Harold Varmus Returns To Politics

The Nobel Prize winner and former NIH director has received another presidential appointment: director of the National Cancer Institute. Ira Flatow and Varmus discuss the intersection of politics and science, the genetics of cancer and the process by which basic research becomes medicine.

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IRA FLATOW, host:

Harold Varmus won the Nobel Prize for his work with cancer genes, but what you may not know is that his college thesis was on Charles Dickens.

He served as the director of the NIH under President Clinton, and more recently as science advisor to President Obama. He's been a long-time president of Sloan-Kettering, Memorial Sloan-Kettering Institute here in New York. And now he's returning to national service, taking the reins at the National Cancer Institute.

Harold Varmus is the author of the book "The Art and Politics of Science" and the newly sworn-in director of the NCI. He is with us here today. Welcome back to SCIENCE FRIDAY, Dr. Varmus.

Dr. HAROLD VARMUS (Author, "The Art and Politics of Science"; Director, National Cancer Institute): Ira, thank you very much.

FLATOW: Well, you know, so you traded the hat of NIH to NCI.

Dr. VARMUS: Well, I'm not sure it was a trade, but, you know, when I was at the NIH as director, I had a very good time, but I was always envious of the institute directors who have the money and authority to make real scientific programs. And that's something people often forget. They think the NIH has a lot of money, and the NIH director is in charge of it. But, in fact, it's a confederation, not a perfect union. And it's very exciting to be back in charge of a large institute that makes a lot of grants and has a very large budget at a time of incredible excitement in cancer research.

FLATOW: Is the NCI in the same pool of money as NIH, or does it have its own pool?

Dr. VARMUS: No, no, no. The NIH, as I say, is a confederacy composed of 27 institutes and centers, each of which is separately authorized and has a director and a budget.

FLATOW: Right.

Dr. VARMUS: And the NIH director is the cheerleader and the supervisor and has some resources of his own, but it's at the institutes that a lot of the most important action actually occurs.

FLATOW: You said that this is a very exciting time in cancer research. Why is that?

Dr. VARMUS: Well, we're finally starting to reap the benefits of a long-term investment in understanding what makes a cancer cell tick. When I I've been in this field now for 40 years. When I entered it, we really didn't know anything about cancer cells, except that they grew in an indiscriminate and aggressive way. And we had very little idea how that happened.

Over the course of that period of 30 or 40 years, by investing in model systems and basic biology and many other things, taking advantage of some clinical opportunities, it's become apparent that we can identify the set of genes that play a major role in cancer.

That role is played when those genes are damaged by mutations or rejoined or amplified or inappropriately expressed in some way. And through the magic of genomics - a science which is now dominating the life sciences - we're now, one by one, picking apart the insides of a cancer cell, understanding how cancers grow, how they invade their environments, how they metastasize. And we're learning this at a level of exquisite complexity, but with tools to identify those elements in the machinery that are most vulnerable to change.

We have some successes over the last 10 years of drugs that are precisely targeted to the damage in the cancer cell that result in dramatic remissions, in some cases, sustained absence of tumors.

FLATOW: Mm-hmm. Do you get tired when people keep asking you when are we going to cure cancer?

Dr. VARMUS: I'm not as fatigued as an instructor as that question might imply. I think the question itself, of course, is very naive, and it's naive in an -actually, in an interesting way. And that is while cancer is united by its mechanism, it's manifest in many different tissues and in every tissue in a different way.

One of the things we're learning is while there are commonalities, every cancer is different in some way. Cancers have lots of changes, and the task for modern cancer biologists is to understand which of those cancers is most significant with respect to the likelihood of the cancer actually leading to death, and more importantly, for the patient, offering a different set of prospects for treatment.

FLATOW: We're talking with Harold Varmus, author of "The Art and Politics of Science," just two days into your new...

Dr. VARMUS: It's two days - sworn in on Monday morning.

FLATOW: Sworn in on Monday morning as head of the NCI. Our number: 1-800-989-8255. We'll take a few calls, but remember, Dr. Varmus cannot give you personal advice, if you have cancer, unfortunately, or if you know people. We all do. So please, if you'd like some general questions about the future of cancer research, we'd be happy to talk about it.

So stay with us. We'll be back with Dr. Harold Varmus after this break. Don't go away.

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FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY, from NPR.

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FLATOW: You're listening to SCIENCE FRIDAY, from NPR. I'm Ira Flatow. We're talking this hour with Dr. Harold Varmus, newly sworn-in head of the National Cancer Institute in Bethesda, Maryland. Our number: 1-800-989-8255. Have you moved your bike?

Dr. VARMUS: It's coming today, actually.

FLATOW: It's - well, that should...

Dr. VARMUS: I'm resuming my 12-mile commute through Rock Creek Park, and can see the route for the first time in 10 years tomorrow morning.

FLATOW: Wow. It's been a while. That's been a while. Let me ask you about the whole new field of genetic testing now. Cancer is - you know, and all of medicine is talking about personalized medicine. What's your take on that?

Dr. VARMUS: Well, I tend not to use that term. I think it's a little misleading. But the point is that it's now possible to learn about the individual characteristics of a specific cancer in a way that allows treatment and prognosis to be tailored precisely to individual cases that may fall under the rubric of one general diagnosis.

So, take the example of the most common form of lung cancer, lung adenocarcinoma: We now know that virtually every cancer is going to differ in some ways, and importantly, for example, 10 percent will have a mutation in the gene called the EGFR gene. And if you have a mutation in that gene, we have a drug that will help.

It's not a cure, but it does substantially help. But it doesn't help - in fact, it wastes time and wastes money - to use that drug if you have mutation in the Ras gene, which occurs in about 20 percent, or 25 percent of the same cancer as looked at by a pathologist under a microscope.

So what genetics is teaching us, and what we're learning when we practice genetically informed therapy, genetically informed medicine, is the characteristics perceived only through molecular biology techniques, that differentiate one apparently similar cancer from another.

FLATOW: Mm-hmm. There was a story a few weeks ago about the discover of what were called longevity genes in people, and that some people who lived to ripe old ages, I mean, 100 or more - I'm sure you've heard of this study...

Dr. VARMUS: Yes.

FLATOW: ...might have protective genes that protected them from getting cancer or other kinds of cancers. Do you believe in that?

Dr. VARMUS: Let's distinguish, Ira, between two kinds of genetic testing. What we were talking about initially when we talked about genetically informed cancer medicine is the genetic testing that's done on a cancer in which you actually compare the cancer to normal tissue from the same individual to look for mutations that occurred during life that gave rise to that cancer.

What you're talking about now is a whole other field called obviously, technically related, in which you look at the genome you inherit from your mother and father for markers that may be useful in determining what your risks are for certain diseases or what your opportunities might be for a long life. And here we have some information that is dramatic because we've known for many years that it's possible to inherit mutations, for example, that give you, say, a 60 percent chance of having breast cancer or a 99 percent chance of having a disease called retinoblastoma or a 95 percent chance of having colon cancer.

And yet we also have a lot of variation in our chromosomes, in our genome, that in its totality, you know, each part may have a very small influence, but in its the totality, may lead you in one direction or another.

The danger right now is people are is people are - I think in some cases -being misled to think that what is ascertained on the population basis to confer perhaps a two-fold risk over a very low overall risk actually pertains to you. Because what we don't know is what that single marker means in the context of your own genome, as opposed to the average genome in the population.

So that complicates the kinds of questions you're raising about whether you can say to any individual you're going to live long because you have a collection of genetic markers that are said to predispose to long life.

FLATOW: You mentioned at the beginning that this was a golden era for cancer research. Does the public understand this? Do you think they feel this way, or are they focused on other things?

Dr. VARMUS: I don't know. I think it depends on, you know, on how much you read about what our understanding of the cancer genome has to offer. And I don't want to over-promise. Because I say it's a golden era for cancer research, the likelihood that any single discovery is going to lead to a dramatic improvement in our ability to prevent cancer, to diagnose it earlier or to treat it will depend on a constellation of other things, whether the particular discovery is one that's conducive to finding a new drug, whether and how frequent that new discovery actually turns out to be in any particular cancer.

But perhaps the best-known example of a triumph of genetically influenced cancer medicine is the case of adult leukemia, chronic myeloid leukemia, where a drug called Gleevec - that I think is now quite well-known - is highly successful in treating virtually every case of this disease. And that's because the disease is very dependent on a single mutation.

The mutation is found in over 95 percent of all patients with that cancer. And, you know, the drug is very well-tolerated and very, very good. In other cases, we've had modest success, as in the example of lung cancer that we talked about before.

In many other cancers, we've identified the mutations. For example, in pancreatic cancer, we know that over 95 percent of those cancers have a mutation - almost always the same mutation, in a gene called the KRAS gene.

But we don't have, as yet, a therapy that reverses the effect of that mutant gene. Now, that's a challenge. It's a well-defined challenge, and it puts us in a very different place than we were 20 years ago, when we didn't really have any idea of why pancreatic cancer might have arisen in the first place.

FLATOW: Mm-hmm. 1-800-989-8255. Let's go to Anthony, in Nashville. Anthony?

ANTHONY (Caller): Hi, how are you?

FLATOW: Hi, there.

ANTHONY: I have a question, and I'll take my answer off the air. I wanted to ask what he thinks the impact of stem cell research will have on cancer research in the future.

FLATOW: What's the impact of stem cell research on cancer research?

Dr. VARMUS: Well, there are several different aspects of that. One is that we -stem cell research, as discussed broadly, involves not just embryonic stem cells, but stem cells that exist in all organs.

We've been using stem cells for over 30 years to treat many cancers, especially leukemias and lymphomas. And the increased activity in the field, obviously, is improving our ability to do that kind of work and to improve stem cell transplants.

But in addition, there are things coming from the study of cell development -and that's what stem cell research is all about - that are affecting our understanding of how cancer arises.

There's a new idea - not fully validated, but with evidence to support it -that cancers can be seen in some ways like organs in the body, and there are a few cells that are especially well-equipped to repopulate a cancer after a cancer has been treated.

We all know of many cases in which cancers have been removed or successfully treated with chemotherapy or radiotherapy that nevertheless recur, and they presumably recur from some cells left behind that have the potential to regenerate the tumor. That's, in a sense, like the way very much akin to what happens when a stem cell regenerates an organ, or a stem cell produces an entire organism.

So understanding the principles involved there I think will give us insight into how we decide which cells in a cancer are most important to eliminate.

FLATOW: You've written a lot, certainly, in your book, "The Art and Politics of Science," a lot about your experiences in the government. Do you think the present administration and Congress I know President Obama says he wanted to restore science to its rightful place, but is there room with this economy for doing that?

Dr. VARMUS: Well, first of all, there's no doubt that the president especially is an enthusiast for science and understands what science can do not just for health, but for many other parts of our society, in economy and energy and environment and many other places.

So his enthusiasm, very important for many of us who have entered government recently with the intention of working with him. But he does have a lot on his plate. Money is limited, and it's difficult to increase budgets.

Nevertheless, I sit in an agency that has a budget of over $5 billion, and we can do a lot with that, and my intention as the curator of that money at this time is to be sure we spend that money as well as we can.

Now, we have a lot of things on our plate - not just laboratory research - that is very expensive - clinical trials. One of my goals is to be sure that what we do as scientists ends up being important to people in many parts of our society. We know that advances in cancer care that result from recent science first gets expressed in academic health centers, like cancer centers. But we want to reach out to cancer community doctors.

FLATOW: Right.

Mr. VARMUS: And we want to be sure that people who are disadvantaged in our society get the benefits. We want to see cancer become part of the global health agenda because we know there are certain things that can be done in even the poorest countries. Efforts to reduce tobacco use, to use vaccines that work against viruses that cause cancers in poor countries. So there are lots of things that we need to do that are going to be quite expensive and there's no doubt that we could use more money extremely well.

FLATOW: Well, then, how do you juggle that? How do you sit down and decide, we should put this money here, this money there, or you know?

Mr. VARMUS: Well, this is one of the great challenges for anybody who runs an institute at this - at the NIH. Of course we have an established pattern. I arrive here and the money is already in the hands of tens of thousands of investigators around the country and indeed around the world. And we have made commitments to those investigators, so we're - what's on the table at any one time is not the entire portfolio.

But every time that the year turns, we're giving out new grants. We have to make decisions based on what we think are new opportunities in science, what we think are public health demands, what we think are new ways of extending our reach by, for example, enriching the communications we send around. We try to do public education. New ways to train scientists and extend our training programs, because we have to think all the time not just about how we apply our most advanced knowledge but how we train scientists for the future, how we continue to invest in basic science, because the ideas that may ultimately influence our ability to control cancer often are born of work that's done with model organisms, in work that's much more basic in character.

Cancer, remember, is a disease that affects the fundamental machinery by which our cells operate, the way in which the DNA is copied, the DNA is expressed, proteins are made, DNA is repaired, and knowing how to - how cancer as a disease affects those normal processes and how we might repair those processes depends upon understand how cells fundamentally work.

So there's a lot for us to do. And I have a very good team here, which I inherited, of grants managers and planners who sit with me to talk about how we allocate our programs. And, frankly, I'm in touch with the so-called extramural community, the community of scholars around the world who are thinking about cancer and are very vocal with their advice.

FLATOW: Talking with Harold Varnus this hour on SCIENCE FRIDAY from NPR.

I'm Ira Flatow, talking with Harold Varnus. Also author of "The Art and Politics of Science." Excellent book if you want insight into what it takes to juggle all those things and the personalities that are involved in working with the Beltway. I don't - you know, I spent 10 years in Washington and I - that was a long time ago. Have you noticed a change over the - you've been there many decades.

Mr. VARNUS: Well, I've been here - this is my - as a - it's - I came down to NIH as a director 17 years ago. I spent about a little over six years here. Then I remained involved. But of course, things change as the White House changes occupants. And of course, at the moment we have a cheerleader for science in the White House, and that is very helpful.

I do sense - one of the things I am concerned about is the support that Congress is providing for the NIH. Many of our great champions - Mark Hatfield, John Porter, Ted Kennedy - have either left the Congress or, in some cases, unfortunately, died. Senator Specter will be leaving at the end of the year. So these are big blows to us because we depend on our champions. And as you - as everyone sees, Congress is a highly partisan place at the moment. Many of us in NIH go and talk to members of Congress to try to show them that NIH is something we should all be supporting.

Disease knows no political boundaries. And in the past, my previous incarnation here as director of the NIH, one of the things I took most pleasure in is the fact that Republicans and Democrats were more or less equally supportive, and I hope that will be the same in this administration.

FLATOW: Oh, you're right. One would think that everybody is for good health, you know?

Mr. VARNUS: And, you know, it's very clear that, you know, debates over healthcare reform aside, everybody acknowledges that if we're going to make advances in the way we treat disease and prevent it, we need to invest in research. And we're having a discussion here today about the economic benefits of research. And one thing that's very clear is that the expenditures the country makes on healthcare dramatically dwarf the very small amount of money that's invested in medical research. So the NIH spends $30 billion, but the health care budget is the trillions. And that investment seems to me to be eminently good sense, and I hope that Congress and the administration view it that way as well.

FLATOW: Mm-hmm. Well, as you say, a lot of the friends are gone and you have to now wait for, hopefully, to influence new people.

Mr. VARNUS: Well, not wait. I think we're going to be out there talking to members of Congress. That's one of my plans, is to go down and explain to them what we do.

FLATOW: Mm-hmm. Have them come up to Bethesda.

Mr. VARNUS: Indeed. That's always been very useful.

FLATOW: It is right at the tip of the Beltway.

Mr. VARNUS: We're just barely inside.

(Soundbite of laughter)

FLATOW: Somebody can get a perspective that that's outside, almost outside the Beltway. I want to thank you for taking time to be with us today. And as always, you've always been a friend of SCIENCE FRIDAY and have been ready, willing and eager to talk to the public, and I thank you very much...

Mr. VARMUS: Indeed, thank you, Ira, for giving me a platform.

FLATOW: You're welcome.

Mr. VARMUS: Appreciate it. Keep up the good work.

FLATOW: Thank you. Harold Varmus, who is the newly sworn in head of National Cancer Institute and author of "The Art and Politics of Science."

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