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Md. gene researcher again takes on the establishment Venter plans fast human genome map


BETHESDA -- J. Craig Venter, the audacious bad boy of genetic research, is at it again.

In the early 1990s, while he was still at the National Institutes of Health, he caused an uproar when he and his bosses tried to patent fragments of genes. In 1995, he and Dr. Hamilton O. Smith of Johns Hopkins shocked competitors by creating the first genetic blueprint of a free-living organism, a bacterium.

Now Venter, 51, and Michael Hunkapiller, a scientist with the Perkin-Elmer Corp., say they plan to draft a similar blueprint of human DNA, and to do it faster and cheaper than the government can.

The federal human genome project, begun in 1990, is a $3 billion, 15-year effort by the NIH and the U.S. Department of Energy to map human genetic material. Many of the 60,000 genes in the human genome are a potential target of or source for new drugs or therapies.

Venter thinks he can map the entire genome in only three years at a cost of $300 million or less. And his announcement this weekend that he and a team of scientists would do just that floored some scientists, who wondered if it would derail the government effort.

"It's been a bizarre few days," said Dr. Eric Green, chief of the genome technology branch of the NIH's National Human Genome Research Institute. "I'm only tangentially hearing about this stuff. It's like grasping at straws. We need to know scientifically what we're doing."

Venter said he was skeptical when he was approached by Perkin-Elmer a few months ago and dismissed claims that its new technology could read the order of the four molecules that make up our genes -- a process called sequencing -- about 10 times more efficiently than current methods.

But a quick demonstration of Perkin-Elmer's new, air-conditioner-sized gizmo changed his mind.

"I think it took about 15 minutes to make the complete conversion" and win him over, Venter said, appearing in blue blazer, khakis and white running shoes at an NIH news conference here.

Now Venter plans to start a private company to set down, once and for all, all 3 billion of the letters that fill the human genetic encyclopedia. And he plans to build the firm on a field next door to the Institute for Genomic Research, his not-for-profit center in Rockville.

Venter is a surfer turned government scientist turned yachtsman and millionaire. Despite his unlikely credentials, he's moved into the front ranks of genetic researchers by launching the first factory-scale facility for sequencing DNA, and drawing the genetic maps of the first free-living organisms.

Earlier, scientists had sequenced the relatively tiny genomes of viruses, which can't live on their own. Instead, they hijack the machinery of living cells to reproduce.

Though Venter sounds confident that he can overtake and beat a dozen universities that have been slogging along since 1990 sequencing the human genome, others have doubts.

Francis Collins, director of the NIH's National Human Genome Research Institute, appeared at yesterday's news conference and raised a number of questions about Venter's approach.

Testing the new method will take about 18 months, Collins said. Meanwhile, he doesn't expect existing research centers to stop their work.

"This is not the moment for genome sequencing centers to go on vacation for a year and a half to see what happens," he said.

Dr. Harold Varmus, who as director of the NIH is Collins' boss, agreed.

"At the moment, we go full-bore ahead" with existing government research, he said.

To succeed, Collins said, Venter's new firm must produce a blueprint that is complete, highly accurate and that is freely available to other scientists. There's no guarantee, he suggested, that the new approach will meet any of these standards.

A key issue is how Venter's new firm will make money from the information. Now, university researchers provide their data on the human genome free to all, within 24 hours of verifying their accuracy, by posting it on the Internet.

The policy, Collins said, is meant "to discourage the possibility a sequence would be hoarded or kept out of the public view because it happens to be interesting."

Venter said his new company would put its findings on the Internet once every three months. But it will seek to patent between 100 and 300 of the genes it discovers -- those most likely to lead to lucrative therapies.

"The data will not be held hostage," he said. "We're not going to patent the genome. We're not going to be patenting chromosomes."

Genes are strings of molecules scattered along the 23 DNA strands called chromosomes that make up the human genome.

Venter, working with bacterial DNA, pioneered an approach to creating genetic blueprints called the whole genome shotgun method. Essentially, scientists take the delicate strands of DNA and shatter them into tiny pieces, which can then be read by machines. Powerful computers then look at overlapping segments of the fragments and figure out how they fit together.

Not everyone thinks this method will work with human DNA.

Varmus noted that the argument over Venter's plan has just begun. Gene hunters from around the world are likely to debate the issue fiercely, beginning today at a meeting at Cold Spring Harbor Laboratory in New York.

Pub Date: 5/12/98

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