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A Race to the Starting Line
— By Stephen Hall’73

Several years ago, the biologist Robert Weinberg of Massachusetts Institute of Technology wrote a book about the genetic origins of cancer called Racing to the Beginning of the Road. The title was a great metaphor about how science really works, and it couldn’t be more appropriate to recent developments in the effort to sequence the human genome—the total complement of human genes, spelled out in the biochemical letters of DNA, that produce a functioning human being.

You may have heard something about this in the past months. Banner headlines. Wall to wall coverage on CNN. Something about biologists getting their hands on "the book of life." The gush of media attention over the announcement last June that two competing teams, one public and the other privately financed, had obtained a rough draft of the human sequence contained more hype per column inch than any event in biology since gene-splicing. I haven’t heard the term "holy grail" invoked so many times since Bob Ray’s course on 20th century American literature at Beloit back in the 1970s.

We’ve come a long way from the Babbling Brook Inn. That’s the hostelry in Santa Cruz, California where a handful of biological dreamers—and a few skeptics—gathered in May of 1985 and hatched what ultimately evolved into the human genome project. You’d never guess that the idea initially struck everyone as ridiculous.

I did my first magazine story on the genome project ("Genesis: The Sequel") in 1988, first interviewed James Watson about it in 1989, knew all the principal players by the time it was formally launched in 1990. To those of us who have watched this effort unfold over the past 15 years, it was surprising, and a little demoralizing, to see the early history of the project subsumed in the entrepreneurial brinksmanship, historical amnesia, and Orwellian newspeak that has increasingly come to characterize contemporary biology.

During a June press conference at the White House, biologists celebrated the "completion" of the sequence; yet everyone in the field knows it is incomplete—perhaps significantly incomplete. We were told a great race had taken place, but we allowed the participants to concoct a self-interested finish line, with no referees to certify the degree of completion or quality. We were frequently reminded of the lone-wolf virtuosity of J. Craig Venter, whose company, Celera Genomics, took on the Whole Government and won; we were too infrequently reminded that the race took place only after the government’s genome initiative had spent years clearing the brush, grooming the track, and winning hearts and minds for a project that was terribly unpopular.

It’s worth revisiting that Santa Cruz meeting to see how much—and how little—things have changed. The meeting was organized by biologist Robert Sinsheimer, then at the University of California at Santa Cruz, who was the first person to popularize the endeavor as "biology’s moonshot."

Leroy Hood, then of Caltech, became excited by the prospect of developing automated machines for such a project (those machines are now standard equipment in virtually every molecular biology lab). Wally Gilbert, who helped develop some of the original DNA sequencing techniques in his Harvard lab, riled the multitudes when he spoke of copyrighting—copyrighting!—the human genome and then selling the information to drug companies. The nerve of the guy! (Thousands of gene sequences have since been patented.)

And then there was David Botstein. This curmudgeonly geneticist, then at M.I.T. and now at Stanford, raised the most prophetic objection of all. Having the entire human DNA sequence, he argued, was like having a complete set of Egyptian hieroglyphics and no Rosetta stone. Without the sequence of other organisms for comparison, especially the mouse (which we are still waiting for), the human sequence remains largely unreadable. And that is where we stand today, several months after the greatest achievement in the history of biology. We have 3.1 billion letters of human DNA in hand, and we’re still functional illiterates when it comes to reading the text.

A few words about that famous race: despite the negotiated "draw," the general spin seems to be that Celera Genomics humbled the government sequencers and won the race. But Arnold Levine, president of Rockefeller University, shrewdly observed recently that Celera enjoyed a great advantage by entering the race when it was nearly over. Part of that advantage was technological, the other cultural.

Back in the days of the Santa Cruz meeting, DNA sequencing was universally dismissed as the work of drones, factory-style "big science" utterly devoid of creativity. It seemed so dull and dutiful that only when the Department of Energy looked poised to take over the project (and, many feared, turn it into a political boondoggle) did the National Institutes of Health reluctantly become involved. More important, the leaders of the public consortium—James Watson, Francis Collins, Eric Lander, Maynard Olson, and later Harold Varmus—gave the project a cultural credibility within the scientific community—that it was doable, desirable, important. Once the government committed $3 billion to the 15-year project, a huge economic infrastructure grew up around the endeavor.

Leroy Hood, meanwhile, left the Santa Cruz meeting more convinced than ever that DNA sequencing machines had a future; Michael Hunkapiller, a post-doc in Hood’s lab, went on to become the unheralded da Vinci of DNA in this whole story, designing wondrous machines at Applied Biosystems, which later became a sister company to Celera called P.E. Biosystems. And it was Hunkapiller who called Venter in 1998 and convinced Celera that with the latest generation of machines, it would be possible to sequence the human genome much sooner than originally thought.

It is true that the public venture stumbled and staggered at some points along the way, and that the competition with Venter undoubtedly accelerated progress. But it is also true that without that initial brush-clearing in the early 1990s, Celera would have had a much harder time finding venture capitalists willing to listen, and without helping itself to the free information posted by the public consortium, it would never have "won" the race so quickly.

If I were a biologist, I’d be a little nervous right now about having raised public expectations unrealistically. The genome project will indeed revolutionize medicine. The question is when. We’ve been reading advance excerpts from the "book of life" for years and haven’t been able to make much headway. Ask the people with sickle-cell anemia: the exact molecular nature of that genetic disorder has been known for 25 years, and still no cure.

Therefore the most interesting question now is the timeframe in which this future unfolds, and whether the public—in this era of HMO distrust and anger over drug prices—has the patience to await the fruits so extravagantly promised last June. On the day the sequence was announced, I called up David Botstein and asked if "biology’s moonshot" warranted all the fuss. "We’ve flown around the moon," he said with a laugh, "but we haven’t actually landed on it, and we haven’t collected anything yet." With a couple months’ perspective, it’s clear that what’s been won—if anything—is the race to the starting line. In other words, only now does the real work—the real biology—begin.

Stephen Hall’73 is a science writer and regular contributor to the New York Times Magazine, where his June 4 article "Brainiacs" was the cover story. "A Race to the Starting Line" was adapted by the author from the September/October issue of Technology Review and appears with permission. He is also represented in The Best American Science Writing 2000, from Ecco Press.

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