A Doctor Who Makes House -- and Senate -- Calls

By William J. Cromie

Gazette Staff

The announcement that Harold Varmus would be the principal speaker at the 1996 Commencement surprised many people. Seniors, staff, and even some faculty wondered out loud: "Who's Harold Varmus?"

Some students called him "Dr. Who?"

Why wasn't a head of state, a great scholar, an influential politician, or a famous alum chosen for the honor?

Actually, Varmus, 56, is all of those things. The "state" he heads, the National Institutes of Health (NIH), is the largest funder of biomedical research in the world. It spends almost $12 billion a year on discovering why people get sick and how illness can be treated.

As a scholar, Varmus' background includes both literature and science. He received a master's in English literature from Harvard in 1962. Watching his friends at the Medical School, however, convinced him that a future in medicine would be more exciting than the pleasures of reading.

Rejected twice by Harvard Medical School, Varmus managed to get an M.D., become a professor at the University of California, San Francisco, and win a Nobel Prize in medicine in 1989.

Although he had never chaired a college department, or run anything bigger than a 36-person laboratory, Varmus took charge of the l6,000-person NIH bureaucracy in 1993. As director, he has proven adept enough to keep peace among 24 quasi-independent internal institutes, as well as to win financial support from Congress, and pacify multitudinous groups who want more funding for specific diseases such as AIDS and breast cancer.

From this perspective, Varmus has been a remarkably successful politician. And, adds his wife, Constance Casey, "the senior class and alumni will have a lot more fun listening to Harold than many politicians who are better known."

Daunting Talk

"I was excited about the invitation to receive an honorary degree," said Varmus. "It's like being invited to a good party and receiving an award for going. But the thought of giving a talk, the talk, is daunting.

"Based on my father's 25th reunion, I have a fuzzy recollection of Commencement day as a time when thousands of people are walking around the Yard, some sober, some not. I'm not sure that they listen to the speaker all that attentively."

With that realistic view in mind, Varmus will speak about the pace of biomedical research and some of the rewards people can expect from it.

"The pace of discovery is accelerating, but the pace of applying new knowledge to the treatment of disease is always going to be frustratingly slow," he noted. "The death of my mother and grandmother from breast cancer played a role in my choice to study cancer in the early 1970s. At the time, it seemed that a solution to breast cancer was amenable to research, but that hasn't yet proved true."

In addition, Varmus may talk about the discovery and isolation of genes, not just in cancer but in many other diseases.

"This is the single theme that dominates biomedical research today," he says. "We must characterize genes that put people at a high risk for illness, and use that knowledge to both treat and protect those individuals. More and more of us will be in a position to find out whether we have inherited deficiencies, and the country will need laws to prevent employers, insurance companies, and others from abusing such information."

Varmus wants to convince Congress and the nation that one of the best things the federal government does is to support basic research, not only in biomedicine, but in chemistry, physics, and other fields of science. "We should not balance the budget at the expense of the research that makes the U.S. strong internally and externally," he says.

A Better Future

Varmus grew up on Long Island, N.Y., son of a family doctor and a psychiatric social worker. His father joined the Class of '28 at Harvard College, but a lack of money forced him to leave school after two years. He later received his M.D. from Tufts University Medical School.

That background steered Varmus toward a pre-med major. He was accepted at Harvard but chose Amherst College in Massachusetts. Classmates there who were interested in literature, inspiring teachers, and a love of reading, however, changed his academic mind. Varmus switched his major to English literature and became editor of the school newspaper. He graduated with a B.A. in 1961, then went on to Harvard for graduate work as a Woodrow Wilson Fellow.

"My year at Harvard was a good one," he remembers, "but I began to feel that I was missing out on something. I went to see some former classmates at the Medical School and got the impression that they were more excited about the future than I was. They invited me to lectures and conferences that impressed me with the possibilities of medicine and medical research. In the end, I decided I was not prepared to trade off participation in these possibilities for the pleasures of reading."

Varmus applied to Harvard Medical School but was rejected. It was the second time; he had also applied as a college senior. When interviewed after his master's, the admissions people didn't think he was mature enough and suggested he join the Army for two years.

Varmus then tried Columbia University. The interviewers there asked him to translate some Anglo-Saxon texts. He recalled that "they seemed much more interested in someone with a literary background than Harvard Med."

Varmus received his M.D. from Columbia in 1966, then did an internship and residency at Columbia-Presbyterian Hospital. He did serious research for the first time at the National Institutes of Health in 1968-70. The experience prompted him to switch from medicine to science.

That decision brought him to the University of California (UCSF) as a postdoctoral fellow. He rose to full professor by 1979 and became American Cancer Society professor of molecular virology in 1984.

Genetic Gold

During 23 years at UCSF, Varmus worked with Michael Bishop, investigating cancer viruses and genes. This research led them to share a Nobel Prize in Medicine in 1989. They uncovered some of the first evidence that we share genes with other species. They also proved that a normal gene in a human or animal cell could mutate to one that leads to cancer.

"All of us have a collection of inherited genes normally involved in doing good for us," Varmus explained. "The gene we discovered, for example, is important in regulating bone growth. But changes, or mutations, caused by chemicals or other factors can alter it in a way that contributes to the development of cancer."

At a banquet following the Nobel ceremony, Varmus gave a short talk. It included lines from Beowulf which he had read as a student of William Alfred, Abbott Lawrence Lowell Professor of the Humanities Emeritus.

He delivered those lines in Anglo-Saxon, a language, he noted, descended from Scandinavian and ancestral to English. The words told of warriors coming to the hall of kings to receive gifts of gold.

"They were very appropriate," his wife recalled. "We were in the presence of the King and Queen of Sweden in this gigantic hall decorated with gold. And we were eating gold-wrapped chocolate replicas of the Nobel medal."

English literature impresses Varmus so much he once considered naming the children he expected to have "Britomart" and "Artegall." The former represents chastity, and the latter, justice in the Elizabethan classic The Faerie Queene. "But we decided it would be easier on them if they had names like Jacob and Christopher," his wife said.

Jacob, 22, studies jazz trumpet at the New School in New York City. Christopher, 18, is a sophomore at Wesleyan University in Connecticut. Wife Casey, now a national correspondent for Newhouse News Service, was a Nieman Fellow at Harvard in 1988-89.

A Successful Switch

Many scientists and politicians were startled when someone with such a background was offered -- and accepted -- the directorship of the NIH in 1993. "Harold will never make it in Washington," said UCSF colleagues who knew him as a dedicated scientist who doesn't suffer fools gladly.

By every criterion, however, Varmus has successfully made the switch from a relatively cloistered laboratory researcher to the high-profile head of a huge federal agency.

How did he do it?

"People on the outside would say my biggest achievement is keeping our budget up," Varmus answers. While most other agencies have suffered cuts, NIH's fiscal '96 budget is $11.9 billion, a 5.8 percent increase over the previous year. All indications are that fiscal '97 funding will be at about the same level.

Casey partially credits her husband's literary background. "He's known on Capitol Hill for clear, short presentations," she says. "That's music to the ears of people who must listen to an endless assortment of people droning on in bureaucratic language. Harold presents his case in a way that lets members of Congress learn something and enjoy themselves."

Varmus insists he is only part of the story. "I have a lot of people working in my behalf and many friends in the Congress who are trying to keep NIH going," he says. "Also I've been lucky to recruit people with outstanding scientific judgment to head the various institutes within NIH."

Among the latter he includes psychiatrist Steven Hyman, former director of Harvard's Interfaculty Initiative in Mind/Brain/Behavior. Hyman took over as head of the National Institute of Mental Health on April 15.

Varmus can't bring himself to give up research. He runs a small NIH laboratory which he visits every day. This lab focuses on cancer genes. Researchers who work there include Jay Debnath, a Harvard Medical School student who just completed his third year.

For recreation, Varmus likes to bike, run, and row. He is considered an overachiever in all three. "I hope to go for a row on the Charles when I visit Cambridge," he noted. "I'd like to get someone to go out with me in a double shell."

Reading remains a passion, albeit one cooled by lack of time. "I have about eight books on my bedroom table," he says. "They include a book about a young woman's experience as a psychiatric patient; one on politics, and one entitled The End of Science." One reason he can't read as much as he likes is writing; Varmus has authored or edited four books and nearly 300 scientific papers.

"Sometimes I'm jealous of Harold because of the nature of his work," Casey says. "He can set his own goals; the answers to this year's scientific questions determine what next year's questions will be. Harold's gotten many rewards, including the honor given to him by Harvard, but he's surprised at being rewarded for work he has so much fun doing."