hat 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.