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Urge
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Through Georgia Tech and graduate work at the University of California at Berkeley in the late '60s, Mullis mixed things well. He was creative and exacting in his work because he loved chemicals and catalysts. He was creative and expansive in his personal life because he loved sex and substances.

One of his thesis advisors at the time, Henry Rapaport, remembers that he was in love with learning; he took so many classes, both in and out of science, that his advisors had to be taskmasters in getting him to finish. Rapaport, who wonders if he might otherwise have stayed forever, also notes that Mullis was "attracted to the obscure and unusual."

It was at Berkeley that he learned to make LSD, and though he wouldn't talk with me about it, a clear theme across the anecdotes in his book is that he likes it still. To him it is indeed a mind-expanding substance.

It doesn't help his image that Mullis looks like a cross between David Letterman and Gene Wilder. His eyes smirk at the world. It's not hard to imagine him smirking his way through his first marriage, through at-home experiments in which he tried to turn off lights by wiring himself into an electrical circuit and then "willing" the lights off, through the seduction of nurses from his wife's medical school with this trick, through suggesting to the queen of Sweden at the Nobel ceremony that his son marry her daughter (she declined) and through the writing of his book, which begins -- in a preemptive strike against those who will laugh at the rest of what he has to say -- with the invention of PCR.

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He was smirking through the windshield of his Honda on a windy road in Northern California late on a Friday evening in May 1983. His girlfriend was in the seat next to him, and they were on their way to a romantic red-wine weekend for two. He held a job at the time in a small biotech company called Cetus, which had been founded by, among others, Carl Djerassi, the inventor of the birth control pill. As he drove, his mind was debriefing after a tough day in the lab. His work at Cetus involved DNA, and, like everyone who worked with DNA in the early '80s, he wanted to be able to make more of it, to get it to copy itself in a lab so he could study and manipulate it. Watson and Crick had shown that DNA is the recipe for life; scientists were desperate for an easy way to read it.

Part of his work involved now archaic ways of getting genes to replicate -- it took months and was heavily error prone. There must be a better way.

The muse descended, the idea came, Mullis pulled over. He searched the car for paper and pen and started writing, despite complaints from the girlfriend that they should go on to the house first. It was so easy, such an elegant idea, simple and effective. The polymerase chain reaction "was a chemical procedure," Mullis later wrote, "that would make the structures of the molecules of our genes as easy to see as billboards in the desert and as easy to manipulate as Tinkertoys."

Genes are double strands of chemicals, and the whole kit and caboodle of them, the entire recipe for life, is made of just four chemicals: adenine, thymine, cytosine and guanine. Think of each strand as a long string of these chemicals lined up in a row like beads. When two strands of DNA come together to make the familiar spiral-staircase helix (which graces the letterhead of so many biotech companies), these four chemicals get very picky: adenine (A for short) will only line up across from thymine (T) on the other strand. You never see two A's or an A across from cytosine (C) or guanine (G). C and G likewise form an exclusive pair.

Here's PCR in a nutshell: Put the gene you want to look at in a pipette with a little liquid. Heat it up and the double-stranded helix breaks apart. Each string of chemical beads drifts off by itself. Throw in a large and random assortment of loose A's, T's, C's and G's, and the individual chemical beads will seek out their pairs on the single strands. Once every chemical letter on each original strand has a new partner bead (the same-letter partner it always has because of chemical exclusivity), you cool down the mixture and the new rows of partner beads anneal into strands of their own, conveniently providing a new half to each original strand.

The helix reforms and -- voilą! -- you've made two exact copies of the one gene you started with. Heat these two up and you have four separate strands. Throw in more loose chemical letters, let them pair up and you have four identical genes. Repeat this process 30 times and you have more than a billion copies of that one piece of DNA you started with -- cartloads of it in lab terms.

So begins the genetic revolution. Without PCR, genetics is like trying to do experiments on one droplet of milk sitting on a white plate. The milk is hard to find, and you only have enough of it to try one thing -- such as add a droplet of orange juice and see what happens -- and that's it. You are limited in experimenting if you only have a tiny amount to play with. PCR makes genes by the milk pail, and scientists are thrilled.

Take Anne Blackwood, an oncologist at the University of Pennsylvania in Philadelphia who treats breast cancer patients and runs a lab looking for a cure. Cancer is caused by the slow accumulation of mutations in the genes of cells. To get any real sense of what's going on in the earliest stages of cancer, when only a few cells are worth looking at, Blackwood needs PCR to multiply the mutated genes.

Blackwood is also developing a long-term database of breast cancer types. She has a library of microscope slides of tissue biopsies -- tiny samples, some of them more than 10 years old. Using PCR, she can tease out the genetic profiles of each tissue sample and make a record of the mutations she sees. Such a large, statistical study of how cancer works is rapidly improving prognostic capabilities. It is also getting doctors much closer to a genetics-based cure.

Genetics-based cures are the Holy Grail of the Human Genome Project, the research that is mapping out all the genes in the human recipe book. Such mapping requires incredible amounts of gene replication; without PCR, it simply wouldn't be feasible.

Next page | He was a free spirit before. Now he's a free spirit with a Nobel Prize