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“Cracking the Genome: Inside the Race to Unlock Human DNA” By Kevin Davies The Free Press; 251 pages, $25 The media’s usual metaphor for mapping the entire DNA sequence of the human genome — biology’s “holy grail” — is spectacularly inappropriate. Decoding the order of the individual chemical bases in humankind’s 23 sets of chromosomes is just a beginning, not an end. More important, cracking the genome is a stunningly Promethean act, arrogating to man what had once been the province of the gods alone. Such desacralization is the ultimate flowering of the Enlightenment dream of reason, not of a religious quest. It gives us the capability to transcend our historical existence as objects passively constituted of inherited DNA. Instead, we can now choose — and manipulate — the DNA of which we want to be built. We’ve become writers rather than mere readers of the book of life. In America, however, such heady talk of transcendence runs smack into the market economy, which always makes the question of who owns what more important than who knows what. The “race” Kevin Davies describes in his entertaining if scattered book, “Cracking the Genome,” has been as much to the patent office and the capital markets as to the laboratory and scientific journals. It’s the story of inventing business models and sequencing genes, a tale of the clash of big egos chasing big dollars as well as the Nobel Prize. And it’s the arena for troubling questions about the extent to which the ultimate commons of the human race, our collective genetic legacy, should be exploited by private interests for private gain. Davies, now the executive editor of Current Biology, has had a ringside seat for recent biotechnology breakthroughs. A geneticist himself, he was the founding editor of Nature Genetics, which, in 1992, was spun out of Nature — one of our premier scientific journals. It was at this time that the human genome project (HGP) got rolling at the National Institutes of Health. Many of the political and commercial dynamics of the genome race played out in the pages of Nature and its rival, Science, as different institutes and biotech startups vied to publish their results first, and in a form that safeguarded potential patent rights in the genes their DNA sequences identified. Davies’ own Ph.D. in genetics makes his account of the science involved more credible — and less sensational — than those of less specialized reporters. “Cracking the Genome” lucidly explains the history and techniques of genetic research from Mendel’s painstaking pea gardening in 1865 to today’s supercomputer-driven sequencing and “in silico” protein modeling. But Davies focuses on the powerful personalities and emotions behind the dry language of scientific discovery. He anatomizes the envy, greed, and lust for fame that fueled both the race to Stockholm and the struggle for control of funding and research programs. James Watson and Francis Crick published their landmark two-page Nature paper on the helical structure of DNA in 1953. Over the next 30 years, the technology for determining DNA sequences and their meaning developed to the point that decoding the entire human genome seemed feasible. In 1988 the NIH was chartered to do so, under the overall direction of James Watson himself. The HGP forecasted that it would take a decade or more to sequence the entire genome, which it proposed to put into the public domain. Enter J. Craig Venter, “the most influential scientist of the 1990s,” according to Davies, whose role in cracking the genetic code would make him one of the “most powerful, controversial, not to mention wealthiest, scientists in the world.” Venter was an intellectually precocious but rebellious teenager who barely graduated from high school and enlisted in the Navy in 1965 instead of going to college. He was shaken enough by his experience as a medical corpsman in Vietnam to want to become a doctor, but shifted from medicine to basic research, getting a Ph.D. in physiology and pharmacology instead. At the NIH in the 1980s, he headed the team that isolated the protein on the surface of heart cells that senses adrenaline and triggers the “fight or flight” response to stress. The project, based on manual DNA sequencing techniques, took five years and cost $10 million. Venter feared that progress in biomedical research would be intolerably slow if this pace and cost was extrapolated for all 60,000 human genes. “Venter’s solution to this problem was characteristically spontaneous and daring,” Davies reports. Venter went off on his own to California and struck a deal with Applied Biosystems (later a division of Perkin-Elmer Corporation) to become the alpha site for ABI’s new automated DNA sequencers. Using the ABI machines, Venter sequenced 60,000 bases of DNA and identified five possible genes in a fraction of the time and at a fraction of the cost of the old manual methods. Applying bleeding-edge technology to promising problems became Venter’s signature approach to genetic engineering. Despite opposition from Watson, Venter’s lab used automated sequencers to pioneer the technique of using standard laboratory collections of purified DNA to quickly generate “expressed sequence tags” (ESTs) or overlapping maps of partial gene sequences that could be combined to identify entire genes. In 1991 Venter published a report in Science on more than 330 genes mapped by using ESTs, and eight months later identified partial DNA sequences for another 2,375 human genes in a paper in Nature. The papers were a slap in the face to the HGP establishment, according to Davies: Venter had sequenced bases at the cost of 12 cents a letter, and had identified more than 5 percent of the total human gene pool in months, not years. Even worse, he had arranged the filing of patent applications on all of the ESTs described in his papers before they were published, even though the sequences for full genes were incomplete and the functions of the genes were not known. Watson denounced Venter’s work as “brainless,” acidly discounting the EST program as something that “could be run by monkeys.” Venter’s lab technicians countered by posing for photographs beside their sequencing machines wearing gorilla masks, but the controversy was far more than monkey business. Venter left the NIH to take the genomic gold rush to the next level, both commercially and ethically. His first stop was a nonprofit research center, The Institute for Genomic Research (TIGR), which would have freedom to publish as long as its for-profit sister company, Human Genome Sciences, got the first look at data and could file patent applications beforehand. Over the next six years, TIGR would partially sequence tens of thousands of human genes and the entire genomes of several bacteria. According to Davies, Venter made more than $9 million on his TIGR stock, buying an 82-foot, $4 million all-aluminum yacht as a trophy — an action more typical of a successful dot-com entrepreneur than of a leading genetic researcher. In 1998 Venter stunned his colleagues by leaving TIGR for the new Perkin-Elmer (now Applera) subsidiary Celera Genomics Group (from the Latin “celeris,” or “quick”). Celera’s business plan was to use even more advanced PE technology to sequence the entire genome faster than the HGP, publish only some of the data, and sell its proprietary information to pharmaceutical companies and university researchers. The longest list of entries about Venter in the index of “Cracking the Genome” is under “animosity toward.” “Darth Venter,” as he became known, reached the apogee of his notoriety when he boasted that Celera would complete the human genome sequence in 2000, five years before the HGP was slated to finish its version. When Venter announced, right on time, that Celera had completed a “rough draft” of 90 percent of the genome in January 2000, Celera’s stock soon peaked at more than $275 a share. Like his fellow high-tech paper multimillionaires, Venter has gotten his financial comeuppance since. Prodded by the U.S. and English governments, Celera and the HGP announced a truce last June. They will now collaborate on publishing a publicly available version of the human genome. Celera’s stock has since tumbled 80 percent, and it’s unclear whether the drug companies will continue to pay big bucks for the proprietary information Celera mines from its database when they can get the HGP’s version for free. What a story, right? All the makings of a headlong “Raiders of the Lost Genome” thriller were at Davies’ disposal. Unhappily, Davies isn’t much of a storyteller. “Cracking the Genome” has the structure of a mazelike “Pulp Science” as it cuts back and forth across its narrative time line and wanders off into disconnected subplots. Example: Venter decided to sequence the genome of the fruit fly as a dry run to validate Celera’s “shotgun” approach to sequencing the human genome using ESTs. Enter Drosophila, and off goes Davies on a five-page history of Thomas Morgan’s 30 years of Nobel Prize-winning research on fruit fly genetics in the dusty attic of Schermerhorn Hall at Columbia University. Fun stuff, but it derails the story. “Cracking the Genome” also doesn’t do justice to the legal and moral issues at the heart of human DNA research. Davies does periodically allude to the controversy over patenting human genes. He dutifully quotes critics like John Sulston, the head of Britain’s Sanger Centre for genetic research, who denounced proprietary genome sequencing as “totally immoral and disgusting” and asserted that Venter “has gone morally wrong” in seeking to restrict the free exchange of genomic data. But Davies doesn’t seem troubled by their criticism of Venter or by the commercialization of basic genetic research. He’s much more interested in the spectacle of big science than in its import. Moreover, patents are only the starting point, not the end point, of the ethics debate. Should control and exploitation of the human genome recapitulate the history of the control and exploitation of the planet’s other natural resources? If so, genetic engineering and its Promethean rewards may be subsumed in what David Shenk has called a “free market eugenic meritocracy.” The ability to prevent, diagnose, and treat disease on the basis of someone’s genome rather than their symptoms — even in utero — raises fundamental issues about how such benefits are distributed. “Cracking the Genome” does not address them. Shenk and other critics foresee a not-so-distant future in which the rich can buy immunity at the cellular level from the ravages of disease and pollution and wealthy parents can buy optimized genomes for their unborn children, while the poor’s DNA continues its uncontrolled and cancerous mutations. If we don’t want that sort of inequality, what degree of collective administration of the gene pool is acceptable — and exercised by whom? For insight into both the utopian promise and the dystopian threat of biocapitalism, one must turn elsewhere than “Cracking the Genome” — to journalists like Shenk and science fiction writers like Bruce Sterling (“Schismatrix,” “Holy Fire”), whose work explores the consequences of the scientific advances Davies only describes. Michael Stern, a former reporter and English professor, is the head of the information technology group of Cooley Godward’s Palo Alto, Calif., office.

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