The Race Is Over

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Back in the U.S., he blazed through college and graduate school at the University of California at San Diego in six years. After a stint at the State University of New York at Buffalo, he was recruited by NIH's neurological institute, where he worked on locating and decoding a gene for an adrenaline-receptor protein in brain cells, but found progress exasperatingly slow. So when he learned in 1986 about a machine that could "read" genes by shining lasers on their dyed letters (A, T, C and G, the four nitrogenous bases--adenine, thymine, cytosine and guanine--that spell out the genome's "words"), he immediately flew west to meet its builder, Michael Hunkapiller, in Foster City, Calif. Though NIH wouldn't pay for a prototype, he got one anyway.

Within a year, Venter had decoded 100,000 letters (the human genome has some 3.1 billion, spelling out some 50,000 different genes, at the best guess). They were hieroglyphics to him, but not, he knew, to living cells, which recognize active genes and spin off single strands of RNA that mirror the DNA's coding. So Venter collected the new RNA, inserting it into bacterial cells and letting them clone junk-free complementary DNA, or cDNA, matching the original genes. His automatic sequencer could then read the letters of these genetic instructions.

By June 1991 he had increased the number of identified genes by 347, up from 2,000. His bosses at NIH were so pleased that they rushed to patent them, only to set off a firestorm. Watson, then head of NIH's part of the Human Genome Project (another part is under the Department of Energy), denounced the move as "sheer lunacy" that would cause paralyzing legal battles. When the dust settled, NIH had withdrawn its patent proposal, Watson had quit the genome project, and Venter and Fraser, a former graduate student at Buffalo whom he had married after splitting with his first wife, were off running their own center, The Institute for Genomic Research (TIGR), in nearby Gaithersburg, Md.

With $70 million in long-term funding from the late biotech entrepreneur Wallace Steinberg, TIGR (pronounced tiger) finally gave Venter freedom to do what he wanted. But there was a hitch. First crack at any genes it decoded went to the nonprofit institute's commercial partner, Human Genome Sciences, led by former AIDS researcher William Haseltine.

Until then, Venter had been randomly sampling and sequencing small bits of cDNA. But one of his new recruits, Hamilton Smith, a Nobelist from Johns Hopkins', proposed a bolder approach: "shotgunning" the entire genome of an organism. The idea was dramatically simple. Using an ordinary kitchen blender, they would shatter the organism's DNA into millions of small fragments, run them through the sequencers (which can read 500 letters at a time), then reassemble them into the full genome using a high-speed computer and novel software written by in-house computer whiz Granger Sutton. By contrast, the HGP divided the genome into larger, known segments, delaying the sequencing to learn more about the genes first. As an added fillip, Venter cross-checked his results by sequencing the genes in both directions, achieving a level of accuracy that so impressed his initially skeptical rivals that British sequencers, along with labs funded by NIH and DOE, later announced they too would adopt this strategy.