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What Shall We Do With a Bumptious Sailor?

What Shall We Do With a Bumptious Sailor?

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September 7, 2010

BOOK REVIEW: J. Craig Venter, A Life Decoded: My Genome: My Life. (New York: Viking, 2007), 390 pages, $25.95 (hardcover).

The problem of J. Craig Venter is one that Western civilization has wrestled with since the Trojan War: How we can harness the energies of our bad-boy supermen without allowing their example to disrupt or reverse society’s slow moral progress?

Venter is the biochemist (and daredevil yachtsman) who directed a small corporate rival of the official U.S.-U.K. genome-sequencing team and fought them to a draw in June 2000. His autobiography makes use of a gimmick that is an extension of his famous achievement. Venter went on to sequence the entirety of his personal genome, and throughout this book he strews twenty-six sidebars that connect his genes to various aspects of his life. For example, he suggests that his “inattention, excessive motor activity, impulsivity, and distractibility” may be due to a genetic stutter: ten repeats of a section in the dopamine transporter gene.

None of these sidebars, however, sheds as much light on Venter’s character as the simple facts of his life. He is clearly brilliant—and clearly despicable. For example, during his first professorship, Venter romanced a graduate-student assistant, Claire Fraser, even though he was a husband and recent father; yet he now has the gall to lament that he was not able to raise his son by his first wife. Or again: When Venter is recalling the White House celebration of his achievement, he derides the contribution of the man who had had the vision to launch, and the courage to subsidize, the project: “He had signed the check” is his dismissive summary.

“Craig Venter is an asshole.” So reads the famous opening quotation in a New Yorker profile of Venter, and no reader of this autobiography can doubt the truth of the remark. But alas, even narcissistic innovators have an important role to play in the world, and a healthy society cannot afford to risk losing their contributions. The difficulty is that our egalitarian age, demanding equal treatment for people regardless of their abilities, finds it difficult to say: “Quod licit Jovis, non licit bovis” (“What is permitted Jove is not permitted a cow.”). Yet that is the truth, or at any rate it is a part of the truth.

BEGINNINGS

Jerk/savants do not generally begin as decorous prodigies and then bloom into misfits; rather, they arise when misfits become late-blooming geniuses. And so it was with Venter. Though he strives mightily to find redeeming features in his youth, it apparently takes an autobiographer’s eye to appreciate them. To an outsider, he seems to have been a wastrel. Conscripted and consigned to Vietnam, Venter returned to the States married, convinced of his complete moral superiority, and determined to make a name for himself.

He began repairing his educational deficit by enrolling at a community college and quickly made up for lost time, publishing an article in a scientific journal on the workings of adrenaline even before he had received his B.A. By the time he was awarded his Ph.D., Venter had published several papers on how adrenaline produces its effects, and he was able to choose among offers of professorships while his colleagues were scrambling for post-doc fellowships. In the end, he chose an offer from the State University of New York at Buffalo and arrived there in 1976.

On his first day at Buffalo, Venter tells us, he presented himself groomed in the fashion of the early Seventies: long hair, pony tail, scraggly beard, polyester shirt, and bell bottoms. Nonetheless, a senior professor in his department graciously invited him to sit in on a thesis defense being given by one of the professor’s graduate students, presumably “to show off his protégé to the new guy from the West Coast.” After it was over, Venter spoke his mind bluntly. The reason, he avers, is that he had just come from UC, San Diego, a school where “you quickly learned not to take scientific criticism personally.” Venter does not tell the reader what blunt remark he spoke on that occasion. I had to check to James Shreeve’s The Genome War to learn the “scientific criticism” that Venter had not meant to be taken personally: “That was the most mediocre load of shit I’ve ever heard.”

Jerk-savants do not generally begin as decorous prodigies and then bloom into misfits; rather, they arise when misfits become late-blooming geniuses.

Professionally, Venter continued his investigation into the workings of adrenaline and its receptor sites on cells. That led him to look into the chemical structure of the protein that constituted the receptor molecule and then, in order to obtain enough of the protein, into the constitution of the gene that produced it: the sequence of nucleotides that make up the gene. But Venter could not be Venter without being obstreperous. After threatening departure from the pharmacology department if he did not get early tenure (the rule was seven years), and after being denied, Venter skipped first to the biochemistry department, and then in 1982 to the nearby Roswell Park Cancer Institute.

Obviously, things were not going smoothly. With his divorce made final in 1980, his ex-wife and son gone off to Texas, and his paramour getting her Ph.D. (followed by their marriage in October 1981), there was little to keep Venter in Buffalo. So, with an offer in 1983 from the National Institutes of Health, Venter and his new wife departed.

NIH

Installed at the National Institute of Neurological Disorders and Stroke (NINDS), Venter once again went after the make-up of the adrenaline-receptor gene, using a sequencing method developed by the double-Nobel Prize winner Frederick Sanger. By 1986, Venter’s team had finally determined the gene’s entire sequence of nucleotides, leading him to publish “the first molecular biology paper” of his career.

Nucleotides are organic molecules, and human DNA is made up of four such nucleotides, designated by their nitrogenous bases: adenine (A), guanine (G), thymine (T), and cytosine (C). Thus, a section of a chromosome’s DNA might run: GAGTTTTATCGCTTCCA. As it happens, an A nucleotide on one strand of the DNA’s double helix bonds only to a T nucleotide on the other strand, and a G nucleotide on one strand bonds only to C nucleotide on the other. Thus, AG and TC are called complementary base pairs. So, the stretch of DNA above would be paired to a parallel sequence that ran: CTCAAAATAGCGAAGGT. A human gene may have anywhere from a few thousand to a couple of million such base pairs, and the entire human genome, comprising 23 chromosomes, is thought to have about 3 billion base pairs—6 billion, if one reckons that a person has two each of the human’s twenty-three chromosomes, one from each parent.

Craig Venter’s career in DNA sequencing got a second boost in 1986 when he read a Nature article that had been written by a group at Cal Tech and that described a new technology which would immensely speed up the reading of the genetic code. Better still, he learned, the new technology was being turned into a machine by Applied Biosystems Incorporated (ABI). Venter was determined to have the first of these new machines, even though NIH denied him the funds and he had to buy the machine out of money he had received from the Pentagon to work on detecting biowar agents. By February 1987, the sequencer was installed, and by the fall it was producing data. By the next year, the leadership of NINDS had changed its mind about Venter’s machine, created a separate DNA sequencing facility, and made Venter its head. Given the mandate of NINDS, however, Venter’s work had to concentrate on genes relevant to neurological disorders.

In September 1988, the great James Watson, co-discoverer of DNA, came to NIH as associate director, in order to launch the Office of Human Genome Research. The idea of sequencing the human genome had been bandied about for several years, but it was only when Watson committed his carefully guarded prestige to the project that the scientific community understood that this was important, cutting-edge science. With Jim Watson in charge, Nobelists and Nobelist-wannabes felt comfortable joining the NIH genome project, and of course Venter (a Nobelist-wannabe if ever there were one) desperately wanted to be in on the research.

Although Watson was skeptical of Venter’s scientific understanding (naturally, since Venter had just started learning molecular biology), he was impressed with Venter’s nucleotide-sequencing results and wanted his proposal to be funded. Here is the account given by journalist James Shreeve, who was allowed to follow Venter’s team during the genome quest:

    Richard McCombie, Venter’s lab manager at the time, said later: “We asked for five million dollars. [Watson] turned to his people and said, ‘This is great, give them the money.’ But they told him that it didn’t work that way. And Jim says to them, “What do you mean it doesn’t work that way? I run this place. What’s the point of running the place if I can’t make the decisions? Give them the money for two or three years, and if they do good work, give them more. If they don’t, we fire them.”’

In short, the bureaucracy forced even the great James Watson to follow procedures. But here is Venter’s summary of the same event: “Watson was a federal bureaucrat, and like any other federal bureaucrat, he was afraid to make decisions on his own.” That is simply unjust, and, according to all accounts of Watson, the very opposite of the truth.

In 1989, Venter had another big idea, and this time it was a really big idea. Begin by finding the active, protein-producing genes in the genome, the parts of the genome that would likely be most useful for concocting drugs or repairing genetic faults. Get those sequenced. Then go after the whole genome, with its “regulatory regions, DNA fossils, the rusting hulks of old genes, repetitious sequences, parasitic DNA, viruses, and mysterious stretches of who-knows-what.”

But this big idea created two big problems. The need for a fundamental understanding of the human genome was being sold to the American Congress and the British Parliament as the road to medically useful discoveries. Craig Venter was now saying: You can discover the medically useful parts of the genome for a fraction of the cost (he called it “a bargain”), then later go after the fundamental science of sequencing the whole genome. All well and good for Craig Venter. He would be collecting his Nobel Prize in medicine, while those who came after him would be trying to persuade politicians to fund the sequencing of “fossils, rusting hulks, and who-knows-what.”

A far more immediate problem, though, was patents. Can one patent a human gene? Well, a person surely could not patent one of my genes as it exists in my body. That would be merely discovery, not invention. But the active, protein-producing part of gene is typically a discontinuous sequence on a chromosome. Suppose one analyzed and then synthesized just that active sequence of the few thousand base pairs needed to produce a given protein or group of proteins. (Our 20,000 protein-producing genes probably generate ten times that number of proteins.) That would definitely be a patentable invention: original and useful. Now, suppose one analyzed and synthesized just a key fragment of the active, protein-producing sequence. Could that be patented? And if it could, would the person who later analyzed and synthesized the whole of the active gene have to pay royalties to the person who had sequenced only one key part? Lastly, suppose that the latter person, who had sequenced only an element, had had no idea what the gene did?

That was the issue roiling genomic science at the end of the 1980s. The fractional gene sequences Venter obtained (called “expressed sequence tags” or ESTs) were like a gene’s fingerprint. An EST allowed him to identify the sequence as a key part of a distinct protein-producing gene. But frequently that was all. Nevertheless, Venter began isolating hundreds of these key fragments, and NIH began applying for patents on them. In April of 1992, James Watson left NIH, allegedly over some financial conflict-of-interest but largely over disagreement with NIH’s patenting policy. Ironically, the next head of NIH, Harold Varmus, appointed by President Clinton in 1993, agreed with Watson’s position and the patenting was suspended. By then, however, Venter had moved on.

TIGR

In the summer of 1992, venture capitalist Wallace Steinberg gave Venter his dream: a research institute of his own, which Venter named The Institute for Genomic Research—and please capitalize the T: “My institute was a Tiger (TIGR), not an Igor.” TIGR would have a ten-year budget of $70 million. In return, it would offer its research discoveries exclusively to Steinberg’s new biotech company, Human Genome Sciences (HGS), for a limited time, perhaps six months, after which the data would be made public.

In 1993, Venter and his team of TIGRs undertook to produce the first complete genome of a free-living organism, the bacterium Haemophilus influenza, which has 1.8 million base pairs in one circular chromosome. The standard method for sequencing a chromosome was to take large chunks, perhaps 35,000 base pairs long, and put them in order. When this map was complete, the chunks would be broken down into small chunks, of perhaps 500 base pairs each, which would in turn be sequenced and then re-assembled by looking for end-to-end matches. The method Venter wanted to employ was called the “whole-genome shotgun” (WGS) method, and though it was similar to what he had been doing, it was on a radically different scale. In trying to determine the nucleotide sequence of a gene, TIGR had been using a computer program to compare ESTs. If two ESTs overlapped by, say, fifty base pairs, then it was likely they should be put together as part of a continuous sequence. Now, suppose one were to blow the whole H. influenza genome to smithereens, sequence the pieces, and then let computers look for overlap. It would require a lot of computing power, and the results would not be complete or error-free, but the sequencing process could be accelerated many times over.

TIGR applied to NIH for funds to pursue the method, and, predictably, it was refused on the grounds that the procedure was unlikely to work. Venter defiantly tacked the refusal to his door: By that time, the project was nearly finished. On May 25, 1995, the TIGR team announced its success, and just for a treat, they threw in the genome of Mycoplasma genitalium, which has the smallest genome of any living organism. At the end of the paper in Science magazine that announced the achievement, Venter observed “The success with H. Influenzae sequence has raised the ante worldwide for sequencing the human genome.”

On July 25, 1995, however, Wally Steinberg died, and Venter knew that it was the beginning of the end for his relationship with HGS. Right at the start, Steinberg had appointed a CEO that Venter did not want and with whom he had never gotten along: William Haseltine. Instead of shopping TIGR’s data piecemeal, as Venter had expected, Haseltine made an arrangement to give SmithKline Beecham exclusive rights to all of Venter’s data. The pharmaceutical company, in turn, used its dominant power to begin imposing restrictions on the distribution of Venter’s data to the scientific community and even on the wording Venter could employ in his scientific papers. After Steinberg’s death, Venter told Haseltine that the time had come for a TIGR/HGS divorce, even though HGS still owed TIGR $50 million. Haseltine objected, fearing it would damage HGS’s relationship with SmithKline, but Venter got SK to agree to divorce in return for some additional rights to use data it already possessed. By mid-1997, therefore, Venter had his independence back—only to surrender it again.

CELERA

Cuban-born businessman Tony White was not refined. He had come up the hard way, rising from peddling surgical gloves at Baxter International to become its executive vice-president. He had not been to Wharton or Harvard Business School, and he figured that his chances of moving into the top spot at Baxter were nil. So, when a ramshackle technology conglomerate called Perkin-Elmer offered White its presidency, in 1995, he accepted eagerly. Among the conglomerate’s assets, he discovered, was a little California company called Applied Biosystems, which produced a DNA sequencer. White thought the life sciences were a comer and wanted to put money into the field.

Few of us fulfill our productive potential as completely as Craig Venter has; few of us fail to fulfill our moral potential so miserably.

The following account of what happened next is most definitely not told by Craig Venter; it comes from Shreeve’s Genome War. At a business meeting in late 1997, the head of ABI, Mike Hunkapillar, did some quick calculations and announced to the assembled group that two hundred of their machines could sequence the entire human genome in three years. A discussion followed, but it quickly grew desultory and cautious. At the end of ten minutes, Tony White said: “Let’s get it over with. Let’s just do it.”

Back to Venter’s narrative: When he finally consented to take a trip west and see ABI’s latest technology, in 1998, Venter was asked by the company executives for a back-of-the-envelope calculation: If all their machinery worked as planned, could he beat the government project for $300 million? His rough estimate: Yes, using the whole-genome shotgun method, it was do-able, but just barely. Challenged by one of his own doubtful colleagues, Venter took a second look at his calculations and found a tenfold error—in the project’s favor. The mistake was unplanned, Venter insists, but it won over the skeptics—except for one.

Venter’s wife, Claire, thought that Craig was mad, having so recently won his freedom, to be considering another business-backed project, with all the corporate restrictions and entanglements that had made him so hated in the scientific community. And it must be acknowledged that, however much reason scientists had to hate Venter for his attitudes and behavior, a good portion of the hatred was due to a hatred of commercial involvement in science.

Venter replied that he had told ABI plainly he wanted to publish all his data and that they had agreed he could. What had not been made quite clear, however, was exactly how Perkin-Elmer hoped to profit from the project. No matter. For Venter, the temptation was simple: “The genome was the biggest prize in biology.” He assured his wife that, if she (a more-than-competent scientist and manager) would run TIGR in his absence for a few years, he would be back as soon as he had secured his victory.

Before starting on the human genome, however, Venter wanted to use the whole-genome shotgun method to sequence the genome of the most famous organism in genetic biology: the fruit fly (Drosophila melanogaster), which had 100 million base pairs and more than 10,000 genes. James Watson, who had taken to referring to Venter as “Hitler,” remarked to a colleague: “I understand the fruit fly is to be Poland.” In the event, however, the fruit fly project was not launched with a blitzkrieg. Just getting ABI’s machines up and running proved to be an ordeal, and the project did not begin until April 8, 1999—approximately the time it was to have been completed. Nevertheless, the sequencing was finished (within the limits of the whole-genome shotgun method) on September 9.

The race for the human genome was on.

A FRAUDULENT FINISH

At the end of October 1999, Celera announced that it had sequenced one billion base pairs in the human genome. The pressure was mounting on Francis Collins (who had replaced Watson as head of the public genome group) to find a way of collaborating, but the public scientists’ insistence that all data resulting from a collaboration must be unrestricted seemed to make that impossible. Meanwhile, journalists were having a field day with the David-and-Goliath angle.

In March 2000, President Clinton issued what must have seemed to him just another statement blathering about the public interest. At an awards ceremony for the National Medals of Science and Technology, he said: “Already the Human Genome Project, funded by the United States and the United Kingdom, requires its grant recipients to make the sequences they discover publicly available within twenty-four hours. I urge all other nations, scientists, and corporations to adopt this policy and honor its spirit.” As far as the stock market was concerned, the statement was anything but blather. Investors interpreted Clinton’s statement to mean: no patents on genes, and therefore no profits. In the next two days, the biotech sector lost half a trillion dollars and Celera lost $6 billion. According to Time magazine, Clinton ordered his science advisor, Neal Lane, “Fix it. . . . Make these guys work together.”

And so it came to pass that Craig Venter arrived at the White House on June 26, 2000, to join with the NIH’s Francis Collins in celebrating the sequencing of the human genome (well, a lot of it)—an achievement brought about by the selfless, harmonious collaboration of public and private efforts. (Right.) No other president, I believe, could have brought Venter to share the day with the public project and especially with Francis Collins, whose religious convictions he clearly disdains. But Venter had by this time become a Clinton groupie, deeply admiring his fellow bad-boy, and even claiming to take inspiration from Clinton’s handling of the Lewinsky debacle. Indeed, when discussing the choice of DNA donor for his project, Venter wrote: “Should we pick an average subject or a President Clinton?”—as one might say “or a President Washington?”

So, for the sake of peace, Venter agreed to share the day with Collins and even with Watson. But he would not use his influence to get Tony White a share of the glory. Rather, Venter spitefully recounts White’s frustration at being sidelined and tells mockingly how a 60 Minutes crew that was walking backwards in order to film Venter himself backed into White, knocking him down and stumbling over him as he lay sprawled on the ground. So much for the man who said “Let’s just do it!”

PROMETHEUS UNBOUND

In 2002, White fired Venter, who could hardly have remained long at Celera anyway, given their relationship. In 2003, the NIH project finished sequencing the human genome to the extent current technology allowed, but by then Venter was no longer in the race. He had begun setting up various organizations to accommodate his different interests, the largest being (what else?) the J. Craig Venter Institute.

In 2005, Venter divorced his wife, Claire, who had held the TIGR fort during the race to sequence the human genome, and in July 2006 he became engaged to a woman twenty years younger than himself, his lovely publicist (a telling choice). In 2006 also, one of Venter’s groups completed sequencing a single human being’s entire genome, very nearly all of the six billion base pairs. It was, naturally, Venter’s own. With that done, he was ready to publish this sneering, snarling account of his life. J. Craig—a venter, indeed.

The result is a sad work—sad for its readership, though apparently not for its author. There is so much knowledge in it—and so little self-knowledge. The sidebars on Venter’s genome are meant to give a double meaning to the title, A Life Decoded. But so far from “decoding” the nature of the life he has led, Venter seems not to have a clue about it. We all have genetic capacities; we all have genetic limitations. Few of us fulfill our productive potential as completely as Craig Venter has; few of us fail to fulfill our moral potential so miserably.

That, however, is Venter’s personal tragedy. It need not be ours, so long as our society does not cease from censuring the transgressions of its great men, even as we provide them with the wherewithal for their achievements—and even as we save most of our admiration for those who consent to work with our bumptious titans.

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