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P&S Journal

P&S Journal: Fall 1994, Vol.14, No.3
Harold Varmus: Nobel Laureate at the NIH
A Director from the Scientific Trenches

"My preparation for this job has been unusual," Dr. Varmus told the Senate. The selection of a renowned bench scientist, as opposed to a clinical administrator, to sit in the NIH director's chair dissolved any lingering perception of a split between central administration and research.
In the Nobel lecture delivered in Stockholm in 1989, Dr. Varmus prefaced a discussion of his (and co-recipient Dr. Mike Bishop's) pathbreaking work on retroviruses and oncogenes with a personal biographical note. He recalled how his "commitment to experimental science occurred, by today's standards, dangerously late in a prolonged adolescence." An English major at Amherst College, he studied Dickens and wrote and edited anti-Establishment journalism while fulfilling his premed requirements. Disillusioned with letters while earning a master's degree in English from Harvard, he applied to P&S. Initially intending to pursue psychiatry, he was attracted to the thrill of hard science in the making. He credits the influence of such challenging teachers as Elvin Kabat, Malcolm Carpenter, and Paul Marks, among others.
Dr. Varmus pursued an internship and residency in internal medicine at Presbyterian Hospital, but the Vietnam War interrupted his plans for an academic career in internal medicine. In part to avoid the draft, he applied for and was accepted for a research training position at the NIH. In the course of his training, Dr. Varmus underwent the transformation from a clinical investigator to a full-fledged basic scientist.
"Science has such a magnetic draw to anybody associated with health," he says, "and biomedical science is surely one of the most exciting intellectual pursuits of our time.
"Are the intellectual frontiers any greater in law or business or in any of the humanities?" he asks rhetorically, as if science itself were on trial and he its most ardent defender. "When the history of this age is written, we'll see that the 20th century is the century of Picasso, of course, but also of the atom, the computer, and the gene. And we're in the phase of the gene right now. It's riveting, I can tell you!"
Working as a clinical associate at the National Institute of Arthritis and Metabolic Diseases, in the laboratory of Dr. Ira Pastan, a thyroid-oriented biochemist interested in bacterial gene expression, Dr. Varmus deepened his involvement in basic research and pursued additional scientific training through evening courses. "The NIH at that point," he recalls, "was a real mecca for people like myself, doctors who had been trained at good medical schools but lacked the background in the basic sciences."
He learned about tumor viruses and decided to enter the field as a postdoctoral fellow under Dr. Mike Bishop at the University of California at San Francisco, where he was rapidly promoted from lecturer to full professor. He holds joint professorships in microbiology and immunology and in biochemistry and biophysics and is American Cancer Society Professor of Molecular Virology.
His and Dr. Bishop's collaborative work on retroviruses in the early 70s demonstrated that cancer genes (oncogenes) can evolve from normal cellular genes, called proto-oncogenes, the discovery for which they shared the Nobel Prize.
Experimenting with the Rous sarcoma virus, which causes cancer in chickens, Drs. Bishop and Varmus tested a then-accepted notion, "the oncogene hypothesis" of cancer causation, which held that the source of the cancer was genetic material from the virus inserted long ago into normal cells. To their surprise, they found that the cancer-causing agent was not the viral gene but a normal cellular gene gone awry that the virus picked up from the cell. The implications of their findings not only overturned the oncogene hypothesis, but also led to the discovery of a cluster of some 40 genes crucial to normal cellular functioning, which established a common causal pathway for cancer and offered a way to plug into the circuitry of the cell.

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