Venter's Bold Venture

By LEON JAROFF

He was a surfer and a hospital corpsman in Vietnam. He is a presidential adviser on germ warfare and a millionaire yachtsman who, in his 82-ft. sloop Sorcerer, won the first transatlantic race he entered. Indeed, Sorcerer is an appropriate name for a boat owned by J. Craig Venter, one of America's most high-profile biologists. For Venter has conjured up an audacious plan that has so shaken the world of science that it was the focus of a congressional hearing last week.

Simply stated, Venter claims that he--virtually single-handedly--can achieve the goals of the mammoth, federally financed Human Genome Project in less time and at far less cost. That would take some doing. When scientists launched the project in 1990, they estimated it was going to take 15 years and cost $3 billion to map the 60,000 to 80,000 human genes and sequence the 3 billion or so chemical code letters in the genome--the tangle of DNA crammed into the nucleus of each human cell.

Venter says he can do the job faster, cheaper and just as well. In May he announced a joint effort between his center, the Institute for Genomic Research (TIGR) and Perkins-Elmer Applied Biosystems that he says will decipher virtually the entire human genome in three years and cost less than $300 million.

That announcement rankled Venter's many critics. At a scientific meeting at the Cold Spring Harbor Laboratory in New York, he was denounced as "the enemy." Some charged that he was not only trying to torpedo the Human Genome Project but was also maneuvering to become the Bill Gates of biotech. Just as Gates leverages his monopoly in computer operating systems to dominate other areas of the software industry, Venter may someday control information about the human genome--which in effect is the operating system of humans. That would enable him to hold sway over the burgeoning, multibillion-dollar business of creating drugs, diagnostic tests and other products based on human genes.

Venter downplays those fears. "We're not trying to steal the Genome Project," he insists. "We're using private money to sequence the human genome. We're going to publish that information, give it to the public for free. We will guarantee that the human genome is not patentable because the information will be public." Still, biologist Francis Collins, director of the National Human Genome Research Institute, is concerned about how freely data from the commercial project will be shared. Testifying last week, he urged against lessening support for the government project. "Having the public effort continue," Collins said, "is the best insurance that the data are publicly available."

Instead of assigning various segments of the genome to hundreds of scientists, as the Genome Project does, Venter plans to use what he calls whole-genome shotgunning. Essentially, he will put the entire genome in a dicer that will chop it into millions of segments. These chunks will be fed into 230 newly developed Perkins-Elmer robotic machines that will identify and sequence the DNA code letters in each segment. The company claims that they are 10 times more efficient than current sequencing machines and allow human operators to input in 15 minutes what used to take 24 hours.

Then the real work begins. Using new software developed by TIGR scientists, Venter's team will begin solving the world's biggest jigsaw puzzle: reassembling those millions of pieces into a coherent whole. It's a daunting task, and some scientists have grave doubts about whether Venter can do it.

At last week's congressional hearing, called to weigh the impact of Venter's venture on the Genome Project, Washington University geneticist Maynard Olson predicted that the Venter map will have more than 100,000 "serious gaps"--regions where the fragments are improperly aligned. "Yes, you'll get a holey map," agrees Rockefeller University professor Norton Zinder, who was chair of the first Genome Project advisory committee. "But we will fill the holes." He anticipates substantial benefits from Venter's plan. "Craig," he says, "has jump-started the sequencing."

Venter exudes confidence and points to TIGR's track record. Using the shotgun approach, his company has already sequenced the DNA of seven microorganisms, including the bacterium that causes ulcers. That number, he notes, represents half of all the genomes decoded to date. "The [human] genome will be accurately and completely covered," Venter promised the science subcommittee last week. And as proof he promised to sequence the genome of the fruit fly (which is far more complex than those of bacteria) within a year.

Late last week, his testimony completed, Craig Venter packed his gear, boarded the Sorcerer and prepared to compete in the Newport-to-Bermuda race. For Venter, this contest should be a cup of tea. Unlike his venture into the human genome, this will be a voyage into fully charted waters.

--Reported by Dick Thompson/Washington

With reporting by Dick Thompson/Washington