Finish line in sight for DNA scientists

Genome: A team of researchers is on the verge of completing the first draft of mankind's genetic code.

May 14, 2000|By Douglas Birch | Douglas Birch,SUN STAFF

ROCKVILLE - On the day he puts the finishing touches on the first complete human genetic text, computer wizard Gene Myers knows just what he's going to do. He'll whip off his lucky green scarf and crank up Wagner's "Ride of the Valkyries" at full volume on his office boombox.

Myers and other scientists at Celera Genomics Group are a mischievous group: They sometimes wear plastic Viking helmets, ambush one another with foam arrows and call themselves the "Celerian Valkyrians." Myers, a boyish 46-year-old professor at the University of Arizona, has an earring in his left ear and can talk like a California mall rat. "The excitement is, like, palpable; you feel it in your body," he says.

But in their pursuit of the 3.5 billion chemical units of human DNA - the human genome - Myers' team knows it is on the threshold of the crowning achievement of modern biology. Embedded in the twisting strands of DNA is mankind's ultimate autobiography, the 100,000 or so genes that make us human. "Everybody in this group," Myers says, "has a sense of destiny."

And a sense of triumph. Celera says it expects to complete an accurate and comprehensive first edition of the genome next month. If so, the company will win the most celebrated scientific competition since the space race of the 1960s, coasting home several years ahead of its rival, an international consortium of university labs led by the National Institutes of Health and Britain's Wellcome Trust.

Consortium leaders aren't buying it. Celera's genome, they say, will be an abridged version with many missing sections of text. They point out that they've already published the bulk of that text, even if it hasn't been corrected and put in order. In the meantime, they're rushing to publish their own "rough draft" of 90 percent to 95 percent of human DNA this summer.

When J. Craig Venter, Celera's brash president, began racing the consortium two years ago, he needed technology that hadn't been tested, lab techniques that didn't exist and software that hadn't been written. So he recruited a gang of leading scientists, spent millions on a warehouse full of fancy machines, and inspired his colleagues to invent and improvise.

Now, in the final weeks, Celera's chances hinge on Myers and his 20-member team. "They've been essential," says Venter. Without them, "nothing would ever be able to go together in the end."

Venter's quest for the genome began by accident seven years ago, when he struck up a friendship with Dr. Hamilton O. Smith, a former Johns Hopkins University microbiologist who shared a Nobel Prize in 1968 for discovering the first tools for cutting and splicing DNA.

The quiet, deferential Smith is probably the world's expert at manipulating the gossamer threads of DNA in the lab. He persuaded Venter to join the race to publish the first genome of a free-living organism, and to do it by reading the DNA of Smith's lab "pet," the bacterium H. influenzae.

Shotgun approach

Smith suggested a risky technique called the "whole genome shotgun" - essentially, shattering the 1.8 million chemical units in the bacterium's genome into tens of thousands of pieces, and programming computers to put them together again. To the astonishment of many biologists, Venter and Smith succeeded. James Watson, the co-discoverer of the structure of DNA, hailed their work as "a great moment in science."

They went on to collaborate on sequencing the DNA of scores of microbes, including those that cause malaria, syphilis, tuberculosis and sleeping sickness. But they didn't seriously consider tackling the human genome until 1997, when Myers and another scientist, James Weber,published a paper claiming the shotgun technique could work on human DNA.

The proposal was considered so "wacko," Myers recalls, that the authors had a hard time finding a journal willing to publish it. When they finally did, the editors insisted on printing a rebuttal in the same edition.

It was a bold notion. The human genome is almost 2,000 times larger than that of H. influenzae and it is far more complicated. About 97 percent of human DNA is junk, meaningless stretches of text that could confuse even powerful computers.

Smith was dubious. But when Venter saw a new DNA-analyzing robot, he decided he could make the strategy work. In May 1998, he announced he was co-founding a company to shotgun the human genome with the Perkin-Elmer Corp. The effort, he boasted, would create a human genetic encyclopedia four years earlier and hundreds of millions of dollars cheaper than the government-led effort.

Myers - one of the founders of the infant field of bioinformatics, the application of computers to biology - flew to Washington and begged to join Venter's team. "I probably would never have forgiven myself if I let that thing pass me by," he says.

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