Varmus was born to Jewish parents of Eastern European descent in Oceanside, New York . In 1957, he enrolled at Amherst College, intending to follow in his father's footsteps as a medical doctor, but eventually graduating with a B.A. in English literature . He went on to earn a graduate degree in English at Harvard University in 1962 before changing his mind once again and applying to medical schools . That same year, he entered the College of Physicians and Surgeons at Columbia University and later worked at a missionary hospital in Bareilly, India and the Columbia-Presbyterian Hospital . Seeking to avoid the draft for the Vietnam War, Varmus joined the Public Health Service at the National Institutes of Health in 1968 . Working under Ira Pastan, he researched regulation bacterial gene expression by cyclic AMP. In 1970, he began post-doctoral studies in Bishop's lab at University of California, San Francisco . There, he and Bishop performed the oncogene research that would win them the Nobel Prize. He became a faculty member at UCSF in 1972 and a professor in 1979 .
From 1993 to 1999, he served as Director of the National Institutes of Health. As the NIH director, Varmus was credited with nearly doubling the research agency's budget . Since January, 2000, he has served as President of Memorial Sloan-Kettering Cancer Center in New York City.
Beginning during his tenure as NIH director, Varmus has been a champion of an open access system for scientific papers, arguing that scientists should have control over the dissemination of their research rather than journal editors . He has advocated a system in which journals make their articles freely available on PubMed Central six months after publication . He is co-founder and chairman of the board of directors of the Public Library of Science, a not-for-profit open access publisher, and he also sits on the board of trustees of BioMed Central, the largest publisher of open-access journals. He currently serves on the advisory boards of the Campaign to Defend the Constitution, an organization dedicated to opposing the religious right, and Scientists and Engineers for America, an organization focused on promoting sound science in American government.
He is also a recipient of 2001 National Medal of Science.
Varmus is an avid bicyclist and an Advisory Committee member of Transportation Alternatives the New York City-based advocacy group for pedestrians and cyclists. He is also a runner, rower, and fisherman. He has been married to Constance Casey since 1969 and has two sons, Jacob and Christopher.