送交者: insight 于 2005-7-22, 01:47:58:
The arrogant adventurer
Craig Venter, high-school dropout turned decoder of the human genome, has plenty of new ambitions, says David Ewing-Duncan. One is to make the first synthetic organism
Thursday July 21, 2005
The Guardian
What would it be like to know all the details of your own personal programming, every A, C, T and G that swirls along the long, sinewy strands of your own double helix? J Craig Venter knows.
He became the first life form on Earth to possess this self-knowledge when in April 2002 he confirmed what many had already suspected: that the human genome sequenced by Venter's former company, Celera, largely comprised Venter's own DNA. An act of supreme ego, it flouted one of the prime directives of modern science: that a healthy ambition is fine, even desirable, but only if a person doesn't tout his own greatness and shows the proper awe and sensibility about the scientific enterprise.
No matter what people think of Craig Venter, he shook things up mightily during the race to sequence the human genome. He had, and continues to have, outrageous ideas that the scientific establishment frequently proclaims are unworkable. Yet Venter has succeeded, drawing on a potent arrogance and self-confidence that have transformed this previously obscure researcher into possibly the best-known molecular biologist in the world after Watson and Crick.
Venter grew up in Millbrae, California, a middle-class suburb near San Francisco airport. He spent his childhood racing planes on his bike, doing badly in school, getting into trouble, surfing, and eventually dropping out of high school, despite an IQ of 142. He was a champion swimmer and was popular with girls. After Craig got caught sneaking out to visit his 16-year-old girlfriend, his father told the girl's father, who arrived and waved a gun in Venter's face, telling him to leave his daughter alone.
In 1964, the year Venter turned 18, he was living in his grandmother's garage, surfing, and working at Sears tagging prices on merchandise. Facing the draft, he enlisted in the navy as a swimmer, only to be caught in the massive troop build-up in Vietnam in 1965.
Because he scored high on his IQ test, Venter was allowed to choose what he wanted to do, so he signed up to be a medic - an option that would get him out of the service faster and back out in the surf. He arrived in Vietnam just in time for the Vietcong's Tet offensive.
Working in triage at the navy hospital in Danang, he spent six months sorting out the dying from those who might be saved. The carnage astonished him and shook him out of his fecklessness as he pondered the fragility of life, much as Francis Collins was shaken when he was training as an intern in North Carolina, seeing the very ill and dying on the hospital wards.
Venter returned home with a Vietnamese wife and a burning desire to make up for lost time. After a stint in a junior college, he enrolled in the University of California at San Diego, earning his bachelor's degree and his PhD in just five years. After his PhD, a now highly ambitious Venter skipped the usual step of a postdoc position and took a job as a junior faculty member at the State University of New York at Buffalo.
With a failing marriage and a two-year-old son, Venter quickly established himself as arrogant, brazen, and very smart. He also met Claire Fraser, one of his students, who married him as soon as his divorce was final. In 1984, the two of them left Buffalo for the National Institutes of Health, where Venter opened a lab trying to tease out genes impacting diseases of the brain - and began scheming to make a name for himself.
Venter continues to dazzle, and to annoy people. Right now, with a nonprofit institute he set up mostly with his own money, the J Craig Venter Institute, he's trying to create the first-ever synthetic organism, while also working on a project to catalogue all the genes on Earth in a global sailing expedition that he compares to the voyages of Charles Darwin.
Supremely immodest, Venter surges forth like a force of nature that can be awesome to behold. Yet he also possesses an element of danger, a sense that this ex-surfer would leap headlong into riding a maverick wave the size of a skyscraper whether or not he could handle it. In a man talking about creating a designer life-form, this maniacal energy makes some people nervous that he may one day push over the brink. Some Venter detractors think that he already has.
During the dash to sequence the human genome, Craig Venter's adversaries called him "Hitler", "an asshole", and "an opportunistic maniac and leech". Collins sometimes ended presentations with a slide of a double helix made entirely of money, preaching against those who would sell the human genome as a commodity. The publicly funded scientists often vilified Venter when talking to reporters, which had its intended effect in the media as newspapers and magazines ran stories about Venter cashing in on human DNA. It was Time magazine that dubbed him the "bad boy of science", leading Venter to tell his wife: "I don't mind being bad boy. I just don't want to be evil boy."
Not surprisingly, Venter's recollections and interpretation of the events during the late 1990s concerning the Human Genome Project differ from those of Collins. For nearly two hours, Venter regaled me with his interpretation of events. The chief antagonists of his version of the story are Collins, Watson, Eric Lander and John Sulston of the Sanger Institute in Cambridge, who won the Nobel prize in 2002 and ran Britain's premier sequencing lab for the international public effort during the Human Genome Project.
"They wanted to win so badly," Venter said, "that they didn't care how they did it." He refers to the celebration, on June 26, 2000, of the completion of the draft human genome, presided over by the then US president Bill Clinton. Sulston's 2002 autobiography, The Common Thread, admits that the public project was not finished at the time of the White House announcement. "This was a stunning confession coming from a Nobel laureate," says Venter.
"Sulston's autobiography was more about me than it was about him," he adds. "And he's trying to degrade everything I contributed." Later, I take a peek at the index in Sulston's book and find that Venter is indeed mentioned on 78 of the 311 pages - 25% of the pages in the book.
What Venter doesn't mention is that Collins, Sulston and others in the public project were equally dismissive of Venter's results at the time of the White House event. Sulston writes in his book that, on the eve of the June 26 announcement at the White House, neither side, in his view, was really finished. "It was not clear that the Human Genome Project had quite got to its magic 90% mark by then, and Celera's data were invisible, but known to be thin," he writes, the invisibility occurring because the company had not yet released its data to anyone other than paid subscribers.
Sulston continues: "Nobody was really ready to announce, but it became politically inescapable to do so. We just put together what we had and wrapped it up in a nice way, and said it was done. Yes, we were just a bunch of phoneys."
Sulston maintains that Celera was fudging, too. He continues a few pages later to describe what he thought of Celera's data when he and the other leaders of the public project finally saw them in an advance copy of Celera's paper on the genome later published in Science concurrently with the public project's version in Nature. "It was the moment of truth," writes Sulston. "We had waited almost three years to see if Celera would be able to make good its claim that it had sequenced the human genome faster, more cheaply and more completely than the public project."
Sulston says that they were "naturally eager" to compare Celera's data with their own. "As we read for the first time through the detail of what the Celera team had done, it became clearer that the whole-genome shotgun strategy had not lived up to the claims made for it.
"We couldn't quite believe it. We had fully expected their sequence to be better than ours, given that they had access to all our data and we knew that they were using it. But they were publishing a sequence that seemed overall no better than the publicly released sequence, and which depended heavily on it."
I ask Venter which genome he uses now - the public databank or Celera's. He said he subscribes to Celera's database for his own research, because it's better. "Do you have to pay for it?" I ask, knowing that since he was fired from Celera in 2002 - they let him go when the genome failed to make the kind of money the investors had hoped for - he is predictably acerbic about the "morons" who controlled the money there and didn't understand his vision. "Of course," he replies.
I ask Venter how he is able to accomplish what he does - what it is about his personality. He says that it's focusing intensely on a goal he believes in and being willing to consider innovations and not get locked into dogma. He casually reels off his current projects: to create synthetic life by engineering a microbe from the DNA up; and to catalogue all genetic diversity on Earth. "Is there anything else you're working on?" I ask.
"Other than trying to create life and catalogue all the genes on the planet?"
"Well, that takes care of Monday and Tuesday," I say. "What about Wednesday?"
"Oh, we're working on some secret things. Because they're really big."
"And you'd have to kill me if you told me. The genome of the universe, maybe?"
"Who told you?"
Yet even as I join his staff in groaning at his jokes, I have to remind myself that this man is actually setting out to create new life forms, a synthetic genome that he will then insert into a microbe that will function according to his instructions. He and Ham Smith are running a Department of Energy-sponsored project to create a bacterium built with DNA arranged by these scientist-creators as one would assemble software in a computer. The goal is to build these organisms to perform a particular function, such as eating up CO2 pollutants in power plants or producing hydrogen for fuel cells.
Only slightly less outrageous is Venter's other project, the Global Ocean Sampling Expedition. This, Venter's self-proclaimed update on Darwin, is roaming the seas in the yacht Sorcerer II collecting not exotic species of animals, but microbes. Researchers on the vessel scoop up buckets of water and run them through filters in a small onboard lab that collects DNA from samples; the DNA is then frozen and shipped back to Venter's lab.
In Rockville, scientists use powerful sequencing machines to isolate and analyse whatever genes and species are present, some of which may hold keys to new sources of energy and other amazements. Venter hopes to discover up to hundreds of millions of new genes, increasing the known number of species on our planet by thousands of times. Venter flies back and forth from the boat to Rockville, splitting his time almost evenly.
In 2003, Venter and his team published an article in Nature about the trip to the Sargasso Sea and what he found when he shotgun-sequenced water from this stretch of ocean near Bermuda. Long considered an aquatic wasteland, the Sargasso Sea turned out to be chock-full of life.
According to the paper, the team discovered at least 1,800 new species and 1.2m new genes. This doubled the number of genes previously known from all the species in the world and included 800 genes involved in converting sunlight into cellular energy. Venter posted the lot of them on GeneBank, the NIH-sponsored online database containing information on known genes that have been publicly released, for anyone to use online for free.
I ask Venter what researchers can learn from all these genes, when scientists aren't even close to understanding the "only" 30,000 genes of the human genome. "It took Darwin years to analyse his Beagle data before he understood what it meant," he snaps.
Of more concern to Venter was the geopolitics swirling around the Sorcerer II expedition. The trouble started in the Sargasso Sea, when environmental groups and other activists criticised Venter for snapping up microbes that belonged to Bermuda because they appeared in that tiny island's territorial waters. Presumably, said the groups, these microbes might have been patented and used to make money for Bermudians. These charges found their way into Nature, Venter says, quipping that the reporter who wrote this article "must have come to Nature from the National Enquirer".
The Bermuda flap was just a warm-up for what happened next in the Pacific. As in the Sargasso Sea, Venter wants to give away whatever genes he discovers in the Pacific, an act of "generosity" that runs counter to United Nations rules.
In French Polynesia, Venter was denied permission by the French government to take his samples, because the government in Paris claimed that it was protecting its "patrimony". "It's French water, so I guess they're French microbes," said Venter. He enlisted the help of the French ambassador in the United States and French scientists, only to have his ship impounded on the French-administered island of Hiva Oa in the Marquesas.
Seizing a private vessel is illegal under international law, so Venter protested to the US state department, which told the French that this was a violation of the "honour of the United States". The ship was released, but Venter's captain was told not to take any samples. Eventually, the matter was cleared up, so Venter could go on with his expedition.
In his office, surrounded by his awards and toys, I ask Venter whether he thinks history will view the sequencing of the human genome as a big deal. Was it a Copernican moment, I ask, a Galileo moment, or a Watson-Crick moment?
"It's none of those," he says. "If you look past all the press, at all the hype statements, you can trace a lot of them back to the NIH. It's a change in basic research, not a change in breakthroughs. There have been very few instant cures, and very few instant insights. Most scientists are overwhelmed by the data, and don't use most of it."
I ask Venter whether he's a dangerous man, and he laughs. It's the end of a day spent with him, and a Maryland thunderstorm is beginning to rage as we are about to get into our respective cars. He shouts over the wind: "Science always has risks."
"But you are creating life. What if something goes wrong?"
"Look, I won't tell you that there are no dangers. That's why this needs to be done out in the open, with careful people making sure that mistakes won't be made."