Originally, research centers were to be established to promote collaboration from investigators around the country, as well as network with similar projects around the world. The Department of Energy’s three national laboratories, as well as 10 to 20 National Institutes of Health start up labs, were to sequence the genome with a target completion date of 2005. These centers were to "become (the) foci for collaboration with investigators at other locations and with industrial organizations that want to develop applications of the research results, thereby creating networks of interrelated projects" (1). This paper will focus on the availability of information generated by the Human Genome Project.
The economic importance of the Human Genome Project and biotechnology in general is obvious. For instance: in 1991, the US Patent and Trademark Office received 4000 patent requests for nucleic acid sequences. In 1996, that number had jumped to 500,000. Pharmaceutical companies are scrambling to increase their genomics work, or form partnerships with other companies if they are not currently doing research in genomics. Clearly, this is an area of huge growth, huge profitability, but also huge risk. The downside of this "genome mania" is high expectations. Current market values of life science companies are very high. Companies are faced with a lot of pressure from shareholders to provide new blockbuster therapies that will net those investors large profits. The problem with this mentality is that research takes a lot of time and a lot of money (2). The fear of some researchers is that industry will not be open with the results of their genome research, sequestering away nucleic acid sequences in private databases, or tying up huge amounts of information in pending patents. This goes against the original aim of the project which was to place all information gathered in free, publicly accessible databases. Recent developments in the Human Genome Project only heightened these fears.
On May 9, 1998, Crag Venter, president of The Institute for Genomic Research (TIGR), announced his company was teaming up with pharmaceutical giant Perkin-Elmer to sequence the human genome in just three years (3). This news took the genetics community by storm. The original plan called for a single, cohesive strategy to thoroughly map the human genome in a linear method. The new Perkin-Elmer/TIGR partnership planned to sequence the genome with a new method called whole genome shotgun sequencing. By this method, DNA would be chopped up, sequenced all at once, and supercomputers would be used to assemble the fragments. Critics argue that this method is inadequate and will not meet the strict requirements of only one error in every 10,000 base pairs outlined in the original plan (4).
Looking more closely, several other red flags appear. TIGR is a not-for-profit research institute founded by Dr. Venter, which will retain 20% ownership in the new partnership company. Dr. Venter admits that the information obtained by the new company will have "significant commercial value". How can TIGR maintain its not-for-profit status if it’s research is funneled directly to Perkin-Elmer? In defense of Perkin-Elmer and TIGR, the new company "plans to make sequencing data publicly available to ensure that as many researchers as possible are examining it and that applications…are as broad as possible" (3). However, the company makes some additions to this statement which seem to lessen its openness. Perkin-Elmer will place all information they find on a database controlled by Perkin-Elmer. "Key elements" of this database will be made available without use restrictions. Other information will be available at a "minimum connect fee". In other words, Perkin-Elmer will completely control what scientists can see without restriction, and what must be paid for. This is fair, since Perkin-Elmer is a for-profit company. However, having a for-profit company doing the research on a project that was supposed to be completely open and free to all makes the whole thing look a little less than above board. On the other hand, Perkin-Elmer says it won’t seek patents on primary human genome sequences, but on new pharmaceutical and diagnostic targets. The wording again is a bit vague and patenting seems to rely solely on Perkin-Elmer's determination of a "primary" sequence (5).
This rush to finish the project early and on their own has some other negative aspects for the genetics community. Recently Incyte, a pharmaceutical company, acquired Hexagen, a small British genomics company. Incyte plans to sequence protein coding regions of the human genome over the next two years and charge stiff fees to give other scientists access to their database (6). This pulls the genome hunt in three directions, that of Incyte, TIGR, and the Genome Project. The result is further sequestering of the data from people who need and are supposed to be able to get it.
Furthermore, this rush worries the original sequencing centers on university campuses across the country. Until now, the Human Genome Project has focused on a completion date of 2005. With the splinter industrially backed groups making claims of better, faster, cheaper, academia is scrambling to find ways to compete. One idea is to improve the methods used to sequence. At the present time, DNA is sequenced, analyzed, pieced together, and then the next stretch of DNA is started. By starting the next stretch of DNA before the current piece is completely done, a lot of time can be saved without any increase in errors. Another idea is to reduce the redundancy of sequencing. Currently, DNA needs to be sequenced 10 times to assure an error rate of less than one in every 10,000 base pairs. Researchers are looking at the viability of only using 2, 4, or 6 times the DNA, again reducing the time needed to move on (7).
A very controversial idea is to complete a "rough draft" of the genome with greater than a .0001% error rate first, then go back and complete the project to the error rate specified in the original project. This plan has several merits. It will allow other researchers to begin designing applications from the initial sequences. Similarly, scientists could start looking for diseases associated with specific genes while the sequences of these genes are being refined, thus giving gene therapies a jump start. However, the problem with shotgun sequencing and a rough draft of the genome is that it fundamentally goes against the original project directives. It produces a "hurry up" mentality among researchers that can divert them from the lofty, but attainable, goals of the Human Genome Project.
In my opinion, the Human Genome Project should continue onward utilizing the plan originally outlined in 1990. The total sequence should be targeted for completion in 2005 and should contain no more than one error per 10,000 base pairs. This is the only way to assure the quality that such a massive and important undertaking demands. Industry has always been welcome to help with the Human Genome Project. However, I feel several points need to be clarified as pertains to industry’s involvement in the project. Industry’s involvement should in no way detract from the "real" genome project, by which I mean the centers which are pursuing the goals set forth in the original 1990 plan. Industry should not seek to outdo or "beat" the genome centers. Instead, industry should act in an assistance role, working hand in hand with the genome centers.
It is imperative that genome information generated by the project be available to everyone and for everyone’s benefit. Patenting of sequences would greatly hinder work on the project. In order for DNA to be patented, it must be distinguished from its naturally occurring counterparts and must be purified, isolated, or part of a vector. I would go a step further and require the sequence to be an actual functioning gene. I recognize industry’s need to protect their intellectual property; without patents, there would be less funding for DNA research and less profit in doing so. I feel patenting genes would protect a company’s investment, while simply being able to patent every DNA sequence a company discovers would hinder further sequencing. A balance must be struck between patenting legitimate, useful discoveries and patenting every single nucleotide, thus hindering the forward movement of the project as a whole (8).
1. The Human Genome Project, http://www.ornl.gov/TechResources/Human_Genome/project/project.html, accessed 10/13/98.
2. J. Enriquez, "Genomics and the World’s Economy", Science, 925-926, August 14, 1998.
3. "Perkin-Elmer, Dr. J. Craig Venter, and TIGR Announce Formation of New Genomics Company", www.tigr.org/new/press_release_may98.html, accessed 10/13/98.
4. Waterston, J.E. Sulston, "The Human Genome Project: Reaching the Finish Line", Science, 53-54, October 2, 1998.
5. J. Craig Venter, M. Adams, G. Sutton, A. Kerlavage, H. Smith, M. Hunkapiller, "Shotgun Sequencing on the Human Genome", Science, 1540-1542, June 5, 1998.
6. E. Marshall, Á Second Private Genome Project", Science, 1121, August 21, 1998.
7. E. Pennisi, "A Planned Boost for Genome Sequencing, but the Plan is in Flux", Science, 148-149, July 10, 1998.
8. J. Doll, "The Patenting of DNA", Science, 689-690, May 1, 1998.