GEORGE STEINMETZ FOR TIME David Baltimore: a Nobel Prize Laureate in Physiology and Medicine

The Pioneers of Molecular Biology: David Baltimore
	With his first experiment on the subject, he shattered existing theories of DNA and RNA function
	By Leon Jaroff

Posted Sunday, February 9, 2002; 10:31 a.m. EST
It was not until the late 1950s that David Baltimore was even aware of the discovery that would change his life. "I was in high school when the Watson-Crick paper was published," he says, "but my teacher never mentioned it, nor did my parents, who were not particularly literate in science." At Swarthmore College, too, no one on the faculty ever talked about DNA. But as an upperclassman Baltimore majored in chemistry and began reading science journals, where he was introduced to the double helix. "I was transformed," he says. "I saw the edifice of molecular biology beginning to appear before me and decided that this was what I was going to spend the rest of my life working on."

Baltimore opted for the study of tumor viruses, fully aware of the so-called central dogma that double stranded DNA transfers genetic information to single-stranded RNA, but that information never flows the other way. One scientist, however, Howard Temin, had earlier hypothesized that RNA-DNA transfer could occur, and in 1970 Baltimore set out to prove him right. Assuming that the accepted wisdom was wrong was easy, he says. "I was trained in chemistry and saw it as a chemical problem."

Baltimore shattered the dogma with his very first experiment. He discovered the enzyme, now called reverse transcriptase, that enables a retrovirus to transfer information from RNA to DNA. The implications were enormous; they suggested that a virus could infiltrate a cell's DNA and turn itself into a gene. The enzyme also turned out to be a powerful tool for probing DNA for individual genes, including the oncogenes that cause cancer. Indeed, his discovery was instrumental in development of the entire field of biotechnology.

Having loosed the genie from the bottle, Baltimore became concerned about the helter-skelter transfer of genes from one organism to another. He feared that putting entire viruses into bacteria, for example, might lead to bacteria spreading a viral disease. Fanciful stories in the press spoke darkly of creation of a "Doomsday Bug."

Concerned, Baltimore and Stanford's Paul Berg organized a conference at Asilomar, on California's Monterey peninsula. There scientists in the field agreed to a voluntary moratorium on certain kinds of biotechnology experiments and containment safeguards on others until the experiments were proven safe. "As far as we know," says Baltimore, "it was absolutely observed by everyone in the community." In retrospect, he believes the Asilomar scientists erred on the side of caution.

Realizing that the new technology might well provide a tool for fighting cancer, Baltimore converted his lab to the study of cancer viruses. Today, as president of CalTech, he's increasingly involved in research on the AIDS virus. In a way he's come full circle. HIV, like the subject of his historic experiment, is a retrovirus.

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