Children of immigrants
Harold Eliot Varmus was born on December 18, 1939, in Oceanside, on the south shore of Long Island, New York. He described himself as a product of the great early-twentieth-century emigration of Eastern European Jews to New York. His paternal grandfather, Jacob Varmus, left a village near Warsaw soon after 1900 to farm in Newburgh, New York, and later worked as a hatter in Newark, New Jersey; his grandmother Eleanor died in the influenza epidemic of 1918. His mother’s parents, Harry and Regina Barasch, came from farming villages near Linz in Austria and founded a children’s clothing store in Freeport, Long Island.
As children of immigrants, his parents were notably well educated. His father, Frank, studied at Harvard College until money ran out and then at Tufts Medical School, becoming a family doctor in Freeport; his mother, Beatrice, studied at Wellesley College and the New York School of Social Work. During the Second World War his father served at an Air Force hospital in Florida, where Harold’s first memories were of long beaches and fishing on a lake with alligators. He grew up in Freeport with his sister, Ellen, preferring reading to team sports and spending summers at Jones Beach, where his father was the medical officer.
From English literature to medicine
In 1957 Varmus entered Amherst College intending to become a doctor like his father, but the pleasures of academic life drew him from science to philosophy and finally to English literature. He edited the college newspaper and graduated with a degree in English. A Woodrow Wilson Fellowship took him to Harvard for graduate study in English, and he earned a master’s degree in 1962, but within the year medicine called him back.
He entered Columbia University’s College of Physicians and Surgeons, at first interested in psychiatry and international health. An apprenticeship at a mission hospital in Bareilly, India, tempered his hopes of practising abroad, and lectures by scientists such as Erwin Chargaff drew him toward basic research. From 1966 to 1968 he trained as a medical resident at Columbia-Presbyterian Hospital.
From the NIH to San Francisco
In 1968, as an alternative to military service during the Vietnam War, Varmus joined the Public Health Service and went to the National Institutes of Health, where he worked in Ira Pastan’s laboratory on how bacteria switch genes on and off. It was his first serious taste of laboratory science and of the excitement of an experiment that works. Wanting to learn molecular biology, specifically the study of cancer-causing viruses, he joined J. Michael Bishop at the University of California, San Francisco, as a postdoctoral fellow in 1970.
In 1969 he had married Constance Casey, a journalist who later became a book critic. They lived for many years in a Victorian house in San Francisco’s Haight-Ashbury district, where their sons Jacob and Christopher were born in 1973 and 1978. Varmus joined the UCSF faculty in 1972 and became a full professor in 1979. His partnership with Bishop, in which they shared space, staff and funds for more than a decade, became one of the most famous collaborations in modern biology.
The enemy within
Bishop and Varmus studied the Rous sarcoma virus, a retrovirus that causes cancer in chickens, discovered by Peyton Rous early in the twentieth century. It carries a gene, called src, that turns infected cells cancerous. The prevailing theory was that such viral cancer genes might be the cause of many cancers. Using a probe that detected only src, they searched the DNA of normal cells and, with Dominique Stehelin and Peter Vogt, reported in 1976 that a version of src was present in normal chicken DNA, and in the DNA of many other species across the animal kingdom.
The conclusion was startling. The virus’s cancer gene was not really a viral gene at all but a normal cellular gene that the virus had picked up from a host cell long ago and carried along in altered form. Our own cells contain such genes, now called proto-oncogenes, which help control normal cell growth and division, and cancer can arise when they are damaged or wrongly switched on. By the time of their Nobel Prize, more than 40 oncogenes had been found by following their lead. In 1989 Bishop and Varmus shared the Nobel Prize in Physiology or Medicine for their discovery of the cellular origin of retroviral oncogenes.
How it changed cancer medicine
The discovery transformed how scientists understand cancer: not as an invasion from outside, but as a disease of our own genes gone wrong, a distorted version of our normal selves, as Varmus put it in his Nobel banquet speech. It launched the hunt for the genes that drive human tumours, and it laid the conceptual foundation for today’s targeted cancer drugs, which are designed to block the specific abnormal proteins made by mutated cancer genes. Doctors now routinely test tumours for mutations in such genes to choose a patient’s treatment.
Varmus kept working at the laboratory bench throughout his career. With Roel Nusse he discovered the cancer gene Wnt-1, founding member of a family of genes that control development; with Don Ganem he studied how the hepatitis B virus replicates; and with Tyler Jacks he discovered ribosomal frameshifting, a trick retroviruses use to make their proteins. Later, with William Pao and colleagues, he helped characterise mutations in the EGFR gene in human lung cancers, including a common mutation that makes tumours resistant to targeted drugs, and his laboratory built many mouse models of human cancer.
Leading American science
In 1993 President Bill Clinton appointed Varmus director of the National Institutes of Health, the world’s largest funder of medical research. During his tenure, which ran until the end of 1999, the agency’s budget nearly doubled, and he was credited with recruiting outstanding scientists to lead its institutes, building strong relationships with Congress, leading on clinical and AIDS research, promoting global health research, especially on malaria, and building a new Clinical Center and a Vaccine Research Center.
From 2000 to 2010 he was president of Memorial Sloan Kettering Cancer Center in New York, where he expanded research, built a new laboratory centre and started a graduate school in cancer biology. In 2010 President Barack Obama named him director of the National Cancer Institute, making him the first person to lead an individual NIH institute after directing the whole agency. He served until 2015, starting new centres for cancer genomics and global health, then returned to New York as a professor at Weill Cornell Medicine and a senior associate at the New York Genome Center.
Free science for everyone
Near the end of his time at the NIH, Varmus became a leading champion of using the internet to make scientific papers freely available. With David Lipman of the National Center for Biotechnology Information he established PubMed Central, a free public digital library of full-length research articles. In 2007 Congress directed that all papers reporting NIH-funded research must appear in PubMed Central within a year of publication, giving patients, doctors and scientists everywhere free access to the results of research paid for by the public.
The idea came to him in December 1998, inspired by physicists’ use of the online preprint server arXiv, and in May 1999 he proposed E-biomed, a free online home for all biomedical research. Commercial publishers and some scientific societies lobbied hard against it, fearing lost income, and the plan was scaled back: the resulting PubMed Central, launched in 2000, accepted peer-reviewed papers from publishers and allowed them to delay free release by up to a year. Even in that compromise form it grew into one of the largest free archives of medical research in the world.
With Patrick Brown of Stanford and Michael Eisen of Berkeley, Varmus also co-founded the Public Library of Science, or PLOS, a nonprofit publisher of open-access journals in biology and medicine. Their efforts helped spark the worldwide open-access movement, which has made millions of research papers free to read for doctors in poor countries, students, journalists and patients researching their own illnesses. He has also argued for cheaper cancer drugs, for routine genetic testing of tumours, and, with colleagues, for reforms to ease the hyper-competitive pressures on young biomedical researchers.
Roots, family and legacy
Varmus has described his family as part of the Eastern European Jewish emigration to New York, and his own story, from immigrant grandparents in farming villages to a Nobel Prize and the leadership of American medical science, spans the whole arc of that immigrant story. He wrote about his life and his views on science and government in The Art and Politics of Science, published in 2009. He has chaired the Grand Challenges in Global Health programme at the Gates Foundation, and since 2021 has chaired the World Health Organization’s Science Council.
He and Constance Casey live in Manhattan. Their son Jacob is a jazz trumpeter and composer, and father and son have performed lecture-concerts called Genes and Jazz at venues including the Guggenheim Museum and the Kennedy Center. A lover of literature, theatre, music and cycling, Varmus has never fully left the English student behind. His legacy runs from a basic insight about the origins of cancer, now the starting point for modern cancer treatment, to a research literature that anyone in the world can read for free.
Sources & further reading
Harold E. Varmus, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 1989, NobelPrize.org · Harold E. Varmus, Banquet speech, NobelPrize.org · Harold E. Varmus, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.