Responding to concerns that a giant public/private enterprise could be transforming itself into a private monopoly, the biotechnology giants who last month proposed a private enterprise to finish up the work begun by the Human Genome Project are taking their case to the research community.
In Friday's edition of the journal Science, a team of authors representing Perkin-Elmer Applied Biosystems and The Institute for Genomic Research sketch out a careful business plan calling for much of the data to remain public.
The group acknowledges that its work would not be possible without the milestones already achieved by the government-funded HGP. Nevertheless, they believe that advances in technology -- particularly theirs -- signal the need for a private entity to complete the sequencing of the human cheat code, which maps the locations and functions of all the genes in the body.
"Our proposal doesn't detract from [the project]," said Michael Hunkapiller, senior vice president of Perkin-Elmer Applied Biosystems. "It's serving as an addition to what's already out there."
The Human Genome Project was launched in 1990 with the ambitious goal of mapping and sequencing the complete set of chromosomes in humans and several model organisms by the year 2005. The endeavor had the backing of the US National Institutes of Health, the Department of Energy, the Wellcome Trust, and other foundations and institutes around the world. It was conceived as a public project that would not only tell us more about ourselves, but also fuel the development of biological technologies and create an industry to serve it.
Eight years later, the project claims many achievements. The current gene map now contains 30,011 gene tags, which represents nearly half of all human genes. This progress translates into a 50 percent chance that a scientist sifting through the genome for a disease causing-gene can find it in the material that has already been mapped. These odds helped researchers isolate the gene that causes Parkinson's disease last year, said National Human Genome Research Institute director Dr. Francis S. Collins in his fiscal budget testimony before the House Subcommittee on Labor, Health, and Human Services.
The project operates on an average annual budget of US$200 million (the current request for 1999 funding is at $237 million), although Collins pointed out that the program has regularly come in under budget. For example, in 1993, $218.9 million was budgeted, but only $170.6 million spent. Still, the directors are actively seeking help to find newer, faster technologies to complete the map.
In the proposal by Perkin-Elmer, the Institute would have what it's looking for, but it is cautiously looking into the deal.
Hunkapiller and his colleagues believe they'll hit their target for completing the project: three years with a cost between $200 million and $250 million. This, they say, makes them the best option for shepherding this project through to its completion.
This Perkin-Elmer technology is the next generation of sequencers already churning through the genome. The original technology was developed by Hunkapiller and his colleagues at the California Institute of Technology and Applied Biosystems in the mid-'80s. But existing technology cannot handle analysis of the larger batches of samples that researchers demand.
"[Sequencing and similar tasks] are just a giant industrial process now," said Arthur Kaplan, director of the Center for Bioethics at the University of Pennsylvania Health Services. "[Perkin-Elmer] will discover a lot more faster."
The current technology requires eight hours of human labor for every 24-hour period because a researcher needs to load samples into the instrument every two hours. "It's tough to schedule people around the clock," said Hunkapiller. "And you have to pay people more to work at night."
With the new instrument, the process feeding the sequencing machine samples is automated to the point where only 15 minutes of human labor is needed for each 24-hour period. This is the difference that could make the private endeavor successful.
Nevertheless, the announcement last month of the Perkin-Elmer/Institute for Genomic Research venture raised the hackles of researchers around the world. The idea that a single company -- and a US-based company, at that -- would hold the keys to such an important resource touched off concerns over ownership and access. Reports in the international press likened one of the project's leaders, Craig Venter, to Bill Gates. Perkin-Elmer, the stories said, would control the human genome and the biotech industry in much the same way that Microsoft controls the computer-software industry.
It is this type of criticism that Hunkapiller and his colleagues are trying to blunt. "We see [our effort] as assisting what's already being done," he explained.
To this end, the Perkin-Elmer venture "looks forward to working with other genome centers to ensure that the sequence meets the requirements of the of the scientific community for accuracy and completeness," the authors wrote.
"An essential feature of the business plan is that it relies on complete public availability of the sequence data."
In the paper, Hunkapiller and his colleagues work to assure the research community that the data they generate will be readily available to other institutions. They say they will work with national DNA repositories, such as the National Center for Biotechnology Information, in updating the database their research will produce. They promise to release sequencing data into the public domain every three months and the complete human genome at the end of the project.
Once Perkin-Elmer completes its database, it plans to make it available online for "a minimum connect fee" as well as access to bioinformatics tools to interpret the information. The company will also develop and sell its new instrument.
At the same time, Hunkapiller and his colleagues are clear that they intend to commercialize some of their work. They do not plan to patent primary human genome sequences, but they do expect to lay claim to certain targets for producing drugs and therapies.
To observers like bioethicist Kaplan, the argument is not about whether the genome project should be private. The fact that private companies will dominate the project is a fait accompli, he said, noting the hundreds of patents that have been issued to deed genes and gene segments to researchers.
"[Companies owning genes] is the gamble you take when you have a patent approach to giving companies the incentive to work on this," Kaplan said.
Instead, the focus should be on how to set limits on what can be held private and what should be made public. "We should be thinking about industrial policy to manage [the project] so that people don't hoard the sequences," said Kaplan.
In the biotechnology industry, where the major operating system is the human genome, the best course of action is to ensure that many parties will be able to develop and thrive from applications -- namely drugs and therapies -- they build from this sequence, Kaplan asserts.
"We have an opportunity to learn from the computer industry to prevent a situation where a Microsoft or any one person has control," he said. "Our best hope is to regulate and encourage legislation [to prevent this]. Otherwise, it'll be too late, and it could slow down research."
While Hunkapiller fights off the monopolistic comparisons to Microsoft, he is not shy about his admiration for the software giant's leadership role. "We certainly intend to be a leading player," Hunkapiller said. "[The venture] is a way for us to provide technologies for the industry."
