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An Interview with Harold Varmus

Catherine Clabby

Harold Varmus, a physician turned molecular biologist, has long been one of this nation’s most prominent scientists. He and J. Michael Bishop won the Nobel Prize in Medicine in 1989 for unlocking secrets about the genetic origins of cancer with their studies of retroviruses. In the 1990s, Varmus ran the National Institutes of Health during a period of unprecedented growth in funding and influence. Today he is president of Memorial Sloan-Kettering Cancer Center in New York. Not long ago he agreed also to co-chair President Obama’s Council of Advisors on Science and Technology, a group expected to have real influence in the new administration.

Click to Enlarge ImageBut it’s only in Varmus’s recent autobiography, The Art and Politics of Science (Norton), that the true scope of his engagement in science becomes clear. The book grew out of a series of lectures that Varmus, now 69, was invited to give at the New York Public Library. It tells the story of the intellectual development of a bright kid, raised in New York on Long Island by first-generation Jewish-American parents. While an Amherst College undergraduate, Varmus was torn between the humanities and medicine, his father’s profession. After earning a master’s degree in English literature at Harvard University, he enrolled at Columbia University for medical training. Later he embraced basic research at NIH, then a refuge for promising young physician-researchers opposed to participating in the Vietnam War. His passion for basic research ignited, he moved to the University of California, San Francisco (UCSF), where he and his collaborators made cancer research history.

In addition to tackling big puzzles and big jobs, Varmus has long been an activist in science. He promoted greater public access to research literature by championing the creation of PubMed Central at NIH and helped found the nonprofit, open access publisher Public Library of Science. He is working to involve more U.S. scientists in promoting science in developing countries through the Global Science Corps, part of the Science Initiatives Group, and has chaired the scientific board of the Grand Challenges in Global Health at the Bill and Melinda Gates Foundation. American Scientist associate editor Catherine Clabby spoke with Varmus about lessons he has learned along the way and about some pressing scientific policy issues.

Did you ever expect to write an autobiography?

By the time I had been the director of the NIH for a while, I thought I had some stories to tell. The only question was whether I’d ever find the time to write them down. By signing a contract with Norton to give lectures at the New York Public Library and then turn them into a book, I naively committed myself to finding the time, even though I didn’t really have it. It is not a typical autobiography, of course, since it addresses questions about career path, science and science policies more than it satisfies any curiosity about my personal life. But I think it says many of the things I wanted to say about choosing a scientific career and getting satisfaction from it.

How important were the places you trained as a young scientist?

The places are actually important. I was drawn to the NIH, in part because I wanted to avoid the war. But I was also drawn because NIH was the premier training ground for academic medical scientists at that time. I think I probably say too little about that in the book. I was drawn to medical school at Columbia University because it seemed like a pretty exciting place with a wonderful reputation, and New York City is a wonderful place to be. I was drawn to UCSF because it seemed fresh and is in a great part of the country. The people I met out there had enthusiasm and didn’t seem tied up in the elite world of Ivy League medicine. Mike Bishop, Herb Boyer, Bill Rutter and Gordon Tompkins, many of these folks loved the physical attributes of California. It seemed like a place you’d be breathing clean air and maybe have thoughts you wouldn’t have in a more traditional kind of place doing medical research. It seemed brand-new.

How can young scientists make the most of the institutions at which they find themselves?

Look at the environment you find yourself in and try to attach yourself to what you think is strongest in it. Every laboratory has good problems and not-so-good problems. Find out what is exciting and likely to lead you to good results. When you are in a scientific environment, attach yourself to people you think are inherently interesting. In journal clubs, seek out the people who ask the good questions, who seem bright and on your wavelength. A lot of this is not just finding yourself in the right circumstance, but placing yourself in the right circumstances by seeing where there is potential.

Let’s turn to science policy. Given the fierce competition for scientific resources, how does someone running an agency as big as NIH strike a balance between basic science and more clinically focused, applied research?

Like any other investor, the person running NIH has to be building a diversified portfolio. You can’t run NIH on basic science alone. That would be silly. Just investing in clinical trials and things that are very disease-specific would be a huge mistake too. Look at what pride people take now in advances made in diabetes and cancer research and infectious disease research. Almost all of it is based on recombinant DNA technology, genomics and protein chemistry. These are methods that grew out of basic science that was funded for years and years in a noncategorical way. Even if you move a little closer to the disease borders, you find that predictability is not the mantle under which we fund this stuff. I was chatting this morning with someone about how much progress we’ve made on HIV through an understanding of the viral genome and learning about enzymes and developing drugs that can inhibit that virus. The fundamental work in those areas was done in the 1970s, not because people were interested in AIDS—AIDS wasn’t known. The research was done by people initially interested in viruses that caused cancer in animals. It was through just a curiosity about how cancer viruses duplicated themselves that these discoveries came about. I don’t pretend to say we have conquered HIV—we haven’t. We still desperately need a means to diminish transmission and block virus infection through a vaccine or something like it. But the fact is that we were quite prepared to recognize this unusual type of virus and to develop drugs against it because of the interest in retroviruses as agents of cancer. There are lots of stories like that. When you build a research portfolio for any single institute, and certainly for NIH as a whole, you need to be sensitive to broad themes in basic biology. That’s the way science advances.

You write in your book about your hope there could be structural changes at NIH. What was needed?

As I left the NIH, I wrote a piece in Science that that didn’t sit well with many people because in saying how I thought the NIH should be rebuilt, I suggested the amalgamation of many existing institutes if we could start at the beginning. I never thought for a moment that we’d be able to rebuild the NIH; it’s too hard to do that politically. I do think that by having made these provocative statements, I achieved something. First of all, I drew the attention of Congress to the fact that there are too many institutes, that the NIH is difficult to manage and that we can’t allow the proliferation to continue. The NIH reauthorization act passed in 2006 makes it nearly impossible to start a new institute. Second, the NIH now has a scientific management oversight group that will be reviewing the organization of the NIH. Third, a number of institutes have pulled together to do things in a more consensual fashion. And the NIH director has a lot more authority. One of the things I complained about was that the NIH director didn’t have enough money or clout to be involved in program development or look in a systematic way at the inventory of NIH research. I always got along well with the institute directors. But the more I meddled and tried to create intra-institute initiatives, the less that worked. Those initiatives almost always required the institutes to give up some funds for a common pot, and that stirred up resistance.

How do you expect the Obama administration’s science policies will differ from Clinton’s?

That’s hard to predict. Obama has inherited—and stated his intention to focus on—a much more difficult set of problems. They are problems that clearly are going to require strong help from the scientific community to solve: energy, climate change, health care and education. I think he sees science as being a central feature of what he’s trying to do. Science also offers opportunities in economic stimulus. We know one of the major drivers of the economic success of our society is science and what’s called “innovation”: taking scientific results and turning them into products. People are often a bit oblivious to the fact that their lovely new iPod, the latest medical convenience and our prospects for having fewer carbon-emitting energy sources all require scientific solutions at the fundamental and applied level. If we don’t have a strong cohort of scientists in the country, and if we don’t have support for budgets for science and sound science policy, this country is not going to prosper.

The new president understands that. He made some amazing appointments, people like Steven Chu [Energy Secretary], Jane Lubchenco [National Oceanic and Atmospheric Administration administrator] and John Holdren [Obama’s top science adviser]. He’s trying to pull together this external advisory panel in a very lively and immediate way that just wasn’t the case in the past. We’re all feeling the strong breeze of support from the White House, even in this early stage, when there are a million other things on the table. There’s a lot to be done. Clinton inherited deficits, but he didn’t inherit an economy that was going down the tubes.

Do you think controversial scientific questions, such as the use of human embryonic stem cells, can ever be removed from politics in the United States?

I think it’s possible. There are two ways to think about this. The United Kingdom has a good way to deal with this. They put together expert groups. They accept the deliberations of the group and develop a policy that applies to whether or not you can do certain kinds of research. In the United States we don’t have quite as expert-driven means of settling these issues, but we tend to decide whether or not we’re going to use federal funds for things. I think that having the British model in the United States is possible, but it would require a number of changes. For example, bringing back something that resembles the technology evaluation office in Congress, so you actually get a technological assessment that Congress is perhaps more likely to listen to. But we do put a lot of things in the hands of a Congress that is very, very busy.

Also open is the possibility of funding these things in other ways. I think it was a serious deficiency to limit federal funding of stem cell research during the Bush administration. The federal budget is big, and it creates an even playing field for everyone in the country. It’s the fair way, the right way, to do things. But the fact is that this country has done a lot of stem cell research, even in the Bush years. The private sector and the states kicked in. A lot of states kicked in a lot of money, California, New York, Massachusetts, Wisconsin and others. And in many institutions like our own we had a lot of money from private philanthropy. Industry was also heavily involved. But it’s not as good as having NIH funding. NIH creates rules that apply across the country. It gives public confidence in the research and makes it seem inviting to people who are deciding on careers. It is hard to decide to enter a field of science where your career may be limited by the fact that you have to get funds from certain nongovernment sources.

As you get more involved and have a more of a voice in Washington, will you try to develop more support for your vision of a Global Science Corps?

That’s something I’ve been doing in the private sector through something called the Science Initiatives Group. I recently started running a committee at the Institute of Medicine that is reevaluating the U.S. role in global health. We issued a preliminary report to the new administration with several key points. Investing in health and science in poor countries should be an increasingly large part of our foreign policy. We should do that because it’s the right thing to do. But it also has very practical consequences that are beneficial to us economically and with respect to our security and reputation. There needs to be someone in the White House who is coordinating global health efforts across many agencies. And we have some specific recommendations about funding levels. One of the best legacies of the Bush years—and there aren’t that many to brag about, frankly—is that President Bush did invest in AIDS relief. Of course, we can’t abandon that, because that would cause people now sustained on antiretroviral drugs to die. We think there are many ways that the program should be expanded and altered with more emphasis on prevention. We need to pay attention to neglected tropical diseases, chronic noninfectious diseases and health systems, in addition to focusing on prominent contagious illnesses such as AIDS, tuberculosis and malaria.

But I’m not in this position [on the advisory panel] to push my own agenda. That’s for sure. My role is to provide scientific advice and get the best people in to advise the president.

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