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ANALYSIS: The Genome s First Anniversary

NEW YORK, June 26 - How much a year changes things. Last June 26, Celera chief scientific officer Craig Venter and National Human Genome Research Institute director Francis Collins met with then-President Clinton at the White House to celebrate the completion of the first draft of the human genome.  At that occasion, the former president declared the map of the genome "the most important, most wondrous map every produced by humankind."

A year later, Bill Clinton is busy mapping out his future and figuring out the best route to the local McDonalds in Chappaqua, New York, while a new president, whom critics have accused of not having the brainpower to comprehend the nature and scope of the Human Genome Project, tries to enforce proposals to limit federal funding for scientific endeavors. While President George W. Bush has agreed to increase National Institutes of Health funding, his proposed budget cuts for another key contributor to the Human Genome Project, the Department of Energy, have caused concern among some in the genomics community. 

A year ago, Venter and Collins sheathed their sequencing swords and smiled at one another, promising to coordinate their publications of their genome data.  

A few months later, however, tension between the public and private sequencing efforts erupted again when the Human Genome Project refused to publish its sequence papers in Science  as long as the publication made what many researchers viewed as a Faustian bargain with Celera. The journal, to which Human Genome Project researchers had initially indicated they would submit their papers, allowed Celera to publish its paper without allowing full and unrestricted access to the sequence data--a decision that seemed to contradict the publication's policy of requiring sequence data from genome-related papers to be published in GenBank.  

Although this renewed strife between public and private sequencing efforts surprised no one, the actual data in the papers did. Both Celera and the Human Genome Project researchers agreed on the shocking conclusion that humans have somewhere upwards of 30,000 genes, not the 100,000 or so that the admittedly anthropocentric scientific community had formerly guessed. Given that  Drosophila melanogaster   has just over 13,000 genes and C. elegans  just 18,424, this low count was humbling news indeed for the human race. 

"We're only about two times more complex than worms and three times more complex than flies," said Washington University genome sequencing center director Bob Waterston, at the time. "We're not so fancy after all." 

This ego-deflating discovery was perhaps an omen for those who rode the genomics gravy train to Wall Street riches. While genomics stocks had not slid far from their March 2000 highs as of last June's sequencing announcement, their slide since then is humbling, if not humiliating, for those analysts and brokers who pitched genomics as the next big moneymaking thing. 

Just look at Celera's stock, which hovered around the $100 mark last July. The share price has now tumbled down to the $36 range. So although Craig Venter still may be smiling, that smile is worth about a third of what it was worth when he visited the White House a year ago 

Despite this loss of net worth, Venter still has plenty to smile about. Celera has moved on from sequencing skirmishes to try to conquer new worlds in the diagnostics and pharmaceutical arena. The company's most recent conquest, the $173.4 million stock deal to acquire Axys Pharmaceuticals, could catapult Venter &Co. to a level of wealth that might make the numbers on Celera's balance sheet exceed the number of base pairs in any genome, sequenced or not. 

Meanwhile, as the genome sequencing party has wound down, Venter has left the public project the unenviable task of cleaning up the code.  

Waterston and others have estimated that two years of painstaking work remain on the human genome. This work will involve sequencing those tough-to-tackle repeats that seem to go as well in one area as another, and figuring out how to sequence those regions that resist BAC cloning. It will also require continued funding, which researchers have worried could disappear as interest in the genome fades. 

Hundreds of other genomes, from those of microorganisms to mammals, also remain to be sequenced. Some researchers have pushed for a project to sequence the chimpanzee, to offer a closer genomic comparison to humans than the mouse, but others point out that public researchers still need to finish the mouse. The mouse sequencing consortium, a public-private effort assembled hastily in the wake of Celera's pay-per-view mouse genome database release last fall, has said it will not finish its work until about 2003. 

So now begins the long working and waiting game, between the initial genome sequencing hype and the time when the genomic discoveries actually begin to bear fruit. This could take some time, and could also be accompanied by serious setbacks that cause the public to wonder why so much US Government funding went into this genome project in the first place.  

In order to keep the projects going and retain public interest, researchers in the public and private worlds may need to continue to work together. In the end, the most memorable part of the sequencing celebration last June 26, may turn out not to be the actual genomic map, but the model of cooperation between public and private researchers that appeared to exist that day. Whether this spirit of cooperation will take root remains to be seen.

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