Rousing the Sleeping Leviathan, NCI's New Leader Gets Down to Business

by Celia Hooper and Rebecca Kolberg

What's huge, innately magnificent, and could use a strong shove to get back on course? The man on the street might answer, "A beached whale." Around NIH, the response might very well be, "NCI." In an interview with The NIH Catalyst shortly after being sworn in as NCI's new director, Richard Klausner made it clear that his leadership team will waste no time in flexing its collective muscle to push NCI's once proud intramural research program off the shoals and into exciting new waters of scientific discovery. For starters, the 43-year-old cell biologist, who has spent most of his past 16 years at NICHD, has already streamlined NCI's division structure and established an advisory board of intramural scientists. He's also injecting some new blood into the scientific community with the recruitment of a noted molecular epidemiologist, Alfred Knudson of the Fox Chase Cancer Center in Philadelphia, and two world-class yeast geneticists from Seattle, Leland Hartwell of the University of Washington and Steve Friend of the Fred Hutchinson Cancer Research Center.

What was your perception of NCI before you came here?

Klausner: I saw it as a somewhat troubled institute that had a very top-down leadership style. It tended to be an institution that ran by fiat and fear - fear of problems, fear of crises. It's no secret that it's not been a place where people have uniformly loved to work ... . That does not mean that there haven't been programs and individuals who have thrived and done well. My own feeling is that it is an intramural program that does not have the feel of the type of the intramural program that I want to be associated with-but I think that it will.

Given your accomplishments as a bench researcher and the current administrative turmoil at NCI, why did you decide to take the job as institute director?

Klausner: I really decided to do it both out of a sense of the challenge that it represented and, frankly, out of a sense of responsibility as a member of the community ... . I felt if asked, I would be willing to serve. I think Harold [Varmus] has provided a fantastic model to scientists for the importance of service and the essential perspective that scientists bring to scientific leadership.

What do you think is the toughest task currently confronting NIH?

Klausner: There's no question that the toughest task is the challenge of these incredible diseases [cancers] that present such a daunting problem. Cancer will be the number one killer of Americans by the end of this century. ... We need to find ways [both to] maintain the spectacular progress in basic science [but], as importantly, to somehow bridge the huge gap between this spectacular progress and the very poor progress that we have made in the cure and prevention of most cancers over the past 25 to 30 years.

What do you see as the greatest strengths and weaknesses of NCI's intramural program?

Klausner: I think the greatest strength of NCI's intramural program is the greatest strength of the NIH intramural program, that is, the available resources and the institutional opportunities to be a real community of scholars, the freedom to conceptualize research programs with very few constraints ... . Such freedom places upon us a compelling demand to respond by making sure ... that this is not only a great place to be, but that this is a place where great science is done.

I think it is an institution that needs a variety of both structural and cultural changes so that it functions as a true meritocracy and that it has real mechanisms [in place] to select for and reward excellence. It needs a culture in which the independent development of the careers of people can thrive. And it must become an institution where all aspects of its administrative function are structured to serve the scientist and not the other way around.

What do you see as the most fruitful and interesting avenues for basic and clinical cancer research at the institute right now?

Klausner: The major areas that I think the NCI needs to think about strengthening relate to cancer genetics and to the many fundamental aspects of the biology of the cell that we now know are directly related to cancer, including genetic and genomic instability, the relationship between genetic instability and the cell cycle, and the relationship between genetic instability and the fundamental decision between life and death that cells are capable of making. ... I expect that we will be developing a very vigorous and active cancer genetics program in terms of basic, clinical, and epidemiological studies. I think the possibility of really integrating clinical, basic and population-based studies here provides many exciting opportunities. And this is reflected in the new division structure, which basically divides the intramural program into three areas based upon the three fundamental mechanisms of approaching the acquisition of knowledge and information-basic, clinical, and population-based. I also see great opportunities in immunology. That's one of the areas in which NCI has always been strong. I want to continue to see that supported and enhanced. ... I hope we can help stimulate a real renaissance in the development of a modern tumor immunology in much the same way that there's been a renaissance in the immunology of autoimmune disease.

Richard Klausner

What steps do you plan to take to enhance the interactions between basic and clinical science?

Klausner: It is abundantly clear from the exciting advances in human cancer biology over the past few years that many of them have come out of the ability of the basic science to inform us about the disease, and, importantly, of the disease to inform the basic science. ... For example, we are going to want to develop molecular pathology, molecular diagnostics, and cancer genetics and integrate such development among these three divisions-basic, clinical and population-based. The three division directors, George Vande Woude, Philip Pizzo, and Joseph Fraumeni, are deep in conversation about how we actually set up working structures so that the level of communication within this institute skyrockets. And there's room for skyrocketing.

The Bishop-Calabresi report made dozens of recommendations on ways of improving NCI's intramural program, and we'd like to get your reactions on a few of them. How do you feel about the recommendation to reduce the current percentage of the budget devoted to intramural research?

Klausner: I don't know what the exact percentage is. It's actually not a number that's easy to get at ... . While I don't know exactly the right number, I do actually think that it's probably too high ... and we will be developing a plan that, over time, brings that percentage down.

What do you think about the suggestion to establish an open grants competition?

Klausner: Well, in the "Klausner" report [issued in 1992 by the Task Force on the Intramural Research Program, which was headed by Klausner], we talked about the NIH creating special fellowships that people would compete for. I really like that idea.

What about appointing lab and branch chiefs and scientific directors for renewable five-year terms?

Klausner: I see pros and cons of that. I'm perfectly happy if in a lab there's a group of people who would like to rotate being lab chief. But the reality is that we have certain expectations of lab chiefs, and those expectations will be reviewed. And if a person is doing spectacularly as a lab chief and wants to remain as lab chief, I don't really see how enforcing retirement helps anyone.

What does the future hold for NCI's Frederick Cancer Research Center?

Klausner: We are actively discussing Frederick. What I can say is that although there have been concerns about closing Frederick down, I see the Frederick campus as a fantastic resource for the NIH and the NCI. I think it would be very short-sighted to close it down, so we will not be doing that.

Will NCI be doing less AIDS research?

Klausner: I have no commitment to doing less AIDS [research], but I think we will be calling less things AIDS. ... We are looking at the programs very carefully to make sure that we are accurately describing the research we do ... . But as to whether the cancer institute does AIDS research [or other] noncancer research, one of the lessons of the past 20 years is the hubris of deciding what exactly is cancer research and what isn't.

What about drug-development activities at NCI?

Klausner: We will be reviewing the Developmental Therapeutics Program. I want the NCI to remain committed to developmental therapeutics, but I think it's a good time to look at that program. However, I'm not singling out that program. Under this new administration, we are going to have real reviews-conceptual reviews, not critique reviews pointing out what's wrong-of all of the NCI's programs, not just developmental therapeutics.

How can intramural researchers help you shape the "new" NCI?

Klausner: Part of the new governance structure is something called an IAB, an intramural advisory board that Claude Klee will chair. This will have about 15 members, intramural scientists from all the intramural divisions and people at all different levels from tenure track to lab chief. This body will be very, very important in reviewing the functioning of the intramural program on an ongoing basis. The first thing they are going to need to do is review the rules, the regulations, the administrative processes, and the communications pathways. This body will provide a filter mechanism so that decisions about the functions of the intramural program will be discussed by active intramural scientists. ... At the same time this committee will set its own agenda to interact with NCI leadership and those responsible for the administrative structures in order to constantly look at how we can improve things and to address the ongoing and changing needs of the scientists. ... This will be a very well- publicized, very accessible group. It will serve as a line of communication between all intramural scientists and the division and institute leadership, without worrying about going through chains of command.

What impact will the changes in NCI's intramural program have on intramural research at other institutes?

Klausner: We are very interested in developing things that I believe will be of real interest to all intramural programs, such as a good, user-friendly information-management system, so that we can, to the fullest extent possible, delegate authorities to the laboratories and out of separate administrative branches.

Now that we've spent a lot of time discussing NCI's future, what about the future of your own scientific career?

Klausner: I'm going to keep my lab. I love being an intramural scientist at NICHD ... and I hope they will continue to love having me there. I'm absolutely committed to maintaining my lab and maintaining myself as an active scientist.

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