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Varmus Counsels Successor, Eyes Future in Final Remarks to Press

By Rich McManus

(Second of two parts)

On the Front Page...

Just before his 73-month tenure as NIH director ended last month, Dr. Harold Varmus spoke at length about the future of NIH, gave advice to his successor, and discussed gene therapy, campus security and other matters. Even though he takes over as head of Memorial Sloan-Kettering Cancer Center in New York City on Feb. 1, don't be surprised if you bump into him on campus; he advised NIH'ers in an all-hands email on his last official day at work that he is still a special volunteer at NCI and remains in charge of the Varmus Lab in Bldg. 49 until that laboratory migrates to MSKCC in April.


So the Varmus Lab is moving with you?

The whole intention of calling my lab the Varmus Lab was that...(having set it up) I would take it down when I left. Several of the folks in my lab are going to be moving, and there are some new people who are already coming to the new lab. I hope by April we're operational up there. I'm looking forward to it.

Is there anyone else from NIH that you're taking with you?

There are plenty of people I wish I could take with me, but nobody I plan to take.

At a ceremony in 1996, at the midpoint of his tenure, NIH director Dr. Harold Varmus participated in a mock swearing-in ceremony at which his wife Connie (l) held a copy of Dickensí Great Expectations for him to swear upon. At his farewell ceremony last month, Varmus joked that he was glad the book wasnít Dickensí Bleak House.
What's piquing your interest in lab work these days?

The major...themes at the moment are developing better models for studying human cancer in the mouse. This has been an interest of mine for some years, although 10 years ago the technology seemed much more limited because mostly what we were doing was making transgenics and crossing transgenics with knockouts. But now there are new levels of flexibility — conditional genes that can be turned on and off...We've been working with gliomas, and now we're working on breast...We're seeing an increasing interest in developing therapeutics and even preventive strategies that are based on an actual knowledge of the genes that are abnormal in human cancers. These kinds of interventions are going to be less toxic and more effective, I hope...One of the things that's been deeply lacking in cancer research is a profound understanding of metastasis...The other part of my lab works on the way in which a set of very important growth factors...called wnt proteins send a signal to the nucleus to change the way in which cells behave...

You've spoken of the importance of keeping NIH funding momentum going forward. Please comment.

This is a very important issue. I think the leadership at NIH and the scientific community need to think about a transition back to a less steep growing curve. That, in my view, should happen some time in the range of 4-5 years after this brisk scale-up. And I use that measure because that's the average length of grants...I don't believe, in the midst of this robust economic environment we're in, with incredible opportunities in research, that we should go back to a purely inflationary rate of increase. My own gut feeling is that we should anticipate moving from sequential 15 percent increases over...5 years, to an era in which there are more modest increases but still above the inflationary rate...I think some modeling needs to be done...about what's happening at our major academic health centers, to get a sense of what the right rate of growth might be over the longer haul...

Are you pleased with the new version of the Sharing Biomedical Research Resources guidelines?

In that arena, we're not trying to lay down strict law. What we're trying to do is move the scientific community into a more generous, and ultimately more beneficial mode of behavior...we're trying to create an environment in which there is at least a movement in the direction of greater sharing...We're not trying to get ourselves into a role of expecting that situations are simple enough that we can anticipate everything that might happen. We're not expecting to be policemen on every corner...

What about your greatest disappointment as NIH director — is there an issue that has just been intransigent?

There have been some. One of the things that I've been working on, but perhaps couldn't expect to see tremendous changes in (during) the course of this short period is increasing the number of investigators from minority backgrounds in science. Now, this is going to take time, but I haven't seen major changes. Perhaps you couldn't in just 6 years...

What advice would you give your successor?

One is to continue the budget fight, second is to take great advantage of the strong advocacy that NIH has. I've been saying to both the scientific advocacy groups and the patient and disease-oriented advocacy groups that they need to work better with each other. NIH, I think, has done a good job working with its scientist constituencies; I think it's done an improved job, and at many of the institutes a splendid job, of working with patient advocates...I think I was slow to appreciate the importance of developing a kind of nonsectarian council of advocacy individuals of the sort that I finally have now with my Council of Public Representatives...I've found my interactions with those folks tremendously useful...I've also tried to remind people of the equity issues...the need to be conscious of health disparities and the need to pay attention to the more general application (of scientific advances), especially as our science becomes heavily technological and potentially very expensive...

Are you going to miss the opportunity as NIH director to address international issues like malaria and tuberculosis, as you've done in the past? Are you going to miss that bully pulpit?

I would miss it if I lost it, but I don't think I'm going to lose it because there are a number of things that I plan to do when I'm no longer at the NIH that I think will still be important. I've been asked to help WHO with their thinking about these issues. I expect still to employ the bully pulpit even though I may be less obviously called; I think I'll still be asked my opinions about things. I plan to continue my interest in malaria — I'm actually traveling to India in a couple of months to look at scientific activities there. I hope to be still involved in the development of PubMed Central, which is an important issue in developing international health because one of the great virtues of developing an electronic publishing network for biomedical research is support of science in the developing world.

You have advice for the reorganization of NIH — would you want to be on any task force that would deal with that?

Sure. But my own view is that the kinds of changes that are being contemplated are, first of all, reasonably radical. Secondly, they may fly in the face of the interests of advocacy groups and Congress, both of which have been extremely generous to the NIH. I feel that it would be wrong for it to appear that NIH was driving these changes. NIH is a publicly created institution, and it's been successful for that reason. Any sense that NIH is trying to take matters into its own hands and make it more convenient for itself I think could produce some waves of disgruntlement that would serve the institution very poorly. My own advice is that at some point, enlightened members of Congress and the administration who understand some of the difficulties that result from having tremendous proliferation of institutes and centers should consider asking the National Academy (of Sciences) to set up a commission to think, over the course of a couple of years, about the future of the NIH...Our budget is soon going to pass the $20 billion mark, we have 25 institutes and centers, and there will be more because things never seem to go backwards. As I noted when I first came here, when you create new institutes, it's like the spring is coming out of a little peanut brittle can and you never stuff things back in. You can't deal with this issue piecemeal — it's very apparent to me that the small institutes simply can't operate with the kinds of efficiencies and carry out some of the tasks the bigger institutes can carry out...I can see an NIH in which there are, basically, five or six organizations or clusters of organizations that work very effectively together and make the whole process of running the NIH one that is much more effective.

You've talked about how costly medicine is becoming, and the average person's increasing inability to afford some high-tech treatments. Do you have a solution?

I think there are a number of solutions. One is that what's high-tech today will become much lower costs over $1,000 to have your BRCA1 gene sequenced but that's going to change, there's no doubt about it. The technological developments that are occurring through the use of DNA chips and other new methods are going to drive those costs down to the point where I would not be surprised if it cost no more than $50 or $100 20 years from now to have genomic assessment as you go off to college, or at some point in your relative youth, to get a pretty wide cut on what your risks are of disease in later life. Some of the therapeutics that are coming down the pike are now, and for the foreseeable future, going to be expensive...We have a problem in the country in that there's nothing people place higher value on than healthy life, but I'm concerned about two things — the number we allocate to health becoming just too great to sustain even for people who are relatively well to do, but more troubling is the idea that we're going to cut a very significant portion of our population out of the benefits of certain kinds of approaches to health that were paid for by public money and ought to be publicly accessible.

Was there anything you couldn't do as NIH director that you will now be able to do?

Sure...I will answer to fewer bosses — that's good. My schedule will be more my own. My interactions with the private sector can be more flexible. I frankly enjoyed my interactions with the pharmaceutical and biotechnology activities before I came here, not because of the financial compensation...but because that's a very vibrant part of the world...Right now my intention is not to be involved in any companies in any obvious way...What I'm most energized about is the idea of just having a good deal more liberty, and being in a less closely watched situation...

What advice do you have for NIH on gene therapy as the appropriation hearings approach?

...There's no doubt that public opinion would be shifted by announcements of real cures...I think we're going to see some of those — the recent announcement of what seems to be an effective treatment for a small number of patients with hemophilia B is a definite encouragement — and I think we'll hear about other things in the not too distant future. The public will have to be reminded that adenovirus vectors — very much in the news because of Jesse Gelsinger's death — are not, in the minds of most of us, the prime candidates for gene delivery, compared to adeno-associated viruses, or lentiviruses or other retroviruses. My sense is that the public will respond favorably to the steps that we at NIH and our colleagues at the FDA have taken in response to some unfortunate events that happened in the University of Pennsylvania study.

Does society do an adequate job of appreciating and weighing the ethical dimensions of emerging topics such as embryo research? Commissions are always lamenting that "science is ahead of society."

Science will always be ahead of society — that's the nature of the beast. But I think we do a much better job (nowadays). Think back to 25 years ago when the recombinant DNA issue was laid on the table. People were pretty shocked. No one had really thought much about ethical issues in biology. They had thought about the atomic bomb as an ethical issue that science had engendered. But the notion that complicated biology could be the fodder for dinnertime conversation was a big surprise to most people. Since then we've had lots of other discussion — in vitro fertilization, heart/lung transplant, cloning, embryo research. I would say, in general, we're much better at this...

If you were around for another 6 years as NIH director, how would you improve the intramural program?

Part of it is location. I'm concerned about having significant components of our program in less than ideal space, and too far removed from centers of activity. I think we're going to have tremendous flowering of the program as a result of the new Clinical Center and Bldg. 50, but there are still outlying groups that worry me. The campus up in Bayview (Baltimore) is going to become more self-sufficient; as we bring the three components that are up there together, they'll have a nucleus of activity. I am worried that we do have pieces, and sometimes almost all of certain other programs not well organized. One of the most promising things that I've strongly supported and have helped to get under way is the concept of having a Neuroscience Center on campus, with some new and renovated buildings in the Bldg. 35-36 complex that will help to bridge some of the chasms that currently exist between some of the institutes, even though they do very similar things.

The FY 2000 budget mentions a need for increased security on the Bethesda campus. Can you say why that's important?

I haven't found this to be an enormous problem. This campus is reasonably safe, but there are people who are worried that it is not optimally safe. I have always been less than enthused about the idea of putting chain fences around the campus. I do think we can improve card access to buildings, ensure that loading docks are really locked at the end of the day. I think the campus has responded quite well to the idea of wearing identity cards...One of the things that we simply cannot prevent entirely are events that occur between angry people. We've been pretty lucky so far. I think that the changes that would result from chainlinking our campus and requiring metal detectors at every entry point just don't have the payoff — they change the atmosphere very dramatically.

Is that what someone is actually proposing — something that dramatic?

The idea of having a fence around the campus has been proposed many times in the past. There's lots of interest in that. And there are many federal institutions that do look that way. I think they isolate themselves quite quickly, and the atmosphere on campus is changed dramatically. It doesn't feel like an academic institution. We're not in the center of a high-crime district here — we ought to remember that. We're in a reasonably safe neighborhood, we don't put chain links around stores and post creates an air of secrecy and will actually create other kinds of problems for us if we're perceived as being a high-security institution that's doing secret work and excluding the public.

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