astute, and even though he had been in Borazon City for only eight weeks, he was exposed to every aspect of rabies vaccine production. He learned many insides and confidential information about industrial cell production, virus production, downstream processes, purification, and quality control. Chris acquired considerable knowledge and, as shown later, gained enormous significance in the future development and usage of the developed technology. Another drawback for the vaccine technology transfer program.

The work continued in the pilot laboratory. One day after work, the Coloso Inc. team, Roger, John, Jack, and David, went for dinner at a shopping mall in the city’s business center. The visitors wanted to savor some unique local dishes, so David suggested the most famous restaurant in the mall, “Tropicana.” Everyone ordered some food and had a good time; the ambiance was gratifying, the music was entertaining, and the food was delicious. Half an hour after finishing the meal, the group was walking in the mall window shopping when Jack, a younger group member, suddenly started to feel very dizzy. He turned pale, sweating profusely, and almost fainted. Luckily, there was emergency medical assistance in the mall who attended to him in a few minutes. He was later rushed by an ambulance to a nearby medical center. Everyone on the team followed Jack to the emergency room, knowing he had been very nervous about being in a foreign country and unable to speak the local language. The physicians and nurses spoke very limited and broken English.

Jack was very distressed as he tried to describe his symptoms. Moreover, his partner John had to interpret the slang words he pronounced in French, his native language, into understandable English, which David then translated into the physician’s local language. The physician’s questions and comments had to be translated in reverse through the same channels back to Jack. The conversational translations went back and forth for at least 20 minutes. The physician performed many physical and laboratory exams. He eventually diagnosed Jack with food poisoning.

Due to the severity of the body reaction, Jack had to spend the whole night in a bed inside a cubicle in the hospital’s emergency room. This time, he was alone, and there was nobody to help with the translations, so he did not know what was happening. Many nurses went in and out of his cubicle, some providing explanations that he did not understand. They took samples of blood and body fluids, and he received intravenous fluid therapy to recover any fluids lost. Jack was reluctant to receive medicines, but he was scared of the thought of dying in a foreign country. He had nobody to talk to and was clueless about what was happening inside his body or whether the medicines would work. Luckily, he survived the whole ordeal and was recovering. The following early morning, he saw John and David arriving at the hospital to see him. Jack probably could not help it, but he immediately turned into tears of pure happiness. He finally felt safe.

While all this was happening at the research laboratory level, the local political country was shaking again. There was a change in the highest-ranking officials in the country, and, consequentially, Larry, the general manager of Totem Inc., was also removed, and a new manager was quickly named. As soon as the news reached the Totem Inc. personnel, they started to prepare a justified farewell for Larry. He had been in charge of the company for the last six years. He was instrumental in obtaining the company’s designation to become the recipient of the technology transfer project from the donor foundation. As mentioned before, Larry converted Totem Inc. into a leading regional manufacturer of high-class veterinary vaccines. His politically motivated removal meant a profound loss for the advancement of Totem Inc. and for the technological improvement of vaccinology in developing countries.

The name of the new general manager was Lucas. He was the successful owner of his own company in an agricultural business. Therefore, he knew how to operate and manage the affairs of the company. Similar to his predecessor, he was soon commonly seen inside the production plant, advising, and directing various processes and repairs. Lucas had a rapid perception of things that might be out of place. Hence, he enjoyed walking through the factory and pointing at any major or minor circumstances that affected the smooth running of the manufacturing plant. However, he had a miserable temper and could not accept lazy people or work done too slowly. Having been commissioned with the continued improvement of the company, Lucas would have worked really hard and efficiently to mimic the work of his predecessor.

Chapter Four

1990–1993

A Flagrant Proposal

While this was happening at Totem Inc., a word came from a company with excellent relations with Antoine, an old-world rabies scientist who had assisted Totem Inc. some years before. The company was a European pharmaceutical giant, and the president asked to be invited to see the structure of Totem Inc. and talk with the general manager. He noted that he had heard too much praise of Totem Inc. by Antoine, so he wanted to see it by himself. Without much hesitation, Lucas invited him to visit Totem Inc., even though he could not understand why a multinational company wanted to know about a small company such as Totem Inc. A few weeks later, the president announced his visit and was later escorted to Borazon by several of his associates. A group of local representatives met the company entourage at the airport and accompanied them to the hotel. The following day, the group was taken to Totem Inc. 

Lucas, Totem Inc.’s new manager, welcomed the visitor to the country and factory. The president explained that he wanted to see everything. For one moment, the local scientists and the general manager of Totem Inc. were not only surprised but felt resentful, worried about the foreign president and his associates stealing some of their precious, well-guarded secrets. The president was very talkative and explained that his company had large bioreactors producing vaccines based on Peter’s primary findings and technology. The locals were relieved to hear that the visitors probably had even better technologies than Totem Inc. Lucas asked David to escort the visitors to see the facilities, since there was no worry about the escape of the local technical know-how. David explained to the visitors that as a precaution, only three visitors simultaneously could enter the production areas.

The visiting company president chose two of his associates and entered the facilities. The group visited every corner of the production areas and asked the professionals, scientists, and operators many questions. Communication was not so smooth due to differences in language; however, David made a solid effort to translate as much as possible so the visitors could understand the locals. Many Totem Inc. scientists and workers were stunned to see foreign visitors inside the production areas, since it was utterly forbidden to allow such visits; something had to be quite extraordinary.

After a widespread visit to the industrial vaccine plant, the visiting president asked for a private meeting with Lucas. He excitedly told Lucas that he was highly impressed with what he saw and wanted to cooperate strongly with the two companies concerning the development of a newer vaccine methodology. Lucas was more than surprised; he could not understand how a multinational company president had such praise for Totem Inc.’s facilities, scientists, and the company. He suspected that something else was cooking inside the mind of the president.

Sure enough, the visiting president later asked Lucas to consider relaying a message to the board of directors that his company was interested in acquiring Totem Inc. He told Lucas that they would buy it if the price were right, adding that before his trip, he had obtained approval from his board of directors to make an offer for Totem Inc. At that moment, Lucas was astonished. He did not realize this, but he was heading a national veterinary biological and pharmaceutical company that was so successful in attracting the interest of a famous multinational organization.

Lucas told the visitor that he could not give him any hint concerning the answer of the board of directors of Totem Inc. and even much less of the opinions of members from the central government. He told the president that he would take his message to the next meeting of the board of directors, with a clear notion of the natural interest of the foreign company. Lucas assured the visiting president that everyone involved would carefully analyze the matter, and he would immediately call the visitor as soon as a reply was ready.

The visitor returned home but was not entirely convinced that he had made a good impression on his host at Borazon City and on his sincere offer. Three weeks later, without receiving any answer from Lucas, he called and asked whether Lucas would go to his country and visit the biological workshop where many vaccines were being produced. Lucas told the executive he was thankful for the offer but could not visit alone. He would need to be accompanied by David, his senior scientist and adviser. The president was more than happy to accept and told Lucas to send all the paperwork, and in return, both would receive the formal invitation and first-class airline tickets.

In another three weeks, Lucas and David received the airline tickets, requested the corresponding visas, and went to Europe. It was the first time David had traveled in first class, so it was quite an experience. He was not used to being attended to without having to wait in line for check-in, much less to be offered a glass of champagne as soon as he got seated inside the plane. David felt like a wealthy man sitting in a generous independent airplane cubicle, very well attended to by gorgeous stewardesses serving all kinds of delicious meals. Time went by relatively fast, and soon, they arrived in Europe. A group of personnel from the multinational company welcomed them at the airport. They got onto a pompous limousine that drove them to a five-star hotel that appeared like a six-star, where they settled in until the following day. At the hotel, David felt very well taken care of; he and Lucas were both offered a lovely suite with a private sitting room and a Jacuzzi. The following morning, after a sumptuous breakfast, they were taken to the vaccine manufacturing plant in another Limousine.

At the factory door, the company president welcomed Lucas and David to the company. Both marveled at the impressive gesture of the executive. The host wanted to show Lucas that he had a strong interest in the deal to acquire the Borazon`s city company. Lucas and David were invited to sit in the board meeting room, were offered a cup of coffee, and heard an explanation of the composition of the manufacturing facility. The vaccine production buildings were huge; the company made all kinds of products in separate buildings, from bacterial and viral vaccines to pharmaceuticals and blood-derived products. Lucas and David immediately felt intimidated by the absolute size of each building and the number of buildings in the place.

The president ensured that the visitors saw the plant where the human vaccines were being produced. Lucas and David, accompanied by the production manager, arrived at the building where the viral vaccines for human use were manufactured. They were adorned in special garments and guided into the corridors where they could see through the glass windows, among other things, the large bioreactors the company had been using to fabricate viral vaccines. They were told that those bioreactors used the underlying technology and components Peter had described in his publications. David was puzzled but did not mention anything immediately; instead, he told Lucas that they would privately discuss the matter later at the hotel.

That evening, the company president invited the visitors, along with several managers, to a delicious meal and gave a toast to the future relations between the two companies. The president praised Lucas again for what he had seen at Totem Inc.’s facility; he said there was hardly any other vaccine manufacturing production outfit in the developing world that could surpass the Totem manufacturing plant’s technology and productivity. Lucas felt very proud to be such a company’s general manager and representative. Looking back at all the things that had happened during this visit, David analyzed how the president ingratiated Lucas. So he planned on a robust effort to convince the Totem Inc. board of directors to accept the buying offer.

Back at the hotel, David told Lucas that the large bioreactors with Peter’s underlying technology were different from what the foundation’s transfer project was about. David explained that Peter’s original idea was to have a mechanism by which the cells could remain inside the bioreactor for a prolonged time, producing virus, while the growth media continuously entered the system and the virus could be harvested from the external vessel, a kind of a continuous flow of nutrients and product retrieval system. He told Lucas that the savings were significant in growth culture media, energy, number of virus particles obtained, space, personnel, maintenance, services, etc., and that the final product would be of better quality.

The most important thing David explained was that the production of the company was a batch system and not a continuous flow, like the technology transfer project. A batch system for vaccine production meant that the total growth media for one operation was prepared simultaneously. In the case of the rabies vaccine, the operational size of the bioreactor that they saw was approximately 500 liters, so each batch had the total virus quantity produced in one operation. Due to the amount of culture media used in the multinational company’s batch system, the losses were unsurmountable if some problem arose and the culture perished. Moreover, the cell concentration was nearly 5 million cells per milliliters, much less than the continuous flow system, at 10 to 12 million cells per milliliters. Therefore, the cost of each vaccine vial was astronomical in the batch system, and the productivity risks were considerably higher.

David and Lucas had been taken inside several industrial buildings inside the premises. One building had caught Lucas’s attention—the one devoted to processing human placentas—and most of the placentas came from African countries in special refrigerated containers. Throughout the processing of the placentas, many sub-products were obtained, and the most interesting was blood serum. Extracted serum was used in many places as a nutrient for the growth of cell lines for vaccine production, and a similar system was used worldwide to extract fetal calf serum for the same purpose. Lucas and David considered a question: What if an unknown virus were to be found in one of those placenta specimens? Any filtration to sterilize this type of product would not be able to remove viruses; only bacteria could be removed by filtration. Both men did not like the outcome of that thought.

As Lucas and David further reasoned the offer to buy Totem Inc., Lucas emphasized that the company probably wanted to buy Totem to prevent competition from the new vaccine, since the new product would be much cheaper and possibly even better than the one available in the market from the company. The multinational could not change the technology to produce the vaccine for the one that Totem was developing. To do so, they would have to start from scratch, since the government would regard the vaccine produced with that system as a new product.

Any new product must go through all the steps for new product registration. Getting certification for the new vaccine would take at least four to six years at considerable expense. The manufacturer would even need to build entirely new facilities at a significant cost. Any new product had to undergo, clinical, and field trials. Even more complex was the fact that the company already had a massive market with enormous profits from the vaccine. The company probably thought that it did not need to change the technology, and it would have been counterproductive to do so.

At the end of the visit, Lucas and David felt completely satisfied. They were very impressed with the different production systems and products in the pharmaceutical and vaccine fields. Both Lucas and David told the company’s president they would talk favorably to the Totem Inc. board of directors to see if the two companies could arrive at a fair deal. Lucas assured the company president that he personally was going to make sure that the executives of Totem and the government agency in charge of the company stock studied the president’s offer with great care. The following day, they both headed back to Borazon City.

Lucas did not wait too long to convene a meeting of the board of directors of Totem Inc. He told them everything he saw and then gave a report to the board, including his findings from the visit to the multinational company and some of his personal opinions and ideas. He commented on the company’s possible picture of buying Totem Inc. to avoid future marketing or technological competition. If multinationals could buy Totem Inc., they could even internationally sell the vaccine produced at the Totem manufacturing facility and create self-competition. They, however, had total control and could sell the vaccine at higher prices than Totem Inc. was projecting. The board of directors’ members listened carefully and asked some questions but were reluctant to comment significantly, so they asked for another meeting to get additional time to gather more information on the pros and cons of making that kind of deal.

Even though the president of the multinational company had not given a specific offer in euros, Lucas told the board that the foreign executive was ready to make a sizable offer that the government could not refuse. The board of directors met again for the second time regarding the offer but the members had divided opinions on the whole deal. They concluded that the decision, one way or another, had some implications for governmental policies concerning vaccines and people’s health. They considered that the matter had to be studied by the ministry of health, so they decided to ask the central government to decide on negotiations with the multinational. No direct recommendation was made to the government, which was the regular decision line of conduct for Totem Inc.

This time, the whole deal was first taken to the agriculture minister, as Totem Inc. was part of that branch of government service. The minister took over two months to examine the proposal with assistants, members of Congress, and the minister of health. It was even discovered that a few local officials of the multinational had been lobbying some members of Congress, urging for the sale of Totem Inc. The minister of health’s opinion was the most powerful against selling the company. He reasoned that if that company had a production facility in the country, it would produce many other products besides the current veterinary vaccines. It would start manufacturing many other human vaccines at high prices, disturbing the regulated market and the government’s already-arranged children’s vaccination schedules.

The minister of agriculture had the final word. He finally summoned Lucas and told him that the government had decided not to negotiate the selling of Totem Inc. with any third party, much less with a multinational company. He emphasized that government officials and the minister of health considered the production of vaccines for human use a matter of national interest. Totem Inc. could not be sold to any foreign agent. Lucas felt slightly embarrassed to communicate this outcome to the multinational president and give him the government’s negative responses. Still, he had no choice, so he got on the phone, and told the foreign executive that the government had decided not to sell Totem Inc. Lucas emphasized that this decision had nothing to do with the president’s company; it had only been taken as a matter of national interest. The president said he was very sorry to hear of the decision but that he later would probably bring a more attractive proposal for the government to consider. That was the end of this business for Totem Inc.

In the meantime, the vaccine technical group at Totem Inc. continued their work. The next step for the working team was to begin standardizing the cell and virus processes; they had to complete that phase before initiating the purification stage of the virus harvests. They also had to run several complete semi-continuous bioreactor cycles, starting with standardizing the ingredients needed to prepare the specialized media components defined by Roger. The group also had to conform to local regulations to develop media, cell growth, virus multiplication, and quality control of these processes.

Roger was present frequently and assisted throughout. He once asked David if he could bring one of his students working on his cancer cell projects to work with the group. The student was a single young girl, Victoria, a native of a developing country. Roger was Victoria’s graduate coach and professor, so he claimed that it was vital for her to observe the almost unlimited growth of cells inside the bioreactors, even though they were not considered malignant.

Victoria was brilliant, diligent, and willing to learn a lot. She worked hard in the laboratories, and everyone liked her very much because she was easy-going, always happy, and very charming. She was in her late twenties, had a thin body, and was not too tall. She had long black hair, and her face was white, elongated, and with a few speckles. Victoria made many friends in the laboratory, and when she mentioned that she wanted to do some sightseeing in the city, there were many male volunteers. Two laboratory assistants finally convinced Roger to go with Victoria and visit a famous cathedral on the outskirts of town. It was a short trip, but Victoria and the group had a good time.

Victoria was also very interested in entertaining and, of course, in the city’s nightlife. One evening, she asked Roger and David to accompany her to a bar to experience local music, drinks, and ambiance. David chose a very cozy bar famous for its quality tropical music, where the three had a good time laughing, singing, and cheering. The local music was so appealing to Victoria that she wanted to dance. Since Roger was unfamiliar with the local music, David volunteered to show Victoria his abilities as a dancer. However, Victoria had a little secret: She had almost become a professional dancer and wanted to learn some of the steps of the local rhythms. But she probably had one too many drinks and started confessing aloud that science was not everything in life. As David and Victoria danced and, having lots of fun, getting too close to each other, stirring some emotions, and together were getting somewhat excited and aroused. Victoria gave the Totem Inc. transfer project a little romanticism, which was very much needed. Roger and his arduous and enjoyable student Victoria returned to their country and research at the end of the week.

Before leaving, Victoria had told David that the experience she had gained, seeing and handling living cells at such high densities, had given her a new outlook on her work as a candidate for her doctorate degree. Victoria turned out to be an excellent researcher and returned to her country after graduation. Sometime later, David learned that Victoria had been named the research director of a famous project in her own country. This fact gave David, and, for that matter, Ryan, great satisfaction, considering that the rabies vaccine transfer project was delivering more than vaccine technology; it was opening new venues for research scientists to diversify other areas of biological research.

Once again, everything ran smoothly at Totem Inc. for a few months until another surprise hit what now appeared like a never-ending vaccine project. One day, when a Totem Inc. technician arrived at the laboratory, he was surprised to see that the breaker that connected energy to the bioreactors of the project had been turned off from their main central board. Consequently, the cell growth cycle ended. All the cells sank and died. The main switchboard was outside the laboratory, where the reactors were functioning, so there was no one specific to blame but sabotage from unknown sources. David and Olga questioned laboratory assistants, but none knew who might have been involved in this deliberate and malicious act.

This circumstance was probably related to another situation that happened many weeks later. One morning, another technician arrived at the laboratory and discovered that the central sterilization apparatus, which, for safety conditions, could also be operated from just outside the working cell growth laboratory unit, had been damaged. The main operating panel was shattered; someone had destroyed it, and now the pilot plant production unit had to be closed until a new switchboard could be found. There was no way to sterilize all the growth media, reagents, and minor components, and the culture cells growing inside a bioreactor also died.

The project was halted for at least five months until a new spare part of the panel board arrived. The equipment’s reinstallation, validation, and standardization took another four months. The project lost almost a year of operating costs, but there was no one to blame for the sabotage from the unprecedented sources. The general manager ordered a thorough investigation to discover who was behind such gruesome acts. The inside investigation of the two unlucky circumstances did not reveal anything. Nobody came forward to give any hint to find out if one or more employees had been involved in those acts, but somebody did not want the project to continue. Were people inside the facility engaged in both events? Nobody outside the company had been found inside the premises on those occasions. After this incident, many things had to be modified concerning vigilance to prevent any other sabotage and the safety of the services provided to the vaccine pilot plant.

Even though the sabotages generated some turmoil, the workers inside the pilot laboratory felt somewhat secure and continued their work with renewed effort. Olga even felt new courage and the need to prove that nothing would stop her from successfully conducting the project. She and David raised the morale of the technicians and professionals. Since the cells grew continuously, a technician or a serviceman had to stay close every night to ensure that everything ran smoothly. The technician in charge of the night shift was instructed to call David or Olga at any time during the night if something unpredictable happened with the cultures.

One day, at 2 o’clock in the morning, the night technician called Olga at her home, and yelled, “The thing is vomiting!” Olga could not understand and, for a moment, thought that the technician was getting sick and vomiting. Olga asked the technician, “Are you sick?” “No, ma’am, the bioreactor is spitting some liquid.” Olga quickly got dressed and went to the factory to fix the problem. A hose connected to the bioreactor was leaking, and the cells escaped from the system. Many cells were lost, but eventually, everything was corrected. Olga and David were lucky that this kind of event did not occur frequently.

A few weeks later, Ryan called David to inform him that an institute in a developed country had published the production of the rabies vaccine using bioreactors similar to the one described by Peter. He asked David if he would be willing to go there and find out what was happening. Perhaps they could find something to apply to the technology transfer project at Totem Inc. David loved to travel, so two weeks later, he got on an airplane and went to the institute in a European country where the news had started. The company did noy warmly welcome him.

After a few words from the scientist describing the technology, David was finally taken to the research area where the bioreactor was located. He immediately noticed that the bioreactor was relatively small and had a glass vessel tank. David could not see other tanks feeding growth media to the bioreactor, and no vessel was collecting the harvest at the other end. Hence, he immediately considered that this was not a continuous flow system. It was only a batch system, similar to the one found in another European multinational but on a tiny scale. If the researchers successfully researched the scale-up process of this system, the vaccine would be pricey at international prices, identical to multinational prices. They obtained cell concentrations of four million per milliliter, in contrast to the twelve million obtained at Totem Inc., indicating a research vaccine production that was not an industrial, marketable product. David praised the researcher for an aesthetic process, thanked his hosts for showing him everything, and returned to Borazon City.

David called Ryan at the foundation and explained what he saw concerning the so-called “new vaccine to control a deadly disease” that appeared in newspapers. He informed him that some researchers had results published in scientific journals and even in newspapers, contrary to their claims of having newer vaccines for different sicknesses. Almost all these publications never end in a process that could be scaled up to an industrial, commercially available product. Unfortunately, the general public feels safer hearing these types of news, even when there is no actual or safe vaccine product on the market to prevent a specific disease.

This has been particularly troublesome when some scientists, mostly from developing countries, adduce in publications that they have a new vaccine. It is even worse when they claim the development of vaccines for some tropical diseases, which at the time did not have a cure, much less a vaccine in the market, only laboratory experiments. A few so-called pseudo-scientists even get considerable funding from their governments for products that never protect the population from the target disease. Many honest scientists from developing countries are harassed at international meetings when other scientists make fun of the many publications from their countries claiming a non-proven new vaccine for a tropical disease. This has been particularly common for old claims to produce vaccines to control malaria, a tropical disease transmitted from mosquitoes with vaccines only now in proven stages.

David knew well that many foreign materials, especially proteins, develop antibodies when introduced into the body and exposed to the immune system. However, most of the time, these antibodies are not protective; hence, the material that has been injected could not be regarded as a vaccine; it could only be called an immunogenic product. Ryan added that several journals frequently publish papers and articles with information and apparent research that end up being fake results, fake news, non-proven facts, and much limited, accurate data.

Ryan and David speculated that in vaccine production as well as many areas of scientific knowledge, it was becoming increasingly common for many persons not directly involved in scientific research to give damaging opinions. The general public easily accepts many baseless opinions without any scientific foundation as truthful facts. It is unknown why some commentators disregard how some lies become proven facts without any evidence and do not question them. Some even toss the news as an actual fact. For many scientists, unproven pieces of information are becoming pseudoscience for the community. To make things worse, David explained that there are politicians and widely known persons with material wealth who, without any evidence, are entirely against vaccines and are also highly spoken about.

For Ryan and David, the attitude of many journalists and newspapers that have published uncountable news concerning vaccines without any investigation into the source of the information and the qualifications of the providers has allowed the appearance of many misconceptions about the actual value of vaccines. The fact is that without the development and improvement of vaccine technology, humanity would have suffered from many pandemics of polio, encephalitis, influenza, small pox and many other killing and decimating infectious diseases. Ryan said that false information on the internet and social media traffics much faster than facts. He was telling David that some people still believe that the COVID outbreak was part of a secret Chinese plot to deploy a synthetically created viral bioweapon across the world.

Back at Totem Inc., the time had arrived for the group with new cell and viral cultures established to change work to the viral purification steps with the Coloso Inc. team. This time, Coloso Inc. designated Kevin, an expert, to be in charge of the purification systems. Kevin arrived at Borazon City airport midway through the rainy season. He thought he was coming to a harsh tropical area, so he wore short sleeves and short tacky pants and did not carry a jacket. The weather was cold and raining heavily, so he had to borrow a coat from the welcoming party at the airport. However, he was a tall and bulky figure, and no jacket of the people that greeted him fit his enormous body. He had to use an umbrella, which appeared funny to everyone because of his attire and size; however, he was generally pleased and content and did not care about what the onlookers thought. He seemed to be a mixed martial arts fighter; his head was almost bald, his eyes were pretty big, his eyebrows covered his entire face, and his hands seemed big and fat. He moved slowly but firmly but did not appear to be a real scientist with expertise in purification systems, so he had to prove he was.

Working in the laboratory, Kevin worked smoothly and at a high speed. The local technicians made an excellent rapport with him due to his ability to communicate, even though he did not know a word in the local language. He was a good teacher, and local technicians were learning very rapidly, notwithstanding that the new equipment was very different from the one they had used before. As time passed, Kevin soon had to return to his country. Kevin left, leaving the materials that he had treated and processed to the quality control specialists.

Mary, the head microbiologist of Coloso Inc., had to teach while performing all quality control tests on the harvest materials obtained up to that time. Mary had to work closely with Olga and develop an amicable association. They needed very specialized reagents for the tests. One was found overseas in Donald’s laboratory. Donald had participated in the original search for the recipient country and worked at a quality control outfit in a government institute. He donated some special “hybridoma” cells to produce the monoclonal antibodies needed for a specific fluorescent antibody assay. Thus, they had a test to measure the antibody immune response to the rabies vaccine in laboratory animals or human volunteers.

There were many samples to be analyzed. Olga and Mary had to work long hours, sometimes even at night. It was amazing to see how two women who did not understand each other’s language managed to carry out such lengthy and delicate procedures. They developed a woman-to-woman relationship, especially in technical and scientific matters. Despite Kevin’s previous hard work, the results showed that none of the harvests complied with the maximum permitted limit of the DNA cell residue. The purification had to remove almost all of the DNA cell residue. Apparently, Kevin had no previous experience with this type of cell or virus.

Ryan and David were disappointed at this drawback. Still, they had to find another mechanism to remove the residual cell DNA from the harvests before the project continued. After several meetings and discussions with the scientist couple, Frank and Elsy, they suggested contacting companies manufacturing equipment that could do the job at the scale of small volumes. Later, they could find out how to scale it up to the larger sizes needed. Time was running out, and the project had to go on as fast as possible. So Elsy found a purveyor of equipment that could do the job.

The foundation provided the funds, the purveyor was contacted, and new equipment was ordered. However, it took almost six months for the equipment to be manufactured and sent to Borazon City. Everyone knew that at customs, the officials expect to be compensated for a quick approval process. However, Totem Inc. personnel were still unprepared and could not be involved in any form of bribery, so the equipment had to wait in the warehouse for another four months. Finally, the approval came, but once again, the local political establishment, without any actual argument, considerably delayed and made the project’s development more expensive. This incident probably is a real example of the slow growth of many countries, or could be another case of amplified government corruption. David thought that it was both.

In addition to the previous delays in manufacturing and customs, David had to immediately call the manufacturing company for the equipment so that they could send a technician to install, validate the equipment, and train the local engineers in the operation and maintenance of the new piece. It took another three months before an engineer was sent from the industrial company. The engineer arrived at the company, inspected the equipment, and was ready to put it in operation. There was another problem: he discovered that the new equipment had been manufactured for operation in the original country, and the conditions in the new place were different. The equipment had to be operated under a high vacuum at shallow temperatures, and the differences in the local energy supply needs and different altitudes could risk the main motor. He reported to his manufacturing company, and they agreed that they would send a replacement set of the operating board that could fit and be adjusted to local conditions.

The technician had to return to the company with the promise of coming back to install the equipment when the new piece arrived. It took another three months to manufacture another original main board. The part was sent to Borazon City, and after being subjected to customs, it was delivered to Totem Inc. Two months later, the expert technician again arrived at Borazon City and started installing the part and training the local engineers. A year and a half passed after the decision to adopt a new purification system, and finally, the equipment was ready to start. Fortunately, the latest equipment was operational this time. Fresh viral harvests were prepared to be purified, and the resistant residual cell DNA was removed. Diego was given the task, since he was the scientist from Totem Inc. in charge of the downstream processes, including purification. He was a trained microbiologist with specializations and had previously been trained at Riley Inc. to perform this process.

Diego was very unpredictable; he would initiate a project and, at the same time, was looking for another, more exciting work to do. He would not stay still for a moment; he had previously abandoned his family and some earlier work at Totem Inc., looking to do another research work overseas. Even though it was an enriching experience for him, he returned to Totem Inc. after six months and, by luck, was accepted back in the same position. This event and similar circumstances forced people to portray him as a non-reliable worker; however, he was a loyal, dedicated, hard-working, and dependable scientist. Diego was a short man, far from the height of his wife. As mentioned before, he loved to run in official marathons in many places, and very early each morning, he would practice for competitions. After a long wait, Diego was able to obtain highly concentrated and purified materials after only eight weeks of work.

Samples of the newly purified harvests were sent for quality control tests. Mary, from the technology transfer team, had to be called again to analyze the new specimens with Olga. Due to other commitments, Mary took almost two months to arrive in Borazon City. Finally, everything was in place, and both women were ready to do the testing. Reagents had to be standardized again, and the work was tedious, but finally, the results were out. Eureka! Most of the residual cell DNA had been removed with the new technology. The research team from Totem Inc. jumped up and down in joy, excited that they finally had an approved harvest that could be used to formulate a vaccine. The news was passed on to Ryan and the Coloso technology transferor team, who also felt significant relief.

Shortly later, Ryan contacted the government health institute at Borazon City to inform them that the foundation had approved the promised funds for upgrading the government quality control laboratories and was ready to be disbursed. This laboratory was another excellent piece of news for the project, considering that the government would have the latest technology and facilities for analyzing forthcoming vaccine samples. Several techniques had to be learned and modernized at the new place.

With new technologies and equipment everywhere, the official health institute group had to adapt to new procedures. One of the most interesting was the brand-new design of a trap to enter the latest quality control laboratory. It is also familiar that at the entrance to safety laboratories where dangerous microorganisms are handled, technicians must go through a two-door entrance and exit gate, where both doors cannot be opened simultaneously.

The new equipment imported for the official health quality control laboratory had an automatic synchronizing mechanism, so that as soon as a person entered the confine and closed the door, a sudden sharp blow of clean, sterile air would come from the ceiling and sides, removing any piece of dirt from the clothes and surfaces. The airflow stopped only after eight seconds before the person could open the exit door. With this interlocking mechanism, the air inside the laboratory was kept clean to a great extent. One of the laboratory assistants loved to have fun with the air-cleaning device. She would not warn the person entering the laboratory for the first time about what would happen. Consequently, many people were scared by the sharp air blow, thinking something was wrong. One time, a girl had felt the harsh air blow upon entering the laboratory and started screaming and hitting the walls until the ordeal ended. The fun-loving laboratory assistant learned a lesson and, after that, changed her behavior.

In developing countries, politics are always insidious in the form of the life of the society. Scientific or technical development is no exception. In this case, Lucas, the general manager of Totem Inc., who was a professional man and had fought hard for the company and the project for only two years, was replaced, and the new manager was a lawyer with political ambitions. The employees received this change with displeasure. By all accounts, everyone in the company thought that the company was doing very well from a technical and economic viewpoint. They argued that the general manager had been very close to all personnel and that they had been very well treated with frankness and openness. Moreover, the manager had always been ready to listen to their complaints and requirements.

The new manager was Vincent. As will be seen later, he probably did not care for a transfer project in which exit needed to be completely assured. He knew that his mandate was not going to last. He also thought he would not see the project’s end or how he could appropriate the success. Vincent was a short fellow, always very well dressed with his hair neatly combed. He had a big, long head, a long neck, and a white face with malicious stares. The road ahead for the project was rough. Under these circumstances, the rabies vaccine project became a child of concern only for David and Olga, since the research was always second in the face of the new administration. The new organization could not see or was not capable of looking into the future. Nobody can judge a new manager’s attitude. However, David was prone to thinking that the new manager was a piece of a demoniacal structure of the political administration in all countries in gradual development. Consequently, Vincent was more concerned about his agenda than interested in what was for him slow, complex, sophisticated, or never-ending projects.

Vincent understood that the transfer project had some very new technologies, but he needed help getting inside the pilot plant to investigate something he needed help understanding. He was curious and wanted the latest knowledge, so he called one of his old friends and named him production manager. The recently named professional had a way to enter the pilot plant and learn the essential things happening there. After the new professional copied some of the basic principles of the operation and techniques of the rabies vaccine pilot plant, and by instruction from Vincent, he tried to duplicate the entire system. He went to another building, where a veterinary vaccine was produced, and tried to set up the new technology. The difficulty was that for the formulation of that specific veterinary vaccine, a different virus had to be grown in another very different cell type. This cell type grew much more rapidly than the one utilized inside the pilot plant for the human rabies vaccine. Consequently, the cells in the new system were out of control, grew too rapidly, and died in only two or three days due to the acidity of the growth media and excess waste materials.

After several months and many trials, Vincent and his new production manager had to give up and forget about his embarrassing research involvement. Neither did they understand why the cells for the human vaccine could grow to high densities without disturbing the acid–base balance in the growing media. They never knew or understood that the well-guarded secret consisted of the chemical composition of the medium for cell and virus growth. The growth medium designed by Roger at his university had a unique buffer or protection system that prevented substrate acidification, even in the presence of numerous wastes.

One day, David asked the general manager for a visit from Frank and Elsy, the biochemists who had previously been consultants for Totem Inc. He needed their assistance in standardizing some biochemical parameters in cultivating cells inside the bioreactor. Vincent and Ryan approved the visit, but when the biochemists were requested, it was learned that Frank had passed away. An overwhelming prostate cancer had taken the life of a great scientist and human being. Frank had been instrumental in many improvements at Totem Inc., such as cultivating cells in large vessels to manufacture veterinary vaccines. He also had considerable influence in designing the pilot plant for the rabies human vaccine transfer project and in many biochemical analyses of cell and virus growth media. The rabies vaccine transfer project lost another significant contributor to the long career for success.

Elsy, Frank’s wife, had already finished the regular mourning for Frank’s disappearance, so she decided to accept the invitation. Two weeks later, she arrived in Borazon City. She started to work with Olga on quality control matters for the rabies vaccine for human use. However, one day, she met Vincent, the new general manager, in the office corridor. He wanted to know how everything was inside the laboratory. Elsy was a mighty woman, so she could not hide any resentment. Instead of answering the question, she gave him a lesson on managing scientific projects and complained that he needed to be up to the challenges the transfer project required. She demanded more attention from him for the group developing biological science for the company. David was told of the encounter and felt satisfied with Elsy’s reprimand; after all, she was older than Vincent and more intelligent and savvier.

As time went by, the vaccine project moved slowly, now mainly under the supervision of Olga; progress was minimal, since some pieces of the puzzle had yet to be solved. There were difficulties with biochemical reactions in the medium where the cells were grown, so Roger, the university professor, was summoned. He came to Borazon City upon Ryan’s approval, and this time, his teenage daughter accompanied him. He was enthusiastic because he considered it time to show his audacity, knowledge, and practicality to solve these drawbacks.

Roger was not only a high-level researcher, but in private life, he was also a bodybuilding man specializing in self-defense techniques. He looked like a man of Norwegian descent with semi-yellow hair, white skin, a happy face, and an outgoing attitude. Roger impressed everyone as a man with very soft manners and easy to connect with. He also had the manners of a university professor, eagerly convincing every one of his ideas and knowledge. Of course, first, he had to gather a group of researchers and technicians from Totem Inc. in the meeting room of his hotel and lecture them for over four hours to explain his ideas of what was happening in the laboratory cell cultures and how he proposed solving them.

Roger’s proposal for biochemical changes to the cell culture media worked to satisfaction. The cell cultures became more stable, and the cells grew to a high density again. Another milestone in the advancement of the project was achieved. This happened due to a prodigious and experienced researcher willing to share his knowledge with a country in need and lead a group of professionals eager to enter the restricted club of highly specialized human vaccine producers.

After hard work in the laboratory, Roger and his daughter decided to rest and enjoy some tourism. The local attractions consisted mainly of museums and a visit to a remote place where Indigenous people had an exhibit to show off their ancient culture to foreigners. One day after the museum visits, David, Roger, and his daughter were ready to hit the road. It took three hours to arrive at the culture exhibit. The show lasted only an hour but was full of music and exotic dances. Roger and his daughter were exhilarated; they had never seen what seemed like a pre-Columbian scene in the twentieth century.

The group later enjoyed a very typical local lunch, which they warmly praised, and the three hit the road again back to Borazon City. After only two hours of openly driving, they found a sudden impediment. All the traffic was stopped, and there was some blockage. After a few minutes, the word came back, explaining that the locals from a tiny community were protesting about the lack of running water. The government had promised to build a new pipe, replace the damaged piece, and connect it again to the primary water source but failed to do so.

Roger, his daughter, and David had to wait for another three hours until a high-ranking government representative showed up and signed a new promise to get the water in service in the community the following week. However, nobody ever found out if that promise was fulfilled. The exhausted group finally arrived in Borazon City around midnight. Roger worked for another two weeks with the Totem Inc. team until some cell cultures showed much-expected progress. Again, a stable cell culture was achieved. The technical group at Totem Inc. was delighted to see a cell culture system that could be repeated several times without disturbing factors or holding back.

Vincent, the new general manager, continued to be jealous of the latest technology transfer that was taking place inside his company without his direct participation. One day, everyone was surprised that he had fired a single, very efficient, and beautiful girl in charge of purchasing. In the beginning, David thought this act was another way for him to slow down the progress of the technology transfer project; however, a few days later, it was widely rumored in the company that Vincent had sexually assaulted the girl in his office, and she had vehemently rejected him. She was petrified but never filed any suit against him, but in revenge for not accepting his intentions, Vincent decided to get rid of her. It also became generally known that several girls in different positions had resigned before, due to the sexual harassment of the general manager, and none of them had filed any suit. Due to this behavior, several girls in the company became reluctant to go alone to the manager’s office unless somebody else was present with them.

Through several amusing and perplexing circumstances, Vincent’s sexual conduct was widely exposed, just after he left the company. Occasionally, he invited several high-ranking company officials to his house for snacks, dinner, and drinks. One day, Vincent asked David and his wife for dinner at his home, along with other senior-ranking officials and their wives. Everyone was seated around a space in a vast sitting room, each on their partner’s side. Suddenly, David discovered that Vincent was sitting in the middle of two women, the lady on his right being his wife, and the other lady on his left was a new company lawyer who was a divorcee.

Everything was fine until somebody found out that Vincent held his wife in one hand and the divorcee in the other. The fellow who discovered this situation made signs so that all could see what was happening. As it turned out, everyone later knew that the lawyer was Vincent’s mistress, and his wife openly accepted that without any remorse. Vincent was not only openly supportive of the divorcee but had also bought an apartment for her and a little boy from her previous marriage.

At Totem Inc., the focus was now on the growth of the infectious virus and producing the rabies vaccine to control the disease. Coloso Inc. and Roger had never worked with infectious microorganisms and could not do so, even if they wanted, considering that they did not have specialized facilities at home to handle highly infectious and contagious microorganisms. Moreover, they needed approval from the government to allow their laboratories to handle infectious microorganisms.

Consequently, Totem Inc.’s scientific team had to take over this project phase. They had worked with a similar virus for many years and were producing a similar vaccine for veterinary use with an outdated roller bottle system. This time, they would work with another highly infectious virus inside a bioreactor but at very high viral concentrations, which they had yet to accomplish before. The research team was inclined to call somebody who knew how to do it safely, with quality, and at high cell culture densities.

A research team on the old continent was working with the rabies microorganism only at the laboratory level, with very high concentrations, and only for research purposes and not inside bioreactors. The Totem Inc. team knew of this group and contacted Ryan, so he decided to go to the old continent in search of a research scientist. After a thorough search, he found a rabies vaccine scientist named Antoine, who had worked for twenty years at a research laboratory developing measurement techniques for the rabies virus. Ryan made an offer to the institute’s directors to allow Antoine to go to Borazon city country to teach some of his technology. In return, the foundation would give an allowance to the institute and a travel allowance to Antoine to work with the Totem Inc. team to solve this drawback. The institute gave Antoine a nod to accept the offer, and he was more than happy to receive it.

Antoine was an absent-minded scientist with little or no interest in his appearance. When he arrived at Borazon City, everyone was surprised to find out that he had stepped off the plane with a casual business handbag as his only baggage, considering that he would stay in the city for at least two full weeks. Antoine looked like a teacher with his hair in apparent disarray, his dress not neatly pressed, a tie out of knot, and his face not completely shaved, but his eyes wide open and with a big smile of friendliness. Antoine spent the two weeks at Borazon, and even though he could not fluently speak the local language, he could communicate with the locals with all kinds of gestures, finger-pointing, and nodding all the time.

Everyone was happy with Antoine in the laboratory. There was an issue: he had a body that was new and strange for the locals. The technicians in the lab were eager to learn from him and stay close to him, but at the same time, they wanted to stay away from the smell coming from his body. Upon returning to the old continent, Antoine probably had many histories to tell at home. Still, the most outstanding thing for the locals was what happened one day in the factory cafeteria. Antoine had gone there to have lunch with Olga and several technicians. The group went through the buffet line, and each chose their meal. The day’s main dish was a famous local chicken soup bowl. Antoine served himself a bowl of good size and, after sitting down, started with the soup. After testing three or four scoops, he suddenly screamed, threw away his spoon, and moved from the table.

Nobody knew what had happened, and everyone suddenly stopped eating, looking toward Antoine’s table. After long seconds of expectation, people adjacent to him found out what had shaken him so much. Inside his soup, Antoine had found a fully cooked, complete chicken head, eyes open and looking at him in despair. He was the only one in the room lucky enough to see the chicken head inside his bowl. The people applauded and laughed simultaneously. This incident was one of the standard practices that local foods developed over centuries. Of course, Antoine could not finish his soup and had to be offered something more palatable with no gazing eyes.

Nevertheless, Antoine’s work was finally accomplished. The locals learned how to be safe and handle the presence of high concentrations of this deadly microorganism. The growth of viruses inside newly modified bioreactors containing considerable amounts of rabies virus was solved, and local scientists were satisfied with the new procedures. Antoine returned to his country with the same dress pant and shirt he had worn during the two weeks at Borazon City. He also carried the same casual business handbag that he had been carrying as his only baggage.

With renewed effort and safer utilization of high-density viral cultures it was time for the project scientists to start one of the latest phases in vaccine production, the final purification of the new product, in other words purifying the harvest containing the virus from the growth media. For this crucial step, the purification specialist team from the Coloso Inc. company was needed again.

Chapter Five

1993–1996

An Unorthodox Change

Meanwhile, significant progress was happening at Totem Inc. Another international and political storm was generated at Coloso Inc. This time, another giant multinational pharmaceutical company made a sizable offer to buy the whole business. Coloso managers and the officials in charge of the government shares did not understand why a multinational whose market was only regional was interested in its business. The managers met for lengthy hours for at least three months to discuss the pros and cons of the extraordinary offer. Was this bid another move from multinationals to stop the technological transfer and the work with Totem Inc.? This was a question expressed by some of the officials. Coloso Inc.’s managers and government representatives thought it possible, so they rejected the offer. They reasoned that they wanted something other than a multinational company with biological producing capabilities inside their country.

However, after a thorough analysis, the directors thought it was an excellent time to sell the company. Hence, the board decided to offer Coloso Inc., instead of the multinational company, to a completely private investment enterprise within their territory. Coloso Inc., a partly owned government institute for many years that initially had a few scholars from an original European institute, was finally sold to a local private commercial company. Coloso Inc. was technically dependent and descendant of world-known European research establishments. The locals and the international scientific community felt that a considerable amount of knowledgeable scientific memory and history was disappearing from the country’s academic and learned society. Most of the technical know-how now remained in the hands of a fully commercially dedicated business company.

What would happen to the technological transfer agreement that Coloso Inc. had with the foundation? The company had already received a sizable amount of grants from the foundation. They had to return some of the unspent money and the foundation find another technical transferor.

Moreover, as shown in this vaccine technology transfer, Ryan said that for him, the most challenging contingency was the one related to economic factors. According to him, many individuals are affected by a technology transfer project; the transferees will receive some technical and positive economic benefits that could last for some time, and scientists, institutes, companies, manufacturers, and researchers will benefit economically. However, unidentified separate entities and people will be negatively affected by new products or services. Many old products will be replaced and probably out of the market. Some people might lose their jobs, and the entire market for some products and services will also affect a community or population. Despite all this, the situation must continue, and new products must replace outdated systems and products.

Ryan was again on his feet and now dealing with a new company with entirely different types of managers who had different views of the vaccine business and a signed technology transfer agreement with the foundation that had not been completed. He was becoming a hard-nosed politician dealing with administrators rather than with technological gurus. Still, he was a scientific research physician in charge of a transcendental biotechnological transfer project from a donor foundation, so he was ready for the coming challenge.

It took a few months of discussions inside the new ownership until, finally, the new administration decided that they would continue with the tech transfer agreement. There was a condition, however, that Totem Inc. would pay royalties when the new vaccine began marketing and insisted that it was now an utterly private company and could not do any more work for free. Ryan remembered that they still had some money from the foundation grant that had yet to be entirely spent. He immediately contacted the new managers of the so-called Spencer Inc. In subsequent discussions, he consistently argued that they had to keep the previous promise to complete the last stages of the transfer project and use the unspent money for that purpose. Still, the new owners reported that they could not find any money left from the foundation grant. This was the second time in this project that grant money to transferors had yet to be wholly spent but had disappeared.

Ryan had already spent the ultimate foundation grant, the technology transfer project had not been finished, and there was no vaccine yet. Moreover, the new company assumed that Coloso Inc. had transferred the entire package of technical know-how to Totem Inc., when, in fact, Coloso Inc. had merely worked with the Totem company scientists in the cell culture system and downstream processes. Coloso Inc. knew nothing about the rabies virus. As detailed earlier, Coloso Inc.’s staff could not even work on the virus on its premises. They did not have the high-security laboratories or the license to work on a highly contagious microorganism.

Another subject had yet to be solved entirely or closed—the new owners wanted some confidentiality agreements to limit the length of intellectual property protection. When the vaccine was approved and marketed, who would be the principal owner of the technology? This impasse had to be solved by lawyers, as several countries’ intellectual property laws were involved. The foundation named an international law firm, and Totem Inc. named another prestigious local law firm. Several months of meetings and negotiations with lawyers from the new Spencer Inc. were carried out. Consequentially, some new confidentiality and property protection agreements were signed between the parties; as expected, it was agreed that the sole owner of the technology was the foundation grantor, and the new owner company had to hand Totem Inc. the standard procedures for the sections of work that the company had guided. That was the end of the negotiations with the new company, but other intellectual property protection arguments were still to be solved later.

Due to negotiations with industrial or research companies, Ryan was drained of energy, dealing with people mainly interested in their own business, which had nothing to do with the vaccine technological transfer. Even though a few entities agreed to do some technology transfer, they would do it just for the money—nothing else. In truth, they were not interested in the technology’s success or failure, and sometimes they used part of those grants for other things, different from the technology transfer project. When problems arose, they declared that the donation had been spent, although they had used the money for other matters related to their functioning, which again was happening with the new company and its new owners. This was not the first time in this project that the transferor had argued and claimed that money had not been completely spent. The same thing happened with the European institute after Peter’s premature demise. The new owner company, Spencer Inc., eventually refused to give back any more money for the technology transfer project.

Ryan was again close to giving up the whole idea of the technological transfer of vaccine production. For the previous twelve years, he had been solving some highly technical matters. However, most importantly, he had been solving numerous difficulties with transferors instead of grantees. But he was stubborn. He returned to his board of directors to ask for more money for the project. A member of the board, same as had happened a few years before exclaimed, “Ryan, Not again.”

There was no way the foundation could grant any more funds for this technology development. Ryan decided he could show the directors that the reasons for not finishing the project had been political and not technical. This time, he proposed to the board that they approve some minimal funds to be handled and controlled directly by the recipient company, and David could be in charge of the funds at Totem Inc. The board was not wholly convinced; however, after a thorough analysis, the members concluded that they wanted to complete this project, since it had become a plan for the board to perpetuate, considering that almost twelve years had already passed. Ryan pulled out another ace from his sleeve, so he asked the most resisting board member to accompany him to Borazon City to see how the people at Totem Inc. were handling the project and the progress that had been achieved. The member reluctantly accepted, and both initialized a trip to Borazon City.

Back in Borazon City, everyone at Totem Inc. had high expectations. A high-ranking official from a world-renowned foundation was coming for an inspection visit that could determine the project’s fate. Everything had to be clean, orderly, and brilliant in appearance. The project working group had all equipment running and shiny, and they even practiced some words and phrases in English to answer any board member’s questions. They knew that the termination of the transfer project was at stake.

David made sure everything was well-prepared in the company; he even sent the welcoming car to be washed and polished. All laboratory garments had been rewashed and sterilized for a second time, and special laboratory garments were prepared for the visitors, considering that they used extra-large sizes that were unavailable in stock. Everyone in the pilot plant had to be alert and ready to answer the most difficult questions. They even had to review all the procedures to ensure that they could explain them to the visitors. Even the general manager of Totem Inc., who had slowly been supportive of the project, was ready to show up in his position. He was getting prepared to greet such distinguished guests.

The board member and Ryan were picked up by David, who had waited for them at the airport. The board member had not been outside his country before, because he had always been involved in projects within the country. When the board member arrived, David saw his face of surprise. He was probably expecting a rundown airport, but it was just the opposite. He also perhaps expected a welcoming fellow with a “poncho” or “ruana” and sandals instead of regular shoes. The visitor was in for more surprises; he was driven in the latest model of a luxury-size limousine to a five-star hotel of an international chain, and his welcoming host wore a flannel suit, red tie, and European shoes. He was even more surprised to find out that the welcoming host spoke English like a native and that he had spent five years living and studying in North America.

After a good night’s sleep, the visitors had a large breakfast and later were taken to Totem Inc. They were then guided first to the general manager’s office. The board members were not ready for more surprises. Still, when he was introduced to Lucas, the director-general of Totem Inc., he immediately discovered that the host had also completed postgraduate work in England, so he spoke fluent English. The visitor felt increasingly at home. Lucas introduced the company and explained its history dating back to 1950. He was especially keen to emphasize the different technology transfer projects that Totem Inc. had in the past. Back in the fifties, there was a technology transfer for a vaccine from a research institute in Italy. Later, in the seventies, there was another vet vaccine transfer from England and, more recently, rabies vaccine technology from a research institute in France. He joked that the only technological transfer missing for Totem Inc. was one from North America. Lucas insisted that the vaccine’s technological transfer was not yet finished and had been dragging.

David ushered the visitor to the pilot plant, and he appeared to be calm and attentive. The board member was a skinny and tall man. He was casual and transmitted trust, which was a relief for everyone. He examined the whole company and was quite relaxed in analyzing the pilot plant area, the personnel, the equipment, the services, etc., but more importantly, he was highly concerned about the quality control of the human rabies vaccine. The visitor spoke at length with Olga, Jesus, and David. He was excited to hear about the technology and how the most complex matters had been solved. He even glanced at the growing cells under the microscope. That was the first time he had seen actual microscopic cells. The board member insisted on keeping all the precautions taken to assure the vaccine’s efficacy but even more to guarantee the product’s safety. He did not want to hear about adverse reactions.

The board member congratulated the entire project team at the end of the visit. He was convinced that it was worthy of a final effort. Before leaving the company, he and Ryan went to the management office to congratulate the general manager and the company. The board member expressed that he had witnessed a very significant undertaking and announced that he would recommend that the foundation continue supporting the project. The board member and Ryan were returning to the foundation with a go-ahead report; consequently, the project survived once more.

David now had total responsibility for the continuation of the work and had to complete the assembly of the research working team to fill the gap left by the absence of the Coloso Inc. team. A new biochemist, Luis, was added to the downstream and quality control processes. Luis was tall but very calm and quiet. He had been a researcher for a long time and was very dependable, serious, and business-like. He spoke only when needed and about the things that were important to him. Luis was somewhat withdrawn and not prone to parties. He was also a member of the National Astronomy Association and participated intensely in their activities. He was an excellent complement to the project.

Two more members were also added to the team: Laura and Javier. Laura was a microbiologist with considerable experience in several vaccine formulations and quality control. She was short, with white skin, bright eyes, a lovely attitude, and a wide-open smile. Laura had the looks of a teenager who appeared much younger than she was. She was always happy and transmitted her attitude to anyone. She was also a problem solver. Everyone turned to her, looking for solutions to their problems, not only technical but also personal. She was now in charge of quality control, and this work had to be executed in complete isolation independently of the production technicians. The production personnel could not influence her in their analysis and results. Laura had to be the final judge to approve the final formulations and last vaccine vials before sending them to the official government control authorities for testing and approval.

The other member, Javier, had a degree and specialization in virology. He turned out to be the team’s youngest member. Javier also had considerable experience producing vaccines in large vessels. He would be a well-respected associate, considering that he had the latest information from the literature in every aspect of the biological sciences. Javier took the first position in his graduation class. He could replace anyone on the team from preparing growing media to cell and viral growth in bioreactors, downstream processes, and even quality control procedures. He was energetic and full of life with his sleeves rolled, ready to do anything you asked for. Additionally, he had the best command of the English language in the group and a clear advantage in communicating with consultants, officials, and the outside world.

The road ahead for the project now had a clear path, and the project was rolling with a new impulse. The team now had the components to produce, purify, and formulate a vaccine with brilliance, pass all necessary quality control tests, and prepare a complete volume of written standard operating procedures, known as SOPs. Quality control tests were rigorous and exhaustive. The potency test was the most important and tricky, subjecting the vaccine to challenge tests in laboratory animals. The variation in results was enormous, since animals are very different from each other, and their physical and metabolic characteristics are very different. Hence, their response to immunization is highly variable.

Following internationally accepted and widely used challenge tests, the vaccine potency tests were reviewed and implemented. After the laboratory animals were vaccinated, the immune response started, and then when the immunity was at its peak, they were challenged with live rabies virus. Immune animals had to survive a challenge with a highly pathogenic strain of the same virus used to produce the vaccine; laboratory animals surviving the challenge were well immunized, proving that the vaccine was effective. By contrast, control animals without vaccination succumbed to the pathogenic virus. It took eight months for different trials with many formulations to obtain one that gave consistent approval results in the potency test.

The final vaccine vials had to pass other tests for safety and purity, but the most dramatic was the one for endurance. Several bottles of the vaccine were placed in a container at thirty-seven degrees Celsius for a whole month in an incubator. When this period ended, a bottle was chosen, and then a group of mice was vaccinated with its components. After an immunization period of another entire month, the animals were challenged in the same way as in the potency tests. The vaccine was kept heated in the incubator for a month, and it had to be completely effective in stimulating an immune response in laboratory animal subjects.

Biotechnological work is highly variable, as it has been experienced in developing technology transfer programs. Aside from the basic techniques and procedures, many variables have influenced the rapid progress of work, and many political factors can have a significant impact on the project, such as the availability of specialized equipment and special reagents. Moreover, in this project, knowledge was spread among several scientists and institutions in different parts of the world. The modern scientific world comprises many minds winding together in a net of expertise and capabilities that, finally, a group can put in the shape of a product; it is an excruciating proposition. Ryan explained that this also mirrors technological and industrial vaccine production development.

What very few people accept is that there is also enormous variability in cell culture types. Cells are living organisms growing independently inside Petri dishes, roller bottles, or bioreactors; most equipment controls temperature, oxygen content, agitation, acidity, and even the usage of growing nutrients. This variability was once exemplified when a cell culture was customarily initiated. However, after three or four days, the cells stopped multiplying. Olga, Jesus, and Javier examined everything thinkable to ensure that nothing had failed. Everything seemed to be under control; the cells had enough nutrient materials, and all physical conditions were at standard levels.

The group took samples and examined the cells under a microscope. The cells looked normal and healthy, with no traces of damage, but sometimes, for no apparent reason, they decided they did not want to multiply anymore. The cells appeared to have a mind of their own. Do they have a brain? Maybe they do. David explained that cells are living creatures. Each microscopic cell has breathing and nutrient organs and a defense mechanism. Each cell has a covering, namely the cell membrane, and DNA, their reproductive material. The outer membrane, however, is the cell’s brain; it allows materials and chemicals to pass in and out of the cell and controls cell survival’s breathing and nutrient mechanisms. However, DNA is only a reproductive material, and it can be removed from the cell, and the cell will continue to exist.

In the development of this project, the technicians and professionals in the laboratory acknowledged that when the cells stopped growing, something must have directly affected their reproductive capacity without their control. When cells die, their DNA becomes liberated, and has to be removed from the vaccine harvest to obtain an ultra-pure virus before formulating the product. A vaccine meant to be injected into a human being should not have traces of a reproductive material from a cell multiplying without control. The DNA must be removed through a highly specialized downstream process. Now, the consulting group had a small-scale system to carry it out. They had to scale it up to an industrial level.

Occasionally, Ryan visited Totem Inc. and overlooked the project’s development. Despite all circumstances, the group was still generating some harvests, with the proper growth of cells and high quantities of purified vaccine viruses. The group formulated a trial vaccine according to its most effective components. Still, quality control in Laura’s hands had to show that these were viable products to be injected into human beings. She conducted many sterility, safety, potency, and endurance tests on the pilot vaccine lots, and after almost four months of back-breaking work, she returned to the team and screamed, “We have a vaccine!” The good news was relayed to Ryan, and he had a sense of profound relief. Even though no vaccine was approved for sale, the transfer project had a product, so he immediately packed a luggage and took a plane to Borazon City, this time again accompanied by a board member.

During this visit, the presence of Ryan inside the Totem Inc. laboratories was not intimidating. He finally had a smiling face that nobody had seen before, 14 years after the board approved the project, an actual rabies vaccine vial was in sight. The product was labeled and tested according to all internal standard laboratory procedures. Even though the vaccine still had to pass clinical trials in human volunteers, Ryan was finally at ease; he was going to show other members of the board of directors that he had been right all the time. He would savor his report of a well-conceived technological transfer program that could take root in a developing country. The local celebration included a big banquet and many cheers for Ryan and a board member of the foundation. Several pictures were taken with the visitors and the group of researchers, proudly showing some labeled vaccine vials. Ryan felt so happy that he could not wait to return to his leaders to relay the best news, so he and his colleague rushed back to their country.

Totem Inc. continued the most natural, although not easy part of the project. The vaccine had to be registered and certified by the government institute in charge of pharmaceutical and biological qualifications. So Olga, David, and the group started applying for accreditation and registration of the vaccine. With these papers of approval, the vaccine could then be commercialized. The government had to do all quality control tests and undertake clinical trials with human volunteers, so the vaccine vials’ official examinations would take another two years.

With time, Vincent, Totem Inc.’s general manager, had other thoughts and ideas. He had not been very supportive of the technology transfer project, considering in his mind that he had not initiated it and that it was not his idea, and he also felt jealous of the initial success. In any event, the product would be for human use, and the company’s mainstream products were veterinary vaccines. He did not care much and even considered that marketing that product would be very different and more complicated than the one for animal vaccines. Vincent was unprepared for those changes, so he got approval from his board of directors to emphasize the remodeling and modernization of a vet vaccine outfit that gave the company the best revenues. Only Olga and Jesus, under David’s direction, could continue with the human vaccine project. Other team members were transferred to additional branches of the company, and some, frustrated, even resigned and left the company.

This decision was another big blowup for the project. David assured Olga and Jesus that they would get all his support and that they would get the new vaccine approved for marketing. Ryan got the fatal news but could not do anything more from the foundation. The project had finished for the foundation’s board of directors; however, Ryan promised that eventually he would divert some limited funds from another project for official quality control. David had to let him know as soon as some vaccine lots were ready for submission to the government.

Olga and Jesus again got busy preparing cell and viral cultures, somewhat isolated from the rest of the company. Other technicians working on different projects inside Totem Inc. looked at them in pity. Most people thought they could not finish the project without absolute support from the directorate. They worked very hard, and David frequently would go down from his office and assist in solving many obstacles they encountered. The mood was getting engaged once again.

Once more, some mysteries of biotechnology were going to affect the project’s progress, the same as had happened before, when the cells stopped growing several times without any apparent reason. This time, the cells were dying during the growing phase of the culture. Olga, Jesus, and David were brought to their knees, and everything was examined, starting with the growth media, reagents, and oxygen supply. The examination included all the physical and chemical parameters of the culture and could not find anything wrong. The cells had been growing up to a certain point, and then suddenly, without any other sign or obstacle, started to perish.

They extensively reviewed the literature and found that these phenomena had been described by some researchers as “apoptosis,” the natural destruction of cells in a growing population. For the three researchers at Totem Inc., this was like cells entering into a suicidal phase. Did the individual cells have the capacity to decide when they would die, similar to a full-grown body like a mammal or human, for that matter? Again, specific cells in a community, like a cell culture, have their own minds. Fortunately, this incident was rare, and work could continue its slow progress.

Olga, Jesus, and David were getting close to having two of the three vaccine lots ready for submission to internal control and later for official government testing. Then, another event interrupted life in the company. In another political and unexpected move, Totem Inc.’s general manager was removed. The board of directors did not have an immediate candidate for the job, so they decided to place an interim manager. They named the administrative manager in charge of the post, while the government agreed on a permanent officer.

The new manager in charge of the company was an experienced administrator with very little knowledge of biological processes. Brian was a decent man with few political ambitions and was more prone to doing a good job. He was a native of Borazon City and a local individual. There were some unique characteristics of male persons born and educated in Borazon City. Everyone described them as elegant, well dressed, well spoken, with educated manners and a particular local slang language. Brian was especially suited for the job. When David told him about the project’s difficulties, he immediately assured him that he would support and help in any way possible.

Olga and Jesus continued preparing several cultures but had some difficulties supplying special reagents that had to be imported from an Asian country. The analysis did not validate one quality control reagent, which was badly needed. Brian was informed of the nuisance and immediately asked the person in charge of imports to contact the supplier. After a few days, the import manager reported that the company that sent the reagent had disappeared. There was no answer by phone, mail, or fax. Brian got mad and ordered a new supplier as soon as possible.

A new supplier was found, but it was located in the same Asian country as before. Brian decided to order the reagent, but this time, with the condition that it would only be paid once it was approved by quality control. The arrangement was that a bank would open a letter of credit to be paid to the supplier. The supplier would send the reagent, which would be held in customs at Borazon City, and then Totem Inc.’s quality control personnel would sample the reagent at customs and analyze it in the laboratory. If the sample was approved, the letter of credit was liberated, and the supplier collected the price of the reagent.

With this promise, a new order was sent, and another shipment of the reagent was made. The latest product was held at customs and sampled by Totem Inc.’s quality control, but after two days, the results showed that the product needed to be more suitable. The product was returned with a collect-on-delivery shipment, and as a goodwill gesture, the provider was allowed to send another shipment. Finally, the last was approved by quality control while kept in quarantine at customs. The Asian company learned the hard way to comply with product quality, but the transfer project suffered another long delay.

Six months proceeded at Totem Inc. without any significant outcome. However, the transfer project was destined to have intractable problems that were not easily overcome. Brian, the recently appointed general manager in charge, had a minor heart attack. So this time, he had to remain in the hospital for at least a month. Fortunately, the secretary of the board replaced him during the hospitalization. The work inside the pilot plant continued without significant obstacles. One month later, Brian returned to work at Totem Inc. and continued with complete support for the technological transfer project. However, only two months later, he was informed of the official appointment of another new general manager of Totem Inc., and two weeks later, the new appointee showed up at the factory.

Angel, the new long-term general manager, was a man belonging to a vast conglomerate of business executives, where he was not on the top ladder. This was a unique opportunity for him to show the community that he was a pragmatic and successful manager. When Angel learned of the technological transfer project, he decided that if the new rabies vaccine for human use could be registered, he would receive considerable credit and appear as the manager who finally did it. He immediately thought about the official inauguration of the pilot plant and receptions with high-level officials from the country and overseas. He realized that he would be the principal host. This was the performance he needed, and he was going for it.

Chapter Six

1998–1999

A Leap Forward

One of the first things Angel did was ask David to show him the project site. He was taken to the pilot plant and introduced to Olga and Jesus. The visit to the vaccine factory was very well received; it had been some time since any high officer from the company, apart from David, had gone down to visit the operation of the rabies vaccine production area. Angel was impressed with the new location; he had never been inside an industrial production facility for any vaccine. He was an experienced entrepreneur but needed to observe the precautions, the exceptional design, the specialized equipment, and the rigorous management that the operators had to go through. The facility had to avoid external contamination from foreign agents or microorganisms.

To enter the new area, Angel had to change his street clothing to dress, especially a sterilized garment covering his entire body from head toe. He also had to wear a sterile mouth cover and special sterilized non-skidding overshoes. Angel probably understood the common saying, “Prevention is better than cure.” The whole scene made a profound impression on him, and after seeing all the processes, he was sure, without any reasonable doubt, that the project would be a success. He liked the project and immediately decided to assist.

The next day, at his office, Angel called David and asked him what was needed to complete the project and quickly register the new vaccine. David described the whole ordeal of the project to Angel, starting from the beginning. He emphasized the many years that had passed and even described the many difficulties he encountered. He also assured him that with his leadership and encouragement, the project could and would end happily.

David next asked Angel to look for and bring back the scientists who had resigned, were dismissed, or were in other projects so the whole old team could be assembled again. Angel immediately agreed, and David contacted the project’s scientists and others from different projects. He also reached out to professionals from the quality control area who had been dismissed. Diego, Laura, Luis, and Javier were reinstated in the company to join Olga and Jesus. The formerly original team was once more together.

The new scientific team started to get acquainted again and was making plans. They had to review what had been done and add several details that would have to be adjusted. In the various meetings, the most critical process was related to the purification of the vaccine. Another concern had to do with scaling up the bioreactor size, considering that the production of the initial vaccine vials that had confirmation in the quality control tests came from small bioreactors. The purification equipment was initially designed for low working volumes. The real challenge was scaling up all systems to the industrial and commercial levels.

In formulating the final rabies vaccine, two specially imported reagents acquired significant relevance: one chemical used for the inactivation of the virus before purification and formulation, and another used for freeze-drying of the vaccine for the long-term preservation of the product. The chemical used for the inactivation of the virus was potent and even carcinogenic, and the supplier required special permission for shipping to a foreign country. David, however, found out that it was possible, with special permission, to carry it with him as accompanied baggage.

The supplier of the chemical inactivant mentioned that it would take at least three months before he had papers of approval for international shipping. Instead, David asked Angel for a plane ticket, traveled to North America, and planned to carry the inactivant as accompanying luggage. He went to the chemical distributor and paid for the product. The company took another day to get permission to ship and packed two tiny bottles of twenty cubic centimeters in a secure bag. They then filled the bag inside a cardboard box full of plastic bubbles and placed it inside a large cooler full of more plastic bubbles to ensure that the tiny bottles would not break. They labeled it and sent it to David’s hotel. David, however, only expected a small box that could fit within his small carry-on business bag.

There was no way for him to carry his suitcase, business bag, or bulky cooler. If he had a large package with a chemical, it would have to be inspected by customs, which would probably require significant time for analysis and taxes. David decided to unpack the tiny bottles, place them inside a small padded bag, and carry them in his pockets. With this arrangement, he got a plane to Borazon City. When he arrived there, a colleague was waiting for him at the airport, but the colleague did not see any package besides David’s luggage, so he asked him where the reagent was. David opened his pockets and showed him the small bag that he had packed. The colleague was shocked. “Are you insane? You carried a potentially carcinogenic chemical inside your pockets? he exclaimed. This episode was not mentioned to anyone else, which could have landed David in deep trouble. David apologized and acknowledged that his behavior was unacceptable—even for a scientific purpose; but the job had been completed.

The group started work in cell cultures with larger vessels with newer decanting gadgets; new cultures were prepared, and the system began to be standardized, but new obstacles began to appear against the project. The pilot vaccine plant depended on many services, including sterile distilled water, dry steam, reagents, chemicals, standard supplies, etc., from other technical areas of the company and the administration. The supplies were being delayed, the services were failing, and the atmosphere of the scientists working inside the pilot plant was tense and annoying. Company employees from different professional areas again became jealous of the vaccine pilot plant personnel.

Angel was informed of the situation. He vowed not to allow the project to fail due to this attitude. He sent a message to the entire organization informing the staff of a weekly meeting in the boardroom. Every department head had to attend; he would be present, and David would be chairman of the meeting. The meeting’s objective was to examine the rabies vaccine transfer project’s progress and how the pilot plant’s needs were met. With this arrangement, the project was brought to real new life using continued leverage from Angel. Department heads were forced to report every week to the general manager regarding what was being done to facilitate the operation of the pilot plant. The full functionality of the plant was finally assured, and the project was again moving on the right track, thanks to the new angle provided by Angel.

Everything seemed to be in place. Cell concentration was now at high-density levels, and the decanting columns worked satisfactorily, preventing cells on top of the microcarriers from escaping from the bioreactor vessels. Jesus had to spend several days overnight at the side of the bioreactors to ensure that nothing would fail until the system had been standardized again. Even though everything was working well, maintenance had to work many extra hours to fix failing equipment. Still, Angel’s new arrangements resulted in considerable progress for the project.

A new working bank was prepared so cultures inside the bioreactors could be started again. Olga and Jesus, with David’s assistance, were able to prepare several cell culture batches, which were then infected with the virus and subjected to all downstream processes. Then came internal quality control tests, and when completed, three consecutive rabies vaccine batches were formulated and freeze-dried to submit to quality control. The internal tests took extended periods, considering that three vaccine lots had to be forwarded to purity, potency, and stability studies, which took over two additional months.

After such long periods of expectation, the internal quality control tests were completed, and three consecutive vaccine lots were ready and approved by all criteria. The SOPs had to be prepared. These documents comprise the way and processes the vaccine had to follow to arrive at a final product. With all these documents at hand, David, and Olga completed the quality control analysis. Totem Inc.’s scientific group also made vaccine consistency lots, fine-tuned the potency of the vaccine, performed safety tests, and completed reports on assays to measure residual cell DNA in the candidate vaccine. All documents and analyses were duly signed and sent to the government pharmaceutical approval authority.

It took a few months for the government entity to review all these documents, and eventually, they advised that they were sending a technician to take samples of the three rabies vaccine lots to initiate their tests. Two government quality control officials came to the laboratory one day without any prior notice. They were asked to be directed to the cold room where the three lots were stored, and in private, they took many samples of the three vaccine vials, kept them in cooling containers, and took them to their quality control laboratories.

As expected, it took several additional months for the government entity to give the results of the tests. The professional in charge of the tests was a woman. She was a trained microbiologist from the best local university and had considerable experience in quality control procedures. She was an afro-descendant with a certain charm, and she always appeared happy and smiling and seemed to be having fun with her work. She was good at making her clients feel relieved and thought that everything was going to be okay.

One day after three months, the woman in charge of the tests returned to Totem Inc. and told David that she had the results of two of the three vaccine lots, but a sample from the third lot had some preservation problems and probably had not been handled well. She could only give the results of the two lots that had been finished once she had the complete results of the three lots. Consequently, she had to take a sample from the third lot again and return to her laboratory to start tests on those specimens. As expected, the new analysis of the third vaccine lot took several months until the samples were submitted to all physical and chemical laboratory tests and animal potency tests.

Finally, three vaccine lots were approved by laboratory tests of the quality control governmental agency. The agency informed Totem Inc. of the results. The laboratory results showed that all three vaccine lots surpassed all analyses and tests, and the product was safe and potent in laboratory animals. Totem Inc. was approved to start the clinical trials. The rabies vaccine would be injected into human volunteers for the next phase, and subsequently, after a period of appearance of specific antibodies, the persons would be bled, and blood serum analyzed. The laboratory would measure the degree of protection the volunteers had from the rabies virus, and the degree of antibodies and absence of side effects would decide whether the vaccine would be approved or rejected for human use.

To start the clinical trials, a specialized medical professional from the quality control entity and a scientist from Totem Inc. initiated a search for human volunteers. Each person had to be willing to go through a vaccination scheme and analyze adverse reactions and subsequent bleeding to determine their immune response. A retrospective study and investigation revealed that first-year university students from veterinary schools who always needed vaccination and rabies protection were the perfect target for the testing group. Therefore, the vaccination team visited several local universities in search of freshmen first-year students who had not received any previous rabies vaccine shot. Unfortunately, they found that most, if not all, students had already received a vaccination scheme for the same rabies virus in the weeks before the vaccination team’s visit.

The team then contacted regional health offices in the country, asking them to visit the veterinary schools in their region to see whether they could find students who had not had a previous immunization against rabies. After six weeks, answers were received from all regions in which vet schools existed. The schools reported that every first-year student in those schools had already been vaccinated at least one month before. Was this a coincidence, or was something unforeseen going on?

After further investigation and study, the group from Totem Inc. and professionals from the government regulatory entity found that a multinational company had gone to almost all local and regional universities around the country, offering free vaccination for the rabies virus. Some multinationals were trying to slow down or prevent registration of a new vaccine that would compete with a great advantage with their product; it was just a matter of “business as usual.” The pharmaceutical conglomerate could not afford to lose or diminish a considerable market. There was a newcomer with a modern vaccine that was equal to or even better than the one they had, and most probably at prices at least twenty times lower.

For Totem Inc.’s company administration and scientists, it was evident that many of the past successes were related to this last incident. After a little more research, other incidents became clearer, and many episodes were found to be related to a conspiracy to stop or terminate the technology transfer project. After further examination, it was found that one pharmaceutical conglomerate had paid some low-rank Totem Inc. employees to boycott the production of the new vaccine. Specific equipment was damaged on several occasions, which caused innumerable delays and extra costs in the technology transfer project.

The inquiry revealed that the same multinational probably offered to buy Coloso Inc. to stop the technology transfer from them to Totem Inc., which did not come about. The same or other pharmaceutical industrial group also made another offer to buy Totem Inc. directly, but the sale, of course, was prevented. Now, another pharmaceutical conglomerate, or even the same one, was trying to boycott the clinical trials. There were too many coincidences, all trying to stop, delay, or even give a big blow to the vaccine technology transfer project.

The vaccination team of the technology transfer in charge of the clinical trials continued a never-ending search. After many frustrations, stress, and pure luck, they found a little-known veterinary school from a recently established university that had not yet received a visit from the other vaccination group interested in the boycott. The number of students was not as large as expected. Nevertheless, the government vaccine registration office accepted it in light of the hinderances encountered so far. The vaccination team from the technology transfer project had to interview each of the students and record any previous vaccinations with other vaccines. It analyzed each student’s immune status, whether they were taking any medicines, and other details. The volunteer students had to confirm their acceptance in writing and sign a consent form to be available one month after the vaccination to be bled for the analysis of the blood serum for their immune response. Moreover, students could not receive any other vaccinations during the testing period, and they would receive only one dose of the vaccine under test. Volunteers would have to record any significant changes at the vaccination site or secondary reactions of any type; however, they would also get an official report with the individual results of the immunization.

The immunogenicity trials and evaluation of secondary reactions in human volunteers were ready to start. The vaccination started with over 200 volunteer students. Afterward, the evaluation team regularly visited the students to ensure that they followed the recommendations. At the end of the immunization period, blood samples were obtained from all students, and serum samples were extracted and submitted to quality control tests at the governmental agency. Eventually, very mild local on-site reactions to the vaccine were reported in only 5 students from the group of volunteers. The physician in charge of the analysis and the institute director-general in charge of biological vigilance reported the results of the tests. There was sufficient evidence from the study that all students were well immunized with the Totem Inc. vaccine.

The scientific and technical group from Totem Inc. then submitted vaccine lot consistency data, quality assurance records, and human volunteers’ immunogenicity data to the regulatory agency of the ministry of health for review. After only four months of analysis of the records, the technical team from the ministry of health issued a license for a new human vaccine for use in Totem Inc.’s country. The rabies vaccine technology transfer project had succeeded and attained its first major step, which, for many years, seemed unsurmountable.

Ryan was advised of the vaccine’s approval and immediately informed the foundation’s board, which was delighted with the new outcome. The board congratulated Ryan for the enormous effort he made for the project’s success. It praised the foundation’s investment in considerable time, energy, and resources. However, the board members felt vindicated by the success of the technology transfer project in a developing country. For them, the project’s end was a significant achievement and a unique investment that merited being shown. At Totem Inc., David, Olga, Jesus, and the rest of the group celebrated with a private dinner.

As several arrangements and considerations went on, Angel and David decided to prepare an official vaccine presentation for the health sciences community and work out the details of a seminar on the results of the whole project. Ryan immediately told them that he was ready to assist in financing the airline tickets and travel expenditures of any international guests who would be invited. Angel and David summoned prominent personalities from world health organizations, Pan-American health entities, North American and European research, and public health offices to unveil the vaccine and seminar meetings.

Several top-notch scientists from the vaccine world, including those from Europe and North and South America, were invited. From Valente, the country of Totem Inc., health and agriculture ministers, such as officials from the health research and biological control offices, were likewise invited and days later accepted the invitation. The meetings took place at a large convention center underneath the hotel where the international visitors were staying. The local press was present throughout the sessions, which lasted for two days.

One day before the seminar, Ryan was the first to arrive in Borazon City to assist with the preparation of the meetings. The next group to reach the place was the previous Coloso Inc., Jack and John, who showed their most glowing smile. Everything was amusing, and most people looked joyful. The heads of several rabies research units from Europe and the Americas were in attendance; the same happened with scientists from the world health community. The country had not had such a vital gathering of essential scientists for a long time.

The new rabies vaccine was exhibited and introduced to seminar attendees. Angel warmly presented the vaccine technology transfer project. He explained the many difficulties and delays that the program had and additionally emphasized the solutions that had been implemented for each interference. Everyone was surprised that the total length of the project, from its inception at the foundation offices to the registration and licensing of the rabies vaccine by government authorities, endured for over 14 years. David and Olga each summarized the vaccine’s technology and quality control, and then the director of the government quality control institute proudly described the human immunogenicity trials. He was particularly interested in showing that vaccinated students had high levels of protecting antibodies and only a few highly limited and mild local reactions. There were no undesired systemic reactions to the vaccine.

The star speaker was Ryan, who prepared and read a paper on the history and main features of the transfer project. The manuscript title read: “A short history of a vaccine technology transfer program.” He emphasized that the most critical features of the program were geared toward the ability to produce tissue culture vaccines and secondary benefits. One of the secondary benefits would be to share the technology between the agriculture and health sciences sectors, improving human health and food production. Another benefit would be acquiring the basic techniques of biology quality control through mastery of all aspects of vaccine production, safety, and efficacy testing. Ryan also explained that the project had to overcome many severe problems: “Admittedly, the completion of the technology transfer program has been delayed—delayed but not stopped,” he said.

Ryan also remarked, “Against this backdrop of technical, logistical, and legal complexities, a less determined institution and a less tenacious program manager would have given up. Totem Inc. did not give up.” He finished his paper with “Today, Totem Inc. enters the exclusive club and elite list of highly specialized and high-tech vaccine producers worldwide that will serve the needs of human beings for generations to come.”

Very few comments were made on the total time that had been lost since the original foundation started to finance the development project for this human rabies vaccine. From that point to the end, with the official vaccine registration, the project was completed in fourteen years. By comparison, how long did it take to create other vaccines? David speculated that it took nine years to develop the measles vaccine, twenty years for the polio vaccine, and twenty-two years for the mumps vaccine. He acknowledged the comparison was not quite accurate, as the new rabies vaccine was just a change in technological processes and not a development of a brand-new vaccine. However, the reasons for this prolonged development time for the new rabies vaccine could be attributed to political and mass-market considerations.

After the seminar, the attendees enjoyed various savory foods and cocktails. The newspapers of the day after the workshop and presentation of the vaccine to the world read something like this: “Totem Inc. develops a new vaccine for rabies,” “A new rabies vaccine for human use,” “New product to control rabies,” and” Totem Inc. develops a unique process for a rabies vaccine.”

After many celebrations, the marketing team at Totem Inc. had to define ways to sell the new vaccine. In any manufacturing business, production is much easier than marketing the product. The team finally had to reinvent themselves, given their limited experience marketing veterinary biologicals and pharmaceuticals. Marketing is a completely different ball game. They had to devise new ways to reach regional health departments and health entities responsible for vaccination programs. The company hired a physician to be in charge of the technical area of the latest health sciences department at Totem Inc., but he faced many misconceptions from regular physicians and some health sciences personnel. Many could not understand and accept that a human vaccine was being manufactured in a veterinary outfit. Therefore, there was a need to break old-fashioned concepts and ideas in the developing world.

Beyond these misunderstandings, the marketing manager of Totem Inc. was a veterinarian and had a degree in epidemiology, but he did not have training in marketing to sell the human vaccine. He had been learning to convince cattlemen to buy some of Totem Inc.’s pharmaceuticals and veterinary vaccines but was unprepared to market the human vaccine. The marketing manager was somewhat against the human vaccine project, because he guessed he would be displaced by a new product that had much more acceptance by the general public than his veterinary products. He preferred dealing with farmers and livestock producers over dealing with health officials; this was another obstacle for the new vaccine.

Another particular concern was the selling price of the vaccine. Totem Inc.’s production costs were considerably lower than any other imported vaccine on the market; it amounted to approximately 3 US dollars per vaccine vial, and the selling price was fixed at 8 US dollars. The market price of one imported competitive vaccine from a multinational company was 50 to 70 US dollars per vial. The difference in the general selling price of the two vaccines was astronomical. Unfortunately, as in many businesses, some customers tend to think that a product selling at a cheaper price may have quality issues that need to be improved. This was already happening to the new human rabies vaccine in the market scene. However, Totem Inc. was making good profits from the low sales volume of the new product. It took a lot of leverage from marketing personnel to convince non-believers of the significant advantages of the modern vaccine. The marketing personnel also leveraged the relationship between the health ministry of the local country and several health institutes in neighboring countries. Due to these connections, many vaccine doses were shipped to those countries and administered by the health authorities.

Has the original technology transfer project been completed? Some people thought this was the end of a cumbersome critical process, coming from a foundation interested in assisting developing countries to attain self-sufficiency in producing newer vaccines. Other scientists, especially those involved since the project’s beginning and who had attended several original task force meetings, thought the opposite. Since the beginning, the foundation had aimed to set up a development project for a rabies vaccine for human use in a developing country, where other countries would send technicians and scientists to the pilot plant for training in technologies to produce newer vaccines. One country with advanced technology for only one disease was insufficient to impact the supply of current efficacious vaccines to the developing world; the discussion was starting.

Four months after the seminar, Angel considered that he had completed his mission. During that time, David was on a business trip to Europe to acquire some exclusive spare parts for the pilot plant. Without previously informing anyone, Angel resigned from his post as general manager of Totem Inc. David was not even informed of this by the Totem Inc. administration. He learned the unexpected news when he got back from his trip. He felt quite devastated. He and Angel had made a critical rapport and assembled a team to certify the new rabies vaccine for human use. Angel had forced the whole company to comply with the support for the project to attain the goal of having a new modern vaccine for sale. Angel left no messages for David; however, he finally got him on the phone. Angel did not explain his sudden departure; he probably had other new, more important business to attend. Consequently, the board secretary was temporarily left in charge of the company until a new general manager was named.

Only one month later, more news was received at Totem Inc. In another coarse political move, Tobias was named the new general manager. The opposition party to the government described the new manager as a puppet who was somewhat elated to the country’s president. Tobias was a cattleman or cowboy who owned farmland devoted to fattening cattle in the southern valleys of the country, so he needed to gain experience in public administration, much less knowledge of a biological manufacturing enterprise. He was confirmed to this position by members of the board of directors of Totem Inc., who were also cattlemen. It was known that they wanted to improve and devote the company’s sales and services only to veterinary vaccines for their benefit, not to the health division of the new vaccine.

David continued to be the scientific director of the company and the director of research and development. He felt that a different strategy had to be proposed if problems arose in marketing the new human vaccine, so he developed a new plan for the human vaccine division of the company. He asked to be heard by the board of directors of Totem Inc. to explain a new program. The project’s main idea consisted of installing a pilot plant in a familiar country with tax-free areas for international companies to establish manufacturing enterprises in their country’s soil. The new vaccine could be exported to countries in the region without difficulties, and the vaccine would continue on the shelves of health institutes in the country and elsewhere. The new plant would also serve as a source of revenue and foreign exchange money for the company to acquire new equipment for other divisions. After a few weeks, the board listened to David with considerable interest and told him they would discuss the matter and that they would conduct their investigations and give a reply.

Two months later, David received a vocal reply from the board explaining that the company was not interested in marketing the new vaccine. They were much less interested in setting up a facility outside the country, which would be difficult to manage. They insisted that the company had no marketing force for any human vaccine and that their only interest was marketing veterinary products. David was appalled and hurt. He could not believe that after 14 years of ferocious battles, the production of the fully licensed golden vaccine would be discontinued by the company.

A few weeks later, David received a visit from the new administrative manager of Totem Inc. in his office, politely asking him how soon he would retire to collect his pension. He explained that the general manager wanted David to rest after so many years of hard work. David considered this to be nonsense and thought the general manager was only after the safety of his own position. Once he got rid of the scientific director, he would have no one to question any technical move by the new administration that was not according to scientific or biological principles. The general manager felt intimidated and apprehensive by a well-trained expert scientist with postgraduate degrees, many years in the company, and many friends in the scientific community, both in the country and at the international level. The recently appointed general manager was just a jealous ranch cattleman owner who wanted David to move out of his way.

David later told the administrative manager that he had already sent his papers to a pension fund ten months earlier, and they had recently told him the study and approval would take at least four more months. The general manager wanted more than the answer he received and wanted to arrange things immediately. So he ordered the administrative manager to move David’s office away from the second floor, where he had an office for the last 20 years. The second floor housed the offices of other high-ranking officials. David was moved to the first floor, where second-level officials of the company were stationed.

The new management wanted to reduce David to a shadow and make him miserable. These moves did not deter David. He contacted many people and started working on a plan with friends from international entities and universities to bring the original foundation plan to life. Could the initial foundation project of a pilot teaching plant for rabies vaccine production technology be revived? Let´s see.

Chapter Seven

1999-2000

Five months later, David resigned from his post as scientific research and development manager of Totem Inc. He received a lifelong pension from the government and started a new retirement life from his duties there. Numerous professionals, technicians, and administrative personnel gathered to offer David farewell from the company. The reunion was very sentimental, considering David had been in the company for a long time, and his abilities as an administrator and scientific director had gained considerable acceptance and admiration from all the people involved. He even received memorabilia with the signatures of at least 100 employees.

Olga, the most loyal of his assistants for the last ten years, told David that she would eventually resign and follow him in any other project, which was emotionally moving for David. It was the most reassuring gesture he could have received to start another project in different surroundings. The Totem Inc. board of directors also summoned David for a special session and banquet to show appreciation for the work done over those long years. They also gave him a letter and a manuscript on sheep-skin paper with sentences of special thanks.

A few days later, David was alone thinking about the future of the foundation’s original vaccine technology transfer project and his future as a scientist and biological entrepreneur. He did not accept that the foundation scheme and goals were finished. So he developed a plan to persuade the foundation to start the project in another country in the Far East or Asia. To convince the foundation of his idea, he thought he had to go first to several international organizations and institutes to explain the plan to set up a laboratory school of vaccine production methodologies. David had no financing, so he decided to utilize most of the retirement funds he had received, intending to travel and visit several places and institutes in other parts of the world. He asked for different appointments, got airline tickets for himself and his wife, and started a business trip, during which they decided to make their second late honeymoon. They intended to visit places in Europe and North America for work and leisure.

The couple visited well-known research and development institutes in England, Germany, and France and paid a call to the WHO in Geneva, Switzerland. The officials and administrators were very interested in listening to David’s ideas in every place they visited. However, in the end, everyone insisted that it was not possible to establish such a school of vaccine production technologies. The most common reason was that nobody would finance such an endeavor. Another reason scientists shared was the belief that no developing country could create or house such an enterprise. Most people told David that he was a little insane about pursuing such an idea.

David was unable to comprehend the WHO’s perspectives. This society has supposedly been financed and sustained by several highly developed countries and the United Nations in the hope of assisting developing countries with research, epidemiology, and control of health-associated disorders. Small countries with deteriorated financial systems and a lack of technology cannot cope with the costs of controlling the spread of many world infectious diseases. This fact becomes more evident at the appearance of an endemic disease or pandemic. Moreover, some highly infectious microorganisms have produced massive epidemics and pandemia, decimating entire regions of the world.

David could not believe some of the excuses given by some WHO officials. They were saying that they could not assist with a plan to help developing countries produce high-tech vaccines? Several doors slammed in David’s face. All the WHO officials and scientists he met seemed so satisfied with their current work and unwilling to offer a helping hand. They were happy with the establishment and did not want any more work or a change in structure. Without exceptions, they were satisfied assisting countries in using available vaccines rather than acquiring technology to produce them. To David, the health officials appeared to be more on the side of the large multinationals that already had the worldwide market for most vaccine production. Those companies would not like or accept any competition. At the end of a long and painful trip, David had to go home empty-handed. However, he still felt like something needed to be done to reverse the trend in the search for and development of new vaccines, and the WHO should play a primary role in that aspect.

Meanwhile, David had received a letter of good wishes from Ryan, who was departing from the foundation. After many years of hard work helping developing countries, he retired from the foundation. He thanked his counterparts during all those years for the collaboration he had received, explaining that he had received 95% of the sweat in many projects and that his contribution had been more on the side of inspiration. He was moving to a university post to continue his work on tropical disease research.

David, however, did not give up. He continued his exploration in North America, where he visited several universities and health sciences institutes. The answers remained the same; most people felt that pursuing that plan was impossible. David and his wife visited Roger at his university post, and he could not give them any hope there either. Finally, David decided that he was going to approach the foundation that had originally initiated the technology transfer project many years before. Even though Ryan was no longer there, other officials at the foundation could remember the plan, and they still remembered David. It was therefore not difficult to get an appointment with the new physician in charge of the health sciences division.

The new man was Robert. He was a tall man of Latin descent, with little knowledge of the foundation’s previous projects. He had a white complexion, black hair, an elongated face, and unexpressive eyes. He looked like an executive from a large conglomerate. David introduced and explained the rabies vaccine technology transfer project to him in great detail, since he had very little knowledge of the project’s intricacies and difficulties from the previous fifteen years.

Accompanied by his assistant, Robert listened carefully and was very happy to hear about the outcome of licensing the new vaccine at Totem Inc. He could not comprehend the latest decisions of the technology recipient, who did not want to pursue the original purpose of the vaccine technology transfer project. Nevertheless, he could not see how the foundation could assist in the future development of this project. Robert promised David that he would consider the matter further, because he had to talk with various board of directors and foundation officials to see if something could be done. Therefore, David had to go home once more empty-handed.

In the meantime, David approached a large international company that manufactured bioreactors. He asked them whether they would be interested in publishing a paper describing the technology that the foundation had financed. The scientific community had to know how to achieve a high-density cell and viral culture in their bioreactors. The company was pleased to hear that and immediately put David in contact with the public relations office. David wrote a paper, and the publication appeared one month after submission. The article was titled “Producing human rabies vaccine at low cost,” and the report appeared in a news magazine. The biotechnology audience welcomed the note, and the paper would also significantly impact the development of vaccine technology transfer projects for David, other researchers, and many companies.

Back at the foundation headquarters, Robert was considering whether it was worth following up on financing a technological vaccine transfer project. Robert, however, was puzzled by the idea of developing vaccine technology capabilities for developing countries. He researched the issue but could not find anything significant that could lead developing countries to find vaccine technology for primary viral infections. Moreover, he found that the limited research in vaccine technology was in the hands of universities and limited to low research volumes that could not be scaled up to industrial products, hence remaining in published papers without any help to the population at large. Moreover, other efforts at vaccine research are in the hands of multinational companies that are not interested in sharing proprietary knowledge.

Two months later, after careful thought inside the foundation headquarters, David received a letter from Robert. In the foundation’s name, the health sciences division decided to finance David to visit several Asian countries. The idea was to explore establishing a pilot plant in Asia to develop the vaccine technology that the foundation had previously funded on the American continent. The exploratory grant would last for approximately eight months. David had to pay for airline tickets, visas, hotel accommodations, incidentals, etc., and then send expense reports after every trip, with a written description of the findings. He would then be reimbursed for all expenses involved. David was thrilled. He foresaw the new pilot plant established in Asia, managed by the old technical team from Totem Inc., and taught modern vaccine technologies in a developing country.

In a letter of acceptance, David suggested a few names of countries and institutions to visit. Robert gave his approval and instructed David not to compromise anything from the foundation. This grant was only an exploratory exercise to see how any interested country or institute would welcome the idea. It was also expected that a local institute or company would be able to contribute to establishing a vaccine technology teaching school. David had a pleasing expectation that this grant would be the pivotal push for establishing a teaching school to train young scientists, considering that the idea had been in his mind as a dream that had not yet come true.

As expected, David planned a series of trips to Asia. Before leaving, he had to study the vaccine production capabilities of several Asian countries and the names of regional organizations and companies involved in research and vaccine production. He wrote numerous e-mails and made telephone calls to vaccine producers in various countries in the Far East. David was pleased, considering he was going on airplanes on long overhauls for the first time in business class.

On his first journey to start the foundation grant, David visited a deep Southeast Asian country. He was warmly welcomed by the government’s health sciences officials as an ambassador from the foundation. Pleasingly, they displayed a poster at the main entrance of the health research and development institute, welcoming David and thanking the foundation for the attention they were receiving. After the traditional handshakes and introduction of the most important officials of the institute, the hosts introduced David to a large meeting room full of several scientists and professionals from the institute.

The ambiance of the room was of high expectation. The institute director introduced David as an ambassador from a famous, well-known, and respected foundation. David explained to the audience the principal components of high-density cell and viral culture production and the quality control technology used to formulate a rabies vaccine for human use. The group raised several questions that were answered satisfactorily, and the institute’s principal scientists appeared to be highly interested in the high-density cell perfusion methodology.

After the questions and answer period, the director invited David to examine the vaccine production area. The facilities for manufacturing the rabies vaccine were ample, well maintained, clean, and with adequate equipment, even though some of them were clearly in need of replacement. The institute produced the rabies vaccine for human use in laboratory animals, not in cell cultures; in addition, the technology was the same that was common at the time in many countries, utilizing suckling mice to multiply the virus. Staff appeared well-trained and well-acquainted with industrial production systems and Good Manufacturing Practices requirements. However, they still needed to comply with all aspects of the GMP, but they were in the certification process. The institute was over-staffed due to excess job offerings and low salaries.

Most people at the health science institute were enthusiastic about developing high-density cell and virus culture technology. As part of the national health institute, they believed that a new project could be formulated with the cooperation of other governmental and non-governmental agencies. Nobody in the country had a vaccine prepared on cell substrates, and rabies disease transmitted from dogs was a substantial human health problem in the country.

To prove this point, David was escorted to a hospital that treated persons who had been bitten from rabid dogs. The group entered a big security door in a separate wing of the central hospital and found numerous cell-like prisons inside. Each cell dwelling was only for one patient. The small room was empty, with no furniture, no bed, no wall posters, and no glass windows, but it had windows and a door with metal bars. The patient had lost complete control of his will and was hitting the walls in hopelessness, although he had nothing with which to harm himself or others. The scene was dreadful and horrible. There is no cure for rabies once the virus takes control of the brain. After the virus takes possession of the brain, physicians only have for the disease to ensue. With this scene, David could not understand why dogs in most places in Asia are not vaccinated against rabies to prevent the disease from being transmitted to humans. Vaccinating dogs against rabies would prevent animals from suffering from or transmitting the virus to the human population.

According to the most knowledgeable scientist in the country who tried to explain this predicament to David, the dog population in Asian countries is primarily, if not entirely, in the countryside, where the animals run freely outside the dwellings of the people. As the dogs do not belong to anyone, they look for food in the same areas and neighborhoods where they wander and can be fed by anyone with food as they come near the houses. This creates a special bond between the dogs and the residents. Governments have made numerous efforts to gather the dogs to vaccinate them to prevent the disease from spreading to the population. However, residents have not allowed officials to vaccinate the dog population.

According to many vocal sources of information, this is due to some cultural beliefs that the vaccine will cause some harm to dogs, so they try to prevent it. David argued that there was no reason for this to happen worldwide. He explained that most countries had extensive dog vaccination campaigns to prevent rabies in the animal population. If there were no rabid dogs, people would not be bitten by these sick, rabid animals. However, with this cultural belief, the need for reliable, safe, and potent vaccines for human use in many Asian countries was obvious to David.

David explained later to the consultants that an added reason behind the need to vaccinate dogs was to protect the dog population from the spread of many diseases that could be transmitted to other animal species and simultaneously to human beings. In the last century, zoonoses have become an essential source of infectious diseases that have caused considerable damage to the health status of human populations. In private conversations he had with several physicians in different sections of the world, it was evident that these diseases were not easily recognized as transmissible from animals to humans. The general public could not easily perceive that the influenza virus, for example, was being carried yearly from Asia to the rest of the world by migratory birds. The situation was similar for many viruses, bacteria, and parasites.

The need to vaccinate dogs to prevent rabies is highly accentuated in Asia due to these animals’ social surroundings, considering that almost all dogs do not live inside the houses of the people who feed them. The societies for the protection of animals in Western societies strive to preserve dog’s rights, health, and social status; however, in the case of rabies in Asia, the dogs are free in the countryside, and many are dying from rabies disease transmitted from each other and also due to the lack of vaccination. How can we prevent this kind of mortality without affecting the social settings of this kind of dog population and, at the same time, prevent the occurrence of human beings bitten by them and in need of vaccination?

After returning to the institute, the director asked David whether the foundation could support the project to establish technology for cell density cultures in the country. David explained that he would write a report to the foundation describing what he had seen, and then the foundation would decide if that was possible. He also explained that he could not make any commitments in this regard. After this helpful visit, several members of the institute’s scientific staff kept in contact with David and, as seen later, made considerable efforts to establish high-density technology in the country. David sorrowfully left the institute to prepare for his visit to other countries. The blurred images of human beings dying from rabies inside metal bars often appeared now in David’s mind. These images made it worthwhile to establish local modern vaccine learning schools.

However, local health officials wanted David to see a new facility that they were ready to inaugurate to produce a bacterial vaccine. The group introduced David to a 350-square-meter wall-paneled outfit with the latest highly sophisticated bacterial vaccine production technology and modern equipment. The government had recently negotiated with a European company to design, construct, and furnish a bacterial vaccine production facility. The design was neat, simple, and built with high-quality materials. It also had the most modern equipment for handling microorganisms and a small area for quality control of the vaccine. The striking finding was the total contract cost for the government. What was revealed for David was the astronomical sum of 10 million US dollars that the government had paid for the technology, construction, equipment, and installation. As David passed the news to his friends, he emphasized that the production of bacterial vaccines was much simpler and less costly to set up than any cell culture viral vaccine.

David dreamed that he would have completed the same manufacturing and quality control of that vaccine for half of the cost the government paid, with many local high-quality materials and hand labor. Many more companies produce bacterial vaccines compared to very few in viral vaccine production. Beyond these considerations, a complete small pilot plant for developing the cell high-density system would, at the time, have cost the government only a portion of the contract. After that enormous surprise, David again promised the researchers to send them news about the request to the foundation for specific funding for the new viral rabies vaccine.

Afterward, David moved to West Asia and visited three companies producing vaccines for human use in the country. The first company welcomed David as a businessman, and he was therefore given an icy reception. They probably thought David was selling them a product or technology they were not interested in. David was invited to discuss the proposal in the main boardroom. Even though David asked his hosts to see their facilities, they were reluctant to show him what they were doing and probably considered David a spy. David asked them if they were interested in seeing a viral cell culture technology, to which they agreed. After adjusting the meeting room for a PowerPoint presentation, the audience of only six executives sat and carefully listened to the high-density cell culture description.

After the presentation, David asked one executive to show him the restroom location, who showed him the way and was ready to wash his hands after a few minutes. On the way out of the lavatory, he noticed that the door knob was entirely contaminated, so he had no choice but to clean it before attempting to grab it. The problem was that there was no toilet or paper towel, so he used his handkerchief to clean the nob. After opening the door, he looked for a wastebasket to discard the contaminated cloth, which was another challenging experience.

David also had one tiny vial of the original registered rabies vaccine in his pocket and placed it on the boardroom table. The hosts were scared, thinking that the virus was not inactivated, but after David assured them that it was a freeze-dried killed virus, they calmed down. Nevertheless, the hosts told David that it was better for him not to carry any vaccine specimen, even if guaranteed its inactivation, as doing so could create some difficulties for him. They also told David that they were very impressed with the technology. Their thoughts, however, were primarily directed at equipment costs, personnel training, and technology transfer expenses. They thought that the foundation was going to finance the whole project. Consequently, David had to tell them that the foundation would be informed of their suggestions and that they would be informed of the outcome later.

The visit to this private company left David with a disagreeable feeling; such a company is typically interested only in profits, not in saving lives. Consequently, most managers were interested only in cost-free technology. Fortunately, there were exceptions. One of the company’s high-level technicians approached David and invited him to dinner at his house. David went to his hotel and, later in the evening, hired a taxi and went to the professional’s house. The high-level professional turned out to have a PhD in microbiology from a European university. He was married and had an eight-year-old daughter. They had an apartment on the top floor of a six-story building, and no elevator was in sight. The dwelling was small, with one bedroom, and the living, dining, and kitchen were open; the only separation from the living to the bedroom was a decorated drape with folds at the room’s entrance. One flat table was hanging from the corners to the ceiling in the living area. This table was the place for doing homework, writing, or playing card games.

They were incredibly generous and a unified family. Dinner was tasty and lean. However, there were no utensils, and the four used their hands to eat French fries and delicious vegetables. David had a pleasant conversation with the family; they appeared to be entirely happy with the things they had. When the fellow was asked about his position in the company, he showed no excitement. With his knowledge, university degrees, experience, and responsibilities in the company, he only had a surviving salary. The owners were only interested in making money. David felt very sad; this situation was the same as what he had seen all over in developing countries, where science and scientific knowledge were not appreciated and always seemed to follow political and economic interests. Unfortunately, this fact is common in countries on the verge of development and is a reason for their fate.

David had to return to the hotel, so he asked his host to call a taxi. But he did not, so David thought they would pick up one on the street. After the farewells with the wife and daughter, David and his host went outside the building, and without requesting a car, a tiny, old-fashioned Renault car with a driver arrived at the door. They both entered the vehicle, and on the way to the hotel, David asked the company executive if this was a taxi or a company car. The answer was that the vehicle belonged to him, and he hired the driver. “How can you pay the driver’s salary,” asked David. According to the host, the driver’s payment was just the daily food he provided to him. In essence, this professional was only doing it as a charity, another vicissitude of a developing world vaccine scientist in a country in social disarray. Before arriving at the hotel, David thanked the company executive for his gesture and courtesy, and later was preparing to go to bed. At this point, however, he could not go to sleep. His thoughts bounced back and forth on the ordeal of the scientist he had just met, who had many years of training but no visible and adequate future, a professional life lost for the well-being of his country.

The next day, David still felt sympathy for the fellow he had met the day before. However, he continued the journey and visited the second company. This time, the owner invited David to enter the vaccine manufacturing area, where production occurred in large bioreactors growing yeast using recombinant technology to produce a bacterial vaccine. The plant’s design was adequate. Everybody inside the plant was very busy, and the whole appearance was of reasonably clean production.

The company followed good manufacturing practices approved by international entities and hoped to export to developed countries. The owner had already applied for exports to North America and was expecting approval at any time. He immediately liked the idea of the high-density cell system but did not show keen interest, considering that he already had another highly profitable bacterial system. The outfit gave them sufficient revenues, even though it was only for bacterial vaccines and not for tissue culture for viral vaccines. The fellow told David they were somewhat afraid of working with cell cultures because they did not have any technology experience, so they needed to figure out what to do. David thanked their hosts for a warm welcome but had to go on. It was important to note that the technicians had significant experience in bacterial vaccine laboratory procedures and quality control processes. This practical knowledge could easily be adapted to handling viruses to manufacture viral vaccines like polio, hepatitis, rabies, etc.

David moved this time to the third company producing vaccines in tissue culture, utilizing roller bottles to grow cells and viruses. This group had already developed and licensed a product cultivating cells and rabies virus on the inner surface of roller bottles and published vaccine production system results. However, the new vaccine had not been scaled up. The main drawback was the limited number of vaccine doses they could produce and the resulting high cost per treatment. There was considerable handling of bottles, washing, cleaning, and sterilizing to produce a vaccine on roller bottles, which also added to the total production cost.

Another hindrance was the purification of the vaccine, which did not comply with international requirements. The group was thrilled at the possibility of adopting a high-density cell and virus system. The administrators, however, mentioned that, at the moment, they did not have any budget to support a new project, and they asked David whether the foundation would give them a grant to acquire the technology and set–up a new manufacturing facility. David had to tell them he would pass on the message to the foundation officials without guaranteeing a positive reply. Privately, David thought this was the kind of technician and professional who merited some assistance from donors or investors.

The publication of this group’s new vaccine in an international journal was straightforward. However, it never reached scale-up levels. Consequently, it was not available for the market or for protection of the susceptible population. From the last group of companies David had overseen, this previous company and its technicians were the best prospects for a suitable place for technology transfer. However, other companies visited mainly because of the need for more funds to research new technology. Even if they had the money for the facilities and significant equipment, they needed a place to obtain or buy new technologies for industrial production. They needed both funds and technology.

After seeing so many needs, David again dreamed of the school for teaching cell culture vaccine production systems. No multinational company would ever teach anybody or any country how to produce modern vaccine technologies. This vaccine group once again had the essential components of a vaccine manufacturing establishment. For David, the main drawback was the lack of managerial expertise to lead to the development of the least expensive and modern technology for a better-quality system.

At this point, it is interesting to note that many small vaccine producers and governmental health vaccine entities see vaccine production as another tool in the quest for disease control. However, nobody had instrumented them to view the development of industrial vaccine production as a business with considerable profits that could be applied to developing other products or other health needs. On the contrary, multinational pharmaceutical giants in several areas of the world see vaccine manufacturing and marketing as sources of enormous revenues for their particular interests. The primary constraint is politics meddling with reasonable human health issues.

In the middle of David’s exploratory trips on behalf of the foundation, some WHO officials heard about his devotion to an inquiry into vaccine technology transfer. A high-ranking official invited him to give an exposition on high-density and perfusion cell culture vaccines at an interregional consultation on disease control in Asia at the WHO headquarters in Geneve, Switzerland. David, however, had to pay for his transportation and hotel. Of course, his trip was approved by the foundation supporting David. This was David’s second visit to the WHO administrative center in Geneve. For the first time, some of the scientists had told him he had to be crazy to pursue the goal of teaching vaccine technologies to the developing world.

This time, David expected a warmer and more cheerful welcome. At the meeting, there were representatives of several Asian countries, research organizations, intergovernmental organizations, non-governmental organizations, a few private manufacturing vaccine companies, and other relevant partners. David’s presentation of the basic high-density cell system was smooth, with minimal questions and little wonder from the listening audience. Some comments were made concerning doubts about the scale-up level of the technology. David sensed he was illustrating something the audience did not want to hear. There was a rival system that could help small countries learn techniques to manufacture their products, explained to people from the current establishment, which depended on selling their products, competitive with the offered technology. Some invitees were sponsored by giant multinational pharmaceutical companies interested in selling their products and were not interested in any competition.

At the end of the session, only a few people approached David, one of whom was a well-known international vaccine expert who was very enthusiastic about the technology. He invited David to give a talk on the technology at a meeting to be held in North America four months afterward, so David accepted with complacency and assured the fellow scientist to be there. Another peer interested in technology was a researcher from the national health institute of a North African country. He also invited David to visit them to discuss a technology transfer agreement. David felt that the presence of several multinational vaccine companies was discouraging other participants. Such companies prevented them from joining discussions of a new system that would compete with their products.

Another company from a West Asian country had a representative at the Geneve meeting. The fellow was the executive director of a private vaccine manufacturing company. He had previously attended a three-month training course on cell culture at a research lab in North America. Following recommendations from the training center, he traveled to Borazon City to visit Totem Inc. for an outsider view of the rabies vaccine production unit there.

The fellow intended to negotiate the acquisition of a rabies bulk vaccine for export from Totem Inc. but had little success doing so. The general manager of Totem Inc. did not show any interest in producing the rabies vaccine for human use, which the company had already ceased to produce. The Asian executive explained to David that he did not understand why Totem Inc. was losing a highly profitable business. He had mentioned to the directors at Totem Inc. that he could be their representative in other Asian countries and expand the rabies vaccine export there. The Asian executive, however, mentioned that his company was now highly interested in acquiring high-density cell technology and promised to return to David soon concerning the possible acquisition of the complete vaccine technology.

The executive director also asked David if he knew a recently promoted research director of a multinational pharmaceutical company he had met a few months before. The global director of the company was Chris. He had told the Asian executive that he had met David at a company in a Latin American country. David remembered Chris; he was the young man that the Coloso Inc. group had invited to Borazon City to get acquainted with the project many years before. With this unexpected finding, David had confirmed that Chris had been a “spy” from the multinational pharmaceutical company to learn what was happening inside the Totem Inc. manufacturing facility in the developing world. Multinationals had been unable to stop the technology transfer program at Totem Inc. Still, through spying, they had managed to know what was happening inside the factory and the project. Chris, the old spy, was then the scientific vaccine research director of this company.

After only a few visits, David was now getting much more insight into the vaccine world in countries under development. Having visited West Asia, David moved on to East Asia. His primary interest was to see a vaccine institute that had recently been conceived through the collaboration of various Asian countries. The institute also had funding from the United Nations Development Program (UNDP), international foundations, and some developed countries. The institute’s director accepted David’s visit and asked him to give the technical staff a presentation on the technology. The group of researchers was small at the time, considering that the institute was still developing.

David got airline tickets and headed for East Asia. At the time, there was limited knowledge of the political situation. Therefore, the visitor was somewhat apprehensive of the safety situation for a foreign guest. Everything was calm and quiet at David’s arrival, so there was no need to worry about safety. David was welcomed by the institute’s director, who was interested in hearing about the development of the technology. After hearing David give a succinct description of the registration of the vaccine, he also could not understand why the original company, elected to be the first recipient of tech development, had abandoned the production of the human rabies vaccine. To him, it did not make any sense from the point of view of scientific advancement, much less from the point of view of profitability and economically beneficial results.

The technology for the high-density cultivation of cell cultures was presented at a small meeting with the director general present. They all seemed very interested in and amused by the technology. However, the institute had just begun building the facilities and still needed a laboratory. The director told David they had the mandate to discover, develop, and deliver safe, effective, and affordable vaccines. The idea was to support global public health, with the final mission of helping developing countries become free of infectious diseases.

Since the beginning, this institute has concentrated its efforts on epidemiology, delivery of vaccines, and evaluation of the use of vaccines to prevent bacterial and viral diseases in tropical countries. The institute was working on epidemiological studies in several countries to assess the impact of diseases. Moreover, with leadership from the UNDP, several Asian countries co-sponsored the vaccine institute. The institute’s management planned to help states upgrade manufacturing methods and quality control of vaccines produced in domestic facilities and to budget for the import of adequate supplies of high-quality vaccines.

The institute has not, and will not work now on developing tissue culture-based vaccines for viral diseases; a separate pilot plant facility intended to produce test lots of bacterial vaccines for training and evaluation purposes was planned but never completed due to a lack of funding. The institute is not teaching developing countries about technologies to produce tissue culture-based viral vaccines. The institute did not have or will not develop the technical know-how to manufacture tissue culture vaccines, much less the technology and facilities to scale up such products.

David left the institute’s offices with a sour feeling. They were not interested and would not set up a pilot teaching plant, and it was confirmed. It remains to be seen whether the institute’s dedication and principal aims have changed the focus to technologies for cell culture viral vaccines over time. Once more, another “international” institute dedicated to the epidemiology of diseases and the utilization of bacterial and viral vaccines, fabricated by multinational pharmaceutical companies, became part of the old establishment.

On a pertinent matter, David remembered that at least eight years earlier, with all expenses covered, a private foundation had invited him to attend a seminar on vaccine production technologies in a South American country. There were representatives from a large number of health government institutes in most countries of the American continent. The main goal of the gathering was to exchange views on establishing joint research development projects to benefit the health status of the continent. As it turned out, a few countries with meager vaccine development programs could not offer any real contributions; they were only interested in their local problems and programs. Everyone expected the foundation to establish a development program; the countries had no interest in forming any intergovernmental program. The foundation’s investment in the research vaccine program plan was diluted.

David had to continue his trips to other places in Asia. This time, he was further south, met by two young research scientists from the country’s health minister. They had prepared a meeting for David’s presentation with the high-density perfusion vaccine technology to a group of researchers. A scientific lady, who was the local representative of WHO for this part of the world, was in attendance. She became very enthusiastic about assisting in acquiring cell culture vaccine technology for the country. Two local biotechnology consultants were also interested in contributing to the plan.

Immediately after the meeting, these last technological consultants tried to consolidate a group with a local university and the health division of the ministry to acquire vaccine technology. They had a meeting the following day, and once again, similar to what had happened in other places, they finally asked David whether the foundation could assist. They claimed that they did not have a budget for this kind of commitment but would continue looking for possible sources of financing. The answer from David was the same: he would transfer the request to the foundation officials without any promise of a positive response. As will be seen later, this same group contacted David some years later.

Even though David was not dissatisfied with people’s reactions to the presentation or the technology, he felt that researchers needed to have entrepreneurial training or abilities to grasp the opportunities. For them, this was a way to acquire completely new technology that could be adapted to many production systems. They did not initially have to build a large commercial production facility but could start at a small level and later scale up to industrial production systems. Most, if not all, government personnel and entities acted as if everything was all right and that there was nothing to improve or worry about—a very common culture in the developing world. Some people in official government jobs acted as if they had tenure. For political groups, the only way to lose a medium- or high-ranking post is through a harsh political move after an election in which the political party in power is defeated. Sadly, this behavior or cultural action also commonly occurs in the countries’ scientific spheres.

It is deplorable to see international entities like WHO looking the other way and pretending to be unaware of the fact that one of their responsibilities is to assist countries in having efficient, low-cost vaccines to control major infectious diseases produced within their territories without dependence on the importation of vaccines at astronomical prices. The local representative of the WHO did not offer a specific plan or suggestion to take advantage of the opportunity presented by David to gather several entities interested in participating in a plan to acquire new vaccine technologies.

David, however, had to continue with the exploration. Next, he collaborated with a fellow researcher and traveled to Southeast Asia. He contacted a scientist from the institute in charge of producing vaccines at the country’s health ministry. David thought that, as agreed, the scientist would await at his arrival point, so he got a plane and arrived at the airport in the country’s capital city. He waited in line at the immigration desk, and when his turn came, the official looked at David’s passport and told him he did not have a visa and asked for the purpose of his visit. David showed his official papers from the foundation, indicating his recognition as a foundation consultant and the name and address of the scientist who had invited him. David informed the official that he had been told that he could get a visa upon arrival. The immigration official, in his language, apparently ordered another man to take David aside to a room, and the man asked him to wait there.

After approximately one hour of waiting, another official returned to the room and, in broken English, told David that they could not grant him a visa and would be detained for attempting illegal entry into the country. David requested the official contact with the scientist waiting for him; he did not receive an answer, and the effort was useless. The officials did not allow David to contact the scientist, who was supposedly waiting at the airport to greet him.

Another fifty minutes later, two armed guards with official uniforms returned and transferred David to another place. The three got into a police car and were driven at least one hour from the airport. When the escorts and David arrived at what appeared to be a detention center, the guards led him into a cell that another guard had opened. He was told, with signs and gestures, that he would have to spend the night there and that the next day, he would be taken to the airport to get a plane back to his point of origin. The guards also tried to show him that his luggage would be waiting at the airport the following day. Consequently, David alone had to spend the night there, only with water, no meal, and no baggage. The cell was crude, with a tough bed and a primitive toilet with a handwashing sink. The following day, David felt a terrible pain all over their body. He had never experienced a night at a detention center, much less in a foreign country, and he was unable to communicate with anyone.

The following day, without a shower, David was escorted to the airport. He recovered his luggage at the airport terminal, had a minimal breakfast at a cafeteria, and finally boarded a plane to return to the city of origin with a reservation previously made by the officials. Nobody told him why he was ultimately rejected entry into the country. David thought he was denied entrance, most probably thinking he was a spy from the foundation of a Western foreign country. Nobody ever contacted David to explain what had happened, and the scientist supposedly waiting for him did not answer any of his emails. The exploratory technology transfer in that developing country was halted as such. Another complicated political situation negatively interfered with technical and scientific development and prevented local infectious disease control with modern vaccine methodologies.

This was yet another frustrating and very uncomfortable and awkward situation for a scientific consultant who was only looking for some means to assist developing institutes and researchers in developing countries. Politics was once more in the way and meddling in health science scientific development. David decided that only later, through the written reports of the consultancy, would he inform the foundation officers of this unprofessional behavior he experienced in the not-very-friendly country.

David still had other places to visit in Asia. He planned two visits to northeast Asia. He got a tourist visa before departing to enter the country. First, he was scheduled to visit a lady scientist at a well-known local university. She was adapting a different tropical virus to the same cell strain that David and the technical group of the project were using. She was interested in making a joint effort to use that adapted virus material. According to David, obtaining funding from an international agency seemed possible. David, however, told her that the foundation that supported the rabies project could not fund this kind of project. There was no room for a rabies vaccine project with this scientific university lady. Here was a researcher with a plausible and possible new vaccine with very little chance to get some funding to continue its development.

For David, the second place to visit was a small vaccine production outfit in the country’s southwest. David was invited to go there by a company representative from a developed country that manufactured modern bioreactors. The company’s scientists wanted to change the rabies vaccine production technology they had for a new system using bioreactors that would allow them to scale up productivity and, at the same time, improve vaccine quality. This company was producing a rabies vaccine for human use on roller bottles and had just acceptable revenues. However, it wanted a higher market share. The scientists had tried to get rid of the roller bottles, which were quite difficult to manipulate.

The high-density system was explained to them, and they immediately considered that they wanted to have it. The company’s directorship did not invite David to see the inside of the production buildings. They were probably concerned about having the visitors see a vaccine operation that was not up to standard. The manufacturing of vaccines in the country was quite deplorable. As usual, they asked David whether the foundation could assist with some grants or lend funds to acquire the new technologies, and David offered the same response: he would relay the message to the foundation officers but had no assurance of a positive reply. David again felt discouraged to see so many needs and very little in the way of sensible solutions.

After this trip, David made a quick one in West Asia to visit a laboratory where some friends were also interested in high-density perfusion technology. This time, David was in a considerably large city. The airplane was almost one hundred percent occupied by persons from Asia. David had to fill out an entry permit, in addition to the visa he had on his passport. The permit request had to include the names, telephones, and addresses of the people he was visiting, including the hotel addresses and telephone numbers. When David arrived at the airport, he submitted the passport and permit request to one male immigration official, who scrutinized, signed, and placed a seal on it.

The immigration official asked David to move forward to another desk, where another male official also examined the passport and the permit request, signed it, and put another seal on the same piece of paper. This official asked David to move to the third desk down the corridor, where another male official signed in a different area of the same entry permit and placed another big seal. Finally, David was moved to a window where another male official asked him the purpose of the visit and the names and addresses of the people he would visit. After that thorough search, the man placed another seal on the same entry request paper and finally sealed the passport. David was now admitted and instructed to keep the request paper, with all record signatures and seals inside the passport, until he was ready to leave the country.

David then had to go to customs to pick up his suitcase. As he approached the luggage carrousel, several airport employees were waiting. One of them asked David for the luggage slip so he could identify it. David gave the sheet, and the man brought the piece to him in a cart and immediately asked for a tip. David gave him a tip and headed toward the exit with his suitcase inside a cart, but he had to place the luggage inside an X-ray machine to exit the area. However, another male employee was responsible for setting the bags inside the machine. David handed the piece to him, and immediately, the man asked for a tip. David had no choice but to give him the tip. He then had to go to the other side of the X-ray machine in another room outside the area to pick up his luggage. He saw his piece coming and was ready to grab it, but another male airport fellow stepped ahead, picked up the bag, and placed it in another cart. Of course, he immediately asked for another tip. David saw no option; he would not get his suitcase back if he did not tip.

Finally, David left the curbside with a cart and luggage. He needs a taxi to get to the hotel. There was a line with many people waiting for cabs. After fifteen minutes, David was ready to board the taxi. Before he could do that, another male fellow transferred the baggage from the cart to the taxi trunk. Yes, you guessed it—another tip was needed! Reluctantly, David gave him the tip. During his ride to the hotel with a male driver, David still could not believe what he had witnessed. There was a picture of an entirely male society and many hands evidently under meager wages, but this was not the end. A few meters before arriving at the hotel, the driver stopped the car and showed the fare to David. He had to pay there, and the driver again asked for another tip. As soon as the taxi halted at the hotel, two male fellows opened the trunk and grabbed the luggage. They carried it to the hotel lobby and showed David where to go for registration. Of course, they asked for a tip.

After the hotel registration, a new male fellow picked up the luggage and escorted David to his room. He placed the piece inside the room, and after a standard welcoming, surprise! David was asked for another tip that would allow him to retire. David was thinking of how lucky he had been to have several extra money bills of low denomination. Otherwise, he would have had to tip many times, investing a lot of money. This was only one of the many things to overcome in a country with many impoverished inhabitants.

The next day, David got a taxi to the laboratory of the vaccine company he was visiting. After the formal presentations, he was invited to see the inside of the production building. The outfit was large and had a good number of varied pieces of equipment. The company also had a bioreactor of approximately three liters. They had some cultures with the same type of cells that David and his group had used. Some of their rabies virus cultures were of apparent good quality. However, they did not have a perfusion system; they only had a batch system. The fellows had already published a paper claiming to have produced a new rabies vaccine for human use. However, the number of vaccine doses they could produce was meager, and they did not have a way to scale up the system. It was unclear whether the technicians complied with all the quality control requirements. The most crucial process missing from the production system was the quantification of residual cell DNA, which measures the efficacy of purification technology.

David concluded that many laboratories were developing products on a small scale, claiming and publicizing them as new vaccines, without any commercial production that could be utilized for a government campaign or to meet the needs of the country. The visit to the vaccine company was quite similar to other places. The scientists were highly interested but would also, like the others, need some assistance. David repeated the same answer; their request would be relayed to the foundation, but he gave them no assurance of getting the assistance. However, this group of scientists would later have another encounter with David.

This visit was the last of David’s explorations. He was then ready to return to Borazon City to write his report. Before starting the report and throughout the return flight to Borazon City, David was entirely discouraged and felt a kind of grief at seeing so many needs in many places and the gloomy and pessimistic perspective of assistance portrayed by the establishment. Developed countries and multinational companies worldwide do not care about the health conditions in developing countries. Is this not a kind of dependence, a way to keep developing countries subjected to their whims and desires? What was more disheartening was seeing how this health issue is directly linked to the economic exploitation of the most vulnerable societies.

The establishment does not allow or support developing societies to produce to meet their own needs—in this case, vaccines—but instead sells them at astronomical prices. Developed countries have an innate desire to prevent the spread and control of infectious diseases in entire regions of the world, and more so in numerous countries in need. Most infectious viral and bacterial diseases have no boundaries; thus, the need to control them persists. This is just one of the reasons for the spread of endemicity, epidemics, and pandemics. The economic exploitation from the world’s developed areas becomes more evident with the appearance of a pandemic like the one currently happening with the COVID-19 virus, in which multinational pharmaceutical companies charge uncountable sums of money for the new vaccines to the developing world. Many questions need to be answered.

The programmed visits for the consultancy financed by the foundation were completed in seven months. In his report to the sponsor, David described and explained the places visited and made recommendations and conclusions, the most outstanding of which were related to the lack of international assistance in cell culture vaccine technology manufacturing in the developing world. Several international agencies were mainly devoting efforts toward studying the epidemiology of infectious diseases and the distribution, use, application, and evaluation of vaccines but not in any local production technologies.

David cited several examples of failed or acquired technology transfer projects. In a certain country, investment had been made ten years before, with assistance from a European country government. A production facility was built for a viral vaccine different from rabies. However, due to the lack of appropriate production technology, the building was still idle, with brand-new equipment that had never been used. David was discouraged at seeing so much modern equipment and reasonable and appropriate installations vacant with no people working with them and no technology in sight. The outfit had even the most modern vaccine-filling equipment from a world-known manufacturer. Was this setup an international technological assistance or a way to eliminate unused industrial manufacturing equipment?

In the report, David offered several recommendations. He stated that a training course for tissue culture vaccine development should be started, including cell handling, viral production, and downstream processing. Studies should also be conducted to modify existing vaccine infrastructures to convert them into tissue culture technologies. More industrial experience and entrepreneurial skills should be brought to small countries to allow for the development of newer and better vaccines. He insisted that countries needed the most entrepreneurial abilities, industrial knowledge, and basic training in tissue culture techniques. David finished the report by saying that there was a job to be done in many places, and he encouraged the foundation to play this critical role. The control of future epidemics and pandemics due to infectious diseases, mostly of viral origin, was at stake.

When Robert and the foundation officials received the report, they felt delighted. They wrote a letter to David expressing their gratitude for the observations and the opportunity to learn about the vaccine production situation in so many places and in such a short time. They reiterated, however, that it was clear to them that the best possibilities for expanding the knowledge of high-density cell culture techniques were in the hands of private companies. It was also clear to them that the foundation could not make any grants or investments in any completely private commercial vaccine company.

The officials also clarified that the knowledge generated from the foundation grant and so many entities in Europe, North America, and Borazon City belonged only to the foundation. Consequently, these knowledge fragments, pieces, and parts within different institutions, and scientists could not be patented by anyone. None of them had the complete package to patent a whole system. The officials thanked David for a fruitful analysis of the situation and the knowledge that had been generated.

The foundation officials and Robert expressly implied that David was now authorized and should be free to expand the knowledge generated from the foundation grants as he deemed so. In other words, David was given the right to transfer the newly assembled industrial vaccine technology to different recipients. The foundation emphasized that David was the only one with the whole technological and industrial package system, and he had in his mind all the knowledge generated by the foundation grants and the exploratory technological phase. David expected that this would be the start of the plan to set up an international vaccine technology school.

Chapter Eight

2000-2001

A Fresh Beginning

With the authorization and consent of the foundation, David started to contact people he had seen during the exploratory phase financed by the foundation. A fellow from a vaccine company in West Asia asked whether he could come to Borazon City to visit David and learn all the technical details of the rabies vaccine technology. David agreed and paid for his hotel reservation. The scientist traveled to Borazon City and met with David. At the end of their talk, the visitor explained that he was mainly interested in quality control technologies to quantify rabies virus suspensions. He needed to prepare to pay for a technology transfer for the total high-density cell culture technology. David prepared a standard procedure for quantifying the virus, and the visitor left with a digital and printed form. David was not entirely sure that he would hear from the visitor again.

A week later, however, the visitor sent a wire transfer covering the cost of the technical know-how that had been transferred with those techniques. The entire visit from the executive for quality control technology left some doubts on David about the real purpose of the visit. The fellow could have asked for the technology by e-mail, and the matter would have been solved through that channel by sending the written SOP. Was there a need for the fellow to take an international airline ticket from Asia to the Americas to negotiate and collect a piece of paper with a quality control process? What was then the real purpose of the visit? David speculated that the fellow wanted to do some sightseeing in the Americas, which was financed by his company and not from his pocket.

In the following months, David continued to contact several companies interested in newer vaccine technologies. One day, he received an e-mail from a company representative who manufactured bioreactors that were especially suited for cell cultures. A Chinese fellow invited David to give a presentation on cell culture and vaccine technology to a group of vaccine producers in a city in southeast China. It turned out that the company was originally from North America and was the same company that, years before, had manufactured the decanting column and gadget that Roger and David had designed for them to use in their bioreactors. The Chinese fellow was the local representative of the bioreactor manufacturing company.

Before agreeing to go to China on the invitation, David thought it was a good idea to set up an export biotechnological service company to negotiate technology transfer projects with any other company. With the assistance of a lawyer, David structured a service company that he called “Newvac Inc.” The company would hire consultants specializing in different vaccine production areas and work on contract assignments that the company would sign.

He then applied for another visa at the Chinese embassy in Borazon City. He opened the embassy page online and hoped to get an appointment to request a visa, but the page advised going directly to the consulate without an appointment. The next day, David was early at the embassy, even before the consulate office was opened for business. When he arrived at the embassy, he did not see anybody at the door. He thought that probably everyone was inside, so David found a ring bell and pushed hard. Momentarily, a guard showed up and asked David for his reason for being there. When he said he wanted a visa to go to China, the guard opened the door and showed him the way in a friendly manner with a bow. Inside the building was a spacious area with a few seats and a window connected to a separate location. The guard then asked David to sit down and wait to be called.

Only one person sat beside him, filling out some papers, and David offered him a tip to fill in his data. David was surprised that only two people were waiting to request a visa. There was a significant difference in the enormous waiting lines at other embassies in Borazon City. Fifteen minutes later, David was summoned to the consulate window, submitted the papers, and was told whether he wanted a two-entry visa or just a single entry. He preferred to pay a little extra for a two-entry visa if needed. Two days later, he was issued a passport with a permit for a thirty-day stay and two entries to visit China. At the time, China appeared mysterious to many people around Borazon City, and more people were interested in sightseeing than in any other business. This was quite different from the current procedure, in which thousands of locals requested a visa to enter China.

With a legally established company and visa, David bought an airline ticket from his pocket and headed toward South China for the invitation. He was met at the airport by Fu “Suerte” and escorted to the hotel to prepare a presentation for the following day. The next day, a conference room was ready at a luxury hotel, and several guests arrived when David showed up. Around thirty representatives of various pharmaceutical and biological companies attended his narrative on cell culture vaccine technology. A pretty good translator was there to translate the presentation from English to Mandarin. There were only a few questions, which David graciously answered.

David found it difficult to sense how the presentation had been heard, since the comments made by the audience were made in Mandarin, and Fu answered them; however, the questions were mostly about the bioreactors that he sold rather than on the technology. The following day, on their short sightseeing trip to the city, Fu assured David that perhaps somebody would be interested later. He told David that an engineer who attended the presentation had told him he would contact his superiors to analyze the technology. The fellow also told Fu that he would hear from him soon.

David and Fu went to have lunch at a fancy Chinese restaurant. Fu asked for the menu, and the attendant handed him a giant book full of pictures of every dish. It took about fifteen minutes for him to decide what to order, and he finally told David he was in for a pleasant surprise. After another fifteen minutes and savoring some entrees, a waiter appeared at the table, bringing a trolley with a large canister full of water. Inside the can were several black flat fish happily swimming, waiting to be picked up by the customers. David was told to choose the most appealing, which he did. The trolley left for the kitchen, and after thirty minutes, the previously selected specimen appeared fully cooked at the table. David tasted the fish, and acknowledged that it was delicious. After the meal, Fu transferred David to the airport for a return trip to Borazon City.

On the return trip, David had little hope of hearing from Fu again, considering that he was merely interested in selling his bioreactors. David had already seen and contacted many institutions and companies that were only partially interested in high-density perfusion technology. In the end, most of them said that it was impossible to transfer this high-level rabies vaccine technology to developing countries. According to Fu, the main reason was that none of them was ready to risk money investing in it.

The communications office of the bioreactor company in North America wrote a note on the gathering in a technical newspaper distributed over the biotechnology news domain, emphasizing that David had stunned the audience. The paper read, “New methods for producing low-cost, high-quality vaccines, affordable for developing nations.” The note indicated that attendants were surprised to hear that millions of doses of rabies vaccine could be fabricated utilizing a high-density perfusion cell culture inside a small bioreactor of only 20 liters. This note from the bioreactor manufacturing company significantly spread the notion that a high-density perfusion system could be applied to manufacture vaccines at a low cost.

Back at Totem Inc., the general manager, who had pushed David out of the company before his retirement, heard of the publications that had appeared in Biological News, describing what the technology was about. Others were about the gathering in China, where David’s name also appeared boldly and was highly praised for showing the high-density cell culture vaccine. With wrong counsel from some of David’s colleagues at Totem Inc., the manager became outraged, summoned the company lawyer, and prepared a letter threatening David. The message read that Totem Inc. was suing him “for revealing some specific knowledge that was the sole property of Totem Inc.” David was taken aback and nervous upon receiving the letter. He contacted a lady friend and lawyer who had also been secretary of the board of directors at the same company, Totem Inc.

The lady’s lawyer told David that the letter was a disgrace. It was biased, baseless, and jealous and only showed the general manager’s frustration and hypocrisy. She said this letter also revealed how ignorant and superficial the total management at Totem Inc. was. The new general manager should have taken more time to study and understand the project’s development. He failed to realize that the only owner of the technology was the foundation, not the local Totem Inc.

David’s lawyer also clarified the property rights of each specific component of the technology. The laboratory design was in the public domain, and many companies offered this service. Growth media components were also in the public domain, and each company provided its own media components for anyone to buy. The cell seed type was also in the public domain; anyone could buy it from repositories or cell banks in several places. The seed virus could also be obtained from international reservoirs or virus banks. Laboratory equipment could be purchased from different companies; each one had its own designs and catalogs. Concentration and purification equipment can be obtained from several commercial specialized companies. The final formulation of the vaccine was different for each manufacturer, vaccine, and country.

In summary, the sole owner of a complete package of technology transfer know-how was the foundation. The new Totem Inc. manager was also unaware that David was the real cognizant of how to put the whole thing together and that he had the right to transfer that knowledge. Moreover, he also had complete technical know-how in his head. Consequently, following instructions from the lawyer, the letter was never answered, and David never heard from the management at Totem Inc.

Following these events, David received several international requests by e-mail to explain the technology and clarify the costs of transferring his technical know-how. As it was almost the rule, the main drawback for the majority of requests was the need for more funds to establish industrial production. Other companies or establishments just wanted the SOPs for free. One researcher from a well-known laboratory in the developed world was interested in the technical know-how and asked for a discount to obtain written descriptions of the SOP technology. However, he wanted the technical know-how for research purposes and to apply high-density and perfusion technology to other viruses and vaccines.

The researcher needed to understand that the package David was ready to help install could be primarily used in an industrial environment. He also wanted the technical know-how for free from the foundation, but that deal did not work out. This scientist and many others thought the foundation had papers describing detailed technical know-how, but only some people realized that all the technology components were already in the open. They can be found in international journals, equipment manufacturers, and reagents. What David had, apparently in exclusivity, was the technical know-how to place all the components together and of all the minute details to make them fit together continuously and on an industrial scale. Another plus of the technical know-how was to identify, manage, and maintain several pieces of unique specialized equipment.

David was discouraged and needed more confidence in the fundamental technology transfer knowledge. However, one month after the gathering in southeast China, a manager from a company located in the northeast of China, who had attended the presentation, emailed David, inviting him to his company to discuss the possibility of signing a contract to transfer his high-density cell concentration and perfusion technology.

David could not believe that a company would finally be interested in applying that technology on a large industrial scale. He hurriedly accepted the invitation and immediately contacted Olga. David explained that they had to prepare up-to-date SOPs in English to offer them to a Chinese company interested in the technology. David also proposed that she retire from Totem Inc. so that they could prepare the documents. He assured Olga that after signing the contract, they could jointly go to China to set up and start some laboratory work for the project’s development. He offered Olga a job in a technological transfer project for a Chinese company.

When David left Totem Inc. for retirement, Olga felt wholly isolated from a technical standpoint. Still, she had to continue working there, since she was involved in the production of the rabies vaccine for veterinary use. When she sensed that the new management wanted to stop making and replacing the human vaccine with other veterinary products, she was already considering resigning her position but was waiting for a nod from David to leave Totem Inc. After considerable analysis and risking her future professional life, Olga finally decided that it was time to leave the company and announce to David that she was resigning.

The preparation of the SOPs between Olga and David took over two months. They had to study changes in new equipment, reagents, and newer technological systems for downstream processes and quality control. They had to ask for advice from some biochemical friends regarding the latest methodologies, since documents involved all aspects of vaccine production, from a description of reagents and cell culture media for production and quality control to the final formulation of the vaccine. These documents contained procedures and processes for all cell and viral cultivation phases, industrial production, purification, validation, and quality control tests. Olga and David finally completed two large volumes—approximately three hundred and fifty pages.

Next, David had to risk taking those volumes to China without any assurance that a contract would be signed. Still, before arranging the trip to China, David contacted a friend’s lawyer to review the draft contract he had prepared. When the draft was ready, he hired an official Chinese translator to obtain a copy in Mandarin. David then sent a set of contract papers in Mandarin and English to the Chinese company for study before the trip. After two weeks, a Chinese sent a note saying that, in principle, they agreed with the contract, but they wanted to personally discuss some specific details before signing it. Consequently, David expected to discuss the draft contract upon arriving there.

With a copy of the draft contract in English and Chinese and two huge volumes in English containing all SOPs, David bought his own airline ticket to go to China and, with some anxiety, departed from Borazon City. The air trip lasted almost 24 hours, with a stopover in Europe, and David arrived in China the next day after leaving Borazon City. He was met at the Shufen City airport by two Chinese fellows. One spoke fair English, and the other, who happened to be the driver, also spoke a little English. This time, there was no need for a translator. In mid-morning, the host accompanied David to catch another flight to another city in northeast China. After another one-hour flight, the two were met at another airport by a group of representatives from the interested company party.

David was taken to the hotel and instructed to lay flat and sleep for at least 5 hours. He was told they would pick him up at six o’clock in the evening for dinner with the company’s general manager. David was exhausted but did not mention it. He also noticed that the hotel belonged to a Chinese chain and did not resemble a hotel with an international outfit, but he did not complain. David was ready at the indicated hour, so the two Chinese escorted him to a nice restaurant where the general manager and Fu, the bioreactor company’s representative, were waiting to welcome him. After the standard “Nijao,” everyone ate their meal, including the driver, who was also sitting at the dinner table, a surprise for David and probably not the last one.

The general manager could not speak English, so Fu had to do all the translations. David was somewhat uneasy. During the meal, there was no mention of the technology or the contract—only personal matters. A few toasts were made for the success of the technology transfer. The toasts were made with several rounds of robust local liquor made from rice with alcohol that had a minimal effect on the brain, so no hangovers were expected. However, the group was making a toast without signing any agreement. The host finally, without any business matter or mention, told David to be ready the following day at nine in the morning to be picked up for negotiations. After more than 32 hours of traveling time, David waited for comments on the contract. Still, no mention was made of it, another purposeful procedure for the Chinese to soften the other side of the negotiating table.

Fu, David’s companion, appeared to be a confident, happy, cheerful fellow, always smiling. He had a round face with black hair covering half of his forehead, and his eyes were bulky and bright. He was a heavy man and also had an enormous appetite. His manners were of a businessman ready to negotiate anything, and he seemed unreliable. He was also in an excellent, wealthy position as a successful businessman and would play a significant role in negotiating and developing this vaccine technology transfer project in China.

The following day, after a good night’s sleep, David, for the first time, went downstairs to the hotel restaurant. He was looking for a glass of orange juice, a cup of coffee, some bread, a piece of cheese, and some eggs, but he could not find any of those items. In a buffet-type arrangement, there were some noodles, mainly cooked pork meat, soybean meals, different kinds of rice, and many other vegetables and elements that he could not identify, since they all had written signs, but in Mandarin, and nobody was there to translate. David described what he wanted, and he finally got through an order of boiled eggs and fruit juice. After fifteen minutes, the eggs and the fruit juice arrived, but David now wanted some salt for the boiled eggs, and he could not find a gesture or body language to name it. He went to the kitchen to locate it; everyone there looked astonished, a foreigner inside the kitchen looking everywhere for something he could not describe. David tasted different kinds of powders until, finally, after more than fifteen minutes, he felt something like salt.

He thought he was safe and went back to the breakfast room but could not find the table where he was sitting before. No wonder a waiter had taken the boiled eggs that David had left alone to go to the kitchen. The waiter probably thought David did not want them and discarded the eggs into the kitchen. David decided to taste a sip of fruit juice and left a little hungry; it was late for the meeting. One of the many lessons to be learned for David was that Chinese servers were ready and very quick to pick up the dishes or anything left on the table as soon as you finished with them or left them alone. However, some years later, David and his wife had dinner at a restaurant, and both of them had decided to go to the buffet to get another dish. When they returned to the table, all the dishes with their food were gone. They had forgotten the lesson of taking turns to go for more food from the buffet while the other person watched the table!

After leaving the hotel, David was accompanied by two Chinese to a small meeting room in an old building, where a negotiation team was waiting. On one side of a long table were five Chinese. They were introduced as the general manager, the administration officer, the comptroller, a lady technician, and a retired vaccine scientist. On David’s side of the table was Fu, the bioreactor salesman, and a woman who would be David’s translator. The administration officer happened to be the translator of the general manager. Later, David discovered that he could translate written or spoken English, but he could not speak fluent English, so he only spoke Mandarin to his counterparts. David had to rely exclusively on his lady translator on his side of the table, so he felt utterly lonely against five Chinese on the other side of the table, considering that Fu on his table was also Chinese, and the translator was Chinese, too.

So, seven Chinese could speak anything they wanted in Mandarin, and David could not understand anything. David immediately sensed that the lady translator was interpreting only a fraction of the entire conversation happening among the rest of the audience. On top of that, he needed help finding out precisely if Fu was on his side of the discussions or defending his client’s interests more for the future sale of his bioreactors. David felt that he had no leverage in talks of the contract, so out of frustration, he employed a funny tactic of speaking softly to himself in a frail voice in his original language. He spoke sentences to assure himself that he would win the deals and with certainty that he would not bend his arm. No one in the room could understand him, but they all probably sensed that he was speaking to somebody and that he was not alone. That worked out particularly well, since David had more time and could concentrate on English sentences and answers that he had to deliver.

Most discussions on the technology SOPs went very well. Members of the Chinese team were satisfied to hear all the advantages of high-density cell concentration and perfusion. They appeared to be eager to finish meetings as soon as possible. They were anxious and wanted to read the volumes of the SOPs David claimed he had brought with him but were secluded in his hotel room. David had to answer many questions, especially from the retired vaccine scientist, a general manager consultant.

The retired scientist was Hui, whose name meant “knowledge.” He was the director of research in the Ministry of Health Sciences in the central Chinese government, devoted primarily to vaccine research. He did not believe or want to accept all the advantages of the high-density cell culture and was naturally more inclined toward the technologies he had used for many years. Hui was incredibly reluctant to accept the purification system that David described and said aloud that he had used a similar system before and had failed to remove the entire residue of cell DNA. That discussion would remain alive for a long time: “cell DNA residue.” Mr. Hui was very calm and did not speak English; he always talked to the local Yawen Inc. general manager in his native Mandarin. Hence, David could not understand what other things he had in mind.

However, from the questions that the general manager was posting, David realized that Mr. Hui was opposed to using other technologies that were different from those he had used all the time. He had also told everyone that it was not possible to grow cells to the very high concentration that David claimed. Mr. Hui was a short and thin man in his late sixties; he dressed like an elder or senior official performing public duty. He appeared to be a judge, waiting for mishaps before making judgments. At times, Mr. Hui acted as if he were the neutralizer of the new project. Hui would be “a stone inside the shoes” for the project’s smooth development in China. David otherwise sensed that the general manager and the rest of the audience were so eager to see and read what was inside the written SOPs that at the time, they were paying little attention to Mr. Hui’s observations and claims.

The discussions on the technology lasted for one whole day. Before returning to the hotel, David asked his hosts whether they could get him another room in an international hotel chain. He explained what had happened that day at the restaurant, and they had an ample laugh. Hosts were so happy with the new technology that they immediately accepted and moved David to a much more expensive Sheraton international hotel, “Sheiladong,” for them. Now David could have some global food, especially an excellent coffee breakfast with different types of eggs. The restaurant in the hotel also offered a wide variety of breakfast foods, some of which were Chinese, and others of the palatable occidental taste. Customers could choose from Chinese noodles that are very common for breakfast, sushi in very different shapes, many kinds of vegetables, at least two or three soups, and several kinds of fried shellfish, shrimp, meat, pork, chicken, and others. Customers could also choose from all sorts of fruits, cereals, cheeses, slices of bread, eggs made to order, different types of teas, and, of course, coffee. There was significant versatility in the choices. David felt entirely at ease in this new environment.

The following day, David was picked up at the hotel for discussions devoted mainly to contract details for the technology transfer project. This would be a much more complicated matter than the one related to technical content, considering that all disbursements had to be made in U.S. dollars. The exchange rate was unfavorable for any Chinese company. David’s proposal consisted of a contract divided into several phases that would develop as the technology transfer progressed. At each stage, David’s company would deliver some additional standard procedures in writing and digital form, which only belong to that phase. Later, David would go with a team of scientists to set up the technologies for that phase and teach local counterpart technicians all that had been done by David and his consultants in that phase. Yawen Inc. would cover contract expenses after the end of each stage. However, to start the project, the company would have to disburse a certain amount as a down payment to ensure the initiation of the technology transfer project and the receipt of the initial SOPs.

Discussions on the total cost of the technology were very cumbersome and awkward, since the Chinese wanted almost everything for free. After reading about how technology had been developed, they felt that the foundation could give them the technology for free. It took two days to convince the Yawen Inc. officials that the right to transfer the technology developed with foundation grants belonged only to David and his newly formed company. The Chinese wanted to know more about David’s freshly structured company, so David showed them one copy of the official company registration as a limited liability company in his country, with an official translation in Mandarin.

The Chinese group took several hours to examine the papers and later suspended the meeting until the following day. The next day, they finally declared that they could not sign a contract with a company from a country they did not recognize and knew nothing about. When David mentioned the name of his country, the Chinese said that they had never heard of that country before and asked where the land was located in relation to the position of the United States. They would understand the approximate location if the country were found near the U.S. David immediately recognized that the Chinese did not know or wanted to know anything about geography, so he answered that the country was just south of the continental U.S. That was sufficient for the Chinese to learn. However, the Chinese thought the company also had to be located or registered in the United States.

Fortunately, David had registered the company in the USA to open an account in an international bank to handle the exchange of dollars for local currency in Borazon City. That night, he visited the hotel’s business center and contacted a U.S. state office. He received a copy of the company’s certification as a limited liability company, with paid dues and active status valid for that year. The following day, David showed the certificate to Yawen Inc. officials, who then said, “Well, if you have a company registered in the United States, then your company exists,” and went on, “We will be ready to sign a contract only with a U.S. company.” The contract was now possible. David understood that China always considered the United States a country to imitate and had complete faith in anything from there. They knew then that the company was honest and that the U.S. government would back it up. In their minds, they felt they would never be cheated on dealing with a U.S. company.

After lengthy discussions and a complete agreement on the contract contents, the Chinese and David were ready to sign the contract. The following day was going to be the signature ceremony, so David was very excited, thinking that his company, for the first time, would sign a contract with a Chinese company; he was unaware of the intractable happenings ahead. The meeting gathered in the same room where all discussions had taken place, but this time, all were together, and everyone was on the same side of the table, David’s. All were exchanging smiles and excellent humor. David had brought along the two massive volumes with documents describing the initial technology in some detail—the SOPs—and they rested on the table like two precious trophies. The Chinese looked at them with admiration, desire, and eagerness to look inside and own them, but David did not show any attempt to open them to allow the Chinese to look inside. The expectation was getting high.

It took some time to read the final contract in two languages and explain how the working phases would be executed. David was unaware that his Chinese counterparts had contacted a lawyer to review the final agreement. This time, David did not have a lawyer on his side, so he had to rely on his experience as an administrator. Now everyone was ready to sign the contract; the general manager of Yawen Inc. signed, and David, the legal representative of “Newvac Inc.,” also signed. Pictures of the ceremony were taken to show the future history of the project. Everyone was happy and exchanged handshakes and smiles. The general manager of Yawen Inc. had a few words of praise for how the discussions had taken place in a very professional, friendly, and polite manner. David also said a few words of appreciation for how he had been treated and was waiting for successful project development.

The next phase involved deciding how to start the execution of the project. As stated in the newly signed contract, Yawen Inc. had to pay Newvac Inc. a down payment to cover the preparation of the SOPs, and then David could hand in or send two volumes with the documents. With this in mind, David, shaking hands with everyone, took the two volumes from the table and started to leave the room for the hotel. The Chinese immediately raised hell: “You cannot return the SOPs to your country. You have to leave them for us.” At this time, they were entirely out of their minds and often asked David, “Are you sure you will return them to your country?” David repeatedly answered and told them, “Yes, I am, and I will send them after you submit the down payment, and I receive confirmation.” The Chinese could not believe that David would take them back with him unless, as agreed, they covered the down payment. Since nothing else happened, David brought his volumes back to the hotel, to his Chinese counterparts’ total despair and astonishment.

David had a return airline ticket to leave Shufen City the next day after the signature of the contract; however, that late evening, David received a call from his Chinese counterparts. They would get money for the down payment, and they had already changed his airline reservation three days later. The following day, David was picked up at the hotel, and the entire group went to the same discussion room. David was informed that it was highly complicated for them to get the dollars immediately because of the need to get the government’s permission and approval of the contract. The officials had to examine the contract and all the company papers that David had offered. That could be easily solved, but another difficulty arose in getting the dollars out of the country. This was another matter that had to be approved by another branch of the government. The review would get at least another week, but David was not prepared to stay that long; hence, he asked his hosts to look for another alternative. David went to the hotel that day, thinking that starting the project would be tricky.

Another day had gone astray, and there was no solution close by. The following day, the general manager of Yawen Inc. came up with another solution. The Chinese government would quickly approve a transfer of U.S. dollars to a bank in Hong Kong, and now they had to find someone of trust for both parties that had an account in Hong Kong and simultaneously would accept receiving the transfer. Later, the money would be transferred from the Hong Kong bank to David’s bank in Borazon City. Mr. Fu, the man most interested in the deal and who would sell the bioreactors to Yawen Inc., suddenly revealed that his company had an account in Hong Kong. He had to contact his superiors in California (USA) for permission to use the account for the transfer. Finally, after another 48 hours, the news came back that the payment could be made to that Hong Kong account and then back to David’s bank account in Borazon City. Was David going to trust that kind of deal? The credibility of the Chinese was questionable, but a bank in Hong Kong was thrust worthy. The money would be inside a U.S. company account but handled by a Chinese official. David had to thrust him. There was no other alternative; David had to trust Mr. Fu and his U.S. company in Hong Kong to receive the down payment money transferred from Yawen Inc. and, hopefully, transfer it to David’s company account a few days later. The first transfer would be done in hours, so everyone could go home to wait.

David could not sleep well. He was so doubtful of Mr. Fu. This man did not appear trustworthy, and much later, it was proven. He also risked the significant effort that Olga and he had devoted to preparing those SOPs. He was also thinking of the extensive travel to get there and now return home with empty hands after giving away the precious volumes with the principal written contents of the technology. On the other hand, he had already signed a contract for the next year and a half, which meant a lot for him and for Olga and other consultants and associates to be hired.

The next day, the group met again in the same room, and David asked for written proof of the transfer to Fu’s company in Hong Kong’s account. Mr. Fu opened his briefcase and proudly showed the audience a small piece of paper with a transfer record from Yawen Inc. to the Hong Kong account. He handed it to David, but there was no printing of any confirmation seal. Most of the records were in Mandarin, and only the total amount was in Western numbers. However, the headings and addresses were in English. Could David trust a deal in China under those circumstances, or could all of this be a scam?

David was full of skepticism but found no way out. He was ready to hand in the two volumes with most of his technical knowledge. He expected the money to be in his company account in another 48 hours, so he had to trust Fu and his company. The down payment money was already in Fu’s hands. A new meeting was again summoned in the same room and prepared for the discussions. The Chinese were beside themselves with happiness; they could not believe that they would have the documents in their hands, and that the printed papers would somehow reveal all the enclosed secrets. This time, the general manager was seconded by the chairman of the board and Mr. Hui, the virus specialist who had retired from the government. Also present were the comptroller, the board secretary from the parent company, the administration official, a lady technician, and a translator who could not speak fluent English but could translate from English to Mandarin.

After a few remarks from the general manager, a surrender ceremony for the most desired scientific paper volumes began. Two photographers were at hand and took pictures of David’s history, handing the first volume of the papers to the general manager. The smile on the face of Cong (general manager) was enormous; it could fill the entire room, but he was utterly overwhelmed. The rest of the group was also satisfied and credulous. They would leaf through the documents without any control. The second volume of materials was handed to the research scientist, who was appointed by the general manager for that action. He was not entirely convinced of the technical content of the procedures. Still, he was thrilled to be chosen as the recipient of an enormous amount of information. The audience fervently applauded, and the group headed to an elegant restaurant to celebrate.

This ceremony would become a common practice for David; dinner time was and is a particular business formality for the Chinese. At any celebration, the highest-ranking official available that day would invite eight or ten colleagues, including the driver and visitors, clients, or guests, to a good restaurant with unique private rooms specially adapted for groups. Rooms were spacious and beautifully decorated, with a small waiting lounge area and a huge round table that would seat at least 12-14 people. The rooms gave newcomers a sense of magnitude and, at the same time, a sense of exclusiveness. The most senior invitee will be asked to sit at the center of the room, facing the entrance, and his wife will sit to his left. The most senior host will sit on his right, and the remaining group will intermingle among the host company and visitors.

The invitee would have to sit first, then the most senior host, and then everyone was seated. Servers immediately started serving green tea in small cups for everyone to enjoy. The senior host discussed with the master chef the dishes that would be served from a large book containing at least 20 pages, with a description of the food and even colored pictures of each plate. This process will take at least 15 minutes. At the end of it, servers were already placing some entrees on plates, sitting on top of a round rotating glass that covered the entire table. It allowed everyone to test any plate by only extending one arm and gathering a piece of food from each dish. Each plate was big, quite full, and usually well-decorated. A regular order will be for approximately eighteen to twenty massive dinner plates for a group of ten persons.

The next agenda was to propose a toast. The most common Chinese drink was served (for Chinese, “wine”). The drink was made of fermented rice, with an alcohol content of approximately 30%. Occasionally, local natural red wine will be available, primarily for ladies. A Chinese toast typically starts with the principal host and the guest of honor exchanging common words of success for future relations and so on. Later, during the meal, the primary host goes to where other guest party members are seated and toast each person separately. Sometimes, the guest of honor would reciprocate and would also go to the seats of each participant in the gathering to have a personal toast. So, there are typically many toasts and a considerable number of alcoholic drinks.

When David returned to the hotel, he remembered some comments from one of the Chinese company officials. The Chinese were very cautious about dealing with any other country different from the U.S. considering that European companies had cheated many Chinese companies. The Chinese mentioned a local company that signed a contract with an European company to transfer technology for constructing and operating a lawnmower manufacturing plant. Construction of the manufacturing plant was completed, pieces of equipment were installed, and transferors left a written description of the process of equipment and control tests. However, transferors have yet to return to complete manufacturing. The manufacturing building had been idle because people needed to learn to manage many aspects of using the manufacturing equipment and the procedures for constructing such an apparatus. The Chinese company went into bankruptcy. The fellow even mentioned that they had seen several similar cases of other Chinese manufacturing companies dealing with companies from Europe.

David mentioned to the Chinese that he had seen other cases that were just the opposite. A Chinese company contracted with a consultant from the United States to design and operate a manufacturing facility to construct overboard motors. The Chinese paid a flat sum for the initial start of the contract. The consultant designed the facility, bought the equipment, and taught the Chinese to operate all significant manufacturing equipment. The company started the production and selling of the motors, so the consultant asked to be paid the remaining of the contract, which was close to sixty percent of the initial agreement. The Chinese claimed they were unsatisfied and told him they would pay later, as the company had revenue from product sales.

The U.S. consultant returned to his country and wrote several notes asking for his money, but there was no reply from the Chinese. He was outraged and assured that he would never make another contract with a Chinese company. After a year and a half, the same consultant received a note from the same Chinese company asking him to return, since the company needed help to solve new troubles with the technology he had designed and assured him they would pay him upon arrival to China. The consultant replied that they had to pay him the money they owed him before going there, and sure enough, after a few months, the Chinese company finally paid the consultant everything they owed. This time, the consultant asked the Chinese to pay everything ahead for this new consultation before he went there to solve the issues, and they did.

After signing the contract with the Chinese, David returned to his country and was eager to start developing the new project. After returning home, he began studying how and whom to contact and hire as consultants. The new group would have to set up a basic plan for transferring the technology and in situ teaching on how to carry out every aspect of the vaccine production process. David again contacted Olga and found she was utterly frustrated and could not understand how the vaccine was discontinued after so many years of development work involving producing and formulating a human rabies vaccine. As David had mentioned before, Olga had said that she had already resigned.

David was very sorrowful to learn again that the manufacturing of the human vaccine product was being discontinued at Totem Inc. Still, at the same time, he was happy to realize that he could now have the best virus microbiologist to work full-time in the new adventure in China. After the general agreement with Olga on the stipend, she signed a contract to serve part-time in Newvac Inc., David’s new company.

She was now a senior research scientist in charge of the company’s cell and viral production technology. She would receive honoraria for any technical meeting in Borazon and for any period spent traveling to China, working there in development and teaching processes. She was thrilled, considering that she had never been outside of the Americas, either in Europe or, for that matter, in Asia. This new project would be a real, unique experience and a new adventure. Moreover, she would be paid in U.S. dollars, a real advantage in her country. David was then planning his first work trip to Asia.

This decision was made after the company bank announced that a money transfer from China had arrived and that the dollars could now be negotiated in the local currency. Fu, of course, had already retained a high percentage as an intermediary of the deal and as a liaison between the two parties involved in the project. David could now hire and pay the local consultants. The project had been saved, and Yawen Inc., the Chinese company, was also preparing a setup for a provisional pilot plant in the city of Shufen.

Chapter Nine

2001-2002

A Different World

Back in Borazon, David worked on his actual in situ technology transfer activities, which would take place in Shufen, a well-isolated town in the northeast of China. Will he succeed against the odds that all had predicted—that China was incapable of mastering this sophisticated and complicated vaccine technology? He had to assemble a group of scientists with considerable experience in vaccine production and prepare to go to China. The group had to create a vaccine pilot plant with well-chosen equipment from different countries and manufacturers. The Chinese did not object to David’s request to order the best equipment, materials, elements, and reagents from any company or country. For the pilot plant, this request was only partially covered.

Before proposing a working contract with the new technical consultants of Newvac Inc., David had to conduct a preliminary design and draft layout of the pilot plant in China. He based his proposal on an initial rough draft that was discussed well with Peter, before his unexpected disappearance. The preliminary draft was completed in three weeks and sent to the Chinese. It was immediately approved, and the wall panels, services, and essential equipment were immediately ordered. The Chinese installed equipment from a previous old-fashioned laboratory and bought brand-new equipment, materials, reagents, and supplies. The situation was quite demanding.

After another three months, a Chinese engineer informed David that the preliminary three hundred and fifty square meter pilot plant had been finished, and they were waiting for new cell seeds to start a few cultures. They had built the pilot plant on the third floor of an old building with very little security for handling a highly pathogenic virus, such as rabies. The Chinese had to order cells from a well-known repository with the backing of a world scientific organization. Since they felt uncomfortable writing such a request in proper English and were afraid of rejection, they asked David to write a draft, which they then signed after including a specific laboratory business vocabulary.

A similar process was involved in obtaining the unique rabies virus strain, which had to be ordered from a world virus repository located in one developed country. In this case, a letter of recommendation had to be written by Newvac Inc., David’s company, assuring that the technical laboratory of the Chinese Yawen Inc. had all the technical know-how to handle highly infectious viruses, as well as all the professional facilities and the trained personnel for those particular activities. David also had to personally endorse the request and accept responsibility for overseeing the management of this essential operation.

Two months later, the cell seeds arrived in Shufen City and were ready at the Yawen Inc. laboratories. The virus would take much longer—at least four or five months. A few individuals had already been hired at Yawen Inc. as assistants, operators, technicians, engineers, and professionals from the biological sciences. The remaining consultants were then hired to work with David and Olga in setting up the entire operation to produce rabies vaccines for testing and, eventually, the final government approval and registration.

To build the team, David again looked for professionals who had retired from Totem Inc. and had initially participated in developing the rabies vaccine technology. David contacted Luis, a tranquil, timid, and private person. Luis’ physical appearance was that of a research scientist. He had big eyes and wore a half-smile, and he was a man of a few words. Luis took a leave of absence to allow him to travel and work with the group. He had already traveled overseas to take courses in virology and molecular biology in Europe but had never been to China.

Jesus was also contacted. His role as an expert technician was pivotal, given his familiarity and practical experience with handling bioreactors to grow the cells and the rabies virus. He had participated from the beginning of the project at Totem Inc. and had recently retired from the company. Jesus was looking for other projects, so he gladly considered the opportunity to join David’s team and warmly accepted. The first vaccine technology transfer team—Olga, Jesus, Luis, and David—was ready.

Meanwhile, one of David’s research fellows called him. He had been fantasizing about finding a company or an investor interested in high-density technology. The fellow was very familiar with the foundation’s rabies vaccine project and accomplishments. He mentioned that he had talked to a group of investors from a pharmaceutical company in the same country. They claimed to be interested in high-efficiency technology to produce several vaccines for human use. The company was from another city, so David made an appointment to hold a meeting with one of the interested investors and present the high-density vaccine production system. David and his research fellow reserved a meeting room at an executive hotel and prepared a projector and a few snacks for the encounter.

The investor was also a board member of a large pharmaceutical company in the country. He arrived at the hotel meeting room and greeted David and his colleague with disdain. David immediately sensed something wrong. After the usual introduction, David dimmed the lights in the room and started the presentation on the technology. However, he could not help but notice that the visitor was somewhat uneasy and frequently shifted from side to side in his chair. After about fifteen minutes, David turned back to look at the visitor and found him motionless in a nocturnal position; he had fallen asleep. David and his friend picked up their belongings and left the room, leaving the sleepy investor undisturbed. As it turned out, David and his friend had yet to hear again from that company or from the sleepy and smart investor.

The first trip to start the laboratory work of the project with the Chinese involved only Olga and David. The idea was to validate all the premises and equipment, examine all the reagents and materials needed for the total vaccine production system, and prepare the master and working cell banks. First, David, and Olga got visas and airline tickets and traveled to China. The international flight, after a stopover in Europe, landed in the capital. For the journey from Europe to China, Olga and David chose reservations on a Chinese airline; however, the experience was not that favorable; they only had noodles for breakfast, which was the standard meal offered to all passengers. David soon realized that 99% of the passengers were Chinese.

At arrival, a representative from Yawen Inc. met them at the airport and handed them another airline ticket for the last section of the trip to Shufen City. After another one-hour air trip, the two arrived at the airport and were received by three fellows, who warmly greeted the visitors. David and Olga had to overcome the jet lag, so they slept comfortably at the hotel. The next day, they were picked up after a semi-occidental breakfast and headed for the newly established pilot plant.

At the entrance of the building, a group of Yawen Inc. professionals was expecting to meet Olga and David, and even Cong, the general manager, was there with happy smiles. The group wanted to show visitors its new laboratories and equipment for the project’s development. Olga and David entered the new area with separate rooms for services, such as washing and sterilization of glassware and media preparation. To enter the production laboratory, there was a changing room to remove outdoor clothing and wear laboratory garments in separate areas for men and women. There were different areas for cell culture equipment, laminar flow hoods to cultivate the cells, a bioreactor room, a separate room for viral seeding, and a last one for viral concentration and purification.

The areas were simple but large enough to handle modest-sized cell cultures and low volumes of rabies virus production. The place at the end could accommodate the production of three rabies vaccine testing lots for government approval and registration of the product. The four-story building housed offices for the general manager, the technical and administrative personnel, the consultant’s office, and a materials deposit. Olga and David were not completely satisfied with the trivial arrangements, but they did not openly complain.

The area where the pilot plant had been established was “rather spartan,” as one previous consultant for the foundation had described the working conditions in China at the time. From their office window, Olga and David could see an adjacent building utilized for apartment housing and dwellings. They could see that the building and apartments’ maintenance conditions needed improvement. The exterior walls of the building were defaced, unpainted, and imperfect and appeared to be remnants of a battleground. However, when they carefully looked, only one apartment in the middle of the building appeared neat and clean on the outside, and even the glass windows were spotless. David and Olga speculated that the apartment belonged to the owner of the building.

The group later learned that the building belonged to the local government. All workers from the new vaccine company, including the general manager, occupied the building. The general manager’s residence was the best-looking and cared for. David and Olga were perplexed to observe that all employees, starting from the professionals, laborers, workers, office personnel, drivers, and the boss with his wife, were all dwelling in the same quarters. Nowhere in the world had they seen anything like that. That was a modified old culture or perhaps a new Asian culture. It was impressive and a complicated model to follow in other places.

The huge advantage was related to the minimal time required for the employees to reach their workplaces and the absence of transportation requirements, such as buses, cars, trains, or any other means of mobility. David considered the time, effort, fuels, repairs, and funds that the new company was saving by not expending on these services. Notably, a few girls in the laboratory commonly arrived at work with their hair in complete disarray, as if they had just gotten out of bed a few minutes before. In their nearby dwellings, they could only use the showers once a week, so they could arrive at the laboratory as soon as they woke up.

A small group of Chinese technicians was designated to accompany Olga and David in setting up the primary tissue cultures with imported cell seeds. This work took approximately five weeks and was very well received by local technicians. The availability of complete facilities for the job was categorically lacking. Some equipment was old and needed more adequate maintenance. The small group worked endlessly under difficult circumstances but with great enthusiasm. However, the two teams did an excellent job, and the cell banks were completed in what appeared to be the shortest possible time. The underlying substrate for preparing a new rabies vaccine was now available. The new group had to succeed in getting a new vaccine in the market against all the odds. So far, this seemed to be a good start in the right direction.

According to the original plan agreed upon by Yawen Inc. and Newvac Inc., the consultants would stay for at least four weeks in China, with the two technical groups working together. The Newvac Inc.’s consultants would then leave some assignments for Yawen Inc.’s team and return home. After two or three months, the Newvac Inc. team would return to Shufen City and start another working cycle. The system will be repeated three or four times a year until registration of the new vaccine. With this in mind, and with the ratification of the Chinese team, the Newvac Inc. team left some assignments for Yawen Inc.’s technicians. The work primarily contained many quality control tests to validate the conditions of the master and working cell banks. These tests would take at least two and a half months. After preparing the cell banks, the consultants were ready to return home.

On their way to the American continent from China, David and Olga had to stop in a city in the west of North America. At immigration, an official asked David what his occupation was and what he had been doing in China. He answered ingenuously that he was working on transferring vaccine production technology to China. The official immediately asked David to step aside, and another official took him to another room and ordered him to bring David’s luggage for inspection. The baggage was open and emptied, and every piece of clothing and sundries was searched for vaccines, restricted chemicals, or virus ampules. David was also searched inside his pockets, and his briefcase was open, emptied, and examined at length. After an hour of inquiry, nothing irregular was found, so David recovered his luggage, rejoined Olga, and went to the hotel. David speculated that the whole ordeal was probably due to the idea of a possible biological warfare specimen he carried. Henceforth, he and the consultants decided that at any immigration point in any country, they would report their primary involvement as special laboratory equipment to avoid suspicious ideas from immigration personnel. Another awkward situation had once again been abated.

The Newvac Inc. team had a meeting to evaluate the work they had just completed in China and to plan for the next working visit. They sensed a good mood, considering that this was a new experience in a different world and an ancient and remarkable culture. However, they felt somewhat uncomfortable when they analyzed the actual technical capabilities of their professional counterparts. As it turned out, the technicians at Yawen Inc. had minimal knowledge of many of the essential components of cell culture technology in the laboratory, and much less of the necessary expertise for the scale-up to industrial levels of the vaccine processes.

Another factor that was only partially predicted was the vast differences in the previous training of the Chinese professionals compared to the training and experience of the consultants. Even though some Chinese professionals at Yawen Inc. claimed that they had master’s degrees, their knowledge level was somewhat even lower than the level of a baccalaureate in the country of the Newvac Inc. team. This fact would influence the project’s probability of success. Another factor in the relationship between consultants and local technicians was the language used for communication. For both the local technicians and the consultants, communicating, and sharing scientific knowledge in English was an hindrance, as it was not their native language. Therefore, David insisted that the directorship should mandate that all local technicians speak fluent English; however, that was only partially accommodated.

For the next trip to China, David summoned Olga, Jesus, and David’s wife, who would serve as the contract’s trip coordinator, the assistant English translator, and the general administrator. Dalila, David’s wife, would be a public relations officer for the group. When the new group arrived in China, they were met by at least four officials. The Chinese group realized and was now completely aware that they would depend on this group of consultants for ultimate project success, so they deserved a great welcome, full of smiles and gratitude. They were taken to the western “Sheiladong” hotel, the standard accommodation place for the team for the following years. After a well-deserved overnight rest, the new group was ready to have breakfast. They did not know what lunch would be, so they had a lot of breakfast. This was David and Olga’s second work trip to China, whereas it was Jesus’ and Dalila’s first time in China. The newcomers had a lot to learn to accommodate the Chinese-Western culture mix of meals.

Once again, David, Olga, and Jesus started the plan to set up the bioreactors where the cells would be grown and prepare them for a genuine start of the cell scale-up system. The new plan was to stay for at least four weeks and then leave some assignments for the Chinese technicians to continue and finish other cell cultures. The rookies of the group soon realized that it was difficult to understand spoken Chinese English. David had to interpret many things for Olga and Jesus. The team once again started to comprehend and discover that both they and their Chinese counterparts also spoke English as a second language. Still, they could have spoken better and more comprehensive English. This language barrier would become one of the main constraints in the serene development of this vaccine technology transfer project. David was saying that this new technology transfer was going to meet expectations.

Like many Chinese cities, Shufen was large and had many people. The congregation was especially noticeable on the streets, which appeared full of bicycles but not many cars. Consequently, city roads outside downtown at times appeared quite empty. At this time, Shufen City had approximately four million inhabitants. The group also commented on the absence of significant high-rise buildings. Instead, there were many old, four-or five-story residential buildings. Most buildings appeared to have been designed by the same architect or built by repeatedly copying the same design, and none had elevators. The laundry area of the apartments was located on the balconies to the outside, which sometimes had some clothes being dried, hanging on a rope at the end of the balcony. This scenery was very common in all Chinese cities. It was evident that some of the ancient and rundown buildings were starting to be demolished to make space for larger, more modern housing projects.

The consultants continued working in collaboration with their Chinese counterparts. The first thing the group from Newvac Inc. noticed was that although some technicians had experience handling several processes involved in manipulating chemicals and some biological processes, none had any experience manipulating living cells. The only professional with some experience with living cells and the rabies virus was Mr. Hui. He had already retired from the highest official governmental post in the capital, where he had been in charge of the programs for rabies control in China, but he was now only a consultant to Yawen Inc. 

The development work had some ups and downs, and the working relations with the local technicians were highly variable. One day, a troublesome Chinese technician came to the cell culture lab and looked at a tissue culture, observing the cells under a microscope. She immediately claimed that the cells were dead. When David and other consultants saw the same culture, they found the cells completely alive and probably growing. The girl vehemently argued for a long time until David finally asked her to leave the laboratory. After some problematic discussion, she left the room. She then went to the general manager and told him about the controversial disagreement with David. Mr. Cong told her that David was the control authority in the pilot plant laboratory, so he asked her to stay away from the cell culture laboratory.

Several other uncomfortable situations occurred with Mr. Hui, the retired government official, primarily based on his previous undisputed technical command in China and principally on decisions related to the rabies virus. For him, some strangers were heading a development project and were new to the Chinese scientific community. Even worse, the strangers were from an unknown country they had never heard of before. Therefore, he looked at the work as something that always had to be questioned. As a new consultant to Yawen Inc., he would turn out to be a real headache and impediment for David’s consulting group and the Yawen Inc. directorate.

The air flights back and forth from Borazon City to China were always full of surprises. On one occasion, the three “Musketeers,” Olga, Jesus, and David, were returning home from China and took an airplane to London for a stopover. From there, they flew back to Borazon City. When they arrived at immigration in London, they were sent to different inspection lines. David and Olga made it through separately with a few questions. However, Jesus was detained at the inspection window for a long time. The inspector questioned or did not understand why an Afro-descendant was working on technological matters and coming from China. He stepped back from the window with Jesus’s passport to probably discuss what to do with his supervisor. After more than twenty minutes, he showed up at the window and told Jesus that he could not stay at the airport for more than four hours enough for the trio to get the connecting flight. This outcome was typical racial discrimination by some white officials in England and in other areas of the world.

Despite the disbelief of many so-called “experts” inside and outside China, the three “musketeers” started pioneering the setup and care for large-scale primary cell cultures in bioreactors. Even though vessels were only of fifteen liters capacity, they could handle sizable amounts of ultra-high cell densities on microspheres and in continuous perfusion of nutrient media. This novel system had not been seen in Asia before. Most technicians in different places only used batch systems for final product volumes and small bioreactors. The Chinese would have eight to ten times higher final product volumes and larger bioreactors with a perfusion system.

A few months later, the consulting group returned to Shufen City. The professionals had started new cell cultures in the bioreactors; it took a lot of wheeling and dealing to control all the parameters involved. The most critical things were the amount of oxygen needed for the cells to grow to total capacity, the acidity level, agitation of the liquid media to keep microspheres under suspension, the temperature level, and a few minor details. The bioreactor cell culture had to grow fully in approximately seven to eight days. When the seven days were up, the three musketeers and the Chinese technicians completed the measurement of cell density.

As the overseas consultants expected, cell growth improved after several cell culture attempts were adjusted. One of the complete trials in a bioreactor achieved a very high cell concentration, and its technical Chinese counterparts were astonished. They could not believe what they had seen with their own eyes, so they decided to count the cells twice, and it was true; they had to tell everyone else. They rushed to the corridor outside the bioreactor laboratory and loudly yelled to everyone, “David is not a liar.” “He is not a liar.” They told the general manager, the administration, operators, drivers, and assistants that they had counted the cells twice, and it was accurate that the cell concentration in the bioreactor was five times higher than they had ever seen or read about.

The general manager and the remaining technicians were quite happy, and for the first time, they believed they had not been cheated. They now knew and understood what the foreigners had assured them at the beginning of the project. That was a novel technology, and now it was also theirs to enjoy, and this was just the start of a warm technical relationship. The technology transfer project was again a more feasible prospect for the Chinese and the consulting team; however, the three musketeers’ team could not foresee the difficulties lying ahead for the project.

Following this development of the project, the first set of rabies virus cultures were started. The virus had to be imported from a well-known repository in a developed country, and a written request had to be made by the legal representative of Yawen Inc. As mentioned, the general manager did not know English, so David was asked to prepare a letter requesting the virus and assuring the repository authorities that Yawen Inc. had proper facilities, adequate procedures, and trained personnel to handle a highly pathogenic virus. The latter mentioned that David and his team had technical credentials overseeing the safety development of the rabies vaccine. Mention was made of the promise not to send the virus to any other laboratory inside or outside China. The letter was signed and delivered, and the virus arrived five months after the request was sent.

Similar to the preparation of the cell banks, the preparation of the virus banks was started. The original rabies virus seed had been stored at minus 197 degrees Celsius, but the Chinese professionals and operators had not worked before with any virus, much less with a highly deadly and pathogenic microorganism, so they were terrified of an accident or direct contact with a highly concentrated viral culture in the laboratory. However, for prevention, both the Chinese and the consulting group had already been vaccinated with an imported commercial vaccine. However, they had to wait for three weeks to develop enough antibodies and defense against possible accidental exposure to the rabies virus. After this period, their blood serum was analyzed for the presence of a standard level of antibodies needed before they could be allowed to enter the premises where the live virus would be handled.

The cell cultures had been prepared well ahead of the arrival of the consultants, and the viral growth in the new cell cultures took only 4 to 5 weeks. Now, the Chinese had to conduct the necessary analysis and quality control of the viral cultures. The consultants left those assignments for their Chinese counterparts and returned home to Borazon City. David, Olga Jesus, and Dalila made at least 8 working travel visits to Shufen City during the following two years. On each trip, some new findings were encountered, and they realized that many things were different from the development of the original rabies vaccine in Borazon City. They were learning many things from their technical know-how and, at the same time, many things from the Chinese. One of the most remarkable things foreigners learned from the Chinese was patience. Most Chinese projects plan for five, ten, or even twenty years ahead and then move slowly toward their goals. After one of those attempts at cell culture standardization, the consulting group was ready to head back to their city, Borazon.

For relief from the stress accumulated from work, Ho, the Chinese team’s closest friend, took the consultants for a nice Chinese experience—a famous bathing scene. The group arrived at a five-story building, and Ho showed the group the types of skills they had announced. The business listed the kinds and types of baths and massages they offer so that clients could choose from the following types: Thai, Indian, Philippine, Korean, Singaporean, Chinese, and others. Once a massage was selected, the group entered the service. Men and women entered through different corridors. Male clients had to go through a locker room, leave all their belongings, get a large towel, and enter another huge room completely naked. In the middle of the room were at least six small water pools, each with different temperatures oscillating from room temperature to 40 degrees centigrade or zero degrees. Women were told that they had everything identical to the men’s area.

Clients, however, had to first go naked to a set of showers with different temperatures. The showers were in an open bath with nozzles at varying heights from top to bottom and different intensities that the client could modify; on top of that treat, clients could choose between different soaps and shampoos. After this enjoyable experience, they went to the pools that had varying temperatures. David could not withstand temperatures above 30 degrees, while Luis and Ho went for 40 degrees. When the bathing trials finished, it was time for the sauna or the Turkish rooms. David and Luis chose the sauna, while Ho entered only into the Turkish room and a quick cooling shower. After that process, the visitors found several stretchers in which a group of Chinese were lying down and having a bath massage with a big brush, soap, and water from a hose. The consulting group did not try that human wash system. After about one hour, the group donned a unique towel bathrobe set and met Olga, Dalila, and a Chinese girl from the laboratory who accompanied them. But the girls had another story to tell.

As foreign girls noticed, there was a big difference between the breast sizes of Westerners and Chinese women. Olga and Dalila, the same as the rest of the girls, were naked, but Chinese girls had not seen a naked Western woman before. They were surprised to see much bigger breasts than theirs and were trying to get a close look at Olga’s and Dalila’s chests. They were not shy and called other girls to take a look. Olga and Dalila did not know what to do; they were embarrassed by the occurrence. Fortunately, the awkward event ended quickly, and they could continue bathing. For Olga and Dalila, the whole bathing scene was highly distressful. They had never experienced this body exposure or bathing place; however, they survived the encounter.

After the baths, the consultants and the Chinese escorts geared toward the body massages. David preferred full-body Chinese massage, while the remaining group chose other Asian massages. For David, it was an exciting experience. In one type of treat, after massaging the lower part of the body, the bargain arrived at the neck. For this massage, David lay face down on a stretcher, and a very tiny and thin young girl crawled up on top of the stretcher and, without touching him and with her naked feet, softly but excellently applied a kneading massage on the neck. The massage not only relieved pain but also removed tension. David told his wife Dalila that he intended to capture and move that girl to their country to have continuous daily massages. The group very much enjoyed the whole-body bathing and massage treatment. They then headed to the fifth floor, where the restaurant was located, and the night finished with a Chinese-style pasta dinner.

It was again time for the consulting team to go back to Borazon City to analyze and evaluate their finished work and make plans for the next work trip. Mr. Ho would accompany Olga, Jesus, Dalila, and David to the capital city, so he booked airline tickets in plenty of time so they could catch the connecting flight to Europe. They arrived at the Shufen City airport and started checking the luggage. The attendant asked for the tickets, but Ho could not find them. He then remembered that while leaving the hotel, he had rushed to the exit and left them on the hotel counter. He quickly phoned the driver, who was already returning to the city, and asked him to rush to the hotel and locate the tickets for them. At that time, there was no electronic ticket; only printed forms were accepted.

The driver sped as much as possible, but the round trip took 1 1/2 hours. So by the time he arrived with the tickets and the group was checked in at the airline counter, the airplane doors were already closed. They missed that flight, and the next flight was scheduled for another hour and a half. They patiently waited, but 30 minutes later, it was announced that the next flight had been canceled, so they would have to wait for another 45 minutes. After the long wait, the four boarded another plane to the capital city.

The time was getting too close to get on the connecting flight to the capital. However, as soon as they arrived at the city capital, the group picked up the luggage and started to run to the gate where the flight for Europe would depart. People were in attendance when they arrived at the counter, but the airplane had yet to leave. Unfortunately, the girl at the counter told them that the immigration officials were gone, and without their approval, the group could not get on the plane. However, the girl said the group was lucky. The following day, there was another flight to Europe, and she then made the necessary reservations. They had to go back to the city center and get a hotel, but Olga was profoundly discouraged, and she began to cry, thinking about her two children, whom she had not seen for over a month and a half. Kids would be waiting at Borazon City airport, a heartbreaking scene. Ho helped the group get accommodations at a decent hotel close to the airport, and the following day, they were exceptionally early to the check-in at the airport.

Photos

Cell culture-preparation of Master cell Bank

1.

Cell culture-preparation of Master cell Bank

Vero cell daily tally

2.

Vero cell daily tally

Multiplying phase of Vero cells under a microscope

3.

Multiplying phase of Vero cells under a microscope

Industrial design stainless-steel media vessels

4.

Industrial design stainless-steel media vessels

Good manufacturing practices - Lab design

5.

Good manufacturing practices - Lab design

Cell and virus culture bioreactors

6.

Cell and virus culture bioreactors

Training vaccine production methodology

7.

Training vaccine production methodology

Handling live virus under ultra-high security

8.

Handling live virus under ultra-high security

Sterile air laminar-flow hoods

9.

Sterile air laminar-flow hoods

Safety sterile garments

10.

Safety sterile garments

Chapter Ten

2003-2004

A Mysterious Stain

One month after the group returned to Borazon City, an urgent call was received from Shufen City. Mr. Su, the fellow in charge of the project there, asked for help solving a mystery they had inside one of the bioreactors. During the cell culture, a black stain appeared in a spotty form inside the cell culture media. They had taken samples of the cells, and they seemed to be in a stable position. They should have grown more, but Su could not find out where the stain was coming from. The Chinese fellows reviewed all the chemical components in the media and found everything suitable. David’s first reaction was complete astonishment.

The presence of a stain inside a working bioreactor was the first time David had heard of something like this happening. He sent an e-mail message asking Su to stop the cell culture, remove everything, thoroughly clean the inside of the bioreactor, and start another culture with fresh new media. Su started another cell culture, following David’s recommendations. However, three weeks later, another call from Su. The black stains appeared again in the media inside the bioreactor. The mysterious stain did not appear in other bioreactors that they used with the exact cell culture origin.

This time, David asked Su to stop the culture and wait for the consultants. The consultants and David were getting ready for another work visit elsewhere, but they got plane tickets and headed toward Shufen City. Su and his group were eager to know what the technicians from Newvac Inc. could do, as the Chinese had not been able to find the source of the black stain. David asked Su and his group for an exhaustive explanation. It was essential to know how they prepared the culture media and assembled and handled the bioreactor for the cell cultures.

After receiving the information, Su, David, and Jesus discussed what to do next, and they finally decided that the bioreactor had to be disassembled completely. Jesus took over the job, and after three hours, he found out what had happened. The stirring shaft of the bioreactor had a magnetic ring, and it rubbed against the stainless-steel cover. The friction produced filings, a fine black powder falling inside the vessel and into the culture media. Jesus arranged the positioning of the magnetic ring, and the rubbing disappeared. The mystery stain was solved. Cell and virus cultures inside that bioreactor would go on as usual, thanks to an experienced technician.

For the next phase, the consultants’ goal was to design experiments to ensure that the cell system they had followed could be standardized and repeated to develop an SOP. This was only the beginning; later, they had to do the same for the virus cultures and the downstream processes of the final product’s clarification, concentration, purification, formulation, filling, and quality control. The most critical was the purification process, considering what Mr. Hui, the local scientist, had also predicted: purifying the vaccine was impossible using the technology that David had claimed to them. Hui said aloud that he had used a similar technology without successfully purifying the vaccine by removing all residual Vero-cell DNA in the final formulation. Those meticulous tests were the most challenging obstacle for the Newvac Inc. team.

The Newvac Inc. team made new plans and started other work trips to Shufen City to standardize cell and virus cultures. At least four visits were completed during the following year. After every visit, the consultants left some assignments for the Chinese. Several unexpected successes marked the project history of this year. The most outstanding was an accident in the laboratory’s washing area, where the glassware and equipment were cleaned and sterilized. The operator in charge of the autoclave, the equipment for sterilizing glassware and other materials, did not follow the usual procedure of manually letting steam pressure entirely out of the autoclave vessel before opening it. Instead, the operator forcibly and suddenly opened the equipment’s door, and, of course, the steam exploded out of the container. The explosion broke glassware, sending pieces of glass all through the air. Portions of glass landed on the operator’s face, producing multiple wounds and bloody scratches. He was taken to the hospital, where the scars were handled, but he could not work for the following two weeks. The skin injuries finally healed over time. This old-fashioned equipment should not have been in operation at the time.

As was common practice in industrial companies around the globe, when an accident occurred, a written report had to be prepared and sent to the safety officer and the general manager for evaluation and consideration of the measures to be taken so that a similar accident would not happen again. In this case, a report was never written. Nobody knew that the report had to be prepared, much less how to prepare it. Consequently, David had to write the report with the recommendation to dispose of the old sterilizing equipment that lacked adequate safety mechanisms and buy a modern apparatus equipped with complete safety features.

The laboratory accident allowed David and the consultants to get in closer contact with the operators. A few days later, they asked to visit the fellow severely hurt in the accident to encourage him. The Chinese culture probably did not understand that gesture. The professionals, much less the directorate and administrators, had yet to visit the ailing fellow. The consulting group was taken to a barrack, a large room of eight-by-eight meters. Along the walls were at least two rows of bunk beds. This was where a good number of male operators, maintenance specialists, cleaners, and laboratory assistants slept. The sick man was sitting in his bed with nobody to assist him; he was full of bandages and concealed. The group also noticed that the floor was bare dirt and that there was only one toilet and washroom for the room’s capacity of at least fourteen people. The fellow was pleased to see David and the group and assured them he was recovering. After the episode, renewed steps were taken regarding personnel safety, and heightened security processes were established.

As a result of this accident, David started to ask Mr. Ho, the most amicable friend he had in China, about the significance of preserving life within the Chinese culture. He wanted to understand how they, as a community, regarded life in general. Mr. Ho used examples of previous events to visualize some of the mysteries behind the significance of life in Chinese culture. For Ho, an accident involving a group of road workers was one of the most striking to analyze. A giant mechanically operated machine occupied the road, and several crew members were closely supervising the operation. By accident, one crew member suddenly fell into a massive hole in front of the mammoth device, but the rest of the workers did not immediately notice. As a result, the machine completely went over the worker’s body, crushing it and covering the entire body with cement. The rolling machine operator did not realize what had happened, and nobody else told him to stop afterward. The crew continued their work as if nothing had occurred, because the work had to be finished first, even though a soul had been lost. David said that this is probably explained by this ancient culture’s lack of religious beliefs, as a very high percentage of the Chinese population were atheists. For them, it was just a lost body—nothing else.

Returning to the laboratory work, it became evident that culturing the rabies virus needed not only the same three musketeers but also other high-level technicians or professionals who knew how to process the harvest of the virus and how to purify and formulate the prototype vaccine. So Luis, the biochemist, was called. Luis had many years of experience handling all downstream procedures for several vaccines at Totem Inc. He had been involved in the initial development of the rabies vaccine at that company. As previously mentioned, he had indicated his interest in working with the team, and he was granted a leave of absence from his research group in the city of Borazon to go to China whenever required.

Occasionally, the work at the pilot plant was uneasy for the consultants. However, the most challenging portion of the situation was related to lunch at the pilot plant. Just outside the main building, in an old rundown shelter, there was a dining area, a kitchen in an open space, and a large room. Food was always old-fashioned Chinese with multiple vegetables, soups, and something similar to bread but without exceptional taste. Seeing that the group ate very little, the cook ordered and frequently served some Chinese red wine, the “Great Wall” trademark. The group never complained, considering they had breakfast and dinner at the hotel with more agreeable Western-type food.

After this work trip and returning to Borazon City, David received a call from a well-known rabies scientist, Donald, in charge of quality control at a health science institute in a developed country. Donald had previously assisted Totem Inc. quality assurance personnel in standardizing the potency test of the rabies vaccine at Borazon City. Donald asked David if he would be willing to assist a small country in Asia with a technology transfer project to prepare the rabies vaccine. Donald had told the requesting company that David was the only one with a complete technological package for the industrial rabies vaccine with the new cell culture systems. Donald could only assist them with processes related to the virus, but he was not associated with scale-up industrial cells and viral production or even vaccine purification.

David was pleased to accommodate the request and contacted the interested party. After several weeks of virtual communications, the interested company revealed that it did not have all the resources. As it finally turned out, the technician wanted to know if it was possible for the foundation to fund the vaccine technology transfer project. David was quick to let him know that it was impossible, as the transfer would require a long-term commitment to work in situ in the vaccine factory, and that someone would need to cover those expenses plus the compensation for the technical know-how. A heartbroken intent of another technology transfer program had failed. It was not clear if due to lack of funds or lack of political will.

Confirming the need for vaccine technology for many institutions and countries on the verge of development, David remembered another similar situation. Roger, the university scientist instrumental in developing adequate tissue culture media for the high-density and perfusion cultivation of cells, received a call. This time, a well-known rabies vaccine company in a developing country asked Roger to assist them in changing the production technology from the growth of cells in bottles to the bioreactor high-density and perfusion technology. Roger was a cell scientist, but unfortunately, he had no experience in scale-up industrial biotechnology. He could only encourage the vaccine production company to talk to David, who, according to Roger, had a complete package to do just that.

When David received the call from the interested company, he imagined all previous failing circumstances, since he and the company’s executives had had many virtual conversations and discussions on conducting a technological transfer project. The body of directors of the interested party finally told David that they did not have enough resources to cover the production facility’s setup and the technical know-how and direction of the vaccine technology transfer. They wanted to know if the foundation would be willing to assist, so David explained that it could not assist commercial enterprises. Furthermore, the technology had to be developed inside the facilities. Again, someone would need to finance the project. David had never heard again from these people. This event was another intended vaccine technology transfer failure.

The transferor and recipient teams continued validating and certifying the cell and rabies virus banks. Once all banks were certified, cell seed cultures were initiated in glass flasks, and cell growth was transferred to the bioreactor after a week. When cell growth inside the bioreactor steadily reached twelve million cells per cubic centimeter, one of the landmarks of the technology, the virus seed was inoculated onto larger bioreactors, and virus growth was followed and supervised for the following twenty days in semi-continuous culture; another technology landmark. Samples for internal quality control of the virus grade and quantity were continually analyzed and supervised by the team to determine their suitability for continuing the downstream process of the vaccine.

The consultants and local professionals engaged in activities other than work. Sometimes, after lunch, consultants interested in table tennis went to the roof of the building to play against the Chinese group. It was a no-brainer; the Chinese always beat the consultants, but they got along well. Those times of relaxation and get-together helped ease some of their differences. It was exciting to see that production processes and in-process quality control of the vaccine were carried out in collaboration between foreign consultants, local technicians, and professionals of Yawen Inc. This whole process was smooth but not without some natural obstacles and accidents. After all, the consultants were advisers, not the real leaders of the technology recipients.

One day, Dalila, David’s wife, was in the office adjacent to a corridor outside the pilot plant. She walked out of the room and came across a technician carrying a small set of glass tubes inside a receptacle without any cover. With curiosity, she asked the fellow what was inside the tubes, and the answer was that he was transferring the samples to the quality control laboratory. Dalila asked if those samples had an inactivated rabies virus. The terrifying answer was that they contained a live virus for viral quantification, and Dalila almost fainted. She had not been vaccinated against rabies, since she would not work inside the pilot plant laboratory. She had always remained in the office area. This time, she was at a significant risk of virus exposure. After this situation, samples of live viruses that had to be taken out of the laboratory for any QC tests were transferred only in special safety containers and outside regular office working hours. This situation was a warning for the consultants, considering that sometimes the Chinese group was not worried about contamination or virus exposure.

On another occasion, the consultants had to show the janitors how to disinfect and clean all areas, tables, walls, furniture, and even the floor inside the pilot plant. They were just not used to keeping such a neatly clean environment. The primary purpose of some extreme measures was twofold. First, the idea was to prevent contamination of any bacteria that could enter any in-process material and destroy the harvest. Even if contamination was not detected during the process, it could have ended up in the final product. This could even affect the health of any person vaccinated with the contaminated product. Second, extreme measures had to be taken to prevent the escape of the live virus from any container. If an accident occurred and a virus escaped a vessel, it had to be destroyed before contacting the operators and technicians inside the pilot plant. A complete protocol for disinfection and cleaning all elements and areas was written, explained, and adopted in the production and quality control processes inside and outside the pilot plant. The recipient group was not too keen to follow some of those guidelines, but the consultants always insisted on tight security and safety.

On another occasion, the consultants arrived at Yawen Inc. laboratories and found a broken pH or acidity measuring device sensor. David started questioning the man in charge of the laboratory, who claimed he did not know what had happened. All technicians in the laboratory were also asked. Unfortunately, no one had the faintest idea of how the sensor had broken. David and the consultants later learned that it was complicated for Chinese culture to accept any fault or shame in public. The sensor had to be replaced, but the accident was never reported. David told this observation of a friend working as a quality control officer at a Chinese car manufacturing company. David’s friend described a similar situation in his company. This same pattern of conduct was found on many occasions inside China.

David and the consultants were always cautious about ensuring the Chinese counterpart technicians learned every step in the production process and had meetings to discuss every minute detail that made up the technology’s success. Some of those meetings were sometimes accompanied by one of the senior administrative officers, “Mr. Garlic.” This officer happened to have a notorious scent of garlic, and when the group was in a meeting, and the door suddenly opened to let him in, the air would become filled with a noxious smell of garlic. Most of the time, somebody would covertly exclaim, “Mr. Garlic has arrived.” With time, everyone probably got used to the aroma, and later, the officer came to the meetings without anyone noticing his presence.

The consultants enjoyed commenting on the everyday use of garlic in Chinese food, particularly during informal gatherings with Chinese technicians from the laboratory. Olga was amazed that the Chinese ate complete pieces of garlic directly from a dish, as people in Western countries ate bits of nuts. She also discussed why some Chinese had an intense smell of garlic, while others did not. The Chinese group explained that not all Chinese used too much garlic. It was more common in the north of the country, and only a few would eat everything with that bulb. They added that most people were used to that strong smell, so nobody noticed it except foreigners.

Similarly, the Chinese once commented that the visitors had a mild smell of another component. The consultants yelled, “What smell?” The Chinese laughed. “You didn’t know that you have a scent of milk?” The consultants were astonished; nobody had even suggested that some Westerners had a typical recognizable smell. The Chinese group added that this was probably because most Chinese did not drink milk at all. Hence, they could easily recognize that smell as foreign. This was another typical difference between distinct cultures. Now, the visitors had something to discuss and make fun of back home.

Regarding the potency of vaccines, the consultants, David’s company, and the vaccine community were constantly under scrutiny, and health laboratories were even criticized for not using other safety tests that would not involve living laboratory animals. In this case, the mice were inoculated with the supposedly inactivated product for the inactivation test, and if they survived, the product was safe. However, if the inactivation system failed for any reason, the animals would die of acute rabies disease. For many years, associations for preserving animal welfare have argued against this laboratory procedure. Until science develope a complete, secure, in vitro system for many quality controls, laboratories could not risk humans using any vaccine without safety controls. Therefore, many animal tests are used to test vaccines, and only in dreams could these safety tests be conducted on human beings.

This latter fact indicates some of the flaws of the worldwide appropriation of research funds, with limited participation in research on the preservation and care of a wide array of animals that continue to be exposed to many life-threatening experimental procedures and quality control tests. Regarding animal welfare, the situation in China was somewhat worse than in Western countries. A significant issue concerning this animal welfare was handling the laboratory mouse colony. Even though some of the buildings were uniquely designed to house the mice in this case, the operation and procedures used to manipulate the animals were sub-standard. The inoculation of the mice with samples that contained live viruses was very crudely conducted with great speed and hence with little concern about the animal well-being and safety of the personnel performing the injections.

After a vaccine virus has been confirmed non-infective through animal tests, the next step is the purification procedure to remove any undesired residues from the vaccine bulk. The process includes removing residual cell DNA from the harvest where the virus has been grown and quantifying the protein content. To remove non-essential materials from the virus harvest, the product has to be subjected to passage through some chemicals inside large glass columns in a process called column chromatography. The purification procedure also requires the removal of fetal bovine serum (FBS) residues. This product has been utilized to assist cell growth all over the world.

Prior to the removal of FBS residue from the rabies vaccine samples made by the Chinese, another incident occurred. On a summer day after work in the pilot laboratory, Jesus decided to walk not too far from the hotel to do some sightseeing, and, without noticing, he got completely lost. He was examining the constructions of the few buildings and did not notice that he did not remember the way back to the hotel. The rest of the consulting group was unaware of what was happening; however, after four hours, they became concerned, noticing the absence of Jesus. They immediately contacted the hotel safety officer, and he, in turn, contacted the Shufen City police. In a few minutes, two police officers went looking for Jesus and, after three hours, came back with him. He was overwhelmed by the situation, considering that he was on the streets of an unknown city without the local language, with signs unable to understand, and did not remember the hotel’s name. The officers told David he was just a short distance from the hotel but needed to know how to go. It was relatively easy for the police officers to locate Jesus. However, another lesson was learned.

Chapter Eleven

2003-2004

Bulk Residues

Work continued in the laboratory, and consultants finally gathered the first virus bulk material. It was subjected to fine filtration through some ordinary filters and continuous passage through the column chromatography for eight hours. The supposedly clean product had to be sampled and analyzed to remove FBS residue. As previously mentioned, this protein is utilized as a cell growth promoter. The results had to be compared with government requirements. The Chinese government had already approved, standardized, and included an old-fashioned test (HI test) in Chinese pharmacopeia to determine the FBS residue in all vaccines that included some animal components in the vaccine manufacture. There was no option; consultants had to rely on this test for this determination, even though they knew this type of test had many flaws, including producing false positives. The FBS residue had to be removed from the vaccine to prevent secondary or allergic reactions in the patients who received the vaccine.

A bulk harvest purified and consequently completely cleaned of residues was subjected to an old-fashioned hemagglutination (HI) test following the government’s specific procedures. The results came out, and to everyone’s surprise, one of the samples of the newly purified rabies virus bulk did not comply with government standards. The product had a large amount of FBS residue. David almost fainted when he received the results. It was impossible; thousands of previous analyses of vaccine bulk with similar final product manufacturing technology in Borazon had always been within accepted limits, much lower than these results.

Sometime later, David emphasized to the consulting group that this test needed some red blood cells, which were utilized as an indicator of the degree of presence of FBS residue. The red blood cells used in the test were of avian origin. Chicken blood with a particular anticoagulant was used as an indicator of the test. David had to explain the variability of each batch of red blood cells to his Chinese counterparts. They had to consider the intermediaries involved in raising the chickens, collecting the blood, and handling blood containers to prepare red blood cells that indicated the presence and quantity of FBS residue. Considerable variations in the type, sensitivity, and quality of red blood cells could be responsible for the overall and probably nonspecific results of such tests.

After two months at Borazon City, reexamining everything related to the HI test, the consultants returned to China. This time, they wanted to check the origin of the blood and chickens used for bleeding samples for the test. David and the group, with a Chinese interpreter and full of courage, took a trip to a small farm where the blood donor chickens were raised. The farmers greeted them with considerable disposition and complacency and showed them everything. The group examined the feed, water, buildings, and animals. The chickens appeared to be healthy, and the animal husbandry seemed to follow the common principles of sanitation, nutrition, and management of chicken flocks. Only one unusual finding was related to the animal handlers. The principal fellow in charge of feeding and caring for the chickens had his living space in a corner inside the open chicken shed where he was sleeping. The consultants were shocked to see that, but they did not find why that should affect the behavior or health status of the chickens.

Back at the hotel, David discussed the finding of the chicken handler living inside the open shed where the chickens were being raised with the group. The proximity and cohabitation between the animal handler and the chickens allowed for the easy transmission of microorganisms from animals to humans. This constitutes part of the zoonotic cycle of viral and bacterial infections that spread east to west. The most common is the influenza virus, which causes infection cycles in chickens and then spreads to humans, creating epidemic cycles worldwide. At that time, other viruses classified as coronavirus affected some human populations in China but did not spread entirely worldwide.

David described a well-known viral coronavirus zoonotic disease in China in 2002. The disease was called “SARS,” a severe acute respiratory syndrome, and the causative organism is a virus belonging to the Coronaviridae family, which includes many viruses that cause the common cold. The virus is thought to pass from animals to humans through close contact. Another coronavirus from the Coronaviridae family also appeared in Saudi Arabia in 2012 and spread through several Middle Eastern countries. The disease was called “MERS” or Middle East respiratory syndrome. The virus is transmitted from infected dromedary camels to humans. These last two novel viruses seemed to be associated with milder human infections but did not spread worldwide; hence, they did not become pandemics. However, some epidemiologists at that time warned of the possibility that the viruses of this group, coming from animal carriers from China, could cause a large epidemic or pandemic—a prediction of the pandemic that was happening at the time of writing this book.

The medical science worldwide needs to pay more attention to the in-depth study of so-called zoonotic diseases, which are transmitted from animals to humans. According to David, scientists believe that there are close to two hundred zoonotic diseases. Zoonotic diseases are transmitted by bacteria, viruses, parasites, and even non-conventional agents. David also noted that many zoonotic diseases have caused innumerable damage to the health status of populations worldwide. Zoonotic diseases include yellow fever, Japanese encephalitis, Ebola, monkeypox, brucellosis, salmonellosis, tuberculosis, bubonic plague, dengue, and toxoplasmosis. They have significantly affected the well-being of the world’s human populations.

The projects described in this book contain information on the rabies vaccine, which is designed to control rabies, a zoonotic disease transmitted to humans from rabid animals that also suffer from the illness. In several countries of the Americas, rabies is also transmitted to humans from vampire bats. In tropical rabies-endemic areas, people have to sleep in beds covered with mosquito nets, preventing them from the bites of rabies-infected blood-sucking bats.

Recently, increasing attention has been paid to Zoonosis, probably due to the appearance of the COVID-19 virus. However, some developing countries have proclaimed zoonosis to be the most critical health threat to the well-being of their populations, predicting that the most significant will be viral zoonotic diseases. Consequently, special measures are being taken to develop special task forces to study the most crucial control procedures for their prevention and control. This is a significant step in raising awareness of the next pandemic.

Returning to the laboratories for the development project to develop a rabies vaccine for human use, the Chinese recipients met with the consulting group without any significant comment on the chicken farm situation. David was disconcerted but soon found out the reason for the lack of interest on the part of the Chinese to find out what had happened at the chicken farm. The general manager, Mr. Cong, greeted the group and told them that he had excellent news. The Chinese central government health department, which examined the situation of human rabies disease in the country and the statistics from previous years, revealed a notorious increase in the number of people bitten by rabid dogs and consequently in need of the vaccine. After this comment, the director added, “The business is getting better; we must hurry up with our vaccine.” The group was muted; nobody would dare make any comments. Business proclaimed ahead of a lifesaving vaccine. This comment by the local boss never stopped echoing in David’s mind.

The fact that the Chinese saw the manufacture of vaccines as a business was nothing new in other world corners. Pharmaceutical giants of developed nations have the same notion and even worse: their selling price of vaccines are at shocking profits. David was again thinking that the cost of vaccines was exceptionally high in developing nations, and it continued to be unaffordable for populations living in developing areas of the world. The vast differences in acquisition capacity between these two completely different worlds make it even harder for governments to encounter enough tools to combat infectious diseases, epidemics, and pandemics. Many countries have been drained out of funds and diverted from other needs, trying to control the effect of the recent pandemic with imported vaccines. This, again, represents another dependence and exploitation worldwide for countries in need.

The search had to go on, and the consultants had to find another way to uncover the cause of the issue with the FBS residue in the quality control process of the product. They had already carefully examined the technology for growing the cells, the virus, and the concentration and purification processes. “Well, let’s give it another opportunity,” said David. The project could not afford to be terminated due to a non-conformity with an old quality test that the consultants were unfamiliar with. By this time, all of Yawen Inc.’s personnel, from the front desk, principal entrance gate, clerks, cleaners, supervisors, maintenance crew, etc., up to the board of directors from the main headquarters in a distant city, were now aware of the drawback: the failure of the new vaccine to pass an FBS residue test.

If the matter was not solved, the trip may be the last to Shufen City for the consultants. David also hired a quality control expert, a woman with considerable experience in this test, to go with the group to Shufen City. However, she did not speak fluent English, so the Chinese had to hire a Mandarin translator for her. The translator was a Chinese man in his late fifties who had worked in a Spanish-speaking country for ten years and spoke fluent Spanish, Portuguese, and Mandarin. Four weeks passed, and the translator worked every day with the lady in the laboratory. The work was progressing, and the translator did a terrific job for the quality control lady and the consultants.

One day, the translator asked if David could talk to Yawen Inc. manager and ask him to order payment for his translation work. He was concerned that if the group left the country before he received payment for his service, he might never be paid. David did as ask, and the interpreter got paid ahead of the group departing from China. The Chinese are well-known for being tight-fisted in commercial activities, but the group did not realize that they also do that to each other. David had to be prepared for “business as usual”, difficult payments.

David, his consulting team, the local technicians, and the professionals were geared up and prepared everything for several new cell culture systems. The process took two long months, with David clocking close to eighteen hours a day, reviewing every movement and step in the coming events. The new growth and purified virus samples were taken and sent to the quality control laboratory for analysis using the same HI test. It was a day of suspense; everyone was in complete expectation and hoping the FBS residue would not be found this time. The results came in, and to the horror of everyone, it was the same: the vaccine sample did not pass the test. Was there too much FBS residue? The Chinese were skeptical that the consultants would be able to solve the problem, since they had bought and tested other old local commercial rabies vaccines, and all those had passed the test-level requirements. Some of the technicians had started acting like the project would soon be terminated.

Everyone had become more familiar than ever with the magical phrase “FBS residue.” They knew of the peril of the new project for the company to enter into the field of biologics but expected to find something other than this. Prior to this, they only dealt with equipment, international exports, and high-tech stainless-steel manufacturing. During this ordeal, David and the group commuted daily between the hotel and the laboratory. One cold winter day, David and his wife, Dalila, were riding in the back seat of a car on their way to the laboratory. Every three of four blocks, the driver would open his window, stick out his head, and spit. Some of the saliva landed in the back seat on David’s and his wife’s faces, who tried unsuccessfully to dodge the assault. The driver could not understand English or realize what was happening.

When he got to the laboratory, David asked his friend, Mr. Ho, to speak to the driver and plead with him not to spit while driving. Mr. Ho gladly talked to the driver and reported back that the driver had understood and promised the incident would not happen again. The following day, the same driver picked up David and Dalila, and to their surprise, he was spitting again. He even drove much slower than before. At the office, David found Ho and exclaimed, “The driver is still spitting, and today, he drove extremely slow.” Mr. Ho answered, “Sorry, yesterday I thought you said he was speeding, so I told him to slow down.” Such an incident is common when the native language of interlocutors is not English.

At that time, spitting on the streets in public was a common practice among many people, both men and women. The habit was common in large Chinese cities, especially in the northern territories, where there are extreme changes in temperature from freezing winters to hot summers. In large plazas, the pavement appeared full of black dots, and no one knew their origins. Suddenly, at the beginning of the spring of 2007, numerous working crews appeared on the streets and public squares armored with large bars scraping the pavement’s surface and removing the infamous black dots. After that, a government regulation was enacted prohibiting the habit of spitting in public places, and anyone found spitting on the streets would be heavily penalized. This was because of the 2008 Olympic Games. The government wanted to remove the old-fashioned custom of spitting on the streets before receiving guests into the country. David and his team finally learned firsthand about the origin of the black dots. Since then, people have rarely been seen spitting in public. Another common cultural practice was removed for the sake of modernity.

The project had to continue, and for the third time that season, David and the consulting group returned to Shufen City to solve the mystery of the FBS residue. However, this time, they had the most unusual proposal: they would design a new testing system to detect FBS residue. They had the feeling or instinct that something was wrong with the test and it was not behaving like usual with the new vaccine product. The Chinese became wholly disturbed; they needed to understand how David and his group would find another test to solve the problem. Moreover, the HI test was the official government test; hence, it could not be modified. Nevertheless, the Chinese decided to put aside their concerns and wait for the results.

David, Olga, and Jesus prepared another set of cell and viral cultures. They had been working at home in Borazon City, designing a new experiment with entirely new modern reagents. The reagents were ordered before they arrived, and they earnestly began to set up the new test. They had based the design on the assumption that the government-approved HI test was old-fashioned and needed improvement. They were presumptuous to challenge the Chinese government’s pharmacopeia. Two weeks of analysis followed; David and the group had some results. Eureka! The vaccine samples in the new test, with standard positive and negative controls, completely surpassed the accepted government levels for removing FBS residue.

The Chinese could not believe it. So they took other samples from other cultures and other vaccines, and they ran the test with all controls; indeed, all materials did pass the test. The product and project had ingredients that could be formulated for a new vaccine. However, the challenging next step was to convince the government that the new test was more straightforward and reliable for measuring FBS residue content. Mr. Su, the general manager, now had to ask some government agency members approving biologics to come to Yawen Inc. laboratories and observe the efficiency of the new technique. A considerable advantage of the new test was that there was no need for animal components. No chicken blood was needed for the tests.

David and the consultants explained every step of the analysis of the new test and the issue with the old HI test. The new rabies virus manufacturing technology produced copious amounts of virus protein, and this significant content of virus protein was interpreted by the old technique as a large amount of FBS. In other words, due to interference, the old test reported viral proteins as FBS proteins. The findings were explained and proven to government officials over four long weeks, and the new analysis system was finally accepted. It was later learned that the government adopted this new test, an enzyme test, as a standard for analyzing FBS residue for all Chinese vaccines for human use. Once again, after so many hurdles and such a long time, it appeared that the project would finally succeed. Let’s wait and see.

Some days later, David and Dalila arrived at the hotel and took an elevator. A man was already inside the elevator, and as soon as he heard Dalila speaking, he introduced himself, speaking the same language as the couple. He introduced himself as Juan and said that he worked at an automobile assembly factory in the same city and was registered at the same hotel. The three were pleased and planned to meet again to exchange experiences about living conditions in China. David, Dalila, Olga, and Jesus met again two days later with Juan, who told the group that he was the quality control manager of the assembly plant. He had only been there for the last three months and later was expecting to bring his wife and a six-year-old daughter.

A week later, David and the consultants met again with Juan, and David told Juan about some difficulties in the work due to cultural differences with the Chinese. Juan replied that he had experienced so many obstacles at his workplace that he was ready to resign. As the quality control manager, he was responsible for the best condition for every automobile that came out of the assembly line. He had a group of his coworkers who should take a vehicle as soon as it came out of the assembly line to be transferred to a private garage and disassembled several pieces. Juan said that he always found abnormalities that had to be corrected. He expected some corrections after advising the chief engineer and telling him of the faulty parts. However, he would later find more cars with the same faulty elements as he did the previous week. To make things worse, those imperfections could have compromised the safety of the vehicles.

The meetings with Juan became more frequent, and the exchanges of experiences were more engaging. On another occasion, Juan told the group that one day he was meeting with the company’s general manager, who happened to be of German nationality, and with the head of the human relations office, a Chinese woman. The manager was furious with the woman about a huge mistake she had made, and he severely reprimanded her. The woman was quiet during the outburst. Suddenly, she put on a cheerful appearance and was almost laughing. Juan and the manager were astonished, thinking that she must have not cared about her boss’s outburst. The meeting finally ended, and everyone left the room. However, a few minutes later, Juan saw the Chinese woman weeping feverishly in the corner of a corridor. He concluded that most Chinese people would not show any emotions in public. Many of them cover up bad experiences. David and his team had encountered similar experiences in several places in China. This was characteristic of the Chinese’s cultural upbringing.

At the laboratory, the mystery of the FBS residue was solved. The consulting group was now concentrating on another complex challenge: removing cell DNA residues. For this crucial step, the technology used by leading rabies virus experts worldwide was column chromatography. The procedure consisted of passing the inactivated virus harvest bulk through a mesh of chemicals inside glass columns to remove as much residual cell DNA as possible. It then had to comply with a standard low level previously determined by the governmental authorities. The equipment for the purification was ready, and the first inactivated virus bulk was also prepared and processed. The purified virus bulk was analyzed for the presence of cell DNA residue, which had to be sufficiently low to comply with government requirements.

To the surprise of the consulting team, the first analysis showed that the bulk had a large amount of residual cell DNA. David repeated the test. The group thought something must have gone wrong with the trial. The test was repeated, still resulting in high cell DNA residue. Another residue was found in the middle of a reliable process. The bulk vaccine for the formulation of the vaccine would not pass a test for residual cell DNA. Everyone was again astonished, and the consultants were completely surprised. It did not seem that the project would have a vaccine. This posed another obstacle to be surmounted.

By now, the Chinese had joined Mr. Hui, an experienced rabies Chinese expert, in his criticism of the project since the beginning of the new technology. He had claimed the technology was of no good and bound to fail. The consultants had no choice but to repeat the cultures and run several additional trials to test again on the bulk virus batch. DNA residue would be the worst nightmare for David and his consulting group. The consultants made various cell and virus cultures during two more visits, and the inactivated virus bulks were also filtered and subjected to column chromatography purification. The results were always the same; the final bulk material did not pass the DNA test residue analysis. This was complete chaos. The Chinese were mad, thinking they had invested a lot of money, effort, and time, and there would be no vaccine in the market and no business. David was again without sleep; failure was not an option under these circumstances. Something must be happening that interferes with the analysis or the results.

The consulting team had to return to Borazon City and review all the analyses and procedures to identify the causes of these issues. Before leaving China, Mr. Ho approached David in the hotel hallway and summoned him separately from the rest of the group. Ho told David that he had cheated them. He yelled at him, saying that the technology was no good and that Mr. Hui had always been right. There was no technology to remove the residual cell DNA, and possibly, there was not going to be a vaccine. David responded in defense and said something had to be wrong in the laboratory. The technology was right, and he would prove it. Mr. Ho said, “You better prove it. Otherwise, we are not going to pay you for the last work that has been done.” David felt very bad and humiliated, particularly because, at the time, Ho was the only real close acquaintance his consulting group had in China. He had been an excellent translator on many occasions and was becoming a good friend to the consultants.

Wholly frustrated and overwhelmed by the circumstances, the consulting group, with their heads down and little hope of finding a solution, returned to Borazon City. They met for many hours, day and night, for over 6 weeks, considering several hypotheses and studying in detail all reagents and how the locals were handling the tests. Finally, they decided again to challenge the test itself. They planned to return to China and modify another testing procedure. This time, the matter was more cumbersome since the government requirements did not specify any particular test but were only interested in vaccine samples adhering to conformity with a low standard DNA figure level.

During these events in Shufen City, two Asians from a commercial vaccine company contacted David. The company’s idea was to acquire new vaccine production technology, and it decided to ask David whether Yawen Inc. would accept a visit from two of its major investors. David contacted Mr. Cong, the general manager, to see if they would allow those people to visit and discuss the possibility of acquiring the technology. Mr. Cong, after expressing some doubts, finally accepted. However, he emphasized that the visiting fellows would not be getting any secrets. David contacted the visiting officials and set a date for him to meet.

A month later, the two Asian fellows and David arrived in Shufen City and were met at the airport by Shun, one of the vice presidents of Yawen Inc. After the hotel arrangements, the group headed toward the industrial manufacturing plant and gathered at the main conference room where Mr. Cong was waiting. The principal host described the company’s development history and the successful technology transfer they had obtained from Newvac Inc. and David. The visitors were interested in the size and scope of the facilities and the unique needs of the equipment and services needed. They also wanted to have an estimate of the total investment they had to make to build a factory identical to the one they saw from the outside. Before answering that question, the host asked the visitors whether they would like to tour the facilities, which they gladly accepted.

This was most unusual, considering that all manufacturing facilities in the world, independent of the product being produced, would only allow visitors inside their premises, cautious about the loss of some private technical know-how. The visitors received laboratory gowns and changed shoes for sterile covers, and they went to the surrounding corridors of the plant. From the corridors, the visitors could see through double glass windows from ceiling to floor, most production laboratories in total activity. They were fascinated to see such a view of clean, orderly, and colorful ambiance. In each area, the laboratory garment colors of the technicians matched the color of the floor, indicating stringent safety measures. This was David’s design and the corridor layout, which the visitors appreciated. However, the visitors perceived that many aspects could make the vaccine business a non-profitable enterprise.

The visitors asked many questions about their complete satisfaction. At the end of the visiting tour, Mr. Cong answered the visitors’ question formulated at the beginning, namely, that a similar rabies vaccine manufacturing plant would cost twenty million dollars. The visitors remained muted. The laboratory visit ended with disgruntled guests. At the hotel, Dalila and David met with the visitors at the bar to chat. The conversation centered first on the type of technology and the difficulty of replicating it. The visitors needed to understand that they could start on a small level and gradually expand to reach accurate industrial technology. Most people would start with a pilot plant facility to become acquainted with the technology and then expand or build a new facility. Initially, the visitors insisted that they wanted a full-size vaccine manufacturing plant in their country.

The visitors also insisted on the cost of building another factory similar to the one they had just seen. They were so impressed with what they saw that they believed the Chinese price was accurate. Dalila and David explained that the investment had to be made over time and that the facilities should be built in stages. They also let them know that the Chinese had exaggerated the cost in an attempt to discourage visitors from competing with their products. In effect, visitors gripped the Chinese bite.

Back at the hotel, for the second day in a row, the visitors wanted to have David’s and Dalila’s opinions about the information they had gathered. The visitors were utterly discouraged but wanted to return to their country with good news. On the contrary, they were carriers of bad news. They concluded that the investors who hired them did not have the money to build a factory at those astronomical figures. They went home empty-handed. This was another futile attempt to establish some competitors against Yawen Inc.

Meanwhile, new rabies virus batches were subjected to purification procedures with newly certified chemical reagents for the purification columns. New samples were taken with great expectations and tested by quality control, and at least three repetitions were completed with several harvests. The whole group chanted, Eureka! The specimens examined met the required level of residual cell DNA. After a curious search, the consultants found new chemical reagents that had been tested for use in the purification system. Modifying the old chemistry of the products utilized for the columns more efficiently removed the residual cellular DNA. Consequently, all tested viral batches were approved. Their DNA levels were below the accepted standard level. Once again, the project was on its way to success.

The next step was to achieve a vaccine that could be administered to human volunteers to measure its efficiency. One of the final components of the vaccine was the formulation of the final product. The purified virus, with highly minute quantities of both the FBS residue and the low level of cell DNA residue, had to be formulated by adding stabilizers to allow for the long preservation of the viral inactivated structure. Once the stabilizers were added, the viral formulation was subjected to a freeze-drying process. This highly sophisticated process would, under vacuum, completely dry the viral formulation. This dried tiny capsule inside a glass ampule was the final vaccine to be injected into a person to prevent rabies when reconstituted with a little half a milliliter of sterile physiological saline solution.

The stabilizers had to be entirely innocuous for human injections and simultaneously inert to the virus particles. The consultants had tried a chemical of Italian origin in Borazon City that had been utilized in formulating the rabies vaccine. They tried it with the purified vaccine at Shufen City, and the results were very encouraging. In essence, the product had to be dried but not burned. According to international recommendations, the humidity content of the final product had finally passed a residual moisture test. After several trials, the lyophilized vaccine was tested with the Italian formulation. The product eventually had to comply with potency, safety, and longevity tests. The vaccine lots were then submitted for these final tests.

Any vaccine must be submitted to potency tests. In other words, it has to sustain proven efficacy in preventing the disease. To achieve this, it must produce many antibodies or defenses against the disease for prolonged periods. In the case of the rabies vaccine, the potency of the vaccine is measured in very young suckling mice. This practice has been criticized by many research and health organizations as well as animal rights societies. However, all health government organizations worldwide have kept that same practice, even though some new laboratory tests could replace that repudiated test. There is no plausible explanation for this. The stakeholders think that since this practice has been around for at least one hundred years, it should be reasonably safe. They do not see the need to replace it. However, the test is highly variable, depending on the conditions and health status of the suckling mice, which is very difficult to ascertain in most cases.

Another consideration for not replacing the potency test with the rabies vaccine might be how the test was developed as a test. The first rabies vaccine developed in the world was produced by Pasteur around 1885. At that time, there was no test to prove its efficacy in treating humans infected by the bite of rabid dogs. Pasteur tested his vaccine by challenging himself with a live virus. He was extensively criticized for utilizing humans to finally test the vaccine’s efficacy, even though almost one hundred percent of persons bitten by rabid dogs without any vaccination would eventually die of the disease. When the suckling mouse potency test was developed, the whole scientific world celebrated a valid and safe criterion to define the actual potency of the rabies vaccine. This may be one of the reasons why no one would dare change it for another modern test.

Newvac Inc. consultants were ready to submit their product to the last stages to prove vaccine efficacy. The next step was to manufacture 3 continuous batches of the rabies vaccine, which had to be subjected to the remaining internal quality control tests, including the potency tests, and then submit them to official government channels for vaccine testing and final approval. If all analyses went as expected, the vaccine would be registered in 18 to 24 months, and industrial production could begin. David and the team were elated; finally, the project was becoming a success. The next step would be to scale up the processes for the industrial production of the vaccine, but such a task should be more manageable than all previous processes. The vaccine is not yet on the market.

The undertaking for registration approval involved the design of an industrial production factory for the scale-up process. This work could proceed while waiting for the government analysis and testing of the vaccine lots submitted to them. This design task could be divided into four major components: vaccine production laboratories, maintenance, and services, quality control laboratories, and animal housing buildings. Each area had unique needs and special safety requirements. David talks to Cong, the general manager, and starts explaining all the primary considerations that must be considered to arrive at a functional and safe industrial vaccine production company. Cong, the general manager, told David that he had already contacted a Chinese architect and would show him the draft of the vaccine production building he had made.

David was surprised. The locals acted so hurriedly that they had already ordered a preliminary design of the new industrial manufacturing building. David could not believe that the design of the most critical areas, the cultivation of cells, and the growth of a very pathogenic virus had been given to a professional architect, who probably had little knowledge of the vaccine production processes. The architect probably needed to understand the unique safety requirements to avoid the escape of the virus and to ensure the safety of the personnel working inside the premises.

Mr. Cong showed David several pages with drawings of the proposed building. David and Olga examined them carefully, and it only took half an hour to realize that the design needed several considerations for the flow of personnel, materials, and waste out of the areas. The most noticeable flaw was the communication of the corridors that separated the spaces, since the passages had many doors that communicated them and could allow a person to go from one area to the next without any control or, for security reasons, the need to change to special outfits. David told Mr. Cong that the design was unacceptable, and that he and Olga were ready to offer a design that would meet international regulations and laboratory safety requirements. Mr. Cong accepted the offer and asked them to expedite the process. The Chinese were more interested in speed than in safety.

It took two and a half months for David and Olga to develop a brand-new design incorporating specific flows for personnel, materials, products, and waste. The laboratory staff had to change their street clothes daily for clean and sterilized garments; such clothing had to be worn in different colors before entering each area to match the exact floor color of the area. This would ensure that technicians were always in the right location, all with the right apparel for the same area. There will be only one entrance and a separate exit to communicate one area with the next, and the materials can only be transferred between areas using pass-throughs with interlocking doors to avoid air passage from one area to the next. The area where the virus would be handled needed negative pressure to ensure that any accidental aerosol would not escape from the laboratory. In summary, the whole design would comply with safety recommendations from WHO.

When the quality control laboratories were designed, the turn was for animal colony housing. This separate building had to be designed to house the mice utilized for quantifying the virus and for the potency test of the vaccine. Once again, the building had to comply with international recommendations for personnel safety and animal welfare. Technicians had to handle mice inoculated with a very pathogenic virus. Consequently, the company needed to gain experience, so it did not try to make a draft design. Finally, they relied on consultants to create a building plan and specifications for the specialized equipment needed.

Chapter Twelve

2004-2005

A Slacken Working Team

For the consultants, the long days and weeks of working in a harsh environment had to be compensated for with some relaxation. One reasonably common distraction for them was walking to a nearby park and getting fresh air. In the park, they always found a group of Chinese doing several kinds of Tai Chi, the most common type of ancient meditative movement and exercise system. For the consultants, it was like an outdoor theatrical show, full of action, concentration, and color from a large group of people who barely knew each other, even though the participants acted as if they had been doing the synchronized movements for a long practice time.

It would be difficult for the consultants to follow the sophisticated movements, so they mainly enjoyed the magnificent art displayed. On many occasions, the consultants also found people of different ages embracing the trunks of old trees and staying there for long periods. According to some local sayings and expert views, it was like an exchange of energies that acted to liberate everyday stress. Some of the consultants tried it and enjoyed it.

The consultants also had to try more moving and exciting activities, so they bought a pair of badminton rackets to play in the park. The first two sessions worked well; however, the third practice session had some unexpected results. Olga probably made an extraneous movement and felt acute pain in her left ankle. She had to stop playing that day, and Luis replaced Olga and continued playing with David. A few minutes later, Luis also felt acute pain in her right leg and had to stop playing. David lost two contenders in a matter of a short time, and half an hour later, Olga could not walk due to intense pain in her ankle. They all went to the hospital taking a Chinese translator with them. After some diagnostic imaging, there was a terrible truth: ankle rupture. The remedy was the installation of a full splinter on the lower leg and the use of a wheelchair. For Luis, after a thorough analysis, only anti-inflammatory ointment and rest for 48 hours were used. The group concluded that for people who lacked the experience, badminton could result in some unwanted results.

For Olga, the episode did not stop there, either. Everyone had to return home five days later, and she needed permanent assistance. To complicate things, David had to visit another country for an interview and could not accompany Olga and Dalila back to Borazon City. The two ladies had to suffer a trip back with a European stopover with immigration, luggage pickup, taxi to the hotel, registration, and the way back to the airport the next day. All of these movements with Olga in a wheelchair, with luggage, and with carry-ons. They were completely exhausted when they finally arrived in Borazon City.

Sometimes, the consultants relaxed by visiting shopping malls for window shopping, even without buying anything. On other occasions, they visited typical souvenir shops to get memorabilia, since many relatives and friends back home wanted typical local handicrafts. Since Dalila continually asked for window shopping, some Chinese at the laboratory associated her with that feature. On a particular occasion, Luis arrived in Shufen City to work on the project, and a company driver picked him up at the airport. On the way back to the hotel, the driver, who was quite talkative, told Luis that Dalila was in the hospital with some sickness, most probably due to excessive shopping. As it turned out, Dalila was only at the hospital exchanging a prescription—another cute example of Chinese gossip.

Four months passed by, and construction of the main building started. It was astonishing to see how fast the build progressed; numerous builders and artisans ran around like ants in an organized colony. Soon, they finished the foundations, columns, and roof of a vast leveled floor, which was going to be the first floor of the building. Later, they finished the precast concrete walls and finished the service floor and the second floor. The third floor, built in the end, would be devoted to the administrative personnel’s offices. David marveled at the notion that everything was happening so fast. He also learned that the local municipal government had ceded a piece of land inside the scientific development area where the laboratory was being built.

The new company, Yawen Inc., could use the land free of rent for five years, with the intention that the new company would create many jobs for local technicians, professionals, and workers in all areas of occupation. Moreover, the provincial government also gave the company free energy and free central steam for the first three years, and after this period, all services were provided at low rates. The consultants now understood how China created companies, jobs, and markets, which explained the economy’s fast development and the benefits to the country’s populations. At this time in China, many provinces and cities fight to have a newly announced company make them its location. Each mayor and governor wanted more manufacturing companies on their soil to provide more jobs, business, and prosperity. Cities that offered more favorable conditions won companies to the benefit of their inhabitants.

The consultants and their local counterparts continued making vaccine batches to complete the technology standardization at the pilot plant. The new manufacturing building was also progressing. From time to time, David had to visit the construction site to ensure that the project was in accordance with the design. Special attention had to be given to finishing tables, walls, floors, and safety arrangements. Furnishing the laboratories was another issue for which the Chinese relied on David and the consultants to advise on the best machinery, equipment, and reliable manufacturing companies. Suppliers were required to have a fabrication guarantee, distribution center, and service personnel within the country. The whole process was very pleasing for the consultants, and once they found the most modern piece of equipment anywhere in the world, the Chinese ordered it without needing to bid or follow similar procedures. The new vaccine manufacturing buildings would be the most modern and efficient construct globally, so the Chinese and the consultants already felt very proud of the outcome.

Finishing all the construction and delivering all major equipment took at least one year. Eventually, consultants were ready to enter the new building and review and validate all small equipment, materials, reagents, cultivation media, and working cell and virus bank storage. The workers were involved in constructing laboratories for quality control and housing the animal colony for virus testing. The design of the quality control laboratories was relatively simple. Special care was given to transferring live virus samples from the production area to the quality control laboratory to prevent any spillage of virus-contaminated materials. Samples had to be contained in special packaging at shallow temperatures to preserve the materials accurately.

One day, David told everyone that he had been suffering from chronic neck pain for quite some time. When Mr. Cong, the general manager, heard of this, he immediately asked David to get ready because he would take him to highly specialized treatment. The next day, the official company car driver took David and Mr. Cong to a remote location in the city’s northern area. It was a very modest place with old housing projects and working people, each doing their own business. The streets were rugged and old. The car stopped at an old house, and Mr. Cong invited David to leave the car and enter the home, the door of which had been opened by a robust lady. Inside one of the large rooms, the group met a man, probably in his seventies, who appeared completely blind. The fellow asked Mr. Cong in Mandarin to tell David to remove the jacket and shirt and to recline down on a particular furniture or high bed for a relaxing massage.

The specialist washed his hands in a bucket and took some emulsified medicinal preparation, which he rubbed into David’s neck, and started giving him a highly sophisticated rubbing massage. It appeared to David that the blind man had seen exactly what he was doing. After about twenty minutes, the man asked David to make some minor neck movements, and with extreme skill, he applied some gentle and fervent muscle massages. The treatment finished in forty-five minutes, and David experienced a very relaxed and appeasing feeling. Mr. Cong paid the experienced man and did not tell David the cost of the treatment.

On their way to the hotel, David saw a small group of people in the middle of the road gathering around a man sitting at a chair with his mouth open and another man with an undetectable piece of metal utilized to extract a piece of denture that was probably completely deteriorated. This was a simple and cheap way to solve a painful dental sensation. The Chinese did not tell David what anesthesia the operator used to mitigate the extraction distress. The man in charge of the operation was very familiar with the procedure and was commonly required by patients in need who did not have any other option to solve their dental maladies. Such practices are very common in China. David was finally dropped off at the hotel with a great sensation of relief. He hoped this would be an experience he would repeat in the future.

The laboratory buildings were finished and completely furnished and ready to use. The Chinese were happy with the new factory and with many things to do, but it took a lot of work for several technicians to follow the rigid standards that the design required. Some special cubicles passed materials and reagents from one corridor to the next, and each pass-thru had double interlocking doors on both sides and glass windows. One day, a Chinese technician was found passing from one area to the next using the pass-thru only utilized for reagents and materials. He was in a hurry, so instead of changing his clothes, he asked another fellow on the other side to open the interlocking door so he could go through. Most of the operators learned the hard way to follow safety requirements. However, the entire safety system functioned to perfection.

While the new industrial laboratory was being completed, the 3 pilot vaccine lots certification process was underway at the government laboratories. Several months had gone by, and no news had been received from the official entity. Yawen’s Inc.’s general manager unsuccessfully tried to find out what was happening but to no avail. The government control laboratory would not give any hints. It was later known that they had already started a human vaccine trial with many volunteers. The results would take at least another 8 to 10 months.

Industrial vaccine production is not free from peculiar circumstances. In the laboratory, numerous quite severe instances could turn into humorous episodes. One day, a mature lady endowed with generous bosoms was working in the mice-breeding area, handling small laboratory mice and separating them by size and weight. She was only wearing a laboratory coat. With rapid movements, she moved one little mouse to another cage, and the mouse unexpectedly changed direction and landed in the middle of the lady’s bosom. She screamed loudly for help, but the people around them were all male, and none of them wanted to intervene. Instead, they started to laugh intensely. Finally, she begged one of them to do something, and he closed his eyes. Guided by the girl’s hand, he put his hand in the middle of her breasts in search of the tiny mouse. After some struggle for quite a long minute, the fellow eventually captured the mouse by the tail and placed it in the mouse cage. The onlookers applauded feverishly, but the lady felt completely embarrassed and mad at the audience. The group still remembered that entertaining event.

The vaccine development work continued. David and the group validated every piece of equipment that had already arrived at the new building. Later, news came from the embassy in China regarding Borazon City. The president of the country was visiting China for a round of negotiations between eighty business people from the foreign government and similar counterparts of economic organizations from China. David, Dalila, Olga, and Jesus were invited to attend a large gathering in a spacious hotel room. The visiting president, among other things, discussed the need to expand the relationships between the two countries and encouraged his country’s business visitors to offer their products to the Chinese commercialists present. At the end of his presentation, an export official from the country’s embassy in China told the audience and the visiting president that there was a freeman who, for several years, was already doing some business in China. The official asked David to stand up, and he received a large round of applause. He showed David as an example of successful cooperation between the two countries.

Back in the laboratory, the consulting group finalized the adaptation of all equipment and started the cell culture in the first bioreactor. The Chinese technicians were astonished to see spotless surfaces on the walls, floor, tables, and equipment. The first cell culture in the scale-up vessel differed from what was expected. One night, a Chinese technician was assigned to supervise the media flow inside the bioreactors to ensure that no beads were expelled from the vessels to the utilized media container. The following day, Jesus arrived to check on the bioreactors and found one bioreactor with only a few beads left inside the vessel. The group later found that the night shift technician had increased the flow speed of the entering media to high levels. The fellow did precisely the opposite of what he was supposed to do. Consequently, the culture was lost, and what was left had to be discarded. Fortunately, incidents resulting in such considerable economic losses rarely happened.

David and the consultants left some assignments for the Chinese technicians and returned home to Borazon City. They met several times with the whole consulting group, along with Luis, to start planning the downstream processes. With the newly adjusted SOPs for the new scale-up system, the consultants headed to Shufen City in China to finish the project. The only tasks they had this time were government approval of the new industrial complex of buildings and the new scale-up processes. During the next five weeks, and with the local technicians and professionals, David, Olga, Jesus, and Luis prepared several cell cultures inside the large bioreactors and carried out all downstream processes. By themselves, the local technicians were able to simultaneously finish several cultures all the way up to the final formulation of the vaccine.

By this time, Yawen’s Inc.’s general manager had received the results of the clinical trials. According to the governmental agency, everything was up to standards, such as the government inspection of the new facilities. Consequently, commercial vaccine production could begin. Eureka, once again, the project was a success! On the last day of the team at Shufen City, a good number of local technicians gathered at the entrance of the central laboratory, giving farewells to the visitors. There were some unhappy faces from a group of locals, but the consultants’ team left for Borazon City after complimenting the Chinese for a job well done.

Two weeks later, after returning home, David sent Cong a proforma invoice that covered the last phase of the project, which, according to the contract, consisted of paying approximately 20% of the total contract amount. Four weeks later, David received an e-mail arguing that Yawen Inc. could not pay that amount. Cong, the general manager, claimed that the latest results from quality control tests of the DNA content of the vaccine revealed that the product was not wholly purified. He argued that the DNA content was too high. David was puzzled. There was no mention of the actual figures of the analysis. David wrote a long letter explaining how the consulting team had worked so hard for many months to solve the difficulty of removing the DNA and how the latest results, before leaving Shufen City, had been so definitely adequate. He clarified that the DNA residue had been solved way earlier when the team had prepared the pilot vaccine lots that the government agency approved. The three lots had already been subjected to all tests, including the DNA test, and the government had already approved the vaccine.

Three weeks later, David received a letter from Cong insisting that the results he had been given indicated a failure of the vaccine to pass the DNA residual test. David was completely furious. He could not believe the situation. While he was present in Shufen City, the vaccine was reported to have met the standards. Now, at 15 thousand kilometers away from David, the vaccine was no longer approved? The disagreement was discussed with the consultants’ team, and the only feasible explanation was that Mr. Cong wanted to delay the payment for unknown reasons. The consensus was to wait until better news was received, hopefully in the not-too-distant future.

The situation was entirely deceitful for David. There was no proof that the vaccine failed any test. Moreover, he distrusted Mr. Cong. If Yawen Inc. was not getting revenues from selling the vaccine, it would have been sending a truckload of complaints to David. Something else must be happening. Clearly, the company was avoiding the last payment of the contract. David calmed himself down. Time would reveal what the issue was.

David got busy working on other projects on the American continent and tried not to remember failed payment for the contract with the Chinese. However, three months later, he received a note from Cong inviting him to go to China to discuss how to formalize the end of the contract. David immediately sensed that the company had been selling the vaccine for a long time and that the product was passing the famous DNA test residue. The company had a pending contract without a conclusion, and the directors wanted to finish it.

After finishing other chores, David got an airline ticket and headed toward Shufen. He was welcomed only at the capital airport by an assistant to the general manager. This time, there was no ticket for a connecting flight to Shufen City. The meeting would be at the city capital, away from the company headquarters. So he was taken directly to a downtown hotel, where he recovered from the jet lag until the following morning. The next day, David wanted to know why he was not invited to the main offices and laboratories at Shufen City. He was ready to listen.

The meeting was in a small hotel room, and he was met there by Cong, the marketing manager, and Fu, who had initially introduced David to the company. This was a highly unusual encounter; no technical matters would be discussed. After all kinds of words of disposition, the host asked for tea for everyone and later started to praise the work that David and the consultants’ team had done for the company. He said that despite the differences with David regarding some vaccine tests, the company was getting sufficient revenue. He claimed that the company had made some significant modifications to the purification, and now the vaccine was being approved by government agencies. He indicated that the contract must be concluded amicably.

David needed to understand Cong’s intentions. He probably was ready to cover the deferred payment due to David. He would not dare ask, so he waited for Cong to finish his long explanations. The audience was waiting for Cong’s final deduction and proposal. Since the chatter was in Mandarin, much time was spent on expressions in the language. The same expression required a few words in English. David was worried that the delay was due to unwanted bad news. Finally, Cong concluded the contract had to be ended. He explained that the company had decided to cover the deferred payment to Newvac Inc. David was getting excited; he thought that, in the end, common sense had prevailed and that he would be paid the amount due.

However, Mr. Cong finished his chatter with the following words: “Considering that our company had to invest significant funds to modify the purification system, we have decided to retain half of the amount due to Newvac Inc.; in this fashion, the contract will be finalized, and both parties agree to have completed all the agreements.” David was shocked but not completely surprised. He knew of the Chinese’s unpredictable behavior in business and funds. Mr. Cong already had a document ready to be signed by both parties, so he handed it to David for his signature. David asked to pause the meeting to quietly read and analyze the document.

David retired to another room, asked for a drink, and started to read the document. Even though the document was in English and Chinese, it took time to understand the reasons for retaining half of the sums due to David. The Chinese had total control of the situation. David knew that the Chinese had not modified anything; they were only bluffing. David eventually agreed to sign the document ending the contract, expecting to receive the transfer of the remaining funds. Everyone exchanged a few smiles, and the meeting was over. The technology transfer project of the high-density perfusion system had completed another cycle, with ups and downs but always moving forward.

The knowledge transfer had been completed, but the wheeling and dealings of the monetary implications still needed to be finished. At the end of the meeting, Ho asked David if everything was all right, assuring him that the funds would be transferred the following day. Considering this was a private conversation, David told Ho that the final decision was unfair. David mentioned that the remaining funds had been cut in half, and then he had to cut them even more to cover the share quota for Fu. He did not understand. Ho asked David if he was giving a percentage of his contract share to Fu, and he answered, “Yes, of course, the same as any previous payment.”

Ho was outraged. He told David that this act was against decency and dignity. Fu had no right to ask David to apportion the payments received from Yawen Inc. Even more shocking was another fact: Yawen Inc. had been giving Fu a percentage of each payment given to David as a voluntary token of appreciation for introducing David to the company. The whole matter was mind-blowing. Here, a man was taking advantage of two parties engaged in a technical and scientific contract, cheating both to get hefty sums of money.

Ho immediately contemplated approaching Cong and informing him of the findings. However, he did not want to upset him, considering that Fu was a representative of the bioreactor company and that they had many business deals with such a company. Cong had to consider the matter and find the best way to solve the impasse. On second thought, Ho told David that he did not have to worry or make any more transfers to Fu. That was the end of that cheater, at least for Yawen Inc. and David.

David later discovered that Fu, the Chinese who had introduced him to several companies, was a swindler. He was getting some money from David for introducing the vaccine companies to him; he was also getting some money from the companies to get David to sign the contracts. Moreover, he fraudulently made invoices for the bioreactors at higher prices than the parent company. This conduct went on for a long time, but the bioreactor company finally discovered the malicious behavior, and he was fired. By that time, however, he was already a rich man in China, considering, for the most part, that all transactions were executed in dollars.

After these distasteful episodes, David again considered the original goal of the initial foundation, which wanted to structure a teaching institute where technicians from developing countries would go for modern vaccine technology training. China’s experiences taught David that this was not the place to look for such an opportunity. But the search for the vaccine’s school had to continue.

Chapter Thirteen

2005-2006

Greater Adventures

The following year, another Chinese vaccine company called David. They wanted to know if it was possible to have direct training in their laboratories to standardize their rabies vaccine. They told David that they had been researching the high-density system with microcarriers, the perfusion equipment, and the Chinese vaccine sold on the market. However, they had some problems with the concentration of cells inside the bioreactors, and more worrying was the fact that the virus growth was relatively low.

The more information they gave, the more David thought something else was happening. This company had operating instructions similar to those that Yawen Inc. had received from David and his group of experts. Had they copied several documents from Yawen without letting them know? David was perplexed at the conception of another company having some or all the original documents handed three years before to Yawen Inc. This company was not prepared to negotiate a contract similar to Yawen’s Inc. agreement. It just needed some consultants who would show them how to do the processes. David was not prepared for that, so the request was denied.

This event left a few doubts in David’s mind, so they had to find out what had happened. After searching with a small number of Chinese friends, an unpleasant incident appeared. It was speculated that an unknown official from the government regulatory authority had copied the documents that Yawen Inc. had summited for registration of the rabies vaccine. 5 copies of those documents were now in the hands of the same number of vaccine manufacturers. Why was the company that called David unable to develop a final vaccine product? And why had no other rabies vaccines been appearing on the market from the companies that had copies of the standard operational procedures that had been copied?

David had several speculations. The most plausible was that producing cell culture vaccines is a highly detailed process, and many different techniques are used simultaneously. Every step had to be studied and adapted to the special conditions and ambiance of any particular time, place, and laboratory. There were dissimilarity conditions in different laboratories. The only way to repeat a specific system in another place was to have the right technical personnel working in situ and adapting, teaching the local technicians the fine details of handling cumbersome procedures. Those procedures had taken many years to be developed and standardized.

Another critical consideration was related to the contents of the SOPs that David and Olga had prepared before. Even though those huge volumes contained particular accounts of cells, viral culture, and many quality control techniques, other key fine details were intentionally omitted. From the beginning, David thought that if someone had unpermitted access to the vast volumes, it would be easier for them to complete some processes. Consequently, critical elements in describing cell culture processes were modified or missing. This behavior was commonly seen in Latin America as being cunningly Indian.

Two months later, on a breezy, chilly day, David received an e-mail asking for assistance setting up the high-density vaccine technology in an African country. The writer was a research officer in charge of development for the country’s national health institute. The institute’s director requested a visit for David to discuss and study the conditions for technological transfer. David was attending other projects then, so he decided to change his return trip to Borazon City and instead wanted to go the country’s capital, Toban City. He asked the inviting official to make a hotel reservation, changed his flights, and got a plane to Toban. David went alone, and no one was waiting for him at the airport. He slept well at a hotel and was ready to meet with the host the next day.

The following day, the company official went to the hotel to pick up David. Jacob was a man in his late fifties, tall and thin, with short gray hair, a light beard, a warm smile, and a sporty look. He appeared to be trustworthy. He introduced himself and started to tell David about the institute’s projects. In this case, the idea was to adapt an old building to develop the industrial production of rabies vaccine for human use. Jacob added that there could be several alternatives for adjusting at least three areas to serve as a site for the new structure. He also explained that the government had detected an increase in the number of people exposed to the disease, so there was a need for the vaccine.

Jacob and David arrived at the institute, and David was introduced to several scientists working with the host of the research department. The most prominent was a lady in charge of the quality control laboratory. Jacob explained that they had been developing cell culture systems to cultivate the rabies virus in small bioreactors; he claimed they had successfully obtained extremely good viral titers. However, they still needed a scale-up product. The reason for calling David was to set up an industrial scale-up process, which could be obtained with high-density perfusion technology. David was then shown a complete tour of the facilities.

The most outstanding was an area where the institute packed a bacterial vaccine for human use; the building was completely updated, and everything appeared brand new, including the imported European equipment. The host explained that they were importing a bulk vaccine from a European manufacturer and filling it for the country’s needs. The whole process complied with the most stringent international requirements, and a representative from the European manufacturer was on site to ensure the quality of the final product, including the quality control tests. The local institute also had a permanent resident of the quality assurance office to maintain compliance with the standards. The vaccine filling area was a clear example of the excellent command that the institute had of the international standards for manufacturing biological products.

David noticed that the rest of the laboratories for research, quality control, and diagnostic procedures were not as neat as the imported vaccine-filling building. Many areas needed to comply with the most common practices of using special garments. For example, some of the ladies had long dresses and laboratory coats that only covered the upper part of the body. With this attire, they worked with their hands inside laminar flow hoods, handling some pathogens. Most of the laboratories were messy, and most personnel needed to comply with laboratory standards.

The discussion started with a group of local scientists working on different projects, such as quality control and diagnostic laboratories. The institute had diagnostic facilities, research areas, quality control laboratories, manufacturing products, and health regulatory and administrative offices on the same premises. Jacob explained the different projects that they had concerning several vaccines that they wanted to develop. He emphasized the progress that they had in the development of a rabies vaccine for human use. They had prepared the vaccine in a small bioreactor on a batch system, formulated a product, and tested it on mice with excellent vaccine potency results. Ultimately, he said they had unsuccessfully tried to escalate to a larger bioreactor.

David finally understood why they wanted to collaborate with him—they did not have an industrial process. A publication by this group in a scientific journal in which it claimed to have developed a new rabies vaccine was inaccurate. It only had a laboratory research product and not an industrial vaccine that could be sold on the market for a population. There were many research papers in different scientific journals also claiming the development of new vaccines for rabies, but not even a single vaccine had come out of those claims. Many researchers in different world laboratories had only focused on small-scale production. Most scientists expected a multinational company to do all the scale-up processes and produce millions of vaccine doses. That thought was again moving David to try to reverse the trend.

David return to Borazon City to start planning the development of Toban’s project. David summoned the consultants to prepare the standard procedures and equipment needs. He started drafting the design of the rabies vaccine pilot plant. Jacob had given David a layout of a building previously utilized to produce another vaccine. The area was approximately the size that had been estimated, and the most significant modification was in the bioreactors’ room, considering that new services had to be added. The work took approximately two months, and David sent the draft design of the pilot plant for study. Jacob answered and asked David to visit and discuss the details of the proposal to start the project’s development with the general manager, scientists, and officials.

David got an airline ticket and packed some documents related to the fabrication of the rabies vaccine for human use. This time, Jacob was waiting at the airport to meet David, driving an old Chevrolet station wagon belonging to the institute. At the entrance of the institute, David noticed at least eight guards in charge of admission to the premises, each one dedicated to one job. They had to check the visitors’ documents, open the gates, call the host’s office, examine the car for dangerous objects, hand in ID cards for the visitors to wear, indicate the place for parking the vehicle, and address other nuisances. Based on the display of processes and the appearance of the premises and buildings, a visitor could immediately tell that they had arrived in an underdeveloped government agency.

David was taken to the main administration building. The process of getting to the general manager’s office was quite complicated. Jacob had to introduce the visitor to a woman secretary backed by a uniformed guard, who then announced the visitors to another office and received a go-ahead to let them in. Jacob and David were taken to another small room where they were asked to sit and wait for a few moments. After twenty minutes, both were allowed to enter a small room with another female assistant and two male guards blocking the entrance to what appeared to be the primary office. A secretary told the visitors they were coming to the next office. After five minutes, another female secretary approached the door and asked the visitors to follow her.

The visitors entered a sizeable spacious room. On the right side was a large, beautiful antique desk, and a small bald man, the director of the institute, sat at the desk. Behind his counter, David saw many antique bookcases full of papers, books, and documents filling the wall. The director spoke on the phone and made a sign for the visitors to sit at the desk’s other end; it took fifteen minutes to finish his phone conversation. Jacob introduced David to the director, and all sat down. The director was eager to know about the project. He praised the technology’s quality, and at the end of the conversation, he told Jacob to study the possibility of signing a contract soon to acquire the high-technology system for producing the rabies vaccine. He also asked Jacob to examine the contents of the SOPs to justify the technology transfer.

David told the director that he would immediately hand in the SOPs for the technicians and Jacob to study. Before leaving the office, another secretary handed a telephone to the director since the director’s desk had two telephone lines, one at each side, and both were ringing. The visitors waited another ten minutes to exchange the final words and were ready to leave. While waiting, David glanced at the back of the enormous room and saw two more medium-sized desks. At each desk was sitting a secretary with various telephones. One of the secretaries was quite beautiful; she appeared to be a beauty queen. When she came closer to hand in some papers to the director, she looked like a model in fashionable clothes. Was she there because of her abilities or her evident good looks? David thought that there would have been many male visitors who would not mind the complex entrance procedures just to come see the beautiful girl in the director’s office.

Jacob and David visited with the lady in charge of quality control. They met her in a small office decorated with old furniture. She was a short woman with a large body and bright green eyes, probably in her late fifties. She was wearing a long skirt and a scarf on her shoulders. The conversation went very well, and David soon learned that the quality control personnel would need specific training in the vaccine potency test technology. Meanwhile, Jacob received a call from the director’s office. The director invited David to dinner at a certain restaurant that evening, which David cheerfully accepted. Jacob told him he had also been invited and that he would pick him up at the hotel.

David and Jacob arrived at the restaurant that evening. Far away at the back of a spacious area was a big table, and the director was sitting in the middle of several local male friends. The scene was of a royal fellow surrounded by others paying homage. It seemed the director was having a party, drinking, laughing, and speaking loudly. He introduced David to the group, praising him for the superior technology he would present to the institute. David and Jacob sat down and were offered drinks and appetizers. However, the director carried on his conversation with his audience for the rest of the evening; he did not pay further attention to David and Jacob. Jacob talked to David about the many sightseeing places Toban had to offer. Both decided leaving some space after the negotiations to go for a city tour was worthwhile.

The following day, David arrived at the institute and, with Jacob, went to visit the institute architect’s office. They went there and were welcomed by a group of male architects at the door. After the formal introductions, they entered the building and a large office full of architectural desks. A large semi-circle desk was on the left side of the room, and a young female architect was sitting there. She was the office’s boss. David and Jacob had previously sent her the pilot facility’s draft design in the area available for a redesign. The lady made several observations about the design, asking for a few changes to make the space more functional, which showed that she had vast experience in architectural drawings. David offered to make the modifications and promised to send her a final draft for approval. The lady commented that the area under study appeared quite suitable for a pilot vaccine production.

Before leaving, David analyzed the differences in social equality between the sexes in Western and Eastern countries. The more advanced countries had long ago solved differences in social and economic aspects between the sexes in many jobs, remunerative positions, and politically authoritative and leadership posts. In Western countries, many women appeared as heads of state and leadership positions. David recalled that in a few Latin American countries, women were not allowed to vote until the middle of the last century. In a good number of Asian countries, women were still in secondary roles and leadership positions; some even have difficulties acquiring a proper education. David was convinced that developing countries needed more women in political and scientific roles.

After two months, David received an e-mail from Jacob with an invitation to discuss the contract with the director of the institute. He wanted to speed up the development of the project. After arranging the airline tickets and visas, David was ready to leave. David risked the investment in preparing work and trips, considering the institute would not pay for anything until the contract was approved and signed. David arrived at Toban City and got a room at a five-star hotel on the thirtieth floor with a beautiful view of a large river. Jacob picked him up from the hotel the following day and transferred him to the institute. The first task was to talk to the people in quality control to ensure they understood the techniques needed to be installed as soon as the project started full development.

Both men then visited the general director of the institute. The director and his lawyer had already reviewed the proposed contract, which was approved for the signatures. To enter the director’s office, Jacob and David had to follow the same procedure they had been subjected to. It took almost half an hour for them to arrive at the director’s desk. This time, a young girl, named Carla, was already there, accompanying the director. She was introduced to David as the scientist named to be in charge of the laboratory work for the project. After the formal exchange of salutations, Carla handed copies of the contract for the director and David to sign. Both signed two prints, and a picture was taken. The director appeared quite happy with the project. He even told Jacob that he wanted things to go on quickly. Going forward, under the director’s instruction, Carla would contact David regarding the project’s development.

Carla was a thin, short girl with an elongated face, big, bright eyes, and a timid posture. Her body was secluded under a large rob. She was friendly and had a particular way of walking like a swan, with swift movements. Carla was going to be quite helpful in the project’s development. David and Jacob exchanged farewell remarks, and Jacob went about other businesses, while Carla and David visited the potential area for the project. David was ready to go home. A new contract had been signed with a governmental institute to develop a rabies vaccine. This contract was the development of a new technology transfer project in a developing country. It could be a small teaching school.

Back at home in Borazon City, David met with the consultants several times to review some of the quality controls related to the purification of the virus. He also sent a preliminary invoice to the institute for the initial studies and preparation of the standard procedures. David received a mail from Jacob three months later, announcing the preliminary payment covering the initial studies and a copy of the deposit in Newvac’s company account. David was happy, feeling the project had started on the right foot. Jacob had sent several studies on the drawings, and a new draft design using the empty building was completed. Shortly later, David received a letter from Jacob. The news, which was about the government institute, was not surprising. The general director of the institute had been removed, and a new director had been named. Jacob would need to explain the rabies vaccine project to the new director and contact David again on any new developments.

A month later, Jacob sent a mail saying that the director was aware of the project and would like to see David and receive the new SOPs. David and Dalila got the visas and airline tickets and left for Toban City. When they arrived, Jacob welcomed them and showed a happy face; David thought the project was starting with a new impetus. Soon after arriving, David and Dalila were taken to the director’s office. This time, there were much fewer guards and secretaries. The previous difficulty visitors experienced in getting into the facilities must have been specific to the former director. The new director welcomed the visitors and received the renewed SOP. He handed them to Jacob and told David that he would try hard to get funds for remodeling the areas so the laboratory work could soon start.

David and Dalila took some time off to do some sightseeing. They went to a restaurant located inside a garden. A new observation happened when they were at the restaurant. A lady, probably of local origin and dressed in a burka, was having a meal with her companion. To take a bite of her food, she would raise the napkin, hold it up, and move the fork with the piece of food underneath the fabric. It was a lengthy, delicate, cumbersome procedure and a big surprise for David and Dalila. This was a skilled cultural costume that they had not seen before. David and Dalila had to go to the hotel afterward. After a good night’s sleep, David was ready to return home to Borazon City and meet with the consultants. They analyzed the situation and concluded that the current project could be another success. Four months passed, and no news came from the government institute in Toban City. David decided to write a note asking for new developments and continued communication.

A week later, Jacob wrote back, saying that the director had to make other urgent investments and needed more money to start remodeling the building for the pilot facility. The director promised Jacob that he would look for another opportunity to get the necessary investments. However, there was no assurance that the director would soon find another budget. David continued with Newvac Inc.’s business, preparing for other projects he had in mind. However, from time to time, he received news from Jacob. The director continued to tell Jacob to wait until the matter could be solved. 2 years passed, and the information was still the same—they had to wait. David was so busy with other projects that he barely remembered Jacob and Toban City.

Two years later, David received news from Jacob that he was retiring from the institute to enjoy his anxiously expected pension. That confirmed the end of an attempt at another technology transfer project to a government agency in a developing country. Similar to other cases, the reasons for failure were related to political and economic decisions rather than health community considerations. The country had solved the rabies health surge using imported vaccines rather than investing in developing its own. It also never considered or understood that the same technology, in the future, would also be applied to producing other vaccines of health importance.

On another sunny summer day, David received a call from another Chinese friend. A client wanted to buy a bioreactor for the high-density system. The company was a government institute in a city northwest of China. The Chinese representative of the bioreactor company told the institute director that David and his team were able to help them adapt their cells and viruses to high density. The institute sent David a contract to develop the technology. He signed it and started planning the trip to Qiu City.

For this assignment, David asked Olga and Jesus to accompany him. The first phase was only exploratory and primarily dedicated to cell culture under high densities—this time, with a new cell type. The cell cultures would later be utilized to manufacture a veterinary vaccine. The new team started the preparation of the documents that they needed for this assignment. When they had everything ready, David asked Dalila to join the team. They applied for a Chinese visa and got their airline tickets. When they arrived, they were surprised to see that the area around the city was quite desertic, with very little vegetation and significantly dried air. The hotel was a Chinese chain; it was spotless but not luxurious, and the food was one hundred percent Chinese but palatable for the visitors.

As usual for David and any newcomer, after the welcoming remarks, there was an invitation for dinner the first night after arrival. In this area of the country, the most typical food was lamb. So the group headed to a popular restaurant to have some. The place was exceptionally well-decorated and bright. The lamb prepared in this restaurant was grilled and cooked with native green species. The group enjoyed it and toasted with the local Chinese wine to ensure the work’s success.

Work in the laboratory started without difficulties. The locals had dedicated a large area adjacent to a cell production area of the main building for the consulting work. There were plenty of large roller bottles where the cell seed for the bioreactor would be prepared. One challenge to overcome was insufficient time to start the cell culture trials beginning from a new cell bank. Hence, the consultants depended on the supply of roller bottles, already seeded with cells from the industrial vaccine manufacturing area.

The first trial inside the roller bottles worked reasonably well. However, the cells grew too fast compared to the cells utilized for the rabies vaccine, and the culture, as a consequence, did not survive long enough to allow for a virus infection. For the second trial, the roller bottle containers were incubated in the research area, but a good number became contaminated with bacteria. Prior to this contamination, the bottles had not been opened in the research area, suggesting that the cells in the roller bottles were already contaminated with the bacteria before arriving at the research area. A trial could not be started with only a couple of bottles that survived the ordeal and uninfected with the bacteria. The consultants had to wait for another round of clean, uncontaminated roller bottles, hopefully, the next day.

When the group returned to the hotel, they met a couple who spoke the same language as the consultants. They had two teenagers and were from a neighboring country in the Americas and mentioned they had been there for a year and planned to stay another year. The plan was to learn sufficient Mandarin to later allow the two teenagers to establish business with Chinese companies later. They had saved enough money for this adventure; they were pleased to be able to do that for their sons. According to them, the future would be more accessible for their youngsters if they could speak and read fluent Mandarin.

The work of the next day concentrated on new trials. More contaminated bottles appeared in the subsequent tests, coming from the production area. David decided to check out the production area and see if his consulting group could get many bottles without any bacterial contamination. He was allowed to enter a large room that served as an incubator for the large roller bottles seeded already with the cells. He was astonished to see a space of about eighty square meters full of racks and hundreds of large roller bottles on top of them. Adding to the giant of the place was the fact that many bottles appeared cloudy and in different colors, evident of bacterial contamination. No wonder the consultants were always getting several contaminated cell cultures.

To ease the tension created by the bacterial contamination, the hosts invited the group to have lunch every day at the company cafeteria with all employees. One day, David asked the hosts to accompany him to the kitchen; he wanted to see how they prepared the pasta. He was taken to the kitchen, where met with surprises. The walls that were supposedly painted white long ago now appeared gray and with black specks. The kitchen floor also looked blackened, and the open door was filthy. All utensils on the countertop appeared to be damaged and ready for repair. David took pictures of the cook preparing pasta and the representative of the bioreactors as well as the locals were all smiling. David learned much about how the cook prepared the pasta with actual ability and experience.

Back at the laboratory, the consultants again received the bottles with cells in the growing stage. They could not see or detect any contamination. However, some developed massive bacterial growth when the bottles were incubated overnight. Little valuable information could be obtained from this first visit. The group was completely upset and finally decided to return to Borazon City. David, Jesus, and Olga met at Borazon to discuss the next work trip. They needed small stainless-steel tanks to prepare the media in smaller quantities for dilution trials. They asked the locals to prepare 4 small tanks for the next work trip.

David and Dalila experienced another incident on their return trip. David had carried some emergency cash to cover the hotel payment for the group. At checkout, he looked for the money in all their belongings and could not find it. The couple search their hotel room, luggage, drawers, and every pocket to no avail. The money was lost, and David had to use his credit card to cover the hotel expenses; however, on the return trip, David and Dalila stopped and stayed at their daughters’ home in another city before going to their apartment. They left one empty luggage partly opened on the floor. Later that day, their daughter’s nosy cat started to forcefully scratch the inside of the luggage. David got curious and removed the inner cover. To his surprise, he found the supposedly lost envelope with all the money intact. The lovely cat had saved the day.

Two months later, the consulting group arrived in China for another work trip. This time, no one was waiting at the airport to meet the newcomers. The following morning, they savored a Chinese-style breakfast and were ready to be transferred to the institute. When they first arrived at the large working laboratory area, they discovered they could see at least 40 medium-sized stainless-steel tanks sterilized and ready to be used with connectors and filters in the back. When David asked the Chinese technicians why those tanks were there, the answer was: “You requested them.” David said no, we only asked for 4. The technicians did not say anything; they were probably afraid of making any comments. This perhaps was an example of corruption inside a government company. The consultants did not try to find out. The tanks were never removed from the area while the consultants worked on the project.

The area around Qiu City was arid. After two weeks in this environment, though David and Dalila had a humidifier in the hotel room, he developed some respiratory sickness. David had to see a medical doctor, so one of the principal hosts took him to a public hospital. David feared the situation’s outcome, considering it was their first time entering a hospital in China. Moreover, he was also concerned about compliance with the basic hygienic norms in such places. The hospital was a little small but well-organized and clean. Accompanied by Dalila, David was sitting in a big room full of people while the host was getting an appointment slip. After approximately twenty minutes, David and the host, as interpreters, entered the doctor’s office.

The examining doctor sat at a narrow table in a vast, unpretentious room without decoration. David and the interpreter sat across the table, and the interpreter described in Mandarin the symptoms David had; the examiner was writing everything that was said. The examiner then asked David to extend his right arm, and he closed his eyes and palpated David’s pulse with his hand. It took the examiner five minutes to ask David for the left arm. Then, he spent the other five minutes with his eyes closed, completing the pulse diagnosis. When he finished the examination, he wrote on a prescription paper the conduct for the patient. Through the interpreter, the examining doctor told David that he knew the diagnosis. However, he wanted to confirm with precise laboratory analysis.

David and Dalila returned to a waiting room. The host handed the prescription to a window asking for the laboratory analysis. David had to wait for another twenty minutes. Then, he was taken to a room with several small tables where a nurse with surgical gloves sat at one of the desks. She got a lancet from the cached after sitting with David, he wiped his right hand. She carefully opened a tiny wound on David’s thumb, then ignored the first drop of blood and sucked the second one inside two capillary glass tubes; she then went inside the laboratory analysis room for the examination. After waiting thirty minutes, David and the translator received the laboratory results. They were asked to enter the doctor examiner’s desk. Looking at the patient, the Doctor proudly said, “I was right; I already had your diagnosis; you have allergic rhinitis. You do not have any viral or bacterial infection; here is your prescription.” The prescription did not contain any commonly utilized antibiotics, only herbal medicines.

David and the associates went toward the pharmacy window with the doctor’s prescription in their hands. The attendant went inside the pharmacy, and after a few minutes, David received the medicines and a bill for the equivalent of 28 dollars. David paid the bill and asked the host if this was only for the medication. The host reviewed the receipt and told David the amount covered the Doctor’s diagnosis, laboratory analysis, and medicines. David explained to the host that the same three transactions would have cost at least fifty times more in his country. This episode was most surprising for the consultants. They also reviewed a copy of the prescription and laboratory analysis and saw a complete blood chemical analysis. It was an analysis made on an imported automatic Swiss equipment. This event showed the perfect combination of an ancient health diagnostic technique using the most modern laboratory analysis at an unbeatable price. It also clearly confirms the unsurpassed example of contemporary Chinese culture.

Two years earlier, a similar health situation had occurred in China when Dalila had some symptoms associated with a thyroid gland deficiency. So she, David, and an interpreter from the hotel went to the hospital for medical attention. The reception lobby was entirely saturated with patients. Still, twenty minutes later, the trio was called to the next room, where at least forty stretchers with patients were distributed. Dalila was contacted by a doctor sitting alongside a big table similar to a reception desk. The Doctor heard the explanation of the symptoms from behind the desk and immediately sent her to the laboratory room for a blood examination without even touching Dalila.

The trio went to another room with three windows with holes at the bottom of the glass separating the patient from a nurse on the other side. After removing her sweater, Dalila exposed an arm through a hole to the other side of the glass. With great care, the nurse took a blood sample for chemical analysis and asked Dalila to wait in the lobby for the test results. Forty minutes later, Dalila was called again and was handed the results.

Everything was in Mandarin, so the trio had to see the Doctor for an interpretation of the results. After another thirty minutes, the Doctor handed the results and wrote a prescription. Dalila paid the equivalent of 30 dollars for everything. Later, David examined the medication, and to everyone’s surprise, it was fabricated in Germany. The prescribed dose was a little high, and Dalila had to adjust it with a local Doctor in Borazon City. This episode was another example of modern local Chinese health management bridging with a world-known multinational pharmaceutical company.

Work continued at the Qiu City lab to conduct more trials on the large bioreactor. However, several tests failed again due to bacterial contamination of the cells arriving from the central laboratory. Another trial was started, and cells were delivered from the central laboratory. Jesus stayed overnight with one of the Chinese technicians to control the bioreactor that had already been seeded with the cells. Finally, that day, by sheer luck, a culture inside the bioreactor gave reasonable cell counts. It was stable for the four days needed for viral infection. The consultants had shown that it was possible to do the escalation process for larger cell and viral cultures. The Chinese were not completely happy; they wanted to see many successful repetitive tests. David did not promise anything; however, the consultants were ready to go home.

At Borazon City, David, Olga, and Jesus discussed the results and decided they needed to guarantee that the bioreactor was in perfect operating condition for the next work trip. There was no guarantee of sterility. Moreover, they needed the cell cultures to start from another original frozen seed and multiply in a different laminar flow. David sent the request to the Chinese to be able to work under more controlled circumstances. They had enough time to wait until the Chinese modified the laboratory to comply with the request. David also sent the invoice for the operational phase they had completed during the previous work trip.

One month later, without any answer from the Chinese company, David sent a mail requesting responses and complained that he had received no money transfer. Two weeks later, David got an e-mail from the company saying it would only pay if the consultants showed that the cultures could be repeated at least ten times with the same results. No comments were made on whether they would modify the cell seed or install the missing table laminar flow equipment. Even if they had already done those modifications, they still had to cover the latest work done so far, in agreement with the contract. Once more, David sent a document insisting that the Chinese had to pay the consultants group for the last work trip and the results.

The Chinese government company never paid for the consultants’ work there. Not surprisingly, the consulting group demonstrated the technique, and the Chinese learned the basic scale-up technology, receiving the capability to transfer their industrial veterinary vaccine production from the roller bottles to the bioreactors.

Moreover, a few years ago, the same government institute purportedly signed a contract with a European transnational to build a large manufacturing facility for the same veterinary vaccine on their premises. This was a joint consortium between the Chinese government and the multinational pharmaceutical. This time, the Chinese had the knowledge they had previously obtained from Newvac Inc. to favorably negotiate the manufacturing of a modern vaccine for the country’s animal industry.

Chapter Fourteen

2007-2010

More in Asia

After another summer without much action, a research group from a Southeast Asian country called David. They wanted to know if he would visit them to discuss a technology transfer for the high-density perfusion system. As had happened, this was the same country that David had visited when making the foundation search consultancy. David decided this was also a good opportunity for relaxation and sightseeing, so he invited Dalila, his wife, to accompany him. They arrived at the capital and met a group belonging to a private enterprise that did not have any relationship with the government institute that David had visited before.

The hosts first invited the visitors to look at a building where they were finishing the construction of a manufacturing facility to produce a bacterial vaccine for human use. They could walk through without major controls because it was still under construction. The wall panels, floor coverings, and all the building elements were excellent. The manufacturing equipment was imported from well-known international companies. David immediately thought that this company could make a superb manufacturing plant for the rabies vaccine; they had at least 70% of the knowledge, basic training, and entrepreneurship needed for that task. This seemed to be a company that would yield a successful technology transfer project.

The next day, a meeting was held at the company’s main offices. The locals were interested in a detailed technology description before negotiating it, considering that they received only limited information via mail. David showed the board of directors a PowerPoint presentation on cell culture, virus multiplication, quality control techniques, and all the equipment and sundries needed to produce the vaccine. After a few questions and answers, the prospects made a few comments, but they thought it would be a great asset for the company, producing the rabies vaccine and developing other products. They knew of their capabilities and were enthusiastic about acquiring the technology, so the chairman asked for some time to meet with them and study the possibilities.

After exchanging ideas, the following day the board members wanted to know the conditions under which they could get the technology. David explained that his company could sign a contract to prepare SOPs and later teach the technology to local technicians. His scientists would follow local technicians in every process to certify the registration of the rabies vaccine. One board member asked David whether it would be possible to negotiate only comprehensive SOPs. David replied that it would be complicated for local technicians to develop complete processes for successful vaccine production without in situ training by expert scientists. He recommended that the investors spend some time thinking about these options.

That night, as a gesture to David’s wife, a female host scientist invited David and Dalila to dinner. She chose a well-known restaurant that had different kinds of seafood. The lady scientist seemed to have another mission. She praised the guests for their technology and presence. She asked David whether he would accept negotiating the technology only with detailed documents describing the processes, equipment, reagents, and techniques—in other words, only the complete SOPs. David was surprised. He could not understand how they would risk investment in just paper information without a specific in situ demonstration of the characteristics of processes, quality control techniques, and even a tested and proven finished vaccine product. He tried to convince the lady scientist that this proposition had considerable risks for them.

The next day, the hosts summoned the guests to the meeting room in the main building. They wanted to know in confidence what the SOPs contained and the exact description of each step in producing a high-quality vaccine for rabies. They also described some complex issues that the country had concerning the appearance of recent outbreaks of rabies and the assertion that most vaccines locally available were imported. David described each section of the voluminous SOP. He described the purpose of each production process, the actual step-by-step procedure, and how to measure and validate the results obtained. He also enumerated what quality control techniques had to be established and how to evaluate them.

After two hours of listening to David, the investors still needed to be convinced that they would really need the demonstration of the technique and training their technicians in the complete production processes. David finally proposed that he would negotiate only the SOPs if they agreed that they would call Newvac Inc. whenever they had a problem during the setup and development of the technology. The investors asked for a recess to meet separately to discuss it further. One hour later, the meeting resumed, and the investors explicitly affirmed that they still did not have a consensus. They had difficulty deciding because they had already invested in a factory for a bacterial vaccine. They wanted high-density vaccine technology but did not know if they could simultaneously handle two large projects. David asserted and told them that they should consider the investment very carefully. He told them not to rush the decision and that Newvac Inc. would be ready to assist whenever they had a decision.

Several things surprised David and Dalila in the city capital. They saw a giant elephant walking in the middle of the street in the heart of downtown. That was quite a treat, having only seen elephants at a circus. Another was the many motorcycles occupying at least half of the main streets; every light would have at least 50 motorcycles waiting for the green light. It felt scary crossing the road with such an array of vehicles. After a sightseeing tour of the local city and surroundings, David and Dalila returned to Borazon City, perplexed about what had happened; it was the first time any company considered acquiring only the SOPs of a highly cumbersome rabies vaccine technology.

Three months later, David received a call from the investors; they had decided to negotiate only the SOP. They would get used to some aspects of the technology before they were involved in developing an entirely new project and building to house it. After a few days of negotiations by email, a contract was signed for private investors to obtain only the SOPs for production and quality control of the rabies vaccine for human use with the high-density cell culture system. David and the group had to prepare a new set of the most updated SOPs’.

This time, David, and the consultants had to ensure that all details were included in the manufacturing processes and quality control tests. Previous SOPs prepared by Newvac scientists deleted some critical procedures to prevent other companies from suspending payments when receiving the documents, thinking that they could produce the vaccine without Newvac Inc. scientist assistance. This time, it was just the opposite: the investors had to accept complete documents that they would later use for the production, formulation, and quality control of the rabies vaccine.

The investors studied the new documents for another month and asked for numerous clarifications and explanations of several highly ponderous processes in detailed written documents. The consultants also had to prepare more succinct descriptions and brief information on several quality control tests, equipment descriptions, and new suppliers available in Southeast Asia. After the whole process was completed, and the buyers were confident they could duplicate the processes and techniques, they ordered the contracted money transfer to Newvac Inc. David charged the investors only 30% of the total cost of the in-situ technology training. This time, Newvac Inc. received the total money included in the contract.

Fourteen years have passed since the SOPs were transferred to this country’s investors, and they have not yet produced a single dose of rabies vaccine for human use. However, they have used considerable information in processes and documents for other purposes and products. This technological transfer project was only half completed, since no new rabies vaccine was available. David felt completely satisfied with this project, considering that the essential technological components of the high cell density system would now be applied to other products, processes, and even quality control techniques.

A few months later, the Newvac Inc. group at Borazon City received a mail, this time from a Latin American country that had heard of the technology the group was transferring in Asia. It produced the rabies vaccine for human use in glass bottles and wanted to change it to bioreactors and high-cell density perfusion technology. It was also using a cell line to cultivate the virus, which the World Health Organization was not recommending for vaccines for human use. The government officials from the country’s institute of health wanted David to go there to discuss a technology transfer program.

A month later, David made some airline reservations, got a visa, and headed for Leon, the country’s city capital. A professional from the health institute, Pablo, was waiting for him at the airport and ushered him downtown, where the local government agency had made a three-day paid reservation at a modest hotel. Pablo told David that he had worked for the institute for the last 20 years and was now responsible for producing the rabies vaccine. Listening to Pablo, David immediately sensed that the fellow was not completely happy about abandoning his old, outdated production technology; he was accustomed to his production setup. David thought this posture was utterly in contrast to the many requests from researchers contacting David to get hold of the high-density perfusion technology. Pablo’s attitude represents one of the common perceptions of many underdeveloped countries.

David was taken to the main buildings of the health institute and introduced to the director of the laboratories. The man in charge was Miguel, who lacked basic vaccine production training and had been relying on his assistants to perform various functions. He was a short, thin fellow with a small, smiling face. Importantly, he was an adherent to protocols and regulations. Two ladies were also in the room with the director; one was Helena, in charge of internal quality control. She appeared to be entirely happy with David’s presence and seemed quite glad about the possible change and modernization of their vaccine manufacturing process. Helena had a big face with big black eyes and a little heavy body. She would be a significant factor in developing the relationship between the health institute and the visiting scientist. The other attentive lady in the room was Isabel. She was a young girl full of energy, and had a slim body and a small, happy face with pretty eyes. She was an assistant in the rabies vaccine production laboratory. She would later become David’s best friend during the relationship between the health institute and Newvac Inc.

Once David knew the principal actors in the work on the rabies vaccine production, the director went straight to the business of the day. He explained to David that the health community had convinced the country’s health minister that it was time to modernize the old-fashioned vaccine production facilities. He also emphasized that the health institute directorship, the professionals, and everyone in the laboratory were eager to learn new techniques, processes, and methodologies. Miguel explained that their technology was clearly obsolete and needed change. David thanked the hosts for their hospitality and expressed his willingness to assist in carrying out a project to subside the current state of affairs. It was then time to visit the laboratories.

David was accompanied by Pablo, Helena, and Isabel to the rabies vaccine production laboratory. The cloth-changing area to access the production labs was tiny and poorly kept. The laboratory was located inside an old structure. The general appearance was somewhat sad; the spaces were big, and, as other scientists had said before, in another project, “rather spartan.” Most of the equipment needed to be updated and in better condition, but the operators were busy trying to handle hundreds of large glassware. The area where the virus was being produced was separated from the rest of the building. However, it did not comply with international recommendations to address highly infectious microorganisms. In fact, inside the room, some idle equipment had no use at all.

The quality control laboratory also stood inside the same building on a separate corridor, and again, some equipment was invariably out of work. It was a big surprise to see other rooms with large, inactive equipment that, at the time, had no job at all. David knew of the precarious conditions for vaccine production in laboratories in many developing countries. This laboratory, however, was below expectations. Much work would be required to set up any new technology in debilitated and unsuitable conditions.

David then showed the directorship and the professionals involved in vaccine production what the new technology was about. A group of eight professionals from the laboratory and the director met in the conference room to watch David’s PowerPoint presentation describing the main features of the high-density cell vaccine production system. Several questions were duly answered, and then the director asked David to follow him for a private talk to discuss the conditions for a technology transfer agreement. David explained the methodology he had followed with other clients, dividing the development into phases and charging the agreed funds to the receiving company at the end of each stage. The director asked David to prepare a proposal for the government to study. Miguel, Pablo, Helena, and Isabel joined David for a meal with typical local dishes.

The following day, Pablo escorted David to see other old buildings that, if refurbished, could be adaptable to the new project. One building had several large rooms with many pieces of equipment in acceptable conditions: cabinets for work under sterile air, autoclaves for sterilization, sensors for measuring acidity, and areas for preparing culture media and reagents. The site could be easily adapted for the pilot plant to develop a new rabies vaccine for human use. It turned out that the area was being utilized to prepare a bacterial antigen needed for another branch of government, and the volume was so low that the area for preparation of the reagent was used only for 30 days every year. David immediately suggested to the director that they could plan to dedicate this area to the new vaccine. The technician in charge of the area was not happy to hear that. This professional considered the laboratory his property and would not allow any changes to the situation, a typical reaction of deficient government organizations in the developing world.

David returned to Borazon City and prepared a proposal for technology transfer to the new clients. It only took him three weeks to prepare a draft contract with a schedule and content similar to previous agreements with other clients. For monetary needs, he decided to charge only half of the regular expenditures agreed upon with different clients; the analysis was that in this case, the government had limited capacity to defray the costs of new technologies. The proposed line of work was sent, and he would wait for a positive reply. At this time, he even contemplated the possibility of applying for a grant from an international foundation to establish a vaccine teaching school in this Latin American country.

A month later, David received a reply from the institute’s director saying that the health minister had approved the project to develop the new vaccine in bioreactors and high-density cell cultures. The problem was that the government needed a particular budget for this kind of research; however, he was going to find other funds to start the project, hoping to add more funds later. In any event, the director asked David to come for a discussion on how to start the project. There should have been an agreement on the payments David asked for in the technology transfer proposal. David wanted to help, so he decided to go again to Leon to see what he could do.

David arrived in Leon City and was again met by Pablo. The host told David the director was happy to hear that he had agreed to visit them, even though no contract or arrangement had been made. He also told David that the director wanted them to consider another area of the old building that could be remodeled for the development of the new rabies vaccine. Pablo guided David to the international four-star hotel where David had reserved a room. He registered and immediately headed to the government laboratories with Pablo.

When they arrived at the laboratory, the director’s secretary asked them to sit for a few minutes until the director finished a telephone call. David immediately sensed the attitude of numerous executives in Latin America that, on purpose, forced visitors to hold back and wait in expectation of showing a fake superiority. The secretary had experience handling this situation, so she offered the visitors a cup of local coffee and started an amicable conversation. Time quickly passed, and fifteen minutes later, the director showed up. He told David that the minister of health wanted to personally see David in his office the following day. The visit to the Minister of Health was mainly business as usual, with a fake interest in the project and no real intention of improving benefits for the country.

After visiting the Minister of Health, Pablo guided David to the laboratory area where they envisioned a possible remodeling for the new project. Samuel and James were introduced there. Samuel was the oldest and most experienced production team member; he was short, half-bald, and quite friendly, with an extended smile. James also had a short body, broad shoulders, and a helpful attitude. Helena, the lady in charge of quality control, was relatively rigid, not only in her mood but also in her body appearance. Her face intentionally demonstrated that she was in the order of the final decisions. Isabel, whom David had already met, was also there. She was more consensual and acted with an open mind. After the introductory salutes, the group headed for the area that Pablo had in mind, adding a wing outside the building. After some consideration, the director agreed and asked David to prepare a rough draft design for the new wing so that the cost would be estimated.

After this proposition, David returned to Borazon City and started to work on the rough design. David’s closest assistant, Olga, joined him, and the two prepared a complete crude laboratory plan of approximately 800 square meters. The rough new design included areas for everything needed and even contained an office to prepare all the paperwork. The draft was sent to the director’s office to the attention of Diana, the office secretary. Two weeks later, the director sent a message to David saying that the draft had been priced and was found to be reasonable. He submitted it to the Minister of Health for funding.

A month later, the director sent another mail to David saying that the country’s minister of health was looking for funding but recommended that the director look for other options. The Minister of Health also explained that he had found a minimal budget, but it was tied up and could only be utilized for equipment. If the rabies vaccine project had any critical equipment to be acquired, the director could use those remnant funds. Pablo and Samuel were told of the news, consulted with David, and immediately prepared a proposal for the director to order brand-new purification equipment. The equipment was ordered, and six months later, it arrived at the laboratory. It was stored until the vaccine project was developed and could be used in the last step of the purification cycle.

Three months later, David was asked to return, this time with an arrangement as a specific consultant to advise on improving the rabies vaccine manufactured by the institute. However, there was no budget to cover this type of project, so the officials decided to ask him whether he could continue to advise the health institute on ways to develop the project but only as a consultant with honoraria for each trip. David bought an airline ticket and traveled to Leon City. The institute covered this bill. David also prepared invoices for the consulting time of that visit, which was also covered. Pablo also asked David to present the technology to all of the institute’s professionals and assistants, who were very much in need. For David, it was time to return to Borazon City, this time with paid honoraria to cover all his expenses; still, he was disillusioned by the lack of an actual project to develop a new rabies vaccine.

A year passed without news from the national health institute in Leon City. Suddenly, David received an email from Pablo asking him to return to Leon with paid honoraria to study another possibility for developing the rabies vaccine project. He greeted David with “good news”: they had a new general director, and the new man wanted to meet David and hear about the new rabies vaccine project. Both arrived at the institute and headed directly to the director’s office. Diana, the secretary, warmly welcomed David as a regular visitor and, as usual, offered him a warm cup of coffee. The visitors were sorry to hear that the general manager had an emergency and was not at the office. Still, he had left a message to allow them to go to the meeting room and study the new plan for adding a new wing to an existing building to house the rabies vaccine project. The idea was mild; however, it would look funny from the outside as an extraneous addition, and in any event, the idea would be functional.

Three hours later, the new director showed up. He was a professional with pharmaceutical training. In fact, he had previously been the executive of a local branch of a multinational pharmaceutical giant. He was a short, semi-bald fellow with big eyes and a skinny body. He warmly welcomed David and told him he would make his best effort and lobby the health ministry for funds to finance the new proposal. David had new hopes that the government would appropriate new financing for a deserved group of professionals eager to modernize their vaccine production laboratory.

Before leaving Leon City, David had enough time to examine the purification equipment that the health institute had bought the previous year. The apparatus had been stored in a room inside the main vaccine production area but wholly covered. The professionals and technicians could have utilized it for the current vaccine production; however, it seemed that they were afraid of misusing it or did not know how to use it. It saddened David to see a brand-new, handy, and pricey piece of equipment covered and stored like old stuff to be destroyed.

It was a long 18 months before David had received any news from the health institute in the city of Leon. The director of the previous year had been removed, and a new director had been appointed. Surprisingly, the recently appointed director was the same as three years before and had been the institute director for only twenty months. Now, once again, he was in charge of the health institute, and he wanted David to show up to see if the matter related to the technology transfer of the rabies vaccine could be reenacted. David still wished to assist, even without a formal contract, so he paid for an airline ticket and traveled to Leon City.

As she had done for so many years, Diana, the director’s secretary, warmly welcomed David with another warm cup of coffee. She had served in that capacity for over 20 years and had received orders from at least 8 general managers. She probably had official career tenure in that position, the same as several professionals and management personnel in the institute who also had tenure. They could only be moved to another post with the same official scale of remuneration. On the contrary, the directors were removed when the minister of health was changed in a political move. The director was quite happy to see David again. He told David that he needed a plan to start the technology transfer soon.

David worked with the whole group, along with Isabel, Pablo, Samuel, James, and Helena, to review the papers that David had left several years before, with a rough description of the entire SOPs for manufacturing the rabies vaccine for human use. The institute had acquired some key elements, equipment, and even reagents that could be utilized for the project over time. The most critical need was a building structure in which the whole system could be housed and complemented with a few pieces of missing equipment. The director would find out what was needed to accomplish that move. David had to leave to go home, another time empty-handed. There was no technology transfer agreement signed—only honoraria.

Six months later, the same director was still heading the government laboratory. This time, he wanted David to go to the institute to conduct cell culture trials inside the bioreactor they had acquired. The director had readied all the papers needed to cover the honoraria for two people. David took Jesus with him and paid for the hotel reservation for two rooms. They both headed for Leon City, where they met the director, who immediately ushered them to the laboratory where they had the bioreactor. From the outside, everything appeared normal; however, Jesus rolled up his sleeves and started dismantling equipment pieces. After an hour or so of high expectations, Jesus asked for a replacement part for a filter needed for the air intake, and Samuel had to go to the service department to find it.

During lunch that day, the director asked Jesus and David if everything was right. Jesus calmly said that everything appeared to be in order up to then. The following morning, Jesus, Diego, and the local technicians examined all the bioreactor components with external and internal complements. It was time to test the bioreactor, so the outfit was sterilized and cooled down. The system was working for almost one hour, and then Jesus discovered that one of the gaskets on the upper plate of the vessel was leaking. This meant that the cell culture medium would become contaminated with bacteria. The damaged gasket of the bioreactor would need to be fixed immediately.

Pablo, Samuel, and James spent the remaining day looking for the gasket in the workshop spare parts office, but no spare part gasket was available at the health institute. Because this was a particular part of the highly sophisticated equipment, the gasket could not be found among local spare parts. It had to be imported from the company that manufactured the equipment. There was no way to run a cell and viral culture test, considering that the spare part would take at least 2 to 4 four months to arrive. The director, the group of professionals, and the technicians were completely frustrated. They immediately ordered the missing part. David and Jesus, as on similar occasions, had to go back home empty-handed.

Five months later, after the missing trial at the health institute, David received an email from Isabel, the microbiologist working as an assistant in the rabies vaccine laboratory. She was frustrated and sad to see so much money expended and a lot of brand-new equipment idle without being used. Isabel told David that a new director had been named, and she asked David whether he could do anything to help move the project again. David replied to Isabel, explaining that he would write to the new director to see if a new plan could be devised and that she would receive a blind copy of the mail. David sent the emails, but he never received a response from the health institute. That was the end of another futile effort to assist a developing country to acquire modern vaccine production technologies.

This process was a considerable waste of time for many technical people, including the consultants of a company ready to assist an institute in need. This was a significant disorganized expenditure of a national health authority. Many pieces of costly, highly sophisticated equipment were left idle. Another country’s political environment in development interferes with scientific advancement, development, and the availability of modern vaccines to prevent significant health issues for its population. David once more felt entirely frustrated.

Chapter Fifteen

2010-2012

Batch System

Two years after the discrepancies with the Chinese Yawen Inc. group, another Chinese vaccine company called David. It was a group called Yihao Inc., located in southeast China. Yihao Inc. wanted to negotiate the complete package of rabies vaccine technology for human use. It had seen the progress of the new rabies vaccine from Yawen Inc. and wanted to enter into competition. David proposed arranging for a visit to discuss the contract details. The Chinese company accepted, and David prepared and then sent a draft contract to Yihao Inc.’s directorship. The Chinese studied the draft, made a few corrections, and a month later sent David an invitation to personally discuss the final arrangements for the contract. The city in the south completely differed from the one up in the north. The temperatures were warmer, the food was not as spicy, and the people were a little more open. People from the south of China were more cordial or sympathetic than those from the colder northern parts of the country.

David arrived at Qiaoxi, the city capital of the province. He was welcomed by Deshi, his Chinese friend, who had already booked a hotel that was partly Chinese and partly Western. The food was more Chinese than Western, but some dishes resembled other delicate dishes of the West. Deshi happily announced that the hotel was the best in town. The rooms were well-kept, clean, and orderly; the hotel staff was competent and cordial; however, their English was deficient, which was a real impediment when ordering food at the hotel restaurant. This was another challenge for David, which would later be an obstacle for the consulting group.

Deshi was a mechanical engineer born in South China who had migrated to North America and ascended in a biotechnological manufacturing enterprise to the post of core designer. He was a short fellow with big, enormous eyes, a half-bald, round head, and a huge smile. His English was quite good and precise compared to other Chinese. He had been involved in designing the bioreactors that David and his group had used for the cell and virus scale-up processes and the continuous perfusion system, an invention that allowed high cell concentrations. Deshi had retired from the North American company and was now a freelance consultant. He had heard of the enormous success of Yawen Inc. in the northeast of China with the bioreactors designed almost entirely by his supervision in North America. He was now interested in assisting other companies in developing the same vaccine technology using his most precious pride: the bioreactors. This could become part of the vaccine school that David had envisioned. We shall see.

The following day, David, accompanied by Deshi, was transferred to the company’s main headquarters in a modest vehicle. David saw at least four large, quite old structures and buildings that could use some first-class pharmaceutical or biological organization. David was anxious about the whole deal but did not reveal his thoughts. He was taken to the conference room, where eight technical and administrative staff members sat at a large conference table. The mood was sober and far from warm. The general manager was Yuxan. He was short and a little heavy, with a round face, deep forehead, and big, bulky eyes that appeared to get out of the face. He welcomed David and then introduced members of the company staff.

A man called Haitao headed the laboratory for vaccine production, and a woman called Chun headed of quality control. They were both present among other technical professionals. Haitao was a little taller than the median Chinese man’s size. His skin was yellowish, and he had prominent black brows and black eyes. He was quiet and did not appear to be in any hurry. Chun was short, a little heavy for her size, had long hair that was entirely disarrayed, and appeared genuinely reserved.

After the usual formalities of introducing the company, the general manager asked David to briefly describe the high-density cell culture technology. He made it clear that they already knew of the tremendous success of Yawen Inc. in northeast China with David’s technology. However, they wanted to ask specific questions about the cell culture media, especially concerning the purification system. David finished his presentation with particular consideration of the two areas that the general manager wanted.

The following day, David was taken from the hotel to a small meeting room, where the general manager, the administrative-financial manager, and the production manager were waiting for him. The purpose of the meeting was to discuss the project contract. Another man, Fenhua, was introduced to David; he was the company’s owner. Fenhua was short, with a small head, pure black short hair, a thin body, and the posture and looks of a very young man. He appeared to be smiley and happy. After the formal introductions, David explained the need to divide the execution of the contract into phases to accommodate the payments according to the speed of development and adaptation of the technology to local conditions. There was only one fixed date for the total length of the project: eighteen months.

The hosts, especially Fenhua, the owner, appeared to be in a hurry, so both parties read and accepted the contract without any modification to the proposed agreement that David had submitted. It was signed, and everyone was ready to start. David was amazed at the speed of acceptance of the contract details. This was just the opposite of several deals David had had before with other Chinese companies, and the behavior raised some concerns in David’s mind. Something else was moving this company to act in such an abrupt way. Nevertheless, David was satisfied with having another opportunity for a successful technology transfer, so he had to start preparing for the new updated standard procedures and the design of the pilot production plant. He hurriedly traveled back to Borazon City to begin the preparation of those documents.

As it turned out, this Chinese company was already producing a rabies vaccine for human use on roller glass bottles and had numerous difficulties. However, the Newvac Inc. team would only work on the new system with bioreactors, microcarriers, and perfusion. The first thing to discuss was the design of the pilot plant, where the project could start specific laboratory work. Guanyu Inc. wanted a reasonably sized structure that could serve as a pilot plant to develop the technology. The company also wanted the same size structure to serve as a preliminary industrial production laboratory.

In essence, it wanted a brand-new building right from the start. It had a sizable land space where the building could be built. The building size would be enough for at least ten million doses of rabies vaccine for human use per year. It had some advantages, but it took some work from the beginning to operate at larger volumes than a pilot plant size. It was like setting up a scaling-up production system and industrial construction from the start. This was a good challenge for David and the consulting group. It was also quite unusual for any vaccine producer.

David started to work on the design. This was the first time David and his consulting team had to design and deliver a project from the beginning and complete an industrial building for the entire production of a rabies vaccine for human use. The building had to be built without designing a pilot plant to develop the technology according to local conditions. Two months later, after considerable effort from the consultants, the design was completed and sent to China. They then worked on the updated SOPs.

Similar to the contract with Yawen Inc., David gave the Chinese a detailed list of all necessary things, including how and where to get them. The Chinese ordered service and production equipment, chemicals, cell and virus strains, and everything that was needed. The construction of the factory took only ten months; it was a simple structure, but it was large and adequate for the purpose. David put together a new consulting group for this project, including Laura, Luis, Jesus, and Javier. Olga, David’s former partner, had gone with her husband to a Latin American country to set up a veterinary vaccine factory. It seemed Totem Inc., the original vaccine technology company, produced more than a handful of entrepreneurs in vaccinology. Several original Totem Inc. team members had expanded the knowledge and experience gained overseas. This probably was small fraction of David’s original dream of a vaccine school.

From time to time, David received emails from researchers interested in high-density technology; most had read one of David’s publications and were wondering whether David could assist them in getting hold of the technology. There was once a request from a university professor and researcher from a Middle Eastern country. He was eager to learn how to get complete knowledge of the technology. The professor indicated that he would ask his superiors to examine the possibility of acquiring the technology. He also told David that he had been trying to culture cells under high densities, but his results were not satisfactory.

Two months later, the university professor came back to David. The negative replies from his superiors were discouraging. None would give him the possibility of financing the technology transfer. The professor did not give up; he contacted a friend working for a health research institute to see if he could find support from the government to acquire the technology. After a month of suspense, the answer came back: the government agency did not have a budget to cover this endeavor. This situation is common across the world. Some investigators from well-known research centers even asked for a free technological transfer. As soon as they heard of a contract and payment of fees, they had to regress. Was this a symptom of considering vaccinology as a business rather than a service for the population’s well-being? Several examples in this book suggest that this is the case.

While the new Guanyu Inc. factory was under construction, the consultants assisted the locals in improving the old-fashioned vaccine technology, which utilized large glass roller bottles instead of bioreactors. There were several difficulties in the processes and equipment, and many things needed improvement; the most significant was a deficiency in the purification of the final vaccine bulk. Something very awkward happened. At the end of the purification procedure, a small black patch appeared on the surface of the liquid. Even though the total concentrated product had gone through the purifying columns, the black artifact commonly appeared on the filtered product at the end of the process. As they did a few times in other projects, the consultants had to thoroughly examine all the methods, materials, elements, and reagents used to prepare the old vaccine. It took close to three weeks of deep investigation before Luis, the biochemist, suspected the cause to be the cell culture material utilized for cell and virus growth. He argued that there was an apparent deviation in the various chemical components of the synthetic media.

A further investigation revealed that the trademark of the cell culture material was the same as that used by other vaccine manufacturers. It was similar to the one utilized several years back in Yawen Inc. However, it turned out that the provider was mischievous. This fellow had been collecting empty containers of the actual media and filling them with a much cheaper product than the original. Once the original culture product was ordered from a reliable distributor and new cultures were prepared, the black patch disappeared, and the final product greatly improved.

The pilot and industrial production building were completed and furnished a few months later. Every piece of equipment was validated, and quality control certified the use of the equipment and air room quality. The consultants then worked on fabricating the cell and virus banks and validating the bioreactors and quality control techniques. David took Luis, Laura, Jesus, Javier, and Dalila for this phase. The beginning of this project phase was quite articulated: everyone did their task, so the project made a significant process for the first six months. The main drawback was related to several quality control techniques, considering that local technicians needed more standard reagents for reliable results. Once a few reagents were modified, the results began to show greater accuracy.

After twelve months of arduous work on standardizing cell and viral cultures inside bioreactors, the downstream process work began. There was some fear about some of the black stain that had appeared in the old factory where the local Chinese were still formulating the old rabies vaccine. After purification, the first cultures showed faint black stains in the bulk material. However, the obstacle disappeared when the cell and viral growth media components changed. Some intermediaries or distributors of chemical elements and media for cell cultures had been cheating, selling substandard media chemicals at lower prices than the original ones. As soon as Guanyu Inc. started to order the media directly from the manufacturer at considerably higher prices, the black stain disappeared.

Luis and Javier worked with their Chinese counterparts on the concentration and inactivation of the rabies virus with all the precautions to handle a large glass container with live concentrated rabies virus. The group had already focused on the virus bulk to facilitate inactivation. To transfer the virus from one glass bottle to another, a lower pressure had to be applied to the first bottle using a pump to push the liquid into the next bottle. On a particular day, for some unexpected reason, after applying low pressure, the first bottle with the concentrated virus exploded, and the live rabies virus was thrown everywhere. There was panic in the area. Luis, the most experienced scientist, calmed the technicians and disinfected the entire room and its contents. He ordered all Chinese technicians to leave, shower, and change clothing. One of the girls had almost a seizure, and Laura had to go to the dressing room to assist and calm her down. The girl cried loudly, worried that she had been infected with rabies virus and would die.

It took almost two hours to calm down the assistant and assure her that she had been vaccinated before and, therefore, previously immunized. Moreover, her serum had been tested for antibodies, and the results showed that she was well immunized. All elements with contact with the live virus and all clothing were sterilized by autoclaving before the regular wash. All technicians in the room at the moment of the bottle explosion had to get a booster shot of a commercial rabies vaccine as a precaution, regardless of their previous vaccination status. Fortunately, no significant health consequences resulted from this hazardous accident.

Eventually, the downstream system became operational. The consulting team continued the cell and viral cultures standardization in larger bioreactors with a working volume capacity of twenty liters. After the quality control unit completed the physical and chemical analysis of the vaccine lots, the vaccine potency was tested in laboratory animals, as was usually done in all rabies vaccines.

After the long and tiring return trip, the consultants’ group safely arrived in Borazon City. The consultants waited for the results of the quality control tests, and three months passed without any news from Guanyu Inc. David decided to email the company’s president asking for the results of the tests. After a week, the answer came back, explaining that some minor problems had surfaced, but everything had been solved. The results were excellent; all vaccine formulations complied with the expected potency levels, so they claimed they had a product. This was completely satisfying for David and the consultants.

The Chinese assumed the approval as official recognition of the vaccine; however, they still had to submit three consecutive lots to the government for laboratory analysis. When these tests were completed and approved, the vaccine had to undergo several clinical studies on human volunteers to verify its immunogenicity, safety, and the absence of harsh secondary reactions. These laboratory evaluations and clinical tests would take at least one or two years. The company’s directorship was unhappy about this, since it had assumed that the product would soon be in the market to compensate for the sad financial situation that the company was undergoing with the old rabies vaccine fabricated on glass bottles.

When David received the news that the vaccine passed the potency tests, he thought that the Chinese’s compliance with payment for that contract phase would be solved. However, the recipients of the technology transfer had other ideas. David submitted an invoice to claim the end of another contract phase because the vaccine technology transferred to the Chinese had been completed. The contract specified that as soon as the vaccine completed all quality control tests, including the potency test, the Chinese would pay the specified amount for the last project phase. The letter to the Chinese was completed with several words congratulating the management and the technicians for achieving an extraordinary feat of having a new rabies vaccine for human use on bioreactors under a continuous flow system.

Three months later, David received news from Guanyu Inc. One assistant fellow and the director claimed that the vaccine could not be placed on the market, since there was no approval yet from the government. Consequently, the assistant specified that the company would not pay for the project phase until the vaccine had been officially registered and could be sold on the market. David was furious; this was not what the contract specified. Newvac Inc. could not be responsible for the work of the government to approve the vaccine for the market. It could take several years to conduct clinical trials in various phases and other tests to determine the product’s shelf life. The promise by David and Newvac Inc. was to produce a vaccine that would approve all quality control tests, including potency tests. The vaccine had already passed all quality control tests, so Guanyu Inc. was responsible for following the contract specifications. They had to wait for a positive answer.

While waiting for news from Guanyu. Inc., David was invited to go to another city to discuss another high-density technology project for producing the rabies vaccine. David already had the opportunity to visit nearly twelve vaccine manufacturing enterprises in China in the same number of cities. Most wanted to have the high-density perfusion technology they had heard of. Each was in different phases of developing or producing rabies vaccines for human use. David and Dalila, accompanied by Deshi, attended this invitation to Bolin, a city in northeast China.

The hosts waited at the airport to welcome the visitors. They were all accommodated in an extensive black limousine and taken to a unique Chinese luxury hotel. It was clear that they wanted to make a good impression on the visitors. That was the first tactic to arrive at a fair deal in the negotiations. After settling in, the visitors were taken directly to the vaccine factory. The locals had a large building divided into two sections: one area was for the industrial production of a rabies vaccine for human use utilizing glass bottles, and the other was for the research and development of a cell high-density system. David and Dalila were admitted to the research laboratory in street clothes with only a head cap and plastic shoe covers. Various rooms, equipment, and vessels were shown, emphasizing different bioreactors, so the visitors assumed there was no rabies virus in any of these areas and did not care to ask.

The host showed the visitors one bioreactor identical to the one utilized by Yawen Inc. They obtained decent cell concentrations but claimed they could not get a sizable virus amount. David and Dalila went through the room, and Dalila asked, “What do you have in the bioreactor?” The dreadful answer was “rabies virus.” David, Dalila, Deshi, and the hosts were in street clothes, with no laboratory garments and no face protection, walking through a laboratory where a concentrated live rabies virus was being grown. To make things worse, Dalila had not been vaccinated recently against rabies; hence, she was entirely susceptible to the virus. The careless and irresponsible behavior of this Chinese company could have caused terrible health problems. David vehemently complained to the hosts, but they did not pay much attention. They were probably used to that way of handling things, even with a highly pathogenic virus.

The group then entered a room with several small stainless-steel vessels and a sizable 250-liter vessel. David asked what they intended to cultivate in that large bioreactor; the answer was that they would utilize it for high-density cell technology. David explained to the hosts that the system would be a batch production for that bioreactor size. If they ever developed the technology at that size of the vessel, the vaccine price would be astronomical and not competitive. Moreover, they first had to develop the technology on a small scale and then scale it up to that size vessel. They had never thought of that simple fact. If ever accomplished, the whole process would be long and enormously expensive and could never be successfully marketed.

The visitors were then taken to the board room to discuss acquiring the high-density system from Newvac Inc. David explained, as had been done on numerous occasions to other companies, the conditions under which a technology transfer could be negotiated. The hosts displayed considerable interest. However, they claimed to be only interested in the SOPs for downstream procedures, especially for virus growth and purification. David slowly and carefully explained that anything related to the conditions for cell growth would affect the downstream viral status. They could only improve the quality of the virus if they verified and improved the circumstances and processes at the start of cell growth.

The meeting ended with David letting them know that if they decided to change their minds, they could contact Newvac Inc. again. David, as had happened multiple times, had yet to hear back from them. However, another friend and researcher from another laboratory later told David that the company had not produced a single dose of the rabies vaccine. Their interests were more about financial or political matters.

As mentioned above, David’s company had to wait for news from the other company, Guanyu Inc., which was supposedly waiting for the government’s answers before starting the final scale-up of the product. It had to wait for the results of the clinical trials on the volunteers and then for government approval and certification of the industrial production plant to start marketing the product.

Five months later, certain disturbing news was received. Law enforcement officials had taken the general manager and the production and quality control managers into custody; they had been accused of falsification of vaccine products. All the rabies vaccines that the company had produced on roller bottles did not pass any quality control test. The directors of Guanyu Inc. had unlawfully decided to obtain packaging materials from a competitor vaccine manufacturer. They filled them with the non-conforming vaccine lots they had with the intention to sell.

The government officials later sealed all the company buildings, including the new manufacturing industrial research plant for the new rabies vaccine. This last building was also emptied of products, cells, and viruses. For David and the consultants, the contract between Guanyu Inc. and Newvac Inc. ended abruptly without finishing the vaccine certification tests. A contract payment for the ultimate work trip due to Newvac Inc. was never made. This was another unfinished business without a registered vaccine. David was perplexed and downcast. A new rabies vaccine technology system was completed, and a potent and safe vaccine was finished and ready to be tested in human volunteers—all gone down the drain.

Seven years had passed since Guanyu Inc. disappeared after the horrendous previous events. A new group of investors bought the factory and research building where the Newvac Inc. scientists had developed the new rabies vaccine. The new owners sought a high-level technician to head a new attempt to bring about the technology. After searching and not finding a capable Chinese inside the country, they finally decided to look for a brain-drained Chinese in North America. The new owners had to offer sizable remuneration to convince the Chinese to return to their country. Yazhu, the new scientist, took over what was then a used but wholly furnished and equipped building for vaccine production. He was probably given David’s complete SOP, which had been handed to Guanyu Inc. many years ago.

Yazhu was now faced with reenacting what had previously been done there and completing any missing links. He was lucky to find at least two of the previous well-trained technicians who had previously been there working for Guanyu Inc. However, there was a challenge: Yazhu had no training in industrial biotechnology, much less in scale-up bioreactor technology. His experience was more on the side of cell laboratory research and development, so he was in for many surprises. He needed someone to go back to solve many uncertainties. After three years of hard work and many successes and failures, he encountered unsolvable problems in keeping high viral quantities and downstream processes, mainly related to the purification of the vaccine to remove residual cell DNA.

After continuous testing and not finding the right path, Yazhu finally decided to look for David and Newvac Inc. He was able to locate David on the internet and asked him for a phone number so they could talk. They later connected on the phone, and Yazhu asked David if he could come to China to assist him in working out effective downstream processes to remove residual cell DNA. David answered that he would be delighted. However, the entire production process must be reviewed to study the downstream processes. David told Yazhu that producing good virus quality and quantity depended on the effectiveness of the downstream process.

Yazhu wanted a different answer: he wanted David to visit the laboratory and review only the downstream purification process, and David insisted that this was impossible. If at all, David would need to do that with his team, and the entire system would have to be reviewed. In that case, Yazhu would have to sign a contract for the services, including some down payment. Yazhu eventually said that he was going to think it over and call back. Many months passed, and Yazhu never called back. His request plainly revealed a lack of knowledge of industrial vaccine production. The quality and effectiveness of a vaccine are related to excellence in the entire process. Six years later, David tried to find out whether Yazhu had ever solved his problems. However, the company had no vaccines in the market. The revival of an unfinished technology transfer project had failed in the hands of inexperience technicians.

This case is similar to the other development projects described in this book. The development of modern vaccines for human use in developing countries is hampered by the lack of expertise, training, and specific knowledge of business administration and primarily by a lack of knowledge of industrial scale-up of large microbiological systems. With sorrow, David again dreamed of the possibility of a vaccine teaching school.

Chapter Sixteen

2012-2014

A Patent Request

Back in Borazon City, David kept working on problems related to his last work trip to Guanyu Inc. Javier, the most audacious consultant of Newvac Inc., was always looking on the internet for new developments about the company. One day, he was disturbed and approached David with puzzling news. While looking for some patents, he found a request for a Chinese patent for the high-density cell and viral system by Yawen Inc., the company in the north of China producing the rabies vaccine with technology transferred ten years before by David´s group. David was chocked. Why in the world could his friends from that company do that? Yawen Inc. wanted to get an undisputed hold of the technology and prevent other companies from competing with the highly efficient vaccine production technology.

Moreover, it was infringing on the contract it had signed with Newvac Inc. The document stated that neither of the signees could ever make any component of the SOP’s processes or contents public. The discovered patent request described in exquisite detail the total critical content of the SOPs. David was furious. He did not know how to handle this treason, but the damage had been done. Now, anyone in the world can access the patent content and obtain considerable information about many of the components of the technology, even if they have not produced a rabies vaccine.

Even if others were unable to replicate the entire system, there were many vaccine competitors who could benefit significantly from many of the content. David got on the phone and called Hu, his closest friend from the Chinese company and the most efficient translator. David asked him if he knew of the patent request; he claimed absolute ignorance but promised to find out as soon as possible. Five days later, Hu called David. He explained that the patent request was an idea of Shun and Su, the finance and production managers of Yawen Inc., the company producing the vaccine. They wanted to show that it was possible to prove the company’s research capabilities while preventing other companies from using the technology to compete with them. David decided to write a formal letter of complaint to Huang and Cong, who were, respectively, the president of the board of directors and the general manager of Yawen Inc. David politely but firmly expressed grief for the action and reiterated the consequences of such a breach of contract.

After two weeks, David received a letter from Cong explaining that it was a misunderstanding by Su, the production manager. The reason for sending the patent request was unclear; it needed an explanation. David informed Cong that he would talk to a lawyer and take appropriate measures. In reality, David did not have a lawyer who knew Chinese laws, and even if he had found one, no foreign lawyer could easily hold a demand against a Chinese company inside China.

Considering the unfavorable circumstances, three months later, David decided to ask for monetary compensation to replace the failed revenues of Newvac Inc. for other projects that had not been able to prosper. David made that request, even though he knew that Yawen Inc. would not accept or honor the petition. After two weeks, Cong’s general manager responded to David’s mail. He said that at the moment, it was impossible to comply with the request; however, the company would consider other alternatives. The answer did not contain any regret or remorse for the behavior of a few of their employees.

Four months later, a letter from Cong invited David and Dalila to go to Shufen City to discuss a new project. David needed to understand how they wanted to consider a new project without attending to the previous request for monetary compensation for the damages infringed upon Newvac Inc.’s currency economics. The general manager sent first-class airline tickets to David and Dalila. After considerable arguments and discussions, David convinced Dalila to accompany him to hear what Yawen Inc. would propose. They had lost much confidence in Yawen Inc.’s directorate. They, however, got on a plane with some resentment and blatant hatred.

The hosts welcomed the couple at Shufen City airport and took them to a five-star hotel. This time, they had a junior suite with a living room, a completely furnished office desk, and a large bedroom with a vast wardrobe. The host group at Shufen City was up to something; they were making a good impression on David and Dalila to mitigate the impact of the previous conduct or to enhance the coming news. David and Dalila retired after an excellent Chinese-style dinner. The following day, after a combined Western and Chinese breakfast, they were ready with great expectations for the meeting.

When David and Dalila arrived at the Yawen Inc. factory, a group was waiting in a large meeting room. Everyone was smiling, joyous, shaking hands, and unmistakably happy to see David and Dalila. Notwithstanding the heartfelt welcome, David sensed that something else was going on. The general manager was first to start talking, giving David and Dalila a warm welcome and briefly describing the latest happenings at Yawen Inc. and the economic progress of the company. He was proud of the business’s incredible growth, and acknowledged that the company started with only 25 employees, and now, ten years later, had over 400.

David finally understood why he and Dalila were there. The personnel were celebrating the tenth anniversary of the company’s foundation. The board’s manager finally mentioned their appreciation for David and Newvac Inc. during its start. He stressed the exquisite technology for vaccine production they had gotten from David and the resounding technological, physical, and economic success that they had. It was clearly stated that everything they had was due to David’s hard work, initiative, influence, and participation. At the end of the meeting, David thanked the board’s manager and executives for the invitation and their kind words.

Another aspect of the celebration that impacted David and Dalila was an elaborate dinner at a fancy restaurant. After several rounds of toast with everyone, a box was brought at the end of dinner, and commemorative silver plaques were inside. Each engraved plaque was inside a beautiful red box lined with red silk. The board of directors’ president handed David and Dalila each the plaque. He also ordered bringing six more plaques for the Newvac Inc. consulting team back home. This elegant gesture still seemed fishy to David. The general manager asked David and Dalila to attend a private meeting with the board of directors the following day. David and Dalila went to bed anxiously, waiting for the next day’s surprise. The company had probably decided to comply with the monetary compensation.

The following day, David and Dalila were taken to the board room, where they met with Cong, Jin, Ho, and Huang, the board of directors. After polite handshakes and smiles, the board’s president, with a translation of Ho, thanked David and Dalila for attending the invitation to visit Yawen Inc. He explained that the company wanted to compensate David and Newvac Inc. for the losses that could have occurred due to the problematic request for a patent from members of the Yawen Inc. staff. The proposal for the compensation was to start a new project to develop a new vaccine for veterinary use, using the high cell density and bioreactor technology. The idea was to prepare a vaccine for hog cholera to prevent this disease in pigs. The Yawen Inc. team was ready to start working with the consultants developing the project as soon David decided. This vaccine for animal use was a project that David had already proposed to the Yawen Inc. staff several years ago without any concrete decision.

Another catch: Mr. Huang needed David to sign some document to confirm that the intellectual property of the technology for the rabies vaccine transferred many years ago to Yawen Inc. belonged only to the original international foreign foundation. The document also expressed that David was the exclusively approved custodian of the technology and consequentially authorized to transfer it. David thought about the request and, of course, waited to decide. He needed to figure out the real purpose of those papers, so he told the Yawen Inc. board members that he had to think it over. Those were enough surprises for the day.

Back at the hotel, David and Dalila elaborated on the real purpose of the papers Yawen Inc. requested to be signed, most probably for the government. Even though the documents described accurate and truthful facts, David needed to be clear about why they were needed. The statements kept ownership of the technical know-how that everyone knew belonged to the foundation. David and Dalila speculated that the real reason was a government request to register in writing that the Yawen patent request could not be ratified, and if that was the case, David could sign it without a backlash. They both decided that it was safe to sign the documents. However, there was still no real compensation for the damages inflicted upon Newvac Inc.’s assets, so they asked for clearer settlements.

The next day, the group met again in the hotel’s board room. The Yawen Inc. staff seemed eager to get David’s approval for the signature and assured him that there was no secret affair. David continued to argue that there was no compensation in the proposed deals; there was only more work on another project. He stated that he appreciated the opportunity but that did not counterbalance Newvac Inc.’s previous losses and the impact on the morale of the Newvac Inc. staff and directorate that the claim of patent had inflicted on them. The Yawen Inc. board of directors requested a timeout and retired for additional private discussions.

After lunch, the group met again. Huang, the general manager in the name of Yawen Inc. staff, revealed that the board of directors had decided to name David as Yawen Inc.’s scientific director for two years, starting immediately with a remuneration on a semester basis. The official presentation of the designation would take place the following day in the Yawen Inc. conference room. David had finally gotten a small monetary compensation for the damages inflicted upon Newvac Inc.’s assets. So all was clear, and he approved and signed the government papers.

With full board members, directors, and research and production staff, a meeting was convened the following day to sign a contract for developing a new vaccine for hog cholera utilizing high-density perfusion technology. The board president, Jin, had asked David if he had a formal coat and tie for the signature ceremony. David did not have one in his luggage, so Jin took him to a store to buy one. The ceremony was formal, with men dressed in coats and ties and women dressed in complete attire. David felt somewhat compensated for previous mishaps. However, he had to return to Borazon City to start working on the SOPs for the new project.

David and Dalila arrived back in Borazon City; they convened the consultants for a meeting and told them about the news. They had a new project for a vaccine for hog cholera. Several years before, they had been involved in the technology for producing the same veterinary vaccine at Totem Inc. in Borazon City. However, this time, they needed to adapt different cells and viruses to the cell high-density perfusion system with micro-carriers, as far as they knew, for the first time anywhere in the world. The reason for this feat was that most developed countries had eradicated the disease from the hog population and did not need a new vaccine technology. This technology was primarily required for developing countries.

The consultants liked the proposal and the new opportunity; they were used to significant challenges, which would be a good undertaking. David summoned the consultants who would assist in developing this new veterinary vaccine: Javier, Grace, Jesus, Laura, and Diego. The latest member was Grace, a microbiologist with a veterinary medicine degree and considerable quality control experience. She had been in charge of potency tests for the rabies vaccine and, at some time, for quality control of hog cholera back at Totem Inc., the veterinary biological company located inside Borazon City. Grace was short, gracious, and always smiling, with black hair, dark brown eyes, and a slim body. She was very professional and prudent, yet quiet, but she exuded a lot of assurance and confidence when she spoke. She was a worthy addition to the consulting team. With the new team assembled, the group prepared for the first trip to Shufen City.

David and the consultants spent two months preparing SOPs to produce the new vaccine. They had previously decided to order new cell and virus seeds for Yawen Inc.; the cell request was easy, but the virus seed request was much more difficult. Twenty-five years before, a female researcher from a European country had developed the hog cholera virus adapted to grow on tissue culture. It was unavailable in international virus repositories, so David contacted the research institute where the virus had been developed.

The senior research lady who did the work on the hog cholera virus was still there, and she was willing to assist. She first needed to know the type of company that would produce the vaccine and whether this company had the technical know-how to take advantage of this particular virus. Moreover, the virus’s intellectual property was in the hands of the institute and not of the researchers; nevertheless, she placed a price on the viral seed at two hundred and fifty thousand dollars. The staff at Yawen Inc. considered this to be high. On the other hand, David remembered that Diego had been at the same European institute many years before, learning some techniques for producing another different veterinary vaccine. He even got the same hog cholera virus seed for Totem Inc. for free. Diego had met the research lady, and he could convince her to find a more convenient way to acquire the virus seed for Yawen Inc.

The director of the European institute would take some time to think it over. Diego sent a letter to the woman researcher in charge of the virus and copied the institute director. When the institute director saw the message, he thought the request was still for Totem Inc. He then explained to the research lady in charge of the virus that they should not charge anything for the seed. The lady was angered; this time, the request was from Yawen Inc., a semi-private company. After a few days, the institute director returned to the research lady and tried to convince her, explaining that the seed belonged to the government research institute. They could risk other government grants if they charge anything for the virus seed because government officials would understand that the institute could independently survive, selling various technical know-how or unique living structures.

Once again, the consultants were ready to go to China and had to get visas. However, they were told by the travel agency that the lines to enter the Chinese consulate at Borazon City for visa requests were becoming extremely long as early as five o’clock in the morning, and the consulate doors opened at nine. They would be better off giving their papers and passports to the travel agency fellow in charge of the task. David thought about the first time he had requested a visa at the consulate several years before, when only one fellow was filling out the application. Travel to China was becoming much more popular among the people of Borazon.

While David and the consultants were stationed in Borazon, other news came back from China. This time, a friend of Ho, David’s friend, knew of leaks from the Chinese government office in charge of pharmaceutical and biological control. Five copies of the rabies vaccine SOPs that Yawen Inc. technicians submitted to that office for the patent request had been distributed to a few vaccine producers in various provinces inside China. The leak was said to have occurred at least two years before this discovery.

The reason for the disclosure was the assertion that none of the companies that had held the SOPs could reproduce the technical methods, much less to get a vaccine ready for government approval. The companies could not publicly complain to anyone, since they had fraudulently obtained the information. There was no information to ascertain whether the authorities apprehended the government officials involved in the leak. The rumors held that several companies had paid up to 100.000 US dollars for a copy of the complete documents.

At the time of writing this book, twenty years have passed since the start of the first technology transfer in China. Despite several disclosures of the original SOPs, there is no other vaccine producer or rabies vaccine on the market with the high-density and perfusion cell culture vaccine besides the one at Yawen Inc.

Prior to the swine cholera vaccine project, on one sunny summer day, David received a note from an Asian business development fellow stationed in China. He was part of the development structure of a multinational vaccine conglomerate and had heard of the successful high-density technology of a Chinese company. He insisted that David was now well-known in the Chinese vaccine and pharmaceutical environment. He invited David to present the high-density vaccine production to the company’s overseas board of directors. The purpose was not quite explicit; they just wanted to listen; however, they would not defray the expenses. David thought for a few days and finally decided that he wanted to look them in the eye. He was also eager to tell them that the technology could not be sold or patented.

David got an airline ticket and traveled to the multinational company’s main headquarters in North America. He would take advantage of the trip and visit a few of his scientist friends. David arrived at the company headquarters. The man who had sent the invitation was there with five top world executives of the multinational pharmaceutical company. The ambiance was quite serious; there were no smiles, just business as usual. David needed to learn how much the entrepreneur had told the board of directors, so deciding what he would say took a little time.

The inviter gave the audience a very elementary introduction of David. They might have already been informed of the guest’s extensive credentials. Directly to business, David started with a very condensed history of the vaccine development project. The audience began yawning, so David accelerated and entered the finished work at Yawen Inc. in China. He wanted to show that the technology had been proven and, more importantly, provided vast revenue to adopters. He then quickly described the technical aspects of the processes. The audience was mute; not a single word was said. Finally, the most technically experienced global health development functionary asked David whether his multinational company could develop the same technology.

David’s answer was assertive; they could. However, it would take at least three to four years to thoroughly prepare it for industrial production. Moreover, if the technology were going to be implemented for an existing product, the complete process to market would take at least five to six years, the same as developing a new product. David also explained that the Chinese company marketing the rabies vaccine had received intensive training in manufacturing the product, with direct assistance from a roster of consultants who belonged to David’s company. David did not offer to transfer the technology, and the multinational officers did not ask for a proposal. The meeting ended without any conclusion.

David thought that the board members were expecting an offer to transfer the technology, and this did not occur. At the end of the meeting, on the way out and outside of the building, the same experienced development officer approached David and congratulated him. He thought that the technology was excellent, beneficial, and highly productive. Unfortunately, he said his company would develop it for products different from vaccines. He thought that perhaps in the future, other scientists would see the use of the same technology to produce other vaccines of importance for the human population. He wished David the best of luck. This ended another encounter with a multinational pharmaceutical company.

David had to continue developing a new method for manufacturing a vaccine for hog cholera. The consultants arrived at Yawen City, this time to work on a project for a vaccine for veterinary use. The technicians and professionals at the Chinese manufacturing plant had never worked on vaccines for animals. They could not imagine selling a vaccine for animals at the same price as one for human use. However, marketing the veterinary vaccine would be much different from commercializing a human vaccine. The general public sometimes does not realize that the vaccine price for animals is based chiefly on the number of doses needed.

The population of swine in China is enormous, as the Chinese are addicted to eating pork. It is estimated that 700 million piglets are born annually in China. Each piglet needs several vaccines before it is sent to millions of Chinese dining plates. To summarize, even if the price of each piglet dose is low compared to the cost of a human vaccine dose, there is a need for considerably higher amounts than those required for rabies immunization in people.

The new team of Yawen Inc. professionals received the consulting group with warmth and openness. The consultants were shown their new offices in the research and quality control building. This time, Jin was the president of the board of directors, and he stayed close to the consultants every time the group was inside China. He became the natural principal host for the Newvac Inc. team. Jin would be instrumental to the well-being of the consulting team. At that time, the general manager of Yawen Inc. was Dewei, a woman who had previously been the marketing manager. She did a fantastic job as head of marketing, so the owners thought she could be an excellent general manager. Sometime later, they would regret it. In the meantime, the group had to deal with her. There were other problems covering the relations with the manager, a woman who lived in the vast capital city and had to travel two or three days a week to Shufen City, so she was absent for long periods. Moreover, she was unfamiliar with technical matters, so little leadership came from that end.

Consultants observed the recently constructed research building of Yawen’s from the inside. It was a five-story building of approximately 5,000 square meters. The first floor was devoted to services and storage areas. The second floor housed the central quality control laboratories for production and research activities. The third floor had about ten rooms with different equipment for microbiological procedures, including bacterial or viral microorganisms. A group of scientists from an Eastern European country was working on a project for nosocomial entities (infections related to a hospital environment).

The consulting group had offices on the fifth floor. Aside from the small group of Eastern European scientists, seventy percent of the building was dedicated to little research exercises that did not represent any consequence or collaboration to the production activities. The Newvac Inc. team was going to use only two or three laboratories. Those were located inside a large building with considerable investment in technical spaces and equipment for minimal activities and fewer valuable results.

The Easter European scientists were very friendly and marveled at the work that would take place with the hog cholera virus. They did not have any experience with research on viruses. The group had a project financed by Yawen Inc. to develop a vaccine for the most common bacteria that appeared in hospitals. Many people who attend hospitals while being treated for other causes are commonly infected with these microorganisms.

This type of ailment is called nosocomial disease. Determining which bacteria to use to prepare the vaccine is difficult. Different hospitals have different microorganisms, which are the most frequent bugs. Hence, there is a need for a compound vaccine with several strains and types of bacteria.

As it came to light, the European team had been at Shufen Inc. for over three years, and the results were not substantial. The most common bacteria they found affecting hospital patients were not very immunogenic. Moreover, there were some differences in the genetic composition within the same bacteria type; hence, it would be tricky to utilize several strains from the same bacteria. If, by pure luck, the researcher found several highly immunogenic bacteria, each bacterium had to be cultivated separately, tested, and combined in one formulation. This process was costly and had a limited probability of success. To complicate things even more, physicians at the hospital had, upon arrival, to convince patients of the vaccination to allow some time for immunity to develop. Hence, the market volume was less restricted and economically unsustainable.

One year later, David learned from Ho that the general manager had to cancel the contract with this group. Yawen Inc. had spent four years supporting them regarding supplies, laboratory facilities, office space, transportation, lodging, etc. No product or vaccine was at hand or even close to being certified. With several research and development investments that Yawen Inc. had made in the previous ten years, the only one giving them revenues was the rabies vaccine for human use, on a signed contract with David and his company.

The Easter European flaw did not deter the new management from using the magnificent research building for several secret kinds of research. The only information leaked was connected to projects on pharmaceutical products and ways to improve or update the production of the old rabies vaccine. The consultants continued with the development of the hog cholera vaccine. The Chinese counterparts had refurbished an old building that had previously been dedicated to researching another viral disease affecting the human population. As expected, precise results had yet to be obtained, but they had made a considerable investment. They decided to stop the old project and dedicate the old building to the hog cholera project.

Work in the laboratory made sustainable progress in a short time. The consultants began to prepare the master and working cell banks. At the same time, it was discovered that one of the bioreactors had already been adapted for a high-density cell culture system. It was evident that the research team of Yawen Inc. had another study without any outcome. The old small building had been refurbished carefully and had well-equipped laboratories. The vaccine’s in-process and final product quality control had to be done on laboratory rabbits; hence, a well-designed and well-built animal house for rabbits was available in the same building. One visiting consultant with considerable experience handling laboratory animals was responsible for the entire virus and vaccine testing operation.

The Chinese professionals were skeptical of the need for more clarity in the consultants’ observations of virus multiplication. It took a lot of practice for the local technicians to become acquainted with evaluating virus multiplication and an appropriate reading of the rabbits’ positive immunization. After at least fifteen bioreactor trials, the multiplication of the HC virus started to level off. Once the HC virus was cleaned and concentrated, the formulation trials were started.

One day, the general manager of Yawen Inc. approached David. She wanted a meeting with David and her high-level technicians. The purpose was to discuss their difficulties with manufacturing the rabies vaccine for human use. Dewei, convened the meeting. The technological leader explained that they needed to obtain adequate cell culture concentrations. The cell counts were much lower than they used to have been 5 years before. He acknowledged that the most critical factor that had been in decline was the rabies virus titer. With lower virus production, the total productivity and efficiency of the operation decreased.

David carefully listened to the Chinese but wanted more information from the contents. Numerous faulty details could be missing from the simple description of the production processes that the Chinese technicians were delineating. As usual, the Chinese needed more support to accept that they had some production difficulties and lower productivity than a few years before. They had some lower rabies virus titers but were unaware or did not accept that they had other hidden process failures. After thoroughly analyzing the possibilities, David told Mrs. Dewei that he would prepare a program of work and a new contract to tackle the low virus productivity.

David’s program and contract included many trials to be carried out in a building where the company had a complete production outfit and had already tested some improvements in the rabies virus titer, but they had failed. After one month of discussion and a new plan, the document was elaborated. The second part of the document included a proposal to develop an entirely new rabies vaccine utilizing different components and processes to improve productivity, higher cell counts, better quality viruses, and, most importantly, the absence of any components from animal or human origin. The documents were sent to Mrs. Dewei. David never heard again from her.

The consulting group, with David’s leadership, had to return to Shufen Inc. to continue working on the hog cholera vaccine. During this new trip, the group had to concentrate mainly on different vaccine formulations. Then, they were tested for the induction of antibody response in the rabbit efficiency test. Grace inoculated the rabbits, and a local technician examined the animals and read, evaluated, and interpreted the results. The local technician concluded that two formulations qualified the product as a potent hog cholera vaccine; he also mentioned that the interpretation was correctly emitted and corresponded to the potency test found in Chinese pharmacopeia. The consulting group of experts had already given the same interpretation and concluded that those formulations also qualified after the heat stability test.

A week later, Mrs. Dewei told David that the local technician had told her the tests were invalidated and had to be repeated. David was angry and informed her that Newvac Inc. could not accept any misinterpretations or changes in the data already obtained. He explained that the formulations had already been subjected to the potency test and had passed it. Moreover, a rise in the rabbits’ temperature would detect the pigs’ immunization. This was precisely the result the Chinese technician had reported; there could not have been any mistake.

David concluded his response by citing the contract. He gave Mrs. Dewei the invoice that covered the last phase of the agreement. The final product had passed all the quality control tests; hence, the compensation was immediately due. Mrs. Dewei said she would consider the request and reply immediately. David and the consulting group had to go back to Borazon without knowing if they would get paid for the latest development of the hog cholera vaccine. After four months without any sign from China, David wrote a note to Mrs. Dewei asking for the overdue payment of the last phase of the contract. In a brief message, Mrs. Dewei answered, saying they had submitted a request to the central government to approve the pilot vaccine.

She claimed that the government answered her by explaining that the government was not ready to approve any private company to fabricate and commercialize a veterinary vaccine. She finally added that, as a consequence, Yawen Inc. would not make any other payment to Newvac Inc., since there was no vaccine to be commercialized. David wrote again to Yawen’s Inc. directorate, claiming they had the complete technology and could produce the vaccine once the government gave private companies the go-ahead to commercialize it. No answer was received in the following two years. Once again, another technological transfer project ended without complete compensation for the transferor and the knowledge stationed inside a shelve on the transferee. Nevertheless, the production of a new potent and safe vaccine for hog cholera was completed using high-density and perfusion technology.

David later learned that despite the Chinese company not covering the total payment stipulated in the original contract, it went ahead and patented a method for producing a classical swine fever live vaccine using microcarrier high-density cell culture technology. It was published in a Chinese patent office newspaper. David and the consultants only learned this fact several years later. This lack of transparency irritated David and his company; the consultants also criticized and described Chinese behavior as opaque and unreliable.

Chapter Seventeen

2014-2017

Underhanded

After finishing the hog cholera vaccine development, Newvac Inc. was called to attend several consultancies in a South American country and North Africa. One day, after listening to those requests, David received an email from Deshi (the retired bioreactor designer) asking if there was any interest in transferring the high-density technology to another Chinese company. David thought this company would register a rabies vaccine, which was a new process, so he nodded in agreement. The company was Yihao Inc., located in Luo City, another populous conglomerate in southwest China. A week later, the company’s general manager wrote an email asking for an estimate of the technology transfer program. David prepared a budget for organizing the SOPs, the pilot plant’s design, and the in-situ training of local technicians. The plan would last eighteen months, up to the testing of three pilot vaccine lots, ready to be submitted for government approval.

After only three weeks, David received a note accepting the conditions and requesting a draft contract. Both parties sent, approved, and signed the contract proposal as specified; Yihao Inc. had to send a bank transfer to cover a down payment to guarantee the deal. David received the transfer, and the project started. The proposal contained drastic changes in the technology structure that had previously been transferred to other companies. The new system contained modifications of cell culture media, cell type, virus strain, bioreactor design, and even a new purification system. David contacted members of the old team of consultants and found Diego, Laura, Grace, Jesus, and Javier.

The new group gathered various times to write a new set of SOPs. The original product’s main objective was to eliminate all components derived from animal or human origin in the production process of the rabies vaccine for human use. After reviewing what was at stake, the group found several elements to be removed. The most striking was the use of FBS in preparing the cell culture media for enhanced cell growth; the new cell growth media was free of FBS. Another aspect was trypsin, an enzyme needed to detach cells to make passages from one container to another. The trypsin utilized in the vaccine process was an extract obtained from swine tissues. The new cell culture media was free of trypsin.

The last was human albumin, utilized in several countries, including China, as an additive in producing and formulating the final rabies vaccine product. The primary purpose of adding albumin was to enhance the immunogenicity of the vaccine and, at the same time, to assist in the long-term preservation and stability of the product. Human albumin’s presence in vaccines was, for a long time, a matter of sharp divergence and criticism among industrial biotechnological companies. The main point of scrutiny was the origin of the source of albumin. For several years, as described at the beginning of this manuscript, albumin from a French laboratory originated from human placentas from African countries. This created the risk of spreading several known and unknown viruses or other microorganisms that could go undetected into the final vaccine products.

The original rabies virus utilized in other projects came from a repository in a developed country’s government health science department. David asked this outfit for the availability of the virus. The answer was that the old rabies virus was no longer available. Moreover, he was told that the old virus was contaminated with a bug, which they had cleared through highly sophisticated genetic techniques. The old mature virus strain had previously been given free of charge to any country and every vaccine manufacturer from the original European institute. However, the new free virus would be provided upon signing a contract and paying royalties to the government repository. David was curious if Yihao Inc. would accept it, so he sent a letter informing Xiaoli, the general manager, of the current events.

After two weeks, David received the answer: The company would pay royalties after discussing the product quantities involved. The consultants continued completing the SOP and describing the quality control measures. One month later, Xiaoli sent another request; he had the idea of using an already built warehouse to modify it into the vaccine production building. He sent pictures of the outfit to David with a detailed layout and complete measurements. After a thorough analysis, David emailed Xiaoli, stating that it would be ideal for initial industrial vaccine production with few modifications. David had analyzed the proposal and needed help understanding why Xiaoli was thinking about industrial production when the work had yet to start in a make-up or pilot laboratory.

To David’s surprise, one month later, he received an email from Xiaoli asking for a budget to prepare architectural drawings of the industrial plant to be built in an old warehouse. David sent a down payment budget, Xiaoli approved it, and a month later, he sent the down transfer payment for the architectural drawings. It took David and the group five weeks to prepare draft drawings with the assistance of an experienced architect. After three weeks, Yihao Inc., with minor modifications, approved the drafts. David discussed the final drawing proposal with the consulting group and sent the final complete drawings two months later. One month later, Yihao Inc. covered the remaining invoice for the cost of the architectural designs. David was astonished; this was the first company that had been so expedited in covering all the payments right on time. Moreover, the new company did not have a rabies vaccine process. Still, they already had a design for the semi-industrial production of the vaccine; however, laboratory work to produce the first cell and viral culture had not even started. David was now wondering whether this new project would be a success or a complete failure.

Yihao Inc. now had a brand-new design for a vaccine manufacturing company in Luo City, China. There were some difficulties, however: the company needed technology to fabricate the product, much less the elements and equipment. Yihao Inc. and Xiaoli, the manager, had started a project and a few investments, probably with the wrong footing. After another month, the printed SOPs for only the cell culture system were ready and sent to Yihao Inc. The Chinese studied the documents, and a month later told David they had rented space in research building where other projects were being conducted; they even sent drawings and pictures of the rooms and some equipment the project could utilize.

David and the consultants studied the pictures and rooms and were initially convinced that they would have everything needed for the smooth evolution of the project. At this time, the cell and virus strains previously ordered had arrived in Luo City. The Chinese ordered the materials and cell media components, and when those came, it seemed that everything was ready to start the cell culture laboratory work in situ. David summoned Diego, Grace, Jesus, and Laura to do this assignment. With visas issued, Dalila and David made airline reservations for the group and began traveling to a new technological transfer adventure. This time, it seemed completely different, with people ahead of previous companies and with more vision and resources.

When the group arrived in Luo City, two fellows welcomed them at the airport. One was Xiaoli, the chairman of Yihao Inc., and the other was Hong, the business manager. The group would stay for three and a half weeks preparing the master and working cell banks. They also reviewed and validated the equipment and materials for viral growth and downstream processes. The group arrived at the hotel and found a lovely building from an international chain. The accommodations were quite comfortable; the restaurant was more Chinese than occidental, and the food was a pain in the neck for the consultants.

Xiaoli was a man in his mid-sixties with big eyes. Despite being Chinese, he was thin and had a semi-bald head. He always laughed and appeared to be a good and decent man. He spoke reasonably good English, which was uncommon in China for a man his age. Based on how the project started, he probably did not know much about biotechnology and much less about vaccine production. David had not seen any project, beginning with designing the building and industrial facilities for a final product when no product was in sight.

The other fellow who welcomed the group at the airport was Hong. He was running the show; he told the group he had a master’s in business administration from an Australian university and had recently returned to Luo City. He and his wife, Olivia, had both taken degrees in Australia. Olivia had a finance degree and was also a member of the company board. Moreover, she was Xiaoli’s daughter. Up until then, it was a family business. Hong was a man in his forties with dark black hair. He was short, thin, and calm. He gave instructions and organized most things, even though he knew little about biotechnology.

A great advantage was that Hong and Olivia spoke almost perfect Chinese English. On top of that, it was the first time David and Newvac Inc. consultants would work with directors with postgraduate degrees. David thought that it was quite something to have such favorable conditions. It could not be better; the communication would be fluent. Olivia was a young girl at the end of her twenties. She was happy and easy talking. Her appearance was of a high school girl with matching outfits, and she was also good looking and pretty. Nobody can find a better arrangement, even with technological entrepreneurs.

The next day, the group was invited to the laboratory to see the preparations for starting the project and working on the cell bank. There was a surprise. The rooms for the laboratory work did not resemble the pictures Xiaoli had sent. The laboratory was located in a large five-story building with rented space for entrepreneurs and different rooms for research on various subjects. Xiaoli rented the area where other people were researching a bacterial agent. The two groups shared the same space. A few rooms were devoted to the rabies vaccine project, but the other project occupied the rest of the area. The office space for Newvac Inc. was shared with technicians from the other project.

It was clear to David that this new family company had started with the wrong footing. They knew nothing about biotechnology in general or much less about vaccine manufacturing. This group was in the wrong place. The matter had to be taken with supreme care. After examining the facilities, the group got together in the meeting room, which later was also going to be converted into the office for the Newvac Inc. scientists. Xiaoli introduced another member of the Yihao Inc. team. His name was Chuping, and he was in charge of laboratory work with other assistants. He spoke fair English but was readily outspoken about the laboratory work. After some discussion, it was clear that Chuping had already done some laboratory work with other cells inside the area set apart for the project. There was a debate over the process of preparing the cell banks, which lasted for multiple hours. Chuping wanted to do things the way he liked, inducing him to have experience in the procedure. Consequently, that was the beginning of a problematic relationship with Chuping and the rest of the company.

David went from complete complacency in working with these people to total astonishment and regret of being in that city. The consultants and David were not expecting that a member of a technology recipient company would argue right from the beginning with the transferor team’s science technicians and propose to do things the way he had done it before. What kind of technology transfer would evolve from this project? That evening, David and the consultants met at the hotel and examined what they had seen. Unanimously, they were also astonished at what they had encountered. This was their first time encountering a laboratory with two completely antagonist projects sharing the same space. This action in itself violated the most explicit mandates of isolation. Arranging this work without any countermeasures to avoid cross-contamination was even more worrying. The idea that the rabies virus could be handled inside such a workout made things even more perplexing. David and the group had to decide what to do next; they even considered leaving the city and forgetting about the whole mess.

However, Newvac Inc. had already invested considerable work in preparing the SOPs, finding cells, viruses, laboratory design, etc. The team convinced Xiaoli, Hong, Olivia, and Chuping that the project could proceed with a less hazardous road ahead. The first thing was to persuade them of the convenience of working at different times on the two projects to avoid crossing between them. Additionally, it had to be stated that the rabies virus could only be worked inside this laboratory if some changes were made, including complete isolation from any other project. The team could start preparing the master’s and working cell banks if the separation of the two dissimilar projects could be obtained. So the next day, David only asked for a private meeting with Xiaoli, Olivia, and Hong. David explained their cumbersome arrangement of two projects sharing the same work area. They had to look for a solution to this impasse. The whole day was spent in meetings, arguments, and discussions on the same subject.

The following day, Xiaoli informed David that the people running the other project had agreed to stop their work for four weeks so that the Newvac Inc. team could freely work inside the areas. This was good news, so the team reviewed the equipment and materials to prepare the cell banks. A review was made of the areas that could be used to handle the virus and downstream processes. Some rooms were small, crowded with equipment, and had many redundant connections. Discussions on the preparation of the master cell bank continued. Chuping wanted to do things differently from the procedure already written and established by the Newvac Inc. team.

This behavior was another awkward condition not experimented with in other Newvac Inc. projects. The project was supposed to be a technological transfer, not a discussion of how to do things. To add to the confusion, Hong and Xiaoli were involved in determining the best way to go, even though they lacked experience with biological products. The basic SOPs have been tested before and validated in many other places; moreover, minor modifications influence the outcomes of the processes. Nevertheless, after another full day and many hours of debate, everyone finally accepted the cell culture method.

The following day, the work on the master cell culture began with the participation of various consultants, Chuping, and associates. This work lasted the next two weeks, with cell passages every three or four days. Simultaneously, conversations began on preparing the virus banks that would have to follow after finishing the working cell bank. Considering that this was the Newvac Inc. team’s first time in Yihao City, David requested a little sightseeing during the second weekend. Hong and Olivia volunteered for the assignment, and the group headed to a famous local zoo. David was happy that the locals were entertaining the consultants.

When the group arrived at the entrance ticket window, Hong stepped aside, and David had to go ahead and buy tickets for everyone, including one for the supposed hosts. It was the first time that David would not be invited by a local Chinese host to at least a simple, inexpensive, and pure entertainment. This was another gesture of the tight-fisted cultural custom behavior of some Chinese. There was an exception: Xiaoli learned of Diego’s keen desire for highly spicy food. So he frequently decided to invite Diego for a meal at a special place where they served the most spiced food in town. Nobody else joined them for the adventure. Xiaoli and Diego had a wonderful time together.

After two weeks, the master cell bank was completed and ready to initiate the working cell bank. The procedure for this task was discussed with Chuping, Xiaoli, Hong, and the consultants. When the details were accepted, Chuping had to complete the assignments. The consultants were almost ready to go back to Borazon City. However, under continuous pressure from the hosts, the consultants spent some time in a meeting room in the hotel trying to define and write the SOPs for the virus banks and virus culture in the bioreactors. The group worked on the documents for another week and left some records but needed help to complete a few details that needed to be defined. The group also left detailed plans for the equipment, reagents, and materials required for quality control of the cell and virus banks once they were finished.

Before the consultants’ departure, Yihao Inc. wanted to show their contract with David’s company to other board of directors’ members. They felt very proud of the deal. The company wanted to follow the path that Yawen Inc. had accomplished in the development of the rabies vaccine for human use. One day Hong invited a company board member to discuss the project with David. The group was sitting at a hotel vestibule, and here came a fast-moving, influential, smiling Chinese. Hong introduced David to the fellow and the visitor, who, without any other words and in perfect English, exclaimed, “So you are the famous David; I finally have a chance to meet the most famous name in the vaccine business in China. What a delight.” David felt somewhat proud but also a little embarrassed. The newcomer was also a proud investor in the new Yihao Inc. experience in the field of biologicals. The remainder of the meeting was business as usual.

David and the consultants’ group left very detailed assignments for Chuping and returned home.

After arriving at Borazon City, David and the consulting group started to work on details for arranging the virus banks and downstream processes. They contacted a new European company that used an ultracentrifugation technique to purify the rabies virus. Many years ago, the Totem Inc. group had already used this type of test in Borazon. The difference between the new equipment was that the technique was on an industrial scale for more substantial volumes, whereas the old one was only for small quantities. This technology would solve the removal of the famous DNA cell residue that had caused so many headaches in previous projects.

One month passed, and Xiaoli and Hong wrote a letter to David announcing that they had finished the preparation of the working cell bank and had started some cultures in a bioreactor. After discussions on the news, David gathered the consultants and could not believe they could have done that feat without skipping some critical steps, such as testing and validating master and working cell banks. The Chinese needed to give details of the procedures that had been followed. David and his team prepared a program for cell cultures for Yihao Inc. and his technicians to follow. The cells could grow to high densities if designed according to the program. The Chinese started several cultures, and the consultants gave detailed instructions by mail for every step during the growth of cells and the bioreactors’ adequate management. A few cultures showed increased cell counts, but they were too modest to be considered high density.

The Chinese should have sent another invitation to the consultants to visit China and assist in setting up cultures and bioreactor cycles. David sent an invoice to Xiaoli to cover the work that had been done at Luo City and the direction of the cell cultures and bioreactor cycles. After two weeks, Xiaoli answered, saying that the work for standardizing the bioreactor cycles had yet to be completed. He explained that they had done most of the work.

There were several emails back and forth for the next six months, until Xiaoli finally decided to pay the invoiced amount. They understood that the consulting scientists had directed the cell cultures and the work inside the bioreactors. They also realized that the payment had to cover just the technical know-how transferred in many fine details of the vaccine manufacturing. David and the consultants continued to send many recommendations for the standardization of bioreactor cycles, but the Chinese needed to follow them. Chuping, in charge of the laboratory work, was doing what he thought was suitable for the cultures, avoiding the directions of David and the consultants. Chuping submitted only some results related to the bioreactor cycles, and much less the quality control techniques they were following.

The results sent by Chupin always appeared to be manipulated and did not follow the regular trend of the process. David often told Xiaoli and Hong that the project could progress only if they followed Newvac Inc.’s instructions. David and the consultants felt that the Chinese had already conducted several cultures with the rabies virus. Moreover, David insistently told them that he and the consultants had the first to go there to handle the bioreactors directly. The Chinese said it was okay for the consultants to go. However, they knew David and the group needed an invitation to get Chinese visas. The same arguments followed for the next four months. To clarify things, David told Xiaoli and Hong that they would have to cover the SOP and the details of the purification procedures in advance. He even sent the invoice to cover that piece of work. The Chinese kept silent.

Six months later, Xiaoli sent another invitation asking David and the group to go there to assist them with viral cultures in the bioreactors. David and the consultants had not participated in preparing the virus banks. It was a mystery how Chuping had done it. Xiaoli insisted that they would cover and pay David’s company for any missing work done by Newvac Inc. as soon as the group finished the purification work. David, as he had replied before, told Xiaoli that it was only possible to go there with advance payment for the purification. Yihao Inc. and its associates have yet to answer a few emails from David asking for the remaining payments.

After the unsuccessful end of his work with Yihao Inc., David looked for other countries that needed a high-density cell culture system. He wrote to the health authorities of several neighboring countries, explaining the possibility of obtaining new technologies to improve their manufacturing processes. Two months later, David received a long letter from a health official from one of those developing nations. He explained that they had discontinued manufacturing the rabies vaccine for human and veterinary use. He said that a few years before, a large pharmaceutical manufacturing conglomerate had offered thousands of doses of the rabies vaccine. The proposal was to give them free of charge for a vaccination campaign. The government accepted them without remorse and used the lavish present well. The following year, the international company made a similar offer for the same vaccine free of charge.

Once again, government officials accepted the offer and thought they could rely on the pharmaceutical conglomerate to provide more support for their vaccine needs in the future. Based on that assumption, they ceased the vaccine production that they had had for countless years. The following year, no offer was made by the international pharmaceutical company. The government officials wrote to the pharmaceutical giant asking for a supply of the rabies vaccine for their needs; they were expecting another free-of-charge shipment. The pharma’s answer was a polite note saying they could no longer provide freer vaccines. The company included a pro-forma invoice with the vaccine’s prices in case they wanted to acquire some doses. That was how the government was compelled to close its antiquated vaccine production and ended up buying vaccines at international rates.

To summarize the contract failure for the technology transfer of the rabies vaccine with Yihao Inc., the main reason was the handling of the inexperienced administrators of a recently established biological company.

The development project also defied the fundamental rules of work with highly contagious microorganisms, like, in this case, the rabies virus. To end the story, the company hid from the consultants’ work to prepare the rabies viral cultures to speed up the project. Finally, they stopped listening to the consultants and continued on their own to try to end the project. The newly established Yihao Inc. invested considerable expenses for David and the consultants, thinking they could manipulate the consulting group and avoid payment for the technical know-how. For the last eight years, no vaccine has ever come out of that society. For David and the consultants, the experience with this Chinese group exemplifies the enormous differences in technology development between Chinese and Western countries.

Chapter Eighteen

2017-2019

Back to Kickoff

One year later, David received an invitation from Mr. Huang, the chairman of the board of Yawen Inc., asking him to come down to Shufen City to see what appeared to be the enormous progress the company had made. They claimed it was all due to the unique technology that David and the group had transferred to Yawen Inc. This was the same company where David and his group developed the first successful technological transfer in Asia for the rabies vaccine for human use 15 years earlier. The invitation included Dalila, so David guessed something else was happening there. Business-class airline tickets were sent, and a month later, the couple arrived in Shufen City in China.

The welcoming scene at the airport was superb. Ho, secretary of the holding company’s board, was there with Shun and Chung, the man in charge of the company at Shufen. The hosts took the visitors to a brand-new hotel in the city’s business center, where they received a junior suit and all kinds of gratuities. As usual, the jet lag faded after a good night’s sleep. The next day, after a semi-western breakfast, David, Dalila, Ho, Shun, and Chung, “the big boss,” met at a small meeting room in the hotel. Chung spoke with tremendous confidence and was full of smiles. He was delighted to see the couple.

Chung clarified that the last 15 years had been quite generous to Yawen Inc.; the company had grown enormously, from 20 employees at the beginning to 420 personnel that year. Its rabies vaccine production increased from 3 million vials in the first year to close to 45 million vials in the previous year. He continued, calling attention to the fact that revenues had allowed the company to build two more manufacturing buildings: a formulation and vaccine filling building, a dispatch building, and a 15.000 square meters five-story research and development building.

According to Chung, even though the company had succeeded, its board of directors had been preoccupied. The company had been investing heavily in several research projects to diversify the scope of its products. It had contracts with several research organizations, but all had failed. The company was still a one-commodity company. Furthermore, several internal attempts to modernize, update, and catch up with the current trend of biological product development have also failed. Even the two previous attempts to develop veterinary products with David’s Newvac Inc. were short-changed with ready-to-use SOPs but without government approval for registration of the vaccines and, consequently, for newer industrial production.

Chung proposed that David develop new cooperation to improve and modernize the old production process and develop new products. The only product that had been producing revenues for the company was the rabies vaccine for human use developed by David and his group. Most of the employees in the company were fully aware of this peculiarity and missed David’s group. David was pleased to hear that his work was being highly appreciated. He remembered how much he had criticized several research projects Yawen Inc. had executed and never completed, especially the one with Western European scientists.

David expressed his gratitude for all the praise from the board’s chairman. He mentioned that he was convinced that they could develop new technical cooperation. He noted that 4 years before, at the request of the previous general manager, David’s company had presented a project to improve viral output and the rabies vaccine purification system. Both projects never received approval, and no explanations were given. He then said that the new proposal should be authentic and truthful. He also mentioned that Yawen Inc. was in debt to Newvac Inc. for developing the hog cholera vaccine, which was never completed and not paid in full.

David reminded them of some recent news about a joint venture between a Chinese government vaccine institute in the western section of the country and a European multinational conglomerate. The arrangement was to manufacture the most common veterinary vaccine for cattle, with the largest market share. Yawen Inc. had received the SOP for this vaccine six years before from David’s group. The company had already lost huge profits and the opportunity to be the first in China to produce that vaccine at industrial levels with large-scale bioreactors instead of roller bottles. The company was in dire need of more state-of-the-art research and development.

Mr. Chung was willing to push forward the current proposal with the company’s new administration. David needed a full understanding of the arrangement, since no mention of recent company management changes had been made. He did not want any surprises. After the visitors had a quick lunch, Chung invited all the staff to the company headquarters. Ho, David’s acquaintance, smiled and remarked that everyone was happy that the company had decided to sign another new development contract with David.

Back at the laboratory complex, there were many smiling people and many old familiar faces. Most original professionals, technicians, maintenance personnel, and office staff were still in the workforce. It all seemed like a new comeback. There were, however, many changes, with the most prominent being in the parking areas of the building complex. Years before, only a few cars had parked near the main entrance. David asked if the company was having a big meeting. The answer was no. He was curious about all the spaces around all the buildings that were now filled with automobiles. There were cars parked in places that were originally only a sidewalk. David was quite surprised to see many high-priced luxury cars near the office building. It seemed that most, if not all, company workers were enjoying a new higher living status. These surprises were enough for that day.

The following day, the visitors attended a gathering in a large meeting room with the entire company’s high-level staff. Everyone appeared happy to see David and Dalila after several years of absence. It was a complete party with only smiles and handshakes. David greeted and chatted with them. There was, however, a new face he did not recognize. A short fellow with a huge smile came in rushing and speaking reasonable English for a Chinese. Board Chairman Chung introduced the newcomer as Zhihao, the company’s new general manager.

Zhihao was a man of cordial manners and a friendly attitude. At first sight, he appeared to be of a mixed Chinese-Western origin. His eyes were bright, his round face with dark brown spectacles covering half of it. He was introduced as a man with considerable experience in biologicals and pharmaceuticals; he had worked for the last fifteen years in several multinational biotechnological companies. He was an excellent acquisition for Yawen Inc. The first words from Zhihao were to explain to the visitors that they wanted assistance from David’s company.

After the introduction, Zhihao called on Su, the man in charge of the industrial production of the rabies vaccine. Su explained to the visitors that they had difficulties obtaining acceptable virus titers in the bioreactor cultures. He said they had also heard of the new technology that could eliminate the need for FBS or any other animal- or human-origin material. They wanted David to transfer that technology to Yawen Inc. David asked many questions concerning the virus titer, but the answers he received did not satisfy his insidious mind. The simple and meager information the Chinese shared was insufficient. David was not surprised to hear that they wanted the new fetal calf serum-free technology and purification processes. There were no secrets between sister companies in the same field in China, and all kinds of information were shared freely. The Chinese were probably wholly aware of the futile transfer of the technology to Yihao Inc. in southwest China two years earlier.

In the next meeting, Zhihao confirmed to David and his wife that they were aware of the work David’s company had entertained in south China with Yihao Inc. in Luo City. He even mentioned that Xiaoli, the manager of the company’s board in South China, had been his friend for a long time. Zhihao added that Xiaoli had visited him at Yawen Inc., offering the complete SOPs for producing serum-free rabies vaccine with David’s technology. Zhihao explained that the offer had been rejected, considering that Xiaoli could not provide a complete package with SOPs and direct scientific in situ training. They already knew that Yihao Inc. did not have any training or, for that matter, positive results on the production of rabies virus cultures. Zhihao explained that Xiaoli was probably blabbering because they had not produced a potent single vial of a rabies vaccine for human use.

Zhihao, the new general manager, immediately told David that he had already been briefed about Newvac’s company and all the previous work between the two organizations. He said he knew about governmental issues but less about in-depth laboratory work and techniques. He emphasized that the fine laboratory work for any new project would only be on David’s watch. David was expecting a biotechnology research and development leader, considering he had recommended that the company hire a high-level Chinese researcher many years before. Zhihao did not wholly match that inclination. However, it was a good asset for the company, and David expected to get along pretty well with his new boss. At least English was not going to be an impediment.

After the remarks, everyone expected the presentation of the proposal for David. Mr. Chung delivered a short speech to clarify the reasons for the board; it had been a long break between Newvac Inc. and David. Even though Chung did not mention details, the immediate resolution was clear. David immediately thanked Chairman Chung and Manager Zhihao for the opportunity to work with Yawen Inc. professionals and technicians on a new endeavor. David stressed that any new project must be executed under stricter confidentiality. He then remembered everyone, that even some of the professionals sitting at the table had previously submitted a request for patenting the rabies vaccine processes that many years before, Newvac Inc. and David had transferred to the Chinese at Yawen Inc. Even though the government denied the patent request, considerable damage was done to Newvac Inc.’s technical know-how.

David also mentioned that previous contracts were only partially completed due to disagreements between the parties. Consequently, according to earlier agreements, Newvac Inc. and David had yet to receive the complete total payments. David made it known that if a new contract was going to be signed, payments had to be made ahead of each contract phase, not at the end of the phases, as had been agreed upon in previous contracts. Zhihao nodded in agreement and told the audience that this time, the execution was going to be according to David’s requirements. He asked David if he would prepare a draft contract document for the Yawen Inc. directorate to study. In turn, they would prepare recommendations and a contract for the final approval of David and his company. David accepted the suggestion and was ready to start working on the draft with Dalila’s assistance. David and Dalila proceeded to an office to prepare a working contract draft.

Forty-eight hours later, David handed a rough but detailed technology transfer contract to the Yawen Inc. directorate and assistants to study and return to David for final approval. The conversations, the whole exchange of observations, and the discussions had revealed an entirely new approach to the relations between Yawen Inc. and Newvac Inc. Yawen’s directorate appeared more open, easier going, and in great need of technical assistance. David was surprised to see the change in the disposition of the high-ranking staff, particularly regarding the need for improvements to the actual manufacturing status. This was comforting for David, but it also indicated other hidden complications.

As usual, the Chinese, as was their culture, were always afraid to openly discuss their grievances. It was unclear what kinds of difficulties the company had in producing the old rabies vaccine. David was going to wait for some time to find out. The couple was ready to return to Borazon City before a succulent meal with the first-level Yawen’s Inc. staff. The toast exchange was exceptional, with a sense of a new encounter.

Back in Borazon, after a couple of days of adjusting to entirely different weather conditions, David was ready to reveal the details of the proposed project to his consultants. He explained that the company now had two simultaneous projects with the same company. He speculated that even the two projects could have many things in common. By developing a new vaccine project, some new techniques could be adapted to improve the vaccine. He insisted that the company and the consultants were used to starting projects from scratch. This time, the work in China had to be straight up. David explained that this endeavor was much more complicated than developing a new system. One significant factor that affected the ease of progress was the reluctance of some technicians to make changes. This was true everywhere in the world, and China was no exception. Many operators felt that there was no need to improve or examine something they had been doing for years. David warned that the consultants would find considerable resistance from their Chinese technical counterparts this time.

The consulting group received the news with great enthusiasm. They mentioned readiness to accept responsibility for the two projects. David explained the preliminary work plan, starting with the preparation of the first work trips to Shufen City. They had to prepare the materials, reagents, and equipment needed. More crucial was the plan to find out what was happening inside the production buildings and which problems the Chinese were facing. According to upper management, technicians had primarily informed them of low virus concentrations and shortened production cycles. Whether this had to be analyzed and fixed was unknown.

The group concentrated on elaborating on the first standard procedures for the new vaccine with new cell cultures, beginning with constructing the master and working cell banks. The most valuable asset was the new cultivation media for cell and virus cultures. The new media has replaced all components from animal or human elements; hence, the vaccine should appear easier to purify. Time would tell if this was indeed true. The elaboration of vaccines free from any foreign protein and its derivatives was, and is, the future of safer biological or chemical products for human or animal use.

Once the new standard procedures for manufacturing the initial part of the cell culture of the new vaccine were prepared, they were sent to Mr. Zhihao. An invoice to cover the first phase of the contract was also included. Mr. Zhihao approved the invoice and sent the payment to cover the down payment of the project’s first phase. The Chinese company finally started covering the payments specified in the contract. In China, a group of technicians at Yawen Inc. studied the proposal for standard procedures for cell cultures. Then, the laboratory area where the work would take place was prepared. The best place to execute the new project’s development was a laboratory previously adapted by local Chinese technicians. By themselves, they had been conducting research in this laboratory on the new rabies vaccine production system, utilizing new media without any animal or human components.

The specific virus strain was the most challenging element to obtain in any vaccine project, and there was no exemption for this undertaking. A new virus, tested to be clean of contaminants, was now available for vaccine production from a research biological repository. This time, the research biological repository also asked the recipient laboratory to sign a contract to pay for some minimal royalties to cover the development of the new rabies virus strain. Yawen Inc.’s directorate had no choice but to sign the agreement. The biological repository laboratory needed the government’s clearance. China was not on the prohibition list at that time, so a permit was issued for the biological repository to send the much-desired rabies virus strain. A policy program to control the dissemination of delicate biological materials had been surmounted.

With David’s leadership, the Newvac Inc. team of consultants was ready to start developing the two new projects at Yawen Inc. This time, the consultants were Diego, Laura, Jesus, Grace, and Luis. They were prepared for the first assistance trip to Shufen City, which David and Dalila led. Two weeks later, after procuring the visas at the Chinese embassy in Borazon City, they boarded a plane with their final destination, Shufen, in northeast China. Similar to David’s previous visits, the welcoming reception was very warm this time. The usual reception dinner was completed with systematic toasts for the projects’ success and new renowned friendships among all attending.

The group was provided living quarters at a brand-new Chinese chain international hotel in the middle of the new business center of Shufen city. The hotel had an underground route to a modern shopping mall. The group felt at home with all the accommodations and leisure at hand. Every day, at the end of their work, the team would meet on the hotel’s executive floor to summarize the work done and make adjustments to the work needed for the next couple of days. The executive floor was ample and had a stimulating view of the city center, which was very relaxing for the visitors.

David and the group were highly impressed with the city’s rapid growth, as seen from the executive floor at the building’s top. They saw several new high-rise buildings with 70 to 90 stories in height. Moreover, it was amazing to see a vast park full of trees and walkways, plus the greenery expanded all around, where groups enjoy walking and running. No cities in other parts of the world could emulate the development in this city. This rapid achievement was obvious in various Chinese provinces.

The start of the laboratory work was full of energy. The consultants met with old acquaintances and brand-new technicians. The locals were eager to show them the place where the new vaccine was being made. The consultants were given a tour of the facility. There were a few bioreactors with the design and all the gadgets needed for the new rabies vaccine manufacturing techniques. It was evident, however, that the equipment had been in use for a long time. David and the consultants felt some relief, thinking that nothing was missing. Still, they felt uneasy, thinking that the local technicians had already tested many things and had failed. Moreover, the locals were reluctant to accept that they had already tried many things, resulting in continuous failures. With that in mind, David and the group prepared to start from scratch.

Everything appeared to be in place; the cells were appropriately stored, and there was enough cell culture media. So the group started fabricating new cell banks. However, the project’s work to improve the actual vaccine was much more complicated. The work would be done in a laboratory in which local technicians produced viral harvests identical to those formulated and sent to the market from the industrial building. However, this building had yet to be approved or certified by the government, so the viral harvests were discarded.

As usual in a Chinese environment of this type, the Chinese were mute concerning the results being obtained so far to improve the current vaccine or if the idea was to get approval from the government to utilize those areas to expand vaccine production for the market. With this predicament, David and the group started to make plans to introduce slight modifications, starting from the beginning of the production process. It was essential to emphasize that the main goal was to obtain a virus of better quality and with better immunological characteristics.

David remembered how, five years before, at the general manager’s request, he had proposed the same two projects, and the Chinese had not approved them. Under David’s watch, it was becoming evident that the Chinese had been doing research for many years to improve the current rabies vaccine while trying to develop a new vaccine without any human or animal serum. However, both had categorically failed. David speculated that even though this Chinese group had worked on basic cell culture technology for rabies for over 15 years, they still needed basic biotechnological knowledge. They had only been following written SOPs for all these years. They could not technically or scientifically modify their current manufacturing procedures, much less develop an entirely new vaccine system.

To continue the work, David decided to split the consulting team into three groups to facilitate the supervision of the work in such diverse conditions and different laboratory settings. Diego and Grace were primarily assigned to the technical research building, where the new vaccine would be developed, while Laura and Jesus were assigned to the old workshop to improve actual rabies vaccine production. To complete the assignments, Luis would supervise all quality control techniques and analyze the results. In each of the two working areas, Yawen Inc. had already assigned three local technicians to assist the consultants.

The first and most striking finding in the current vaccine production was related to the low level of cell concentration during the operation of the bioreactors. Fifteen years earlier, the consulting group had previously left the bioreactors’ standard operation at 12 million cells per cubic centimeter. Still, the bioreactor’s cell concentration was only 8 million per cubic centimeter. After so many years of operation, this was considerably different from the original technology. The low cell concentration level meant low rabies virus production, diminished viral quality, and transformation of the cell-virus production system. The reasons for this striking change were unknown to the Chinese, or maybe they wanted to keep the secret.

All the operational parameters of the bioreactors in the research workshop were analyzed and compared with the conditions initially set up. It was evident from the start that the local technicians had made considerable modifications to the functioning and operation of the bioreactors. How much influence each cell culture modification had on the apparent low virus quality was unknown. However, there could have been other alterations to the original technology. The Chinese were mute about so many problems that might have happened.

For the consultants, several lengthy international trips ended with health problems. This time, David started to develop chest pain and difficulty breathing, so a visit to the nearest hospital was warranted. The physician in charge, using Ho as the Mandarin translator, listened to David’s complaints and, after a thorough physical examination, gave his diagnosis: David had acute pneumonia. The doctor had to confirm his assessment, so he quickly ordered an X-ray chest examination. With the help of Ho, Dalila paid for the examination using an electronic machine that already had the order and was conveniently located in the hospital corridor. The machine printed the payment confirmation, and with this paper at hand, the group headed for another hospital floor and looked for the X-ray room. The technician there told Ho to sit with the patient for fifteen minutes while the equipment warmed up.

After twenty minutes, the technician appeared, asked David to enter, and took several X-ray pictures. He asked David to wait for another ten minutes so that he could print the images. When the pictures were printed, the technician immediately asked him to hand them to the examining physician. The group returned to the original examination room to give the printed images to the doctor. He was busy with another patient, so he asked David to wait outside for a few minutes. When the doctor finished with the other patient, he asked David to go in and, after examining the X-ray pictures, told him his diagnosis was correct. David had to be treated immediately to control his acute pneumonia. He sent David to another room with an order for antibiotic injections. David paid for the treatment at the cashier and was rushed to another enormous room full of beds, only three meters apart from each other.

Afterward, a nurse carrying a large medicine bottle was ready to prepare David for an intravenous injection. David, in rotten Mandarin and with a few gestures, asked the nurse to let him see the bottle’s labels. After reading them, David knew it was from a well-known European manufacturer, so it was safe. The nurse asked David to remove the jacket, lie in bed, and then introduce a needle in an arm vein to inoculate the medicine. The girl asked David to stay quiet for an hour until the medicine bottle had been completely emptied. When the time was up, the nurse removed the needle and asked David to return for five more days, every twenty-four hours, to complete the intravenous injections. David completed the prescribed treatment, and the ailment subsided. As before, with other Chinese health treatments, the hospital staff, physicians, and assistants were diligent and gave David excellent treatment. In other countries, the same treatment for acute pneumonia would have required complete hospitalization for at least five days. In China, treatment as an outpatient was quite simple and ended with a complete recovery.

After the health mishap, the consultants were ready to return home to Borazon City, so they left some assignments for the Chinese technicians. Back in Borazon City, David and the consultants met regularly every week to review the preparation of the cell and virus banks. Two months later, the consultants returned to Shufen to start the work on the bioreactors for the new vaccine and to continue in another building with an analysis of the actual production technology, where the manufactured vaccine was not being sent to marketing. The work on developing the new rabies vaccine proceeded with Diego’s and Laura’s supervision. As mentioned, the counterpart technicians appeared familiar with these new processes, which was a big surprise for the consultants.

Analyzing the project to improve the manufacturing processes for actual vaccine production, Jesus and Grace found more complicated issues. The area, apparently identical to the one producing the existing vaccine for the market, was confusing. One simple observation was that certain stainless-steel vessels were ten times bigger in capacity than the regular ones utilized in the main industrial production building. They were empty but raised some concerns for the consultants. The question was whether the local technicians were trying to scale up the processes to much larger bioreactors without the knowledge of the consulting team. The local technicians did not accept using those vessels for any tests; they claimed to have no idea of their use—another awkward reaction to blindfold the consultants. The Chinese were hiding another type of experimentation with no apparent success.

Furthermore, the regular bioreactors utilized in this area had some minor modifications compared to the ones used by the consultants fifteen years earlier in this same company. Grace and Jesus supervised the setup of two bioreactors handled entirely by local technicians. There were minor structural differences; however, the cell cultures grew much more rapidly than before. It was difficult to decide if that was an advantage for virus multiplication or inhibition. This posed another challenge to investigate. The local technicians and even the professional supervisors did not have any explanation or suspicion to explain the considerable differences in the incredible speed of cell growth. This was another somewhat awkward situation. For this Chinese group, everything is hidden.

This trip of the full Newvac Inc. consulting team was highly productive. The consultants had an excellent flow of information and physical progress, mainly in producing the new vaccine. However, it also left some critical doubts about the possibility of the success of work on the project to improve the rabies virus concentrations on an industrial scale. The consultants explained to the Chinese professionals that starting new cell cultures from the original cell seeds was feasible and simple. The original cell seeds were stored in liquid nitrogen at a temperature of one hundred and fifty-three degrees centigrade below zero. This is how any international cell storage repository has kept cell cultures for at least the previous one hundred years without any modification in cell behavior. This procedure was again suggested to the directorship of Yawen Inc. for consideration. However, it was never accepted, suggesting that a secret was being hidden. How did the Chinese expect to quickly improve the current procedures of the now-old rabies vaccine if they refused to reveal what had been done before and did not want to start cell cultures from the original seeds? This had become a mystery.

The consultants were ready to retire for the day. They enjoyed walking around the hotel’s neighboring park for sun and fresh air during their leisure time. On one sunny day at the end of their regular walk, Dalila and David saw a small group of people in a stretch park corridor surrounded by small trees. When the two curious onlookers arrived at the scene, they saw two men sitting on chairs with a white cloth covering their bodies up to the neck. Two other men with combs and scissors were intricately cutting the hair of the sitting men. Other clients were standing around and waiting for their turn. The scene was amusing for visitors but natural for the barbers and their clients. It was a simple setting for much-needed grooming and was probably much cheaper than a regular barbershop, with no need to pay rent.

David and the consultants returned to China again to work on the two projects. The reception at the airport was not as warm. The technicians and local associates were apprehensive at work in their laboratories. Perhaps they felt that some objectionable secrets were going to be revealed. The consultants speculated that most technicians did not want to participate in modifying the technology or developing a new vaccine. In either of these two options, they would have to learn new procedures, new controls, and new techniques. This would require many more working hours and more complex work until the processes became standardized.

One day, Mr. Zhihao approached David and Dalila. He wanted to let them know that he would be spending much more time at the headquarters company’s laboratories in the city capital. He said that his original living quarters were there; he claimed that he needed to consistently participate in the project at Shufen City laboratories. He added that Mr. Chung was a “powerful man” in the company and would temporarily act as a substitute general manager. At that time, Mr. Chung was the marketing manager.

Mr. Zhihao also told David and Dalila that he was working at the city capital laboratories to complete the development and official registration of several vaccines that the previous general manager had initiated but were not completed. The original company plan was to produce the most common bacterial vaccines utilized for children’s immunization in government health targets. This plan was set out to complete a vaccine portfolio for the company; however, after five years, no vaccines had been registered. This was another reason David and his company were contacted to develop a new vaccine to augment the company’s portfolio.

David received the news of Mr. Zhihao leaving as a huge surprise but was relieved to hear that Chung would be the new man in the decision-making post. A similar situation had occurred in the company several years earlier. A lady who was the marketing manager had been moved to the general manager’s post, which proved to be a disaster for the company’s progress. This time, it was going to be different. Chung had been a good friend to David, so he expected a reasonably good relationship.

The work in the laboratories continued at a reasonable speed. Several bioreactors continued with acceptable results in the project to develop a new vaccine. The most significant cell counts came from the cultures with the new modified medium without animal or human components. The cell growth was superb, at three times higher than the counts with the previous cells grown in the old cell growth medium.

This was not necessarily complete advantage. With many cells, the medium could become acid from cell wastes and would not be entirely suitable for virus growth inside the cells. This would be the first significant challenge for the consulting group. The consultants had been used to working in surroundings where cell growth had to be increased with various maneuvers. Now, they had the opposite issue, with too many cells becoming a challenge to address.

Laura and Jesus did not have it easy. Minor modifications to the two cell cultures they were following did not substantially improve the appearance of the culture conditions. However, old cells were growing faster in those bioreactors than in the previous cell cultures of fifteen years. Cell counts were much lower than before but at a much faster rate. This was one of the new company’s difficulties in the bioreactors producing the vaccine for the market. The consultants also had to find ways to slow cell growth to see if that could improve virus quality and quantity.

At the conclusion of the visit, the consultants left some assignments for the local technicians and started to prepare for the return home. They first had to discuss what mechanisms they could research to find reasonable cell counts that would deliver high virus growth. Too many cells would destroy the cultures due to the medium’s acidity; too few cells meant a low virus concentration. The group admitted that seeding fewer cells at the beginning of each bioreactor run was the first course of action for developing the new vaccine. However, the group needed to be aware of the more difficult challenges it would have to overcome with Yawen Inc.

Back at home, some consultants embarked on short, relaxing trips as modest vacations. David and Dalila traveled to a summer retreat with some friends. After a week, David felt some headaches, mild fever, and weakness, so he rested at the hotel while the remaining friends went outside. He took some medicines, assuming a common cold. David felt some relief in forty-eight hours and went outside with the rest of the group; however, it was not the end of the sickness, and he was uneasy. The group was completely unaware of the eminent situations ahead. The news from Asia described a cause of worry: there was an extraordinary outbreak of an influenza type of illness. The center of the outbreak appeared to be located in China. David and Dalila speculated that they must have barely missed it, since they had just returned from China.

One month later, the news from China was extraordinary. Thousands of people were simultaneously coming down with a virus resembling influenza but with more intense symptoms, and many with pneumonia-like complications. The government was taking acute isolation measures in the affected area, but the virus spread was getting out of hand. A few weeks later, the virus appeared in other regions of China. The disease was out of control. By this time, the virus had been characterized as a coronavirus or COVID-19, and the spread of the disease was described as an epidemic.

No vaccine was available to control the disease or its dissemination to other people and areas. A month later, the coronavirus appeared in different countries and other continents. The most striking finding was that asymptomatic persons carried the virus worldwide. It was then clear that a new pandemic had appeared. That word was scary, but the world would be through more surprises. The world was at a standstill; everyone had to stop moving around. Only emergency vehicles and food distribution were allowed. It was uncertain what could happen to Newvac Inc. and the projects running in China. Whether the pandemic terminate David’s quest to establish a vaccine teaching school around the globe was also at stake.

Chapter Nineteen

2020-2023

The Coronavirus Pandemic

Once the pandemic was declared worldwide, China closed its doors. Yawen Inc. was almost entirely shut down. The manufacturing of the regular commercial rabies vaccine suffered a considerable drawback; only a few operators were able to remain inside the laboratories. They established living quarters inside the plant and received some provisions for survival. The Chinese saved only a minimal portion of the cell and viral cultures that were in full growth to prevent the complete loss of the cells. The company’s productivity diminished by close to seventy percent. The scheme lasted approximately five months.

Sometime later, the Chinese government started to ease restrictions, and then a small number of operators in the vaccine manufacturing plant were able to return to work. The group working on the research and development projects with David’s company was divided into two groups by the manager, Mr. Chung, and only half of the group was allowed to enter the facility. The cell and viral cultures growing inside the bioreactors were lost during the pandemic, and now, work had to start all over from frozen cell seeds. The services and supplies for the company were scarce, so the work started quite slow.

Eight months after the declaration of the pandemic, a few local technicians in charge of handling the transfer project with Newvac Inc. were allowed to return to the laboratories. This time, only half of the staff was allowed one day, and the other half could go the following day. The cell culture work started with new cell seeds, and the connection with the transferor team in Borazon City was maintained virtually online. In the beginning, communication was rare. However, after the cells grew inside bioreactors and the Chinese prepared new virus seeds, communication became relatively frequent.

The instructions of the Newvac Inc. team began to be needed more and more because the Chinese recipients felt unsafe, considering that it was the first time they received virtual instruction for the operation of the equipment and tests through written texts on the internet rather than by face-to-face consultation. The matter was more complicated because it was impossible to utilize video, since the company did not allow videos inside the laboratories. Its main concern was to prevent the leaking of its technical know-how.

Every day, the consultants had to answer more complex questions. At the same time, errors in equipment manipulation by the Chinese became more frequent, which meant that several processes had to be repeated several times. The situation was completely abnormal. In the past, the consultants would regularly prepare all the equipment and materials, and the technological recipients would observe and later perform the processes independently. Procedures that in the past took half a day now required at least two and a half days. Soon, communication became a daily affair. Due to the time difference with Asia, the work of the consultants started at seven in the morning Eastern time, with an analysis of the previous day events in China and deciding what to recommend for the following day, as would be late at night for the Chinese. This daily mode of operation continued even after the end of the main pandemic restrictions.

The exchange of communications and instructions from the consultants of Newvac Inc. to technicians in China turned out to be a nightmare. Quite often, the Chinese counterparts claimed that they needed help understanding the instructions from the consultants. On other days, they needed to give complete results. On another occasion, the Chinese did not send the results of the procedures they had already finished. Clearly, Chung and his technicians were handling the development of the technology in a way that slowed down the completion of the contract. Despite these difficulties, the new vaccine project experienced slow recovery. Finally, in the middle of 2021, the cell culture system for the new rabies vaccine in the small bioreactors was entirely standardized. Similarly, the work on improving the existing vaccine manufacturing technology, which was first devoted to focusing on low virus quality, was entirely astray.

Two months later, David received a note from Chung, the man in charge, stating that they had problems starting some bioreactors in the building where work on improving the actual vaccine technology was taking place. There was no mention of how much time it would take to have bioreactors available, so the improvement work could be reinstated after the halt due to the pandemic. Two months went by without any news from Chung. David guessed that the Chinese were doing some work in those bioreactors and wanted to avoid discussing it with the consultants. However, he knew that improving the vaccine system without the direct in situ presence of the consulting team was extremely difficult. He could not imagine if anything could be accomplished through only internet communication. Sure enough, two months later, Chung requested to cancel the contract to improve the actual rabies vaccine available for marketing.

Even though David knew that the Chinese were doing additional work on this subject, it was hopeless for the consulting team to do anything from far away. David accepted Chung’s request to cancel the contract. Yawen Inc. paid Newvac Inc. for the work that had been done up to that time. David also knew that the purpose of signing the contract to improve the actual rabies vaccine was to remedy failed attempts made by the Chinese during the last three or four years. The Chinese had to continue with low productivity, low quality, and perhaps undesired local reactions to the actual rabies vaccine on the market. They probably decided to cancel the contract because they were still earning considerably high profits from vaccine sales. They also agreed that they would continue with the contract to develop the new rabies vaccine technology without human or animal components.

On several occasions, there was an attempt to establish direct verbal communications between Newvac Inc. consultants and the professionals of Yawen Inc. However, obtaining clear, understandable answers from Chinese technicians required a lot of work. Moreover, they had to look for many written results, figures, data, and so on and read them to the consultants at Newvac Inc., but the mistakes needed to be corrected. It was agreed and decided that the Chinese would send the consultants at Newvac Inc. only written tables, figures, and all kinds of results and observations through the internet. Typically, in the laboratory, the Chinese wrote all the results in Mandarin and had to later translate them into English, with many misinterpretations.

The work on the virus cultures for the new vaccine started with preparing the master and working virus banks. With continuous direction from consultants, this work on the virus banks was accomplished relatively quickly, so virus cultures in the bioreactors were ready to start. Once more, David asked Chung to send invitations for the consultants to do the training directly inside the pilot plant and prepare the virus cultures and, later, the downstream processes. The answer from Chung was the same: the Chinese government suggested that no visitors should be received except in real emergencies. The claims by Yawen Inc. did not correspond with those of the Chinese embassies in Latin America, which had been giving tourist visas to those who requested them. It was already early 2022, and the pandemic had been called off. The written daily communications between the two teams continued. Viral cultures and related work that took just six months in the past were completed in over twelve months. However, despite so many difficulties, a few high-quality batches were ready to be formulated into vaccine samples.

Newvac Inc. consultants spent several months researching numerous components that could be utilized as vaccine support and enhancing the immunogenicity of the inactivated virus for approval of the final vaccine. At least thirty formulations were tested in potency tests over fourteen months. Even though the two formulations barely passed the test, the Chinese did not accept them as passing that phase. For unknown reasons, Chung wanted to increase each phase’s duration and the extent of the entire project. Another trial with eight formulations finally gave two formulations that, with a sufficient margin, exceeded the acceptance level of the potency test. The consultants and David were exhilarated; Newvac Inc. finally had another new rabies vaccine for human use, and this time without any human or animal components.

Following the news of the results of the last trials, David sent a note to Chung asking for invitations for the consultants to visit the company so they could complete the last phase of the project and perform at least three scale-up cultures in larger bioreactors to show vaccine production on an industrial scale. David also included an invoice to cover this phase of the project. After close to three months, Chung replied that they were busy with some annual reports for the board and could not start the last phase of the project. David waited patiently. However, he finally decided to write to Ho, the most loyal friend at the main headquarters, to see if he could find out what was going on at the company. A week later, Ho answered, explaining that he had been informed that the vaccine company was quite busy with other projects and that Chung was asking for more time to continue with the industrial phase of the project. It was not specified how long this cessation of the project would last.

The fact that the final formulation trial of the new vaccine was going to be done entirely by the Chinese group without any direct “in situ” supervision by the consultants brought to David´s mind the following anecdote: When Antoine, the European scientist, years before, was working with David´s team, he was getting quite concerned on the final formulation of the rabies vaccine. The reason was that the virus was being grown on scale-up bioreactors and the virus quantities were much bigger that he used to have. At the same time, he was watching the local technicians trying to formulate the vaccine adding only the virus needed to barely pass the potency test, so they could formulate many more vaccine doses. In essence they were diluting the vaccine.

As soon as Antoine realized what was happening, he exclaimed “Do not dilute my vaccine”. Just the opposite was then occurring to the formulation of the vaccine, but many years later in the hands of the technicians from Yawens´Inc. At that moment, David´s group were highly concerned with what was being done in China. They were suspicious that the local technicians were going to dilute the vaccine to augment the number of doses to be sold to increase their revenues. They had to do something. Antoine´s lesson had been learned “Stop diluting my vaccine”

The discontinuation of the project meant a big blow to the finances of Newvac Inc. The last payment from Yawen Inc. had been sent six months before. According to the agreement, payment had to be received before the start of the industrial phase of the project. It was quite uncertain when David could defray the company’s costs, and more worried about covering the payments for the consultants. Two months later, David decided to get a bank loan to cover the minimal wages of the consultants, office employees, taxes, and other company expenses.

David and the consultants speculated that the Chinese had decided to start on their own by the industrial phase of the project, with the scale-up cultures at larger bioreactors. The project obtained a new vaccine, which was another technology transfer achievement for David and his consultants. At the writing of this book, it was unknown whether the new vaccine would soon reach the market and be available for the needs of many people bitten by rabid dogs. David also thought that the original plan to set up a vaccine teaching school was still undetermined.

The long delay in continuing the project, apparently due to the need to develop other projects at Yawen Inc., raised innumerable questions and speculations from the viewpoint of the Newvac Inc. consultants. A few of them thought there was enough evidence from several comments from the Yawen Inc. technicians that they wanted the final industrial phase of the production of the new vaccine. Other consultants assumed that the administration expelled a few local technicians involved in the initial project to improve the old rabies vaccine.

The third consulting group, including David, had yet another suspicion: the rabies vaccine technology that, twenty years before, had been transferred from Newvac Inc. to Yawen Inc., was compared with the technology of one COVID-19 vaccine available in the market since 2021. David recognized that this COVID-19 vaccine had identical technological components to the rabies vaccine that Newvac Inc. transferred to Yawen Inc. Several features are similar: the cell culture where the virus was grown, namely the Vero cell strain; the cultivation of cells and virus in bioreactors with the high-density perfusion system; and the inactivation of the virus with beta-propiolactone. Furthermore, the rabies vaccine and the COVID-19 vaccine are inactivated vaccines. David suspected that the Chinese at Yawen Inc. might be developing the COVID-19 vaccine inside one of their buildings and did not want any foreigner to find out, which may explain why they did not wish to invite the consultants to work in the industrial phase of the new rabies vaccine project.

The consultants were of the opinion that one Chinese COVID-19 vaccine had minimal, if any, adverse reactions in persons who had even three doses of the vaccine, somewhat similar to no reactions or relatively mild, in people vaccinated with the Chinese rabies vaccine. They found this to be quite different from the acute secondary reactions seen in people vaccinated with the COVID-19 vaccines prepared with genetic manipulations. All COVID vaccines were accepted for use in humans without the usual long-term developmental testing, adding that they were for use only during the pandemic. With the World Health Organization declaring the end of the pandemic, there was a need for improved COVID-19 vaccines without any adverse reactions and for a much longer testing period in clinical trials.

The final scale-up phase for the new rabies vaccine for human use was completed. Still, the directorate at Yawen Inc. should have made more effort and accepted that the scientists from Newvac Inc. should go to China to supervise the local technicians and perform the entire procedure. This lack of continuation of the agreed-upon and signed contract meant that Yawen Inc. would not pay David’s Newvac Inc. to verify the industrial scale-up, as stated. The pandemic had impacted considerable tolls on vaccine research and development.

This last effort to conclude another technology transfer for a new rabies vaccine for human use was completed when this book was written. A complete vaccine system technology transfer was completed, and a new rabies vaccine vial was internally approved for all technical parameters. Newvac Inc. completed a new industrial inactivated human rabies vaccine production technology without any animal or human components that was already scalable by using modern perfusion cell cultures inside bioreactors. The new technology operates bioreactors with cell culture concentrations of over 20 million cells per cubic centimeter. It also employed new purification and formulation procedures. Throughout formulation, it is expected that Yawen Inc. will not begin “diluting the vaccine” just to gain more revenues.

Epilogue

A viral vaccine technology transfer program started by a New World foundation in the early eighties had numerous ups and downs and specific accomplishments. A few companies and laboratories made use of the basic technology generated by the foundation’s efforts and the resilience of a good number of scientists and professionals in the vaccine manufacturing business. At least a few products were registered and reached the market, and one Chinese company was birthed through the technology transfer project. Twenty years after its inception, the same Chinese company still produces a novel rabies vaccine that, during this time, has saved the lives of at least 850 million people bitten by stray rabid dogs.

Like many other outcomes, developing basic conventional vaccine production technology for viral diseases affecting the world population has numerous secondary benefits. For China, developing and establishing a modern rabies vaccine for human use has enormously affected the well-being of hundreds of professionals, technicians, and operators working within and supporting the production facility and marketing the product. Many personnel tied to the new business have gone from a meager income to a top-level middle-class category.

To parallel new Chinese families with their Western counterparts, the author found that two vaccine executives of a new Chinese vaccine manufacturing company sent their youths to universities overseas for specialization in modern high-tech communication systems. However, there were no fellowships for these candidates. Their parents had to cover all trips, studies, and expenses. This was a dream come true for the students, and their families were able to defray the high cost of studying abroad. These kinds of students have been returning to their original birthplaces and have significantly affected the well-being of their communities and China’s prosperity level.

Another secondary impact of the long history of vaccine development depicted here has been reflected in the upgrade of China’s vaccine industry. Government officials in charge of quality control have utilized the high standards in the new vaccine manufacturing facility and modern quality control techniques to request an upgrade of many old companies producing different vaccines for human use. Several companies that could not cope with the new high-level requirements were forced out or dissolved by the government.

The Chinese regulatory government branch in charge of registering new products and vaccines has also utilized some quality control techniques developed within the technology transfer project to simplify, upgrade, and make greater accuracy in due processes. The most significant is using a new measuring technique (ELISA) to determine the protein content in the vaccine’s final product. A biochemist and a microbiologist working for the technological transfer team developed and adapted this technique. This procedure has been adopted as a Chinese standard for measuring protein content in all vaccine workshop manufacturers. The government now distributes the gold-standard controls for this test to all Chinese vaccine companies.

The work of a group of foreign consultants in China has shown that the fundamental technology developed for the production of a rabies viral vaccine for human use can be adapted for the industrial production of other vaccines. The most outstanding of these are Japanese encephalitis and, more recently, the coronavirus (COVID)-19 vaccine. For the last three years, 2021–2023, a new company in China has been producing a COVID-19 vaccine, utilizing the same technology transferred in 2002 to a Chinese company from a Latin American company headed by the author.

The new Chinese company uses the same cell substrate (Vero cells), cell growth medium, microcarriers for the cell culture, identical bioreactors, and even chemical inactivation of the virus with beta-propiolactone, a chemical reagent. If the foundation’s original plan were to impart the capacity to manufacture modern vaccines with modern methodologies to several countries, this extraordinary feat would ultimately have been achieved. The new rabies vaccine for human use and the COVID-19 vaccine from China have saved the lives and suffering of millions of people worldwide.

It is essential to acknowledge the main reasons for the memorable success of the now firmly established Chinese company in the rabies vaccine market. Using a technological transfer project, this company is now the leader in Asia in manufacturing a high-quality rabies vaccine for human use. Let’s analyze a few reasons for their success. The first component of any favorable industrial development is having a sizable market. The author estimates that yearly, China now needs approximately 75 million doses of rabies vaccine to prevent the disease in the human population. Therefore, the market was there.

The second most important component for success is having a proven technology—in this case, vaccine production. The Chinese company acquired the technology from a proven provider. The third important consideration for successful vaccine development is the availability of sufficiently trained personnel capable of handling the development process. The Chinese company procured the assistance of a competent technological company and scientists who personally transferred their technology to local skillful professionals and technicians.

The fourth consideration is to have readily available channels for product distribution. Here, the only client to buy the vaccine is the Chinese government, which distributes it to patients at nominal prices. Another central point to consider is the selling price of the product, one that allows the company to make sizable profits for company endurance. The product has a selling price with high profits. Typically, the selling price of any imported vaccine is at least ten times higher than the local production. In summary, the successful outcome of the technological transfer project for the rabies vaccine was entirely assured. The results are now open for everyone to see.

This writing progressively shows the arduous and sometimes painful road to transferring vaccine technologies to countries on the verge of development. The author unsuccessfully tried to transfer the high-density rabies vaccine production technology to at least eleven companies on various continents. Most of these companies are owned by local or national governments. The most probable failure in these cases was attributable to political reasons. On numerous occasions, production directors and general managers were constantly replaced by political reasons, which stalled the continuity of the vaccine research production projects. Moreover, some vaccine production directors lacked biological, technological, managerial knowledge, or training, which sometimes led to inadequate decisions and supervision.

Beyond these challenges, all of the countries contacted had a consistent and undeserved lack of funds, which also resulted in very little progress. An important point for consideration is the need for administrative and leadership qualities in governmental agencies and their leaders. In some cases, with more decision-making capabilities, vaccine development projects could even surface despite other shortages. The vaccine development failures in private companies were similar. However, for them, the most probable reason for failure was the lack of capable technicians or scientists with adequate training in industrial microbiology. Very few, if any, of these companies had technicians with some knowledge of scaling up vaccine production techniques. Many lacked the knowledge of the total entrepreneurship needed to start up and maintain a profitable vaccine production business.

China is one exception regarding countries lacking funds for developing biotechnological and scientific projects. Some people may argue that China is not a country in technical development. However, many of the situations and experiences of a group of highly qualified professionals and technicians working in Chinese companies reveal the opposite. The description of the development of a viral rabies vaccine for human use depicted in this book shows that Chinese students with apparently high degrees in biology and microbiology lack the fundamental basic biological and technical knowledge for the research and development of biotechnology. Highly notorious is the fact that professionals and operators in many Chinese vaccine production companies visited are mainly, if not only, trained to follow written or verbal instructions. Most concepts are learned simply by memorization rather than by analysis, interpretation, and drawing conclusions. These pose severe hurdles for researching and developing new products and even for improving and modernizing old products. These particularities are one example of why many Chinese companies ask for technological transfer from other countries and scientists in diverse areas of technological development.

Another peculiarity of the Chinese way of developing business contracts is related to the fact that most, if not all, companies and their leaders avoid or delay payments as much as possible. In at least seven contracts between a Latin American company and Chinese vaccine production companies narrated in this writing, the Chinese evaded paying the total agreed-upon emoluments, giving all kinds of excuses. The Chinese could abandon the agreements specified in the contracts, considering that the foreign contractors would have considerable difficulties persuading a judge to impose any penalty for evading payments. In any event, the contractor’s lawyer would have to be Mandarin-speaking Chinese, so the contractor would need to be better informed about the outcome of the discussions. Moreover, contracts have to be subject to Chinese law. It is worth mentioning that the author of this writing observed an evading payment culture, even in agreements between two Chinese companies. It is widely known that the Chinese are tight-fisted regarding money. Still, the behavior of avoiding payments appears in this writing for several foreign companies doing business in China.

The readers are drawn here to the fact that any vaccine production company or institute must be highly technical, efficient, and profitable. Notably, the vaccine under development must be directed toward an essential improvement in the population’s health status. Another matter is that local production must have all of the above characteristics, mainly an identified market. If the local market is inadequate, it must be expanded to neighbors or for general exports. Another crucial issue repeatedly mentioned is the notion of profitability. The vaccine enterprise, institute, or company must be profitable. If it is a government-owned institute, the government must buy the vaccine from the vaccine production company and make it accessible to the affected population through vaccine campaigns. Sometimes, the government provides it to customers in need at a modest price. Worldwide, and especially in developing countries, it is clear that governments need to be more efficient administrators of commercial companies. If the ownership is one hundred percent governmental, it is constantly subjected to political pressures, and failure is expected. If, however, ownership is shared government–private, the possibilities of success improve considerably. In this case, an equilibrium must be gained between profitability and social health needs.

The technological transfer of vaccine production raises some unequivocal questions concerning where to get training in the industrial processes for the fabrication of vaccines and concomitantly in the administration of such enterprises. Are there any schools for learning how to produce vaccines on an industrial scale? There are numerous scientific publications in prestigious journals with reports on the fabrication of different types of vaccines. There are even reports of official government registration of fabricated vaccines. The vaccines have consistently been proven to be effective. However, none of these reports coincided with the production and marketing of the vaccine at the industrial level. The fact is that the work reported in those publications was done at the small-scale laboratory level. In these cases, research and development have yet to be made to scale up the product. Several scientists have even argued that these products should be called laboratory products, not vaccines. A vaccine is a high-quality product that is industrially manufactured and applied to the population to prevent infectious and contagious diseases.

A discussion point that must be consistently recalled is utilizing laboratory animal tests to prove the safety, efficacy, potency, and long-term durability of many vaccines. Some animal advocacy activism groups are against using animal models to establish and assure the suitability of vaccine products to protect the human population from deadly diseases. The rabies vaccine situation could be examined as an example of such utilization. Several laboratory animals, mostly suckling mice, have been used to prove the potency of all rabies vaccines around the globe. In this case, the baby mice are vaccinated with the test vaccine. After the appearance of defenses or antibodies, the animals are challenged with a live pathogenic rabies virus and compared to animals that have not been vaccinated.

The vaccinated mice must survive the infection, while the non-vaccinated mice perish, unable to overcome the challenge. There are no arguments that a similar system can be applied to human beings. Undoubtedly, there could be a much cheaper laboratory test that could eventually replace the animal challenge test. However, government regulations worldwide would be cautious about changing to other tests due to concerns that their vaccine might not be accepted in the international market due to a lack of mice challenge test data.

The book shows that despite the multitude of impediments from many sources, a new modern methodology was developed for the fabrication of a rabies vaccine for human utilization. This feat was possible in a few countries that needed the vaccine. Moreover, this methodology was used and proven to produce a vaccine to prevent Japanese encephalitis, and the described methodology can be exploited to fabricate vaccines to prevent polio, hepatitis A, and rotavirus and to cultivate other viruses that can grow in so-called Vero cells. It is also worth mentioning that since 2020, a COVID-19 vaccine has been prepared in China with an identical methodology and utilized worldwide. All of these accomplishments were possible due to a grand vision and continuous support from an international foundation interested in the well-being of humankind. However, the search to organize a school that teaches industrial-scale vaccine manufacturing must continue.

"It does not matter

how slowly you go

as long as you do not stop"

– Confucius

Acknowledgments

It would take a good number of pages to mention and thank each one of the many people who have contributed to the writing of this book.

First and foremost, I want to acknowledge the invaluable contribution of my team of fellow researchers and scientists. Their dedication and hard work over the past thirty years have been the backbone of this book. Their sweat and hustle, combined with my inspiration and guidance, have brought these pages to life. I deeply appreciate their commitment and the integral role they’ve played in this project.

I owe a special thanks to every member of my extended family, both present and absent. Their love, care, time, influence, and support have been instrumental in shaping my intellectual and emotional journey. It is their contribution that has allowed me to dedicate the majority of my life to research and the examination of biological events. I deeply admire their role in my life and their engagement in my work.

The work and accomplishments described in the book wouldn’t have occurred without the contribution of numerous teachers, top-quality professors, friends and colleagues who generously instructed and guided me into scientific events early in life and throughout my professional career. I am deeply grateful to all of them.

The Author

EDUARDO R. AYCARDI, DVM, MS, PhD. He earned a Doctor of Veterinary Medicine degree at the National University of Colombia, his MS at Cornell University (USA) and his PhD in 1970 at the University of Wisconsin (USA). He became director of a veterinary research center in a government institute in Colombia and director of a postgraduate center where he taught virology and epidemiology. For ten years, he also was director of veterinary research at an international research center located in Cali, Colombia. He has published over 100 hundred research papers in international journals. In 1983 he moved to a veterinary vaccine and pharmaceutical company where he was production and research manager. With international assistance from an American foundation and international consultants, he was instrumental at development of the medical division of the company where a tissue culture rabies vaccine for human use was developed in 1999. Dr. Aycardi obtained a retirement pension and in 2001 established a consulting company. He with a group of virologists, biochemist and vaccine specialists has pioneer the development of modern tissue culture vaccine methodology and industrial manufacturing in several countries of Asia and South America. In 2004 Dr. Aycardi received the Chinese government friendship medal for his contribution to the scientific advancement in vaccine research.