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July 2001
Vol. 4, No. 7, p 65.
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Cracking the GenomeCracking the Genome:
Inside the Race to Unlock Human DNA
Craig Venter, Francis Collins, James Watson, and the Story of the Greatest Scientific Discovery of Our Time

The Free Press, New York, 2001, 310 pp, $25 hardbound
ISBN 0-74-320479-4

Hardly a better person than Kevin Davies could have been chosen to producethis first major cut on the contemporary history of the behind-the-scenes politicking and palavering surrounding the finally completed Human Genome Project. Davies is the founding editor of Nature Genetics and was an observer of and in a sense (by his editorial role) a participant in the entire process—the ideal fly on the wall with both access and credibility.

The book moves rapidly through the origins of the Genome Project and its early days under the direction of James Watson of DNA fame through his conflict with NIH director Bernadine Healy that resulted in his stepping down. Much of the subsequent text examines the careers of the two principal protagonists of the genomic end game—Francis Collins on the public sequencing side and Craig Venter on the side of private enterprise. Both men are treated with sympathy and humor by Davies, although it’s fairly obvious that his true appreciation lies with Venter.

more good reading
The Gene Wars: Science, Politics, and the Human Genome
By Robert Cook-Deegan W. W. Norton and Co., 1995

In the Name of Eugenics: Genetics and the Uses of Human Heredity
By Daniel J. Kevles Harvard University Press, 1995

The Code of Codes: Scientific and Social Issues in the Human Genome Project
By Daniel J. Kevles and Leroy Hood (Eds.) Harvard University Press, 1993

A Century of DNA: A History of the Discovery of the Structure and the Function of the Genetic Substance
By Franklin H. Portugal and Jack S. Cohen, The MIT Press, 1977

Since “Venter-bashing” in some circles is as facile and entertaining an enterprise as picking on Bill Gates, this book provides a useful antidote to this trend by pointing out that Venter was indeed not just the industrial showman but a critical scientific player. In his early days at NIH and later, as he established The Institute for Genomic Research (TIGR), Venter advanced the cause of cDNA cloning to get at the actual genes expressed by the genome using expressed sequence tags (ESTs).

His automated cloning approaches shook up everyone and provided a counterpointto what is oftentimes the lethargy of big government projects with long-term deadlines. Venter was undoubtedly the main force behind the push to get the genomes of a multitude of species, including the human, quickly and easily. However, and this is a big however, Davies’s book swings the pendulum too far the other way, falling into the more typical media trap—Venter worship.

Here is the true take-home message about the Human Genome Project, although it is only a subtext in this book. Remember it when all the Nobel Prizes are awarded to production bigwigs, Venter, Collins, whoever. Hamilton Smith (already a laureate for his work on characterizing the first restriction enzymes) was the man who proposed the shotgun strategy of chopping genomic DNA into thousands of pieces, sequencing each fragment, and then using computer analysis to put the pieces back together—the basis of Celera’s whole triumphant leap forward. And Mike Hunkapiller, Leroy Hood, and colleagues at the California Institute of Technology developed the fluorescent dye labeling approach to DNA sequencing (in which each of the four base pairs is tagged with a different colored fluorescent marker) to replace Fred Sanger’s original method, which relied on radioactive tracers. The automation of this approach allowed the explosion of research necessary to reach the end. According to Venter, “there would be no genome field at all if it wasn’t for Mike Hunkapiller.”

The declared “finish” of the Genome Project in the summer of 2000 had ironies and politics of its very own, given that at best only some 80–90% had been sequenced. According to The Economist, it was celebrated prematurely to ensure that the public project did not get beaten to the punch by the upstart private company, Celera. An additional explanation: “There was a more pragmatic reason for the June 26 announcement . . . it was the only time that a gap could be found in [Bill] Clinton’s and [Tony] Blair’s schedules.”

As for the title of this fascinating book, semantic purists will of course complain that a genome is not “cracked” until its actual meaning is deciphered—which is exactly what we did not get with the completion of what should have been called the Human Genome Sequencing Project. So in that sense, the book is hype. The real Human Genome Project remains the work of the future—figuring out what it all means and how we can best make use of it. But sequencing was the critical first step, and the struggles between Watson and Healy and then Collins and Venter shall forevermore be a significant part of human history, along with a host of other conflicts with higher body counts and less salutary ends.

—Reviewed by

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