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April 30, 2002

Thrown Aside, Genome Pioneer Plots a Rebound


George Ruhe for The New York Times
Dr. J. Craig Venter at Yale, where he spoke of making landmark achievements despite a lack of lacking federal support.


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What do you do for an encore after you have decoded the human genome? Dr. J. Craig Venter has had to ponder that problem sooner than he expected after being forced out as president of Celera Genomics in January.

He has now made his decision, to start two institutes and to write a book. One institute, he said in an interview last week before giving a lecture at the Yale School of Medicine, will study issues of science policy like the genetic basis of race and stem cell research. The other will try to engineer microbes genetically to convert carbon dioxide into hydrogen, producing clean energy and averting greenhouse warming in the same step.

As for the book, that will be based on his own genome, which he has now declared to be the principal human genome decoded by Celera. "I will do a detailed examination of my genetic code and use that as a basis of writing my book on genomics," he said.

The new turn in Dr. Venter's career does not seem likely to be significantly more placid than the previous phases. In conversation, he still alternates between assertions of his achievements and aspersions on his academic critics, some of whom attacked him again in an article in March in The Proceedings of the National Academy of Sciences. He is proud of what he achieved at Celera, but perhaps still a little bruised by the buffeting that he received there from the demands to generate revenue, as well as scientific results.

"There was severe pressure on me from the people who put up the money, as well as from the Collinses and Landers," he said, referring generically to his academic rivals in the race to decode the human genome, Dr. Francis S. Collins of the National Institutes of Health and Dr. Eric S. Lander of the Massachusetts Institute of Technology. "So I was walking a tightrope, though at times it felt like sliding along a razor blade."

Although best known for his role in decoding the human genome, Dr. Venter had made three prior landmark scientific discoveries. All were achieved because of his skill in spotting the gains that could be reaped from the new DNA sequencing machines made by Applied Biosystems of Foster City, Calif.

As a little-known researcher at the National Institutes of Health, Dr. Venter used the first generation of the machines to discover hundreds of human genes by decoding just short parts of them. A biomedical entrepreneur, Wallace C. Steinberg, who died in 1995, set up Dr. Venter in a nonprofit institute, the Institute for Genomic Research, or TIGR, to pursue the advance in harness with a commercial partner, Human Genome Sciences, headed by Dr. William A. Haseltine.

At TIGR, Dr. Venter assembled a loyal and talented group of scientists that included Dr. Hamilton O. Smith, a Nobel biologist. The team's second coup was to decode the full genome of a bacterium, handily beating the government-supported effort in 1995.

At the Yale lecture last week, Dr. Venter retold the story of how he applied for a National Institutes of Health grant to decode the bacterium by a novel method but was rejected by a panel of academic genome scientists who declared his decoding method unworkable. Dr. Venter had to finish the project with his own funds, he told the audience, but not before Dr. Collins had turned down an appeal, repeating the grant committee's finding that Dr. Venter's method could not work. Dr. Collins, through a spokesman, declined to comment.

"While the N.I.H. is not very good at funding new ideas, once an idea is established they are extremely good," Dr. Venter added, noting the profusion of the institutes' money now devoted to decoding other bacterial genomes.

Dr. Venter was then invited to sequence the human genome by Dr. Michael W. Hunkapiller, head of Applied Biosystems.

Given the chance to trounce his rivals on their principal project, Dr. Venter accepted and set up his company, Celera Genomics, that started sequencing the human genome from scratch. He tested his novel decoding first on the fruit fly genome, his third major scientific achievement, and then turned to the human genome, which both he and the government consortium completed in draft form in June 2000.

Celera's plan was to sell its genome data to subscribers. Dr. Venter said that this became a profitable business of more than $100 million a year, a figure that "not many biotech companies have achieved." The problem was that the government was giving away much the same data for free. Dr. Venter declined to address directly the question of whether he thought it a proper role of the government, which usually supports just precommercial research, to compete with his database.

Given Celera's high stock price, investors wanted more than just the income from the database. "The experiment worked, but not on the level wanted by people who wanted to become billionaires out of it," Dr. Venter said.

His original plan, Dr. Venter said, was to stay at Celera for four years. He made it through a "very strenuous" three and a half. "I had the demands of the pressure of the human genome race," he said. "I was trying as an absolute novice to run a New York Stock Exchange company and dealing with some of the issues and personalities associated with that."

But on leaving Celera, it was not so easy for him to return to his home at TIGR. In his absence, his wife, Dr. Claire M. Fraser, had taken over the institute and built its staff to 300 people, with $40 million a year in research grants, including financing to sequence the anthrax DNA. "So I said it was much better, rather than disrupt that structure, to form these sister organizations where I could play a role," Dr. Venter said.

He is starting his institutes, the TIGR Center for the Advancement of Genomics and the Institute for Biological Energy, with the money that he made from his stock in Human Genome Sciences and Celera. The policy institute may weigh in on political issues like stem cell research and what Dr. Venter calls "the confusion over genetic determinism."

His energy institute is centered on a group of ancient microbes, archea, which inhabit the deepest parts of the earth and ocean. The archea do not infect humans, making them safer to manipulate. Dr. Venter said he hoped that they could be genetically engineered to suck out carbon dioxide from the atmosphere, relieving the threat of greenhouse warming, and to convert the gas into hydrogen, a source of nonpolluting energy.

At 56, Dr. Venter is still full of vigor and ambition. He seems to thrive on opposition, missing no chance to skewer his academic critics. Yet he enjoys the academic approval of the prizes and honors that are showering down on him.

"I've always felt part of the academic community," he said. "I had to form Celera to get the money for sequencing the human genome."

He professes complete lack of concern that he has not been elected to the National Academy of Sciences, an elite group that has honored his chief academic rivals.

He responds heatedly to the criticism that he is brilliant at spurring public interest in his projects but seldom finishes them. "Do I come up with new ideas and move on to other things?" he asked. "Yes. I could easily spend my entire life working on any one of these things, but science is a lot further ahead because I didn't."

Later he referred to his role in life as "like a superenzyme." "I'm catalyzing things," Dr. Venter added.

The policy and biological energy institutes represent new areas where, he concedes, he is a neophyte. At TIGR, where he is still chairman of the board, he intends to decode more genomes, particularly those that throw light on one of his deepest interests, evolutionary biology.

He said he thought that he could get "most of the chimp genome" with a shortcut based on comparing it with the human genome. "But the real things are the blue whale, the dolphin and the elephant," he says. "There are no bad genomes to do."

No bad genomes an appropriate motto for the man who was first to decode the 1.8 million DNA units of the bacterium Haemophilus influenzae, the 120 million units of the fruit fly Drosophila melanogaster and the 3 billion units of that distinctive variety of person, Homo sapiens var. Venter.

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