© Oxford University Press 2006.
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John Niederhuber: Thinking Like a Director
When the announcement came on Aug. 15 that he would be appointed the 13th director of the National Cancer Institute, John Niederhuber, M.D. was not surprised. One could say he's been heading toward this moment from the earliest part of his career.
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Niederhuber had become acting director of the Institute less than 3 months earlier, after Andrew C. von Eschenbach, M.D., departed for the U.S. Food and Drug Administration. But he has been a visible part of the cancer establishment for decades. He was chair of the National Cancer Advisory Board, a comprehensive cancer center director, and a member of dozens of committees involved in NCI work, including the recent Committee to Restructure the National Cancer Clinical Trials Enterprise. For the past year, he's been a deputy director at NCI.
"I've been coming here to NCI for more years than I'd like to admit in one capacity or another," says the 68-year-old surgeon. "I've known personally all the directors over the years—Vince DeVita, Sam Broder, Rick Klausner. I suppose at times I thought, ‘Gee, wouldn't that be a neat opportunity.’ But I didn't think about it seriously. I never expected the opportunity."
Now that he has the chance, he is setting priorities based on a wide-ranging view of the National Cancer Program, with a focus on patients' needs because of his wife's experience with breast cancer. Tracey Niederhuber died of the disease in December 2001.
Although many people are reserving judgment—several scientists contacted wouldn't comment for this article—Niederhuber has fans who think he makes a good choice to be NCI director.
"John has a depth and breadth of knowledge and experience as a physician scientist," says Martin Abeloff, a longtime friend and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. "And I think he's a man who sets very high scientific and ethical standards."
Not Perturbed by Budget Woes
Niederhuber has taken over NCI's leadership at a time when biomedical researchers are facing harsh realities now that the so-called doubling of the NIH budget is complete; NCI actually received an 80% increase between 1998 and 2003. The subsequent flat budgets, which haven't even kept up with inflation, have been a blow that has alarms sounding throughout the research community.
At this June's National Cancer Advisory Board meeting, Niederhuber cast the hardship in a positive light. "Absolutely, this is a stress time, a problem time. But we're better off as a research community in 2006 than we were in 1998. We have more people working in science, more people funded. We're not worse off, but we'd have liked to have been better off. If not for Iraq and Katrina, we wouldn't be having quite this painful discussion today."
| Niederhuber has held several other roles in the cancer community:
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In a later conversation, he took the longer view. "Throughout my career, the federal budget has gone up and down. But we can no longer as a country afford to fund biomedical research in that fashion." He suggests the country should commit to a budget that grows at least with inflation to create stability and to attract young people to biomedical research.
In the meantime, he says, the research community is going to have to make tough choices, though he's not ready to be specific. "There are going to be things we simply aren't going to be able to do and some people won't be happy. But, in the end, it's about trying to make a difference, to lessen the burden of cancer."
A Career in Oncology
Born in Steubenville, Ohio, a small coal mining town, Niederhuber started relatively close to home, attending Bethany College in West Virginia with a dual major in chemistry and mathematics and then Ohio State University's medical school. After 2 years in the Army, stationed at the U.S. Biological Laboratory in Fort Detrick, Md., Niederhuber began a residency at the University of Michigan. He says his early training there, and later his position as an assistant professor of surgery and assistant professor of microbiology "was one of the most important things that happened for me."
"When I took on administrative jobs later on, I always felt I had a much better appreciation of what got both basic and clinical scientists up in the morning and got them to work. I had an understanding of the faculty working in anatomy and microbiology and an appreciation of those who worked in medicine or psychiatry."
His emphasis as a surgeon has been on gastrointestinal cancer, hepatobiliary cancer, and breast cancer. He was the first to demonstrate the feasibility of a totally implantable vascular access device.
After almost 14 years at Michigan, he joined the Johns Hopkins University School of Medicine from 1987 to 1991 and then moved to Stanford University as chief of surgery, a post he vacated in 1995 because of what he calls "leadership changes at the institution." He remained at Stanford until 1997, when he became director of the University of Wisconsin Comprehensive Cancer Center. At Wisconsin, he melded the McArdle Laboratory, a basic science cancer center, and the UW Comprehensive Cancer Center into one institution, but he left this post as well at the end of his wife's illness.
Niederhuber was hired by von Eschenbach in September 2005 as NCI's deputy director for translational and clinical sciences. He has set up a lab on campus to study tissue stem cells as the origin of cancer as well as the relationship of tumor cells and their microenvironment.
Time To Reassess
Even with his cancer background and NCI links, the job won't be easy. Robert A. Weinberg, Ph.D., of the Whitehead Institute for Biomedical Research in Cambridge, Mass., has been openly critical of NIH's current funding policies, specifically targeting NCI "grand projects." He says NIH is diverting larger proportions of funds to research collaboratives "to the detriment of small, investigator-initiated projects," and this "threatens to drive a whole generation of young people away from careers in basic biomedical research," he wrote in a stinging commentary in the July 14 issue of Cell.
| Niederhuber's Spending Priorities:
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Weinberg notes that over the past generation, Ph.D.s are waiting 7 years longer to obtain their first R01 award from NIH than they did a generation ago. The average recipient age of first R01 award, which supports a discrete, usually investigator-initiated, project, increased from 34.2 to 41.7 years.
Niederhuber says he's worried about young faculty too, but the intent was never to fund 100% of applications. "If NIH can be responsible for seeing that one-third of faculty in our medical schools and universities working in areas of biomedical research can be successful, we're probably doing a good job."
We're not there yet. According to NCI figures, the R01 success rate for fiscal year 2006 is estimated to be 18%, down from 23.7% in fiscal year 2002.
Niederhuber dismisses claims that the big programs launched under von Eschenbach are eating up too much of the pie. "I hear the criticisms about the big programs," he says, but the highly visible projects in biospecimens, nanotechnology, proteomics, the Cancer Genome Atlas, and CaBIG account for about 1.5% of NCI's $4.8 billion budget.
And he doesn't apologize for them. "The National Cancer Institute has always been the leader in biomedical research and in the development of enabling technologies," he says. "I think it's really imperative for us to carefully and wisely invest in opportunities for collaborative science that bring scientists from different disciplines together to work on cancer in ways I don't think we would work on otherwise. We're creating enabling technologies of the future that, in fact, will be necessary for our individual R01 investigators to do the kind of work they'll need to do in the years to come."
Besides, he adds, "I don't think there's a loser in that group of [big programs] we've invested in. Each one has leveraged tremendously in the extramural community in terms of private resources and philanthropy."
The one topic Niederhuber seems to avoid is the 2015 challenge goal—to end suffering and death due to cancer—that became a target of criticism for von Eschenbach. Niederhuber has no interest in saying anything negative about the man who hired him, calling him an individual of "tremendous vision and energy." But he sees his colleagues' point.
"I think a lot of scientists—both basic and clinical—felt that putting a date on something as complicated as cancer was just not terribly realistic. They had problems with it. But that doesn't mean it was a bad thing."
Tom Kean, incoming executive director of C-Change (formerly the National Dialogue on Cancer), says he met with Niederhuber the day after the White House announcement, congratulating him on the appointment. Kean says he sees four priorities for the NCI: 1) assuring an adequate budget for NCI's work; 2) maintaining a healthy balance among the many NCI research priorities—from prevention to survivorship and end of life and everything in between; 3) seeing that NCI research results are effectively applied; and 4) addressing cancer disparities, "which are still a very real issue for us as a country."
Niederhuber, who is on the board of C-Change, lists priorities that are a bit more research focused (see box p. 1267). They include the focus of his NIH lab's work—stem cell biology and the tumor microenvironment—as well as developing new drugs, examining clinical trial design, leading development of a technology infrastructure, and bringing "science to the patient" through community cancer centers' outreach research.
Access is a big issue for Niederhuber. "We are going to find ourselves very quickly in a situation where we have made tremendous scientific advances in our ability to get at this disease. But I don't think we have in any way the means to deliver this to the people where they live." He predicts that access will become a greater determinant of mortality from cancer than anything else.
Much of his view on access is informed by his wife's battle with breast cancer; she died at age 50 (their son, Matthew, will be a freshman at Ohio's Kenyon College this fall). As he talks about her experience, the emotions are not far from the surface.
"I know what it's like to sit in an exam room and wonder if somebody forgot you," he says. "When you experience these things, it changes how you function as a physician. I told Tracey I would try to make a difference for patients with cancer. I would try to work on some of these access issues. She went through so many treatments because she was not a quitter, by any means." The only way she could get one experimental treatment, he says, was to travel from home and family in Wisconsin to the NIH Clinical Center. She did it, "and everyone at NCI was wonderful to her. But we both talked about the fact that, in this age, we ought to be able to do it better—to bring our science to where people live."
The patient perspective colors his views on clinical trials recruitment as well. He recalls his wife, during a conversation about her participation in a clinical trial, asking, "Why would I want to participate in that? You're asking me to participate in three toxic drugs versus four toxic drugs. Don't you have anything better?" Recalling patient interest in the early trials of angiogenesis inhibitors, he says, "If we have exciting things to offer, we won't have trouble accruing to trials."
Niederhuber seems eager to face the challenges ahead, including those brought on by these tight financial times. "It's probably appropriate for big organizations every now and then to go through a time when they need to really look carefully at what they're doing and to make tough decisions about how to be leaner and more effective and more appropriate with their investments," he says.
"I am very honored and very grateful to have this opportunity to serve the American people," he says. "And obviously, it's a huge capstone on my career, having spent my whole life on cancer."
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