Private Genome Sequencing Effort May Hasten Separate Public Venture

Leaders of separate public and private efforts to sequence the human genome used words such as "cooperation," "collaboration," and "partnership" to describe their intentions toward each other during a hearing last month in Washington, D.C. But both projects appear headed on separate, although not quite independent, courses. The private project--a joint venture between Perkin-Elmer Inc., a Norwalk, Conn.-based manufacturer of sequencing equipment, and J. Craig Venter, president of The Institute for Genomic Research (TIGR) in Rockville, Md.--seeks to complete its version of the human genome by the year 2001. The yet-to-be-named company will use highly automated sequencing machines that Perkin-Elmer recently unveiled, greater computational power, and the "whole genome shotgun" sequencing strategy to blast 10 human genomes into billions of base pairs, then reassemble them, in order. The federally sponsored Human Genome Project, will continue to plug away using a clone-by-clone approach to slowly build billions of DNA pieces into the approximately 60,000 genes that make up the human genome. However, employing similar technology and sharing data with the private project could move the federal project's finish date up from its anticipated 2005 conclusion, federal officials involved with the project testified during a June 17 hearing of the House Subcommittee on Energy and Environment. Like the separate strands of DNA's double helix, private and public efforts have been twisted together since the efforts to sequence the human genome began in 1990. Both J. Craig Venter, president of The Institute for Genomic Research (TIGR) in Rockville, Md., and Ari Patrinos, associate director of the Department of Energy's (DOE's) office of biological and environmental research, acknowledged those ties during a recent hearing in Washington, D.C. The hearing explored how a joint effort by Venter and Perkin-Elmer Inc. to sequence the human genome will affect the federal effort. Venter began his scientific career with the National Institutes of Health. After 10 years spent hunting for the adrenaline receptor gene, Venter and other federally funded colleagues developed a faster strategy: Expressed Sequencing Tags, or ESTs. Meanwhile, in the late 1980s, a company named Applied Biosystems Inc. developed a machine that improved the speed at which a DNA sequence could be obtained. Venter's NIH lab and Applied Biosystems entered a commercial research and development agreement, the first such pact between NIH and a commercial organization, according to Venter. Linking the EST strategy and the new machines hastened sequencing speed even more, Venter said during his testimony. It also had positive effects for Applied Biosystems. "While our new strategy was not yet widely accepted, I learned that orders for the Applied Biosystems DNA sequencers that we had used in our experiments skyrocketed." Venter left the NIH to form TIGR in 1992 and used the EST strategy to sequence several organisms. TIGR received funding from both DOE and NIH, while Venter and colleagues devised the "shotgun" sequencing approach the new effort will use on the human genome. TIGR has since sequenced seven genomes with the strategy. "It is notable that NIH- and DOE-funded basic research (at TIGR and here) laid the foundation for the sequencing approach being proposed by PE-TIGR [Perkin-Elmer and Venter]," Patrinos testified. Perkin-Elmer purchased Applied Biosystems in 1993. The company has since developed the ABI Prism 3700. The machine, unveiled during a May 9 announcement along with the company's intention to sequence the genome, is both faster and more automatic than existing machines. After the hearing, Venter noted that heads of other genome centers have been making inquiries about the $300,000 machines. -P.S. In an earlier interview with The Scientist, Venter had rhetorically proposed ways in which the two efforts could meld to speed up the completion and interpretation of the human genome (P. Smaglik, The Scientist, 12[12]:1, June 8, 1998). However, some unresolved issues prevent a closer working relationship, Francis Collins , director of the National Human Genome Research Institute, said, reading from his prepared testimony during the June hearing. First, sequencing experts have yet to agree on the completeness the new approach will yield. Venter has said the "shotgun approach" will leave some gaps, but that the genome will be relatively accurate. Collins estimated the number of gaps in the tens of thousands, while Maynard Olson , professor of medicine at the University of Washington in Seattle, predicted that the private approach will leave more than 100,000 holes in the genome. The federal project calls for a complete genome. Drastically altering federal and international efforts in light of such uncertainties would be a gamble, Olson said, since the project likely won't produce any human data for about 18 months (Venter has said the company will begin sequencing Drosophila in April. After Drosophila is finished, the company's 230 sequencing machines, to be housed in a building under construction on TIGR property, will begin around-the-clock work on the human genome). The international sequencing community also requires that participants release data within 24 hours. Representatives of the private venture have said they will release raw sequence data into the public domain every three months. Other data produced by the venture, like single nucleotide polymorphisms, will only be available through for-profit databases. In his prepared statement, Collins noted that officials who met recently to plan the next five years of the federal project worried about a private industry holding the data hostage--something Venter promised would not happen. "Some concerns were expressed that the private effort's commitment to data release might diminish over time, if business pressures came to the forefront," Collins read. David J. Galas , president and chief scientific officer of CHIRO Science R&D Inc., a Bothell, Wash.-based biotechnology firm, testified that even a "rough draft" version of the human genome, released at three-month intervals, will have some bearing on the federal effort, and, therefore, should not be ignored. "I do not believe it is sensible for the federal government to [remain] unchanged in strategy." Olson--the most vocal critic of the private venture to testify--agreed that the "shotgun" data could aid the federal effort. "Even such fragmentary data will certainly have considerable biological utility. Furthermore, it may prove to be a substantial help in the final push toward a high-quality human sequence, although this prospect is less certain." Collins, who has repeatedly characterized the two efforts as "complementary," provided some examples following the hearing of how the two efforts could benefit each other. Existing data from the public effort could be used to check new sequence information released by the private venture and fill in any gaps. Similarly, investigators in the public effort will likely match the private data against their work. The combination of the two sets of data could provide both greater breadth and depth of knowledge. "Even if there is no formal collaboration between entities, people will use the data," Collins told The Scientist. Collins admitted that formal collaboration has been difficult to achieve at this stage of the process. "Everyone's a little cautious right now." A more detailed analysis of how the two programs will affect each other--and whether or not the federal program will make any strategic adjustments in response to the public effort--will be available this fall. For complete versions of prepared testimony, please see "hearings" under http://www.house.gov/science/hearing.htm.

Private Genome Sequencing Effort May Hasten Separate Public Venture

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