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The writing life of Nobel Prize-winning scientist Harold Varmus

By Harold Varmus
Sunday, September 19, 2010; BW11

When high school students ask to spend their afternoons and weekends in my laboratory, I am amazed: I didn't develop that kind of enthusiasm for science until I was 28 years old. In the 1950s, in my Long Island public high school, science courses were at best uninspiring; it would never have occurred to me to sacrifice after-school hours to a laboratory. But as the son of a family physician and a psychiatric social worker, I assumed I was destined for a medical career, so I was diligent in those classes, even though I preferred novels to chemistry and tennis to science fairs.

Later, at Amherst College, my exposure to science was dutiful, pre-ordained by an inflexible curriculum and pre-med requirements. My pleasures came instead from Chaucer, Milton, Dickens and college journalism. After college, finally acknowledging what I enjoyed, I entered graduate school in English literature, heading toward a scholarly career that would emphasize the 17th century.

Then disenchantment with Harvard graduate school and anxiety that I was irreversibly detaching myself from the modern world sent me to medical school at Columbia. I had learned of Gertrude Stein's bon mot that medicine opened all doors. This prompted me, in different moods, to view my future life as literary psychiatrist, globe-trotting tropical disease specialist or academic internist.

Anyone graduating from medical school in 1966 had first to fulfill military service before launching a career. Fiercely opposed to the Vietnam War, I sought to avoid it through an assignment to the Public Health Service. Despite my lack of scientific credentials, I was able to secure a training position in the laboratory of Ira Pastan, a young physician-scientist at the National Institutes of Health. There, for the first time in a lengthy education, I learned the joys of science. I was asked to attack an important unsolved problem (how cyclic AMP, a chemical mediator of cell action, controls gene activity). I devised an accurate test that convincingly answered the question. Then I told other scientists about my pretty findings, wrote papers for publication, received praise and contemplated the next experiments.

I had learned that science is a rewarding, active process of discovery, not the passive absorption of what others had discovered. It was so exhilarating that I decided to abandon medicine and pursue a scientific career, studying viruses that cause cancer in animals. This precipitated a move to San Francisco, a long-term alliance with a like-minded young scientist (J. Michael Bishop), and the gradual mobilization of a team to figure out how those viruses multiply, how they cause tumors in animals, and what they can teach us about human cancer.

I have pursued these questions (and other questions that the answers prompted) -- working initially at a laboratory bench with my own hands and, increasingly over time, overseeing experiments done by others -- for almost 40 years. But until a few years ago, I could not have imagined myself writing a book for a general audience about my life as a scientist. I thought that the routines of a medical scientist in a laboratory -- unlike the peripatetic, glamorous and even dangerous exploits of, say, an Amazonian ornithologist -- would seem physically dull and intellectually impenetrable. I didn't realize that we had stories about discovery -- about the logic and excitement of science and about the people who did it -- that could be told and were worth telling. Moreover, I was wary of being personal on paper, of getting away from the secure data and cautious interpretations that are the reliable tools of those writing for scientific journals.

But suddenly, in 2004, I found myself obliged to write that book anyway. I had been asked to deliver a series of three weekly lectures at the New York Public Library. The offer was seductive: a familiar and limited format (50-minute lectures, with slides), an interested but non-technical audience, a prestigious venue and an impressive title: the Norton Lectures. Sponsorship by a publisher meant that the lectures would eventually be turned into a book.

The imperative to connect with a lay audience on three fall evenings seemed daunting, but I settled on three narrative lines that seemed interesting, one for each lecture. In the first, I would recount my meanderings as an adolescent and a young adult through literature and medicine toward science. In the second, I would outline our experiments with cancer viruses that unveiled genes now implicated in human cancer and describe how those genes are used as targets for novel therapies. In the third, I would describe my unexpected foray into public policy after President Bill Clinton chose me, despite my lack of administrative experience, to become the director of the National Institutes of Health in 1993. This final lecture would allow me to speak, albeit briefly, about several matters of interest to both scientists and the general public: how the government funds science, how a large federal agency works with Congress, how the NIH oversees controversial research (for instance, on stem cells or embryos), how scientific work is published, and how science and health can be promoted globally.

Turning these lectures into a book was a more complicated business than conceiving and delivering them. The task of becoming a different kind of writer took almost four years. Once the constraints of a 50-minute lecture were removed, I became aware of a new and intimidating freedom -- in principle, I could go on as long as I wanted! Moreover, I needed to learn to write in a new way, a way that established relationships with readers, encouraged humor, commanded a reader's sustained attention, and exposed an author's feelings and personality.

It was not enough to summarize our major findings about cancer viruses and cancer genes or their recent applications to patient care. I wanted to describe how and when ideas popped into my head (for instance, while wheeling our infant son around an English churchyard). I tried to see a pattern to my experimental failures (such as when I committed the sin of Thinking Too Much and advised my trainees to take what proved to be the harder and slower routes to answers). Because I have benefited enormously from scientific collaborations, I also sought to show how our students and colleagues at other institutions helped to make discoveries and how I entered -- and many years later left -- an unusually long and productive partnership. None of this could have been done in 50 minutes at a podium or without a newly liberated attitude toward my role as a writer.

If I could describe my writing experience as a kind of science, the lectures were the pilot experiments, and the book was the full analysis. But I can also see a story emerge: As an author, I discovered things about myself and was changed in the process. Perhaps, after all, I still prefer novels to chemistry.

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