June 27, 2000

READING THE BOOK OF LIFE

Craig Venter: A Maverick Making Waves

By NICHOLAS WADE

	Marty Katz for The New York Times
	Dr. J. Craig Venter.
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n intense focus on putting genes to practical use has propelled John Craig Venter from an obscure federal researcher to a principal decoder of the human genome.

Born on Oct. 14, 1946, in Salt Lake City, he earned a doctorate in physiology and pharmacology from the University of California at San Diego and entered the world of biochemical research at the National Institutes of Health.

Frustrated at having to spend 10 years trying to isolate a single gene, Dr. Venter realized there was a quick way to fish out the genes, which in the case of humans occupy only 3 percent of the genome.

The technique was to capture the normal copies of genes made by living cells and to decode a few hundred DNA units from part of the gene.

These partial transcripts, known as EST's (expressed sequence tags), could be used to identify the gene-coding regions on the DNA from which they came.

Dr. Venter's use of EST's had two eventful consequences. One was that Dr. Bernadine Healy, then director of the National Institutes of Health, decided to apply for patents on the genes he had found, a move strongly opposed by Dr. James Watson, director of the N.I.H.'s human genome office. The issue was among one of several differences with Dr. Healy that led to Dr. Watson's resignation from that office in 1992.

The other consequence was that Dr. Venter's work caught the eye of a venture capitalist, Dr. Wallace Steinberg, who wanted to start a gene-finding company -- with Dr. Venter as its head.

But Dr. Venter insisted on a nonprofit venture, so Dr. Steinberg set him up in the nonprofit Institute for Genomic Research supported by a new company, Human Genome Sciences.

At his new institute, Dr. Venter generated thousands of EST's to the human genome. These became the intellectual property of Human Genome Sciences which, under Dr. William Haseltine, has developed far-reaching claims to many medical genes of interest.

Dr. Venter then spotted another frontier where the DNA sequencing machines might break ground, that of sequencing the genomes of bacteria.

The N.I.H.'s human genome project was then working on E. coli, a widely studied bacterium, but progress was slow.

In a prelude to later events with the human genome, Dr. Venter figured he could be first to decode a bacterium with a novel method called the shotgun technique. He applied for an N.I.H. grant but started the project with other money. When it was almost complete, he has said, he received a letter from the N.I.H. rejecting his application because, in the view of an expert committee, it would not work.

The committee included scientists involved in the N.I.H.'s part of the public consortium. Their rejection of Dr. Venter's idea set the pattern of an adversarial relationship that has continued until the last few weeks.

Haemophilus influenzae, whose genome Dr. Venter decoded, was the first bacterium and the first living organism, not counting viruses, to have its full DNA decoded. The result gave scientists their first glimpse into the set of genes necessary for life.

And it set off a revolution in medical microbiology, inspiring efforts to decode every major pathogen and learn the microbes' entire playbook for attacking human cells.

In setting up his institute and decoding the Haemophilus genome, Dr. Venter showed he could attract talented people as colleagues.

Much of the essential work on Haemophilus was by Dr. Hamilton O. Smith, a Nobel Prize winner, whose contribution Dr. Venter freely acknowledged.

Dr. Venter's technical judgment and organizational abilities appealed to Dr. Michael W. Hunkapiller, president of the company now known as PE Biosystems, which made the leading brand of DNA sequencing machine. When a new, labor-saving generation of his machines was developed, Dr. Hunkapiller figured that a private company using a large suite of the new machines could decode the human genome faster than the government could.

He persuaded Dr. Venter to run the company, which came to be known as Celera.

Leaving his institute in friendly hands -- its new president is Dr. Claire Fraser, his wife -- Dr. Venter began Celera in May 1998.

His rivals in the public consortium were soon providing him with the psychological stimulus he seemed to need, by pronouncing his human genome decoding strategy certain to fail.

Within a few months he had hired a staff, set up a large plant and begun decoding.

Although Celera is in business to make money, principally by selling subscriptions to its genomic data base, Dr. Venter seems eager for the academic world's approval and has continued to publish scientific articles, maintaining a presence in both the science and business worlds.

Dr. Venter became wealthy when he left the N.I.H. to set up the Institute for Genomic Research, and superwealthy when he became president of Celera. But apart from indulging his passion for sailing, he has not let sudden riches divert him from his path.

Whether in working on EST's to pull out the genes, decoding the first pathogenic bacteria, or racing to complete the human genome, he has been driven by getting practical results.

Celera's corporate motto, that "Speed Matters" for treating disease, is a little hokey but reflects Dr. Venter's consistent focus.

"It has always been Craig's view that what is important is not some abstract view of the genome but its utility," said Dr. David Lipman, director of the National Center for Biotechnology Information. "Craig has always pushed in the right direction, and the public program needed pushing. When he started Celera it made the public program open their eyes and take a different approach."