Human Genome Project Deadline Moves Up Two Years, to 2003

GENOME SYMBOL: DNA strands form the basis of a graphic symbol of the genome project. They said it wasn't a race. When a private venture announced plans in May to produce a version of the human genome four years ahead of the international nonprofit Human Genome Project's deadline, scientists associated with the public project insisted that the private effort wasn't really a challenge to theirs. The private effort would present, at best, a "rough draft" with many holes--if it worked at all, they argued [P. Smaglik, The Scientist, 12[12]:1, June 8, 1998]. Now, however, leaders of the public project have responded by announcing that the international effort will produce its own "working draft" of the human genome sequence by the end of 2001--roughly the same deadline for the project sponsored by the company now known as Celera Inc., a Rockville, Md.-based business formed by J. Craig Venter, former director of The Institute of Genomic Research, and Perkin-Elmer Inc., a Norwalk, Conn.-based instrument company. The "working" or "intermediate" draft will help speed the completion of the whole genome by the end of 2003--two years ahead of earlier projections. The public effort's response, in effect, raises the stakes, because, by sticking with the clone-by-clone approach, public scientists expect their working copy to be 90 percent complete and 99 percent accurate. Although Venter has insisted that the Celera copy will be as complete and accurate, other sequencing experts have expressed doubts, since the shotgun method has never been attempted on such a scale [P. Smaglik, The Scientist, 12[14]:1, July 6, 1998]. Public scientists point out that reassembly of the millions of fragments could be difficult. Reassembly appears less of a daunting task for the clone-by-clone sequencers, since that approach requires putting together many smaller genetic puzzles first, before combining those puzzles into a finished genome. The "shotgun" approach requires piecing the billions of pieces together at once. PUBLIC CREDIT: The NHGRI's Francis Collins notes that, if the public and private genome projects merge their data into one "working draft," neither entity should take complete credit. PRIVATE GENOME: Celera Inc.'s efforts to do a shotgun sequence of the genome by the end of 2001, led by Craig Venter, may help the public Human Genome Project's separate effort. The change in plans, announced Sept. 14 during a meeting of the National Advisory Council for Human Genome Research at the National Institutes of Health campus, provides a curious mix of cooperation and competition. Members of the advisory council spoke optimistically about "synergy" between the two projects. Data from one will provide guidance for the other--both for double-checking the accuracy of new segments and for filling in gaps. Some members of the advisory council, as well as Francis Collins, director of the National Human Genome Research Institute, remarked that this relationship will be somewhat skewed in favor of Celera, since the international effort will continue to release data within 24 hours, while Celera will post its data once every three months. "It will probably help them a lot," Collins told a group of reporters during a break in the meeting. "And you know, I don't really care. My interest here is seeing the sequence done in a publicly acceptable form, and if this strategy fits that, in part because it becomes a more synergistic opportunity with a private endeavor, that's great." Collins did issue an indirect warning of sorts to Celera, basically admonishing the company not to claim sole responsibility for their finished project, should they complete it first. That project's success, he noted, depends, in part on the public effort. "An attempt on their part to take their data, merge it with a large amount of public data and then claim 100 percent credit for it will not be well received." In a previous interview conducted shortly after the May announcement, Venter acknowledged the debt to which the private effort owed the public and also suggested that the two efforts could collaborate [The Scientist, 12[12]:6, 16], June 8, 1998]. In a separate interview, Ari Patrinos, associate director of the Department of Energy's office of biological and environmental research, acknowledged that commercial entities' aggressive moves to lock up the rights to genomic information such as single nucleotide polymorphisms (SNPs) have provided an incentive for the public process to pick up the pace. In a candid moment, Patrinos characterized the international project's new pace as "damage control," in part to prevent businesses from snapping up all the SNPs. "The reason for the intermediate product is getting that biological information to the community sooner--including the SNPs." Some companies--including Celera--have at least partially based their business plans on patenting SNPs, then selling licenses to the pharmaceutical information. Such practices mean that some patented SNP data might not be publicly available. That especially bothers Patrinos, since the nonprofit efforts essentially laid the informational infrastructure these companies are exploiting. "The issues associated with hoarding biological information is obviously very vexing to us," Patrinos said. It also bothers his sense that scientific information should be available to all. "In the hoarding of biological information--especially when it comes to human biological information--I have philosophical anxiety." Despite these issues and anxieties, Patrinos thinks that the two sides will benefit each other. "Clearly there are differences in some approaches and there are differences in attitudes and there are big personalities and huge egos, but I'm very optimistic," Patrinos noted. "Preliminary discussions we have had recently--we have had several with Craig Venter and his colleagues--have shown great progress in terms of building a substantive collaboration between the private and public sectors." Just what form the relationship takes depends, in part, on the success of Celera's first project: a complete sequence of Drosophila. The company plans to start that project next April and finish it in less than a year. Avarinda Chakravarti, professor of genetics at Case Western University in Cleveland, and a member of the advisory council, noted in an interview that the value the private venture has on the public effort depends on the type and quality of data the Celera project will produce. This will become apparent as Celera begins releasing Drosophila information. "I'd like to actually see the sequence traces," Chakravarti noted, adding that those traces will reveal the quality of the company's approach. "It's very easy to produce 500 base pairs of sequence. It's actually quite a task to produce 500 base pairs of good sequence." A "good sequence," Chakravarti continues, means "the quality is good enough that you can distinguish which of the four bases really stands out, that you're really confident about the call that you are making." Collins, Patrinos, and Chakravarti all noted that several factors--not just improved technology--will make the more ambitious goal possible for each side. But technology does seem to be one of the biggest variables. When Venter and colleagues announced their plans in May, they touted the speed and automation of a new line of Perkin-Elmer sequencing machines, which they planned to couple with state-of-the-art bioinformatics, to form a giant sequencing center. Recently, the Sanger Centre in Cambridge, England announced that it, too, is enlarging its sequencing capacity. "We are looking to triple our capacity in terms of the number of DNA bases we can sequence in a year so that we can match the pace of what has been going on recently," reports Jane Rogers, the Sanger Centre's human sequencing project manager. And the race is on.

Human Genome Project Deadline Moves Up Two Years, to 2003

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