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By Kevin Davies 
Editor-in-Chief

Kevin Davies, Ph.D.Editor-in-ChiefIn the never-ending saga of the Human Genome Project, the public jousting continues to overshadow the sequence itself. Such public displays of aversion became routine during the early rounds of the project, but must they continue in the post-genome era?

Unlike many of the other key players, one of the most crucial figures in the decade-long sequencing spectacle —Britain's Sir John Sulston, former director of the Wellcome Trust Sanger Institute — has seldom commanded attention this side of the pond. Back home, by contrast, Sulston's noble acts in pursuit of biology's Holy Grail and free access to the sequence have catapulted him, somewhat reluctantly, into a national celebrity, leading the charge against gene patenting, corporate monopolies, and of course, Celera. Sulston has just completed the first personal account of the quest for the genome, entitled The Common Thread (Bantam Press), co-written with Georgina Ferry, although his low profile States-side has failed to attract an American publisher.

Sulston's kiss-and-tell story is interesting, if hardly captivating. He hints at the thinly concealed tension and ambition among his allies within the genome consortium, and clearly relishes the opportunity to rally against commercialism and corporate greed. And there are occasional moments of comic relief, such as when he had to be hauled out of the pub for a last-minute booking on the BBC's Newsnight program.

But the narrative crackles when the subject turns to Craig Venter and Celera's slick publicity machine. Sulston asserts that Venter's hostile takeover of the genome project in 1998 meant "the whole future of biology came under threat" — and that's just page 2 of the preface. Sulston and his public consortium comrades pledged to make the sequence — "our inalienable heritage" — freely available to prevent Celera monopolizing the genome. "We wrote this book so that people might understand how close the world came to losing that freedom."

Despite Venter's steadfast insistence that Celera would make the raw DNA sequence available, Sulston was suspicious. In 1989, Sulston defied Celera's sister company, Applied Biosystems Inc. (ABI), by developing his own program to manipulate DNA sequencing traces produced by ABI machines, saying "we had to take control of the software." He slams the publication of Celera's paper in Science in February 2001, because of Celera's precedent-setting refusal to deposit its sequence into GenBank in order to retain access control. He also criticizes the American Society of Human Genetics, which bestowed its prestigious Allen Award in 2000 to Venter, Eric Lander, and Francis Collins. "Had this ever happened before," asks Sulston incredulously, "that an internationally reputable society would give an award for research that was unpublished and unseen? ... First science by press release, and now awards by press release!"

A more sober appraisal indicates that the Celera database, combining public data with proprietary sequence, has been a qualified success. Some 200 organizations, including pharma, biotech, and some surprising subscribers, e.g. the medical research councils in Australia and Britain, have subscribed to Celera's sequence data. Two Canadian geneticists, Stephen Scherer and Joseph Cheung, recently compared the two genome databases for Current Biology and found only "incremental" differences. Although they judged Celera's database to be more complete (as would be expected), the public assembly outperformed its commercial rival in ordering repetitive DNA regions. However, the new mouse data are "an indispensable resource for interpreting the human genome." Supporting that claim, researchers from Columbia University mining the Celera mouse sequence recently reported in Nature Neuroscience that they had identified about 1,300 related olfactory receptor genes.

Meanwhile, the sparring is set to intensify. Along with Eric Lander and long-time ally Robert Waterston, Sulston recently published a critique of Celera's 2001 genome paper in the Proceedings of the National Academy of Sciences, charging that the Science article failed to validate Celera's vaunted whole genome shotgun (WGS) approach to the human genome. In a teasing play on Celera's motto, the authors conclude, "When speed truly matters, openness is the answer." Venter was preparing a rebuttal as this issue went to press.

This is more than a battle over bragging rights. The value of WGS for large, complex mammalian genomes must be settled quickly, if huge resources of money and manpower are not to be wasted, either in preparing unnecessary physical maps or in constructing inadequate sequence assemblies. Though one genome center is now collaborating with Celera on the sequencing of the rat genome, a welcome development, there will be no victors if the feuding drags on. In his book LifeScript, New York Times correspondent Nicholas Wade projects that Sulston, Waterston, and Venter might end up sharing the Nobel Prize, and decorum surely must prevail in the presence of the (Swedish) King.






For reprints and/or copyright permission, please contact  Jay Mulhern, (781) 972-1359, jmulhern@healthtech.com.