The Gene: An Intimate History - Siddhartha Mukherjee Page 0,97

and an instructor at the course, called Berg urgently. Pollack argued that the dangers implicit in “bridging evolutionary barriers that had existed since the last common ancestors between bacterium and people” were far too great to continue the experiment casually.

The issue was particularly thorny because SV40 was known to cause tumors in hamsters, and E. coli was known to live in the human intestine (current evidence suggests that SV40 is not likely to cause cancer in humans, but the risks were still unknown in the 1970s). What if Berg and Mertz ended up concocting the perfect storm of a genetic catastrophe—a human intestinal bacterium carrying a human cancer-causing gene? “You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosol. . . . But you cannot recall a new form of life,” Erwin Chargaff, the biochemist, wrote. “[The new genetic hybrids] will survive you and your children and your children’s children. . . . The hybridization of Prometheus with Herostratus is bound to give evil results.”

Berg spent weeks deliberating over the concerns raised by Pollack and Chargaff. “My first reaction was: this was absurd. I didn’t really see any risk to it.” The experiments were being carried out in a contained facility, with sterilized equipment; SV40 had never been implicated directly in human cancers. Indeed, many virologists had become infected with SV40, and no one had acquired any cancers. Frustrated with the constant public hysteria around the issue, Dulbecco had even offered to drink SV40 to prove that there was no link to human cancers.

But with his feet slung on the edge of a potential precipice, Berg could not afford to be cavalier. He wrote to several cancer biologists and microbiologists, asking them for independent opinions of the risk. Dulbecco was adamant about SV40, but could any scientist realistically estimate an unknown risk? In the end, Berg concluded that the biohazard was extremely minimal—but not zero. “In truth, I knew the risk was little,” Berg said. “But I could not convince myself that there would be no risk. . . . I must have realized that I’d been wrong many, many times in predicting the outcomes of an experiment, and if I was wrong about the outcome of the risk, then the consequences were not something that I would want to live with.” Until he had determined the precise nature of the risk, and made a plan for containment, Berg placed a self-imposed moratorium. For now, the DNA hybrids containing pieces of the SV40 genome would remain in a test tube. They would not be introduced into living organisms.

Mertz, meanwhile, had made another crucial discovery. The initial cutting and pasting of DNA, as envisaged by Berg and Jackson, required six tedious enzymatic steps. Mertz found a useful shortcut. Using a DNA-cutting enzyme—called EcoR1—obtained from Herb Boyer, a microbiologist in San Francisco, Mertz found that the pieces could be cut and pasted together in just two steps, rather than six.II “Janet really made the process vastly more efficient,” Berg recalled. “Now, in just a few chemical reactions, we could generate new pieces of DNA. . . . She cut them, mixed them, added an enzyme that could join ends to ends, and then showed that she had gotten a product that shared the properties of both the starting materials.”

In November 1972, while Berg was weighing the risks of virus-bacteria hybrids, Herb Boyer, the San Francisco scientist who had supplied the DNA-cutting enzymes to Mertz, traveled to Hawaii for a meeting on microbiology. Born in a mining town in Pennsylvania in 1936, Boyer had discovered biology as a high school student and had grown up idealizing Watson and Crick (he had named his two Siamese cats after them). He had applied to medical school in the early sixties, but was rejected, unable to live down a D in metaphysics; instead, he had switched to studying microbiology as a graduate student.

Boyer had arrived in San Francisco in the summer of ’66—with an afro, the requisite leather vest, and cutoff jeans—as an assistant professor at University of California, San Francisco (UCSF). Much of his work concerned the isolation of novel DNA-cutting enzymes, such as the one that he had sent to Berg’s lab. Boyer had heard from Mertz about her DNA-cutting reaction, and the consequent simplification of the process of generating DNA hybrids.

The conference in Hawaii was about bacterial genetics. Much of the excitement at the meeting involved the newly discovered plasmids in E. coli—the circular mini-chromosomes that