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While Berg and his colleagues were agonizing about the possible dangers posed by their experiments, two other scientists were planning an even more dramatic display of gene splicing. One of them was an intense biochemist named Stanley Cohen, 46, whose lab was only two floors below Berg's own quarters at the Stanford Medical Center research building. The other was Boyer, who worked just an hour's drive away at the University of California at San Francisco. Their partnership had emerged accidentally. In November 1972, after a long day of listening to scientific papers at a conference in Hawaii, they met in a Waikiki delicatessen for a midnight snack. Gossiping about their work while munching on corned-beef sandwiches, the two discovered that their research dovetailed in a way that opened up some highly intriguing possibilities.
Almost all of E. coli's 4,000 genes are located in a single circular chromosome. But Cohen had isolated some bits of genetic material that float freely in the bacterium outside this main genetic repository. These bits of genetic "small change" are known as plasmids. A plasmid contains as few as three or four genes linked in a small circle, yet it sometimes is crucial to bacterial survival.
During normal bacterial reproduction, the cell simply divides, passing exactly the same genetic information on to each daughter cell. Thus they are natural clones, genetically identical to their single parent. In this kind of unisex reproduction, there is no chance for bacteria to inherit fresh characteristics that might help improve their chances of survival. But every so often two cells have a sort of sexual dalliance called conjugation. They approach each other, send out thin tubes that bring the cells together, and transfer genes. In the exchange, a bacterium may pick up, say, a gene for making an enzyme that cuts up and destroys certain antibiotics. All the bacterium's offspring will then inherit this life-preserving resistance and, in this way, defy medicine's best efforts to do them in.
Like Berg, Cohen wanted to insert new genes artificially into bacteria. But where Berg resorted to a virus as his transport system, Cohen opted for plasmids, which he had been studying in his lab. As he listened to Boyer's description of his work that night in Waikiki, however, Cohen realized that there might be a short cut. Boyer and his associates had found a so-called restriction enzyme that cuts DNA precisely at predetermined points, and performs this surgery in an especially helpful way: at each end of the severed, twin-stranded molecule, it leaves an extra bit of single strand poking out, automatically creating the "sticky" mortised ends that Berg had labored so hard to achieve.
The twin breakthroughs—Beyer's surgical enzyme and Cohen's plasmids—opened the door to an extraordinary scientific capability. If they were used together, almost any gene—from a virus, a frog or a man—could be spliced into the plasmid. Cohen named