THE BIOTECHNOLOGY ERA: RAMIFICATIONS OF GENELABS DIAGNOSTICS V INSTITUT PASTEUR
| Published date | 01 December 2001 |
| Author | KWEK MEAN LUCK |
| Date | 01 December 2001 |
The process of using living micro-organisms to produce useful products has been with us for a while. The production of ethanol from yeast cells is as old as history1, and as early as 1873, a man by the name of Louis Pasteur, had obtained a US Patent for a living organism, claiming ‘[y]east, free from organic germs of disease, as an article of manufacture’.
It has been however, a long road from the fermentation of yeast cells to what we know today as biotechnology. It was not until 1953, that James Watson and Francis Crick published in Nature2 their one page article defining the structure of deoxyribonucleic acid (DNA)3. As important as this event was, it was not until 1980 that an event occurred which triggered the commercialisation of biotechnology. On 17 June 1980, the Supreme
Court of the United States ruled in Diamond v Chakrabarty4 that a new strain of bacteria produced artificially could be patented. Four months later, on 14 October 1980, the biotech company Genentech went public. In the space of one hour, the stock went from $35 to $89. It closed the day at $71.25. Genentech raised US$35 million from the IPO5. The circle of interaction between science, law and finance in the biotechnology industry had begun.
Ten years later, in 1990, the seed for what is today commonly associated with biotechnology was laid with the initiation of the Human Genome Project, a publicly funded international consortium of scientists that targeted the sequencing of the human genome by 20056. In 1998, the members of the Human Genome Project received a rude shock when Craig Venter of Celera Genomics announced that he would sequence and assemble the entire human genome by the year 2001. This turned the sequencing of the human genome into a race, throwing the Human Genome Project into a state of major overdrive. Officially, this race has been declared a tie. On 26 June 2000, both parties came together to announce the completion of a working draft of the human genome. In itself, the map of the human genome is nothing more than a string of 3
billion letters7. It is however, a necessary first step from which scientists can understand how the genetic code affects the body. The promises of being able to uncover the blueprint to the functions of the human body, laying bare the genetic triggers for diseases, devising pharmaceutical drugs tailor made to our genetic profile, and more, has poured renewed attention into the biotechnology industry.
Within Singapore, there has been a slew of initiatives to position the country for the era of biotechnology. By September 2000, over $2 billion had been committed by the Government to the development of the biomedical industry8. This industry has been identified by the Economic Development Board as the potential fourth pillar of Singapore’s manufacturing sector. The goal is for Singapore to be home to 15 world class life science companies by 20109, and for Singapore to be the regional centre for clinical trials and drug development. The Centre of Drug Evaluation, which is under the purview of the Ministry of Health, has been created to provide regulatory evaluation of new drugs, while the Intellectual Property Office of Singapore (‘IPOS’) will become a statutory board in April 2001 to allow better response to local R&D developments. IPOS plans to create a registry of patent agents in the year 2001, with the aim of registering about 50 patent agents over the next few years.
In the midst of this activity, at the dawn of the biotechnology industry in Singapore, a case twenty years in the making, with ramifications for our biotechnology industry, made its way to the Court of Appeal in September 2000. The case, was Genelabs Diagnostics v Institui Pasteur and anor10.
In 1981, doctors in Los Angeles and New York found themselves baffled by the affliction of diseases upon apparently healthy young men. The young men in Los Angeles developed pneumonia caused by a
micro-organism called Pneumocystis carinii. The young men in New York were found to have a rare skin cancer called Kaposi’s sarcoma. Both afflictions were previously only reported in people with damaged immune systems.
In 1982, the Center for Disease Control in Atlanta, United States, produced a provisional case definition for the disease. It was called AIDS, Acquired Immune Deficiency Syndrome, and defined then, as the presence of reliably defined diseases that are due to an underlying immune deficiency, such as Kaposi’s sarcoma, and where the immune deficiency is not due to other known causes such as immuno-suppressant drugs or cancer.
The savage arrival of AIDS thrust a desperate urgency into virological and molecular biological research throughout the world. One of the leaders in this field was an American scientist, Robert Gallo (‘Gallo’), from the National Cancer Institute of the United States. Some years earlier, in 1979, Gallo and his team had isolated the Human T-Cell Leukemia virus, or HTLV, the first retrovirus11 discovered to cause disease in humans. Gallo was convinced that AIDS was caused by another HTLV virus.
Across the Atlantic in Paris, research conducted at the Institut Pasteur under the guidance of the French scientist, Luc Montagnier (‘Montagnier’), suggested that Gallo’s anticipation was wrong. Montagnier’s team found that their lymphocyte cell cultures derived from an AIDS patient kept dying. Such cell behavior was contrary to that of HTLV infected cells, as Gallo had demonstrated that HTLV infection caused infected cells to go on dividing into more cells without dying. In January 1983, Montagnier’s team isolated the AIDS virus. They published their report in May of the same year. The virus was named lymphadenopathy-associated virus, or LAV.
In May 1984, Gallo and his team isolated another virus which caused AIDS, which they called HTLV-III. In the months that followed, a rivalry developed between the American and the French groups, each claiming to have isolated the virus first. The virus isolated by Gallo’s team was subsequently demonstrated to be the same as the LAV discovered by the French. It was in fact found to be too identical to that isolated by Montagnier’s team, differing in its genetic sequence from the LAV isolate by less than one percent. It was a degree of similarity that was inconceivable for two different isolates of a virus, that were supposed to have been taken seventeen months apart, from two men living on two different continents, and it led to allegations of viral theft.
In late 1985, Institut Pasteur filed a lawsuit against the National Cancer Institute of the United States. In the investigative work, And the Band Played On, former San Francisco Chronicle reporter Randy Shilts writes12:
Though the suit asked only for a share of the royalties that the NCI had accrued from its AIDS blood test patent, the scientific community understood that the French were really suing for the full recognition that had been denied them … they … felt that they had been robbed of the recognition of their most important achievement, the discovery of the elusive AIDS virus.
The United States government … tenaciously held on to the myth that Gallo had discovered the AIDS virus. This meant adhering to Gallo’s notion that the virus was a relative of the HTLV family that Gallo also had discovered, and that he had the right to name the virus, as viral discoverers always do. Ultimately, it had taken an international committee to rule that, no, this was not a leukemia virus and no, Dr. Gallo did not have the right to name it. To smooth ruffled feathers, however, the committee arrived at a compromise name: Human Immunodeficiency Virus, or HIV.
Throughout 1986 however, the Pasteur Institute pursued its depositions and Freedom of Information Act requests against the National Cancer Institute … Facing the possibility of open court hearings, the U.S. government began to reconsider fighting the French … Ultimately, the settlement was signed by President Reagan and French President Jacques Chirac in a White House ceremony … The settlement accorded each researcher partial credit for various discoveries on the way to isolating HIV.
In 1991, Gallo conceded that the virus he identified originated in tissue samples sent to him by Montagnier. Gallo maintained that inadvertent contamination had caused Montagnier’s virus to enter tissue samples Gallo
was working with and from which his virus was eventually isolated. Federal charges of scientific misconduct were brought forth, but withdrawn in late 1993. In 1994, the U.S. government conceded that France’s Institut Pasteur deserved a higher percentage of patent royalties from AIDS tests that utilise HIV, in view of its role for the virus’ discovery. Under the new arrangement, the French government received 50 percent of royalties, the United States 25 percent and the World AIDS foundation 25 percent13.
In October 1985, Montagnier found blood samples, derived from immigrants originating from Guinea-Bissau in West Africa, that tested negative to the HIV despite the fact that the patients were obviously suffering from AIDS. A second AIDS virus was subsequently found and isolated by Montagnier’s team, and was later labelled HIV-2, to distinguish it from the original virus, which was renamed HIV-1. Although both HIV-1 and HIV-2 operate in the same manner, and are similar in their chemical and genetic structure, there are sufficient differences to require different detection tests.
Institut Pasteur applied for and was granted a European patent in respect of the HIV-2 virus. It gave an exclusive licence over the patent to Pasteur Sanofi Diagnostics, a company which had been incorporated in France for the purpose of commercialising the products of the research institute. Profits from...
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