I dream of genomes

July 23, 1999

Maverick scientist Craig Venter isconfident he can win the race tounravel our genetic blueprint. He tells Tim Cornwell he plans tomake the results available to all- but only at a price

If Craig Venter did not exist, somebody would have made him up. At the turn of the millennium, he has vaulted on to the scene as the fiftysomething "it" boy for the biomedical revolution. The former surf-bum and Vietnam vet has turned the hunt for the human genome - the blueprint for mankind that is written into every human cell -into a horse-race, and if his scientific acumen comes anywhere near his appetite for self-promotion, the game is already over.

In a measure of Venter's celebrity, he was featured recently on the front page of USA Today's Weekend section, pictured alongside Copernicus, Galileo, Newton and Einstein. "Will this maverick unlock the greatest scientific discovery of our age?" asked the newspaper. In the same issue, he upstaged actress Alicia Silverstone on sexiness and thriller writer Tom Clancy on the future of the world.

Americans love upstarts, particularly successful ones. Venter stunned the United States research community in May 1998 when he promised that his privately funded laboratory would be the first to decode mankind's genetic blueprint. With a fraction of the funds and staff, he pledged to finish his work - albeit cutting a few corners - ahead of the Human Genome Project, with a $3 billion price tag jointly funded by the US government and the Wellcome Trust. Venter's challenge to the cream of the scientific establishment has been compared with a private company trying to beat the US to the Apollo moon shot. But can he deliver?

The impression of the original 1953 discovery of the structure of DNA, as chronicled in James Watson's The Double Helix, is of a world of paper drawings and wire models, with academics in jackets and ties cycling round to each other's rooms in Cambridge. At Venter's company, Celera Genomics, by contrast, 30-40 scientists run gene sequencing programs on some of the most powerful computers in the world. In the suburbs of Washington DC, they are number-crunching the three billion-plus letters of the genetic code, the helical chain of chemicals that makes possible the transmission of inherited characteristics from parent to child. "We have no doubt," Venter says, about getting there first -by the end of 2001, in fact - cheaper and faster than the government programme.

His is an effort that has irritated many. After Venter devised a short-cut system for sequencing genes, Watson, the Nobel prize-winning co-discoverer of DNA, famously called it work that "any monkey" could do. Other critics have compared him to Microsoft's Bill Gates, a comparison he does not particularly dislike.

Venter's vision of third millennium genetics is sweeping in scale. "In the past couple of decades, the big news was that somebody discovered a gene that exists," he says. "The future is going to be discovering the function of all the genes and how they link to human traits." It goes well beyond the potential for alerting patients that a certain genetic characteristic puts them at high risk from colon cancer. He says: "If we sequenced your genome and we had a list of the spelling of your genetic code, it would simply be a matter of going to the computer and logging on to the Celera web site as each discovery was made in order to understand it."

Accessing the web site would automatically call up the user's records, just as Amazon.com will recognise customers as buyers of certain types of books. "We could send you an email about a discovery made yesterday, saying you have an "a" instead of a "t", at base pair four million and 12 on this chromosome, and this means that you are going to have a certain kind of metabolism and you should definitely avoid this type of fat," he explains.

The young Venter left high school in San Francisco, aged 17, then headed for California's beaches as a teen surfer. He changed course after conscription in Vietnam. In an interview with Discovery magazine, he described his days as a hospital corpsman at Da Nang, scene of some of the war's heaviest fighting. Two cases stuck in his mind: a young man killed by a bullet that left only a tiny track through his head, and a soldier with multiple wounds who survived for weeks. "I started asking myself big questions," he says. "What is life? What makes it work?" Venter returned from Vietnam with a late developer's drive, and in just six years, took his BA and then a PhD from the University of California at San Diego, an emerging power in the biotech field. In 1976 he moved to the State University of New York, where he met and married fellow scientist Claire Fraser, launching a powerhouse partnership. She has lately taken over as the day-to-day director of The Institute for Genomic Research, TIGR, established by Venter and a financier partner in 1992, with a $30 million grant.

Venter's office at Celera is two miles away (he remains chairman of the board at TIGR), but the couple rarely have time to do lunch. Recently they found themselves chatting from different airports, syaing: "If this is success, we are doing something wrong. She was in London, I was in California."

When Venter started out in gene research, it was a laborious business. Researchers visually scanned long columns of DNA code, the paired combinations of the four bases in the DNA "alphabet" (adenine and thymine, guanine and cytosine, or A,T,G, and C), trying to separate that for the genes themselves from the so-called "junk DNA". It took ten years, until 1986, to identify a single gene.

Thereafter he put himself at the forefront of efforts to speed everything up. The late 1980s saw the arrival of automated sequencers, employing lasers and computers to read the bits of code. Venter's lab at the National Institutes of Health was designated the first test-site. Then he switched his attention from DNA itself to "complementary DNA", a copy manufactured by the cell, that edits out the junk DNA. Ever more powerful computers could match fragments of the cDNA, which Venter calls an "expressed sequence tag", or EST, to build the sequence of the gene.

It was Venter's interest in EST research that took him outside the NIH and the Human Genome Project. First NIH declined a $10 million grant request, then came a row over the patenting of of EST. He left and founded TIGR, backed by $70 million in venture capital and tied to a private corporation that was guaranteed a first look at TIGR's results.

It would cast him, in the eyes of critics, as the personification of brash commercialism. But the partnership was phenomenally successful, with TIGR ploughing through ESTs for tens of thousands of human genes and becoming the first to sequence the genome for an entire living organism, the Haemophilus influenzae bacterium, in 1995. In 1998, Venter went on to launch Celera, again with commercial backing.

Celera, he says, has already drawn in $100 million from pharmaceuticals companies wishing to buy into its database. This year, it aims to expand its customers to agricultural companies, biotech companies and universities. To customers, he says, it will deliver a rapidly growing collection of human gene ESTs and the genome of the Drosophila fruitfly, which Celera is tackling as a prelude to the human genome itself.

The Human Genome Project's approach to breaking the "Book of Life" is portrayed in the press as a ponderous process. Venter's method is messy and - with luck- quick. Critics argue that a large part of his purpose has been to lock patents on the genome as he discovers it. Venter responds that he will make everything available - for a price, much like a newspaper database. "For some reason gene patents have been portrayed as an evil thing," he says. "Most medical research wouldn't happen without them. If it were not for gene patents no diabetic would have human insulin right now."

Even as he approaches his publicly proclaimed goal Venter says it is "overrated", more a milestone than an end in itself. Scientists on the Human Genome Project have had to portray it as equivalent to the moon shot to justify billions in funds, he says. "If genomics has taught us anything, it is humility. Reporters will be asking scientists at the end of the next century where we are with understanding the human genome."

He has graduated from a government researcher parched for cash, to an entrepreneur with a private yacht, The Sorcerer, who flies private jets from one corporate meeting to the next. Whether or not he gets there first, no one denies that Venter has shaken up the field. "I think my life has shown that one or two people can make a huge difference. With a small research team, Claire and I have accomplished a tremendous amount by doing things everybody else said were impossible."

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