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BOOK REVIEW

Venal Combat

Paul Rabinow

The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. James Shreeve. x + 403 pp. Knopf, 2004. $26.95.

The completion of the sequencing of the human genome was by any standard a technological triumph and a scientific landmark. It was widely publicized as a "race," although exactly what it meant to complete the task was never made very clear. But the race turned out to be, in a sense, rigged: Ultimately, political intervention at the highest levels ensured that the competitors would cross the finish line together, allowing President Clinton and Prime Minister Blair to come together at the Rose Garden in June 2000 to celebrate the achievement.

Who were the competitors in this supposed contest? There were two: A public consortium—which grouped the National Institutes of Health (NIH), the Department of Energy, multiple university laboratories receiving federal grants to carry out the sequencing work, the world's largest philanthropy (the Wellcome Trust in Britain) and smaller publicly funded genome projects from the United Kingdom, France, Japan, Germany and China—was pitted against Celera Genomics, a biotech company in Rockville, Maryland.

Francis Collins, codiscoverer of "the cystic fibrosis gene" (for which he shared a patent), represented the public effort as director of the NIH Human Genome Project. Craig Venter, an outspoken maverick and chief scientific officer of Celera Genomics, represented the private endeavor. He had previously worked for the NIH and while he was there had made his name (and many enemies) by attempting to patent stretches of DNA known as expressed sequence tags, even though their biological function was unknown—an effort many considered scandalous.

Leaders of both the public project and Celera portrayed the attempt to sequence the human genome in epic terms. Addressing scientists assembled at the mecca of molecular biology, Cold Spring Harbor Laboratory, Collins said, "I hope this doesn't sound corny or grandiose, but I feel this . . . is the most important scientific effort that humankind has ever mounted." Sir John Sulston, head of the British project, called the achievement of one milestone along the way (the deciphering of chromosome 22) "as important an accomplishment as discovering that the Earth goes round the Sun or that we are descended from apes." Venter also engaged in hyperbole, albeit of a more modest nature, when he said, "We're going to establish a new paradigm. We're going to prove you can do open research and make money at the same time." Each of the three men craved publicity and was relentlessly competitive: Venter reveled in his bad-boy reputation, Collins consistently promoted himself as "selfless," and Sulston seemed convinced that he had been designated (I suppose by the Goddess of Reason) to defend humanity.

James Shreeve, a science journalist, has written a riveting account of the two parallel campaigns to sequence the human genome. He gives us an extraordinary blow-by-blow narrative of how the technological and moral battles were staged and fought. Shreeve had untrammeled access to Celera during the whole course of the events. Yet, strangely, he had much less access to the public project, whose representatives not only politely refused to let him observe their meetings but also blocked significant portions of the public record that Shreeve sought access to through a Freedom of Information Act (FOIA) request. This fact, which comes only at the end of the book, in a "Note on Sources," is a shock. Shreeve dryly observes that

I was told by the head of NIH's FOIA office that they were permitted to deny access under Exemption 4 to the FOIA, which prevents the release of "commercial and financial information that is privileged and confidential." Considering the concerted efforts the HGP leaders made during the race to distinguish their totally free, totally public version of the genome from Celera's commercial one, the explanation sounds oddly discordant.

The Genome War should be read by all who are concerned about the conditions under which science is practiced today. For balance, readers may also want to consult some of the accounts defending the public side. John Sulston has written one (with Georgina Ferry) that tells the story from his perspective—The Common Thread: A Story of Science, Politics, Ethics and the Human Genome [reviewed in the May–June 2003 issue: http://www.americanscientist.org/BookReviewTypeDetail/assetid/18850].

By the end of The Genome War, the reader will have abandoned any illusions that this was a combat between knights in white armor. The duel to achieve a technological goal was accompanied by a rhetoric of moral combat marked by ferocity and fueled by righteousness and ego.

At a Congressional hearing, Collins made this remark:

Many in the scientific community are concerned about a circumstance where large amounts of this critical information might, in some way, be constrained from utilization by everybody who wants to use it. It is such basic information, and the notion that it would, in some way, be moving out of a public domain enterprise into a single private company has raised some cautions in the minds of many of my advisors.

Although the emphasis is on "basic," it probably should have been on "single," because as Shreeve documents, the public project was involved in relations with commercial firms well-known for their aggressive patenting. So despite the participants' rhetoric of moral purity, the personal battles were, above all, about credit, personal credit—as the book recounts at length.

Among the many virtues of The Genome War is its adept chronicling of complex alliances and the strains on them. On the Celera side, the differences (sometimes minor and sometimes major) between the idiosyncratic and provocative Craig Venter and his boss, the no-nonsense businessman Tony White, are clearly set out. Venter's commitment to make the genomic data available—with a delay—came into increasing tension with White's business strategy. This conflict was exacerbated by the tactics of the public project, which constantly painted the staff of Celera as betrayers of mankind and incompetent scientists whose sequencing strategy would never work. James Watson was fond of referring to Venter as "Hitler," and Sulston told Science that Celera was involved in a "con job."

The tension between the camps and even within them was also heightened by the (little known) fact that, while providing a steady stream of righteous moralism to its academic troops and the media, the public project had contracted with the California biotech company Incyte Pharmaceuticals, which was all the while busy patenting genomic information and selling it to a handful of major pharmaceutical companies. In fact, Incyte was a better example of the dangers of mixing commerce and science than was Celera. Incyte had been one of the pioneers in patenting DNA fragments in an aggressive manner and then marketing them at high prices to pharmaceutical companies. Celera's business plan was never as exclusionary and was based on better-substantiated claims to having identified functional sequences.

In 1999, Incyte CEO Randy Scott claimed the company had hard evidence that the human genome was made up of 140,000 genes, whereas most researchers believed the figure was about 100,000 genes. One of the many things learned from the sequencing is that humans actually have a far smaller number of genes, perhaps as few as 26,000 (although these may encode a much larger number of proteins).

There is an almost Shakespearean quality to the narrative (which may also bring The Sopranos to mind). We see Shreeve portray Collins and his allies as relentlessly performing their sanctimonious Boy Scout cheerleading in public in passages like these:

The Human Genome Project, Collins told himself, was about community, about the rules that applied to all, about the sacrifice of individual motives for the collective good. It was even a bit about God. . . .
"If you drew a circle around what God knows, it would be unimaginably huge," [Collins] later said. "What I know is a teeny, teeny dot within the circle. But every once in a while we humans get to sneak out of the little dot and find something that wasn't known before. That's the way it was with the cystic fibrosis gene. I felt I was getting a tiny glimpse into God's mind."

Shreeve describes at great length evidence that Collins and his loyalists, while defending Humanity, God and Science, simultaneously engaged behind the scenes in politics most venal: Specifically, Shreeve alleges that they threatened journalists and distinguished scientists, stooped to vulgar name-calling, reneged on agreements and refused compromises proposed by other government officials.

The book paints a portrait of Venter that is more nuanced and complicated than the one that his opponents and other journalists have given us. The aggressive, competitive, driven and blunt dimensions of Venter's character are well-known, and Shreeve provides numerous vivid examples of this side of the man's persona. He also presents other facets of Venter's personality, and of the internal dynamics of the company, which fill out and complicate the picture. We meet Venter the scientist, who finds himself in increasing disagreement and eventual fierce combat with Tony White. Venter is humiliated on a number of occasions and thwarted on others. Shreeve witnessed the frustration in Venter's relations with other business allies. He also saw Venter chafing at the bit when company lawyers placed constraints on him as Celera moved toward a public offering. To Shreeve's credit, he gives us enough of a sense of the man to overcome easy moral judgments, and enough information to decide ourselves whether to applaud or condemn the whole enterprise. That complexity is one of the book's strengths.

Although early sections of the book fall into an overwritten, breathless style, once the narrative pace picks up, Shreeve is masterful at keeping the chronicle in constant motion while providing sufficient explanation for the reader to grasp the technological challenges and scientific import of events. He also explains the science behind the sequencing in plain English. Shreeve presents the moral and political events in all their rawness. The reader comes away informed—if shaken.


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