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The Pioneers of Molecular Biology: Kary Mullis
	A serendipitous discovery opened the door for DNA fingerprinting and disease diagnostics
	By Jeffrey Kluger

Posted Sunday, February 9, 2002; 10:31 a.m. EST
Kary Mullis has a little bone to pick. "I was nine years old in 1953 and I was really precocious. I presented the structure of DNA as a science project and Watson and Crick stole my idea—those bastards."

OK, Mullis doesn't really believe this and he doesn't expect you to take it seriously either—which is pretty much the case with a lot of things he says. But when he talks about genetic science for real, he does expect you to listen, and well he might. His development of polymerase chain reaction (PCR)—a bit of DNA-based science for which he won the 1993 Nobel Prize—may have had a greater impact on the field of genetics than any insight since the discovery of the double helix itself.

Mullis didn't pay much attention to DNA until 1966, when he was earning his Ph.D. in biochemistry at the University of California, Berkeley. He remembers not much caring for the aesthetics of the thing. "I like organic molecules because you can draw them and know what they do," he says. "But DNA just spirals off without limits and only ends because it gets broken or because it spontaneously terminates out of a morbid fear of being endless."

Nonetheless, when Mullis went to work for the Cetus Corporation in California in 1979, DNA was what he wound up working with, trying to help the company develop a method for isolating—and thus analyzing—specific stretches of base pairs. The difficulty with doing this is that DNA is cluttered up with a lot of other junk, particularly deoxynucleotide trisphospates—the raw material from which pure DNA is made. Mullis was contemplating this problem as he drove along a highway in California's Mendocino County and realized that if he polymerized the unwanted stuff—strung it together, basically—he could chemically sweep it out of the way.

Suddenly, it occurred to him that with the right enzymes and nucleotides, he could apply the same principle to the DNA itself, causing it to replicate exponentially. All at once, a vanishingly small scrap of genetic material could become an unlimited supply of it, making possible a whole wealth of things from DNA fingerprinting to virus analysis to the diagnosis of genetic diseases. "This was the aha! moment," he says. "I thought, ŒWhoa, stop the car.'" In 1993, the Nobel Committee acknowledged his discovery with its chemistry prize—and with every subsequent report of a disease that has been sequenced or a crime that has been solved or an Egyptian mummy whose lineage has been traced, all thanks to PCR, the world has been tipping its hat to Mullis too.

These days, Mullis has largely left the science dodge, spending most of his time writing. Nonetheless, he does spend a fair amount of his time thinking about what his discovery wrought—and worrying about it too. "We already know the sequence of the human genome," he says. "Next are we going to want to know what every individual's is?" It's not a prospect that seems to please him. Evidently, the aesthetics of the double helix wasn't all that gave him pause.

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