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Volume 84 Issue 27 | pp. 12-17 | Profile
Issue Date: July 3, 2006

Cover Story

Elias A. Zerhouni

NIH director has steered agency through congressional inquiries and paltry budget increases with bold actions to position agency for future
Department: Government & Policy | Collection: Entrepreneurs
Credit: PHOTO BY PETER CUTTS
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Credit: PHOTO BY PETER CUTTS

When Elias A. Zerhouni was growing up in Algeria in the 1950s, the idea of running a multi-billion-dollar U.S. research institution never crossed his mind. But a few decades later, after immigrating to the U.S. and becoming a leader in the fields of radiology and medicine, that is exactly what he is doing.

Zerhouni, 55, became the 15th director of the National Institutes of Health in May 2002 and quickly began to make his mark on the agency. Within a year-and-a-half, he introduced a multiyear, $2 billion strategic plan called the NIH Roadmap for Medical Research, a major new effort to address medical research problems that aren't confined to a single institute or center (C&EN, Oct. 6, 2003, page 10).

Not long after the rollout of the NIH Roadmap, Zerhouni found himself in the middle of congressional inquiries. The first involved allegations of inappropriate interactions between NIH senior scientists and drug and biotech companies (C&EN, Dec. 15, 2003, page 10). At about that time, Zerhouni was called before Congress to explain why the agency was supporting grants dealing with human sexuality studies that some members of Congress saw as improper spending of taxpayer funds (C&EN, Feb. 9, 2004, page 23).

Zerhouni also was under pressure from Congress, as well as from various patient and scientific groups, to develop a policy for making journal articles resulting from NIH-funded research freely available to the public in a timely fashion (C&EN, July 26, 2004, page 12).

Adding to these stormy times at NIH was a dramatic slowdown in the growth of the agency's budget, which, since the completion in 2003 of the congressional commitment to double the budget over five years, has not kept pace with inflation. This tight budget environment has also fueled some outspoken concerns about the NIH Roadmap, which some scientists worry is taking funds away from research project grants.

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But throughout all of this, Zerhouni has remained a strong leader and has met each challenge head on. His ability to remain resolute even under considerable pressure is due in large part to lessons he learned while growing up.

Born in Nedroma, Algeria, Zerhouni is part of a large family. He grew up with seven brothers, who, he says, helped him become tough as nails. He credits his parents for teaching him strong morals and his father, who was a math teacher, for teaching him math and physics. He also learned during these years to be self-reliant and to take risks.

These experiences have served Zerhouni well throughout his career. For example, during his years at the University of Algiers School of Medicine, he chose to specialize in radiology at a time when the field was not considered a top area in which to practice. Although he was questioned by colleagues for his choice, Zerhouni has become a widely respected leader in medical imaging. He has won awards for advances in both computerized axial tomography and magnetic resonance imaging (MRI). He's a member of the National Academies' Institute of Medicine and consulted for the World Health Organization and to the White House under President Ronald Reagan.

Soon after earning his medical degree in 1975, Zerhouni left Algeria to do his residency at Johns Hopkins University, in Baltimore. Here again, his penchant for taking risks and his ability to be self-reliant served him well. For instance, Zerhouni was raised speaking French and Arabic, and he studied German in school. But to come to the U.S., he knew he had to learn English. Not a man for formal classes, he taught himself English with the help of some friends and passed his English equivalency test on his first try.

Coming to the U.S. also meant leaving family and friends behind. As there was not a large Algerian community in the U.S., Zerhouni had to work hard to develop a new circle of friends and colleagues. Building this network further strengthened his self-reliance, he says.

Since arriving in the U.S., Zerhouni has thrived. He completed his residency at Johns Hopkins and took a position as an assistant professor there in 1979. He spent a few years in the department of radiology at Eastern Virginia Medical School and its affiliated DePaul Hospital before returning to Johns Hopkins in 1988. He eventually would lead the school's MRI division, chair the radiology department, and serve as dean for research at Johns Hopkins.

Zerhouni remains proud of his Algerian heritage, although being of this heritage has not always been easy for him. As an Arab American and a Muslim, he has faced prejudice throughout his career. These experiences have given him an appreciation for diversity and shown him firsthand the importance of judging people on the basis of their merits.

Zerhouni recently sat down with C&EN Associate Editor Susan R. Morrissey to discuss how the slow budget growth is affecting programs at NIH and how he is dealing with the various issues that have faced the agency during his tenure.

C&EN: What's it like to run a $28 billion agency as diverse as NIH?

Credit: PHOTO BY PETER CUTTS
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Credit: PHOTO BY PETER CUTTS

Zerhouni: It depends on what day of the week you ask. It is the most complex job I've ever done. It requires you to think on your feet very quickly and to be a good communicator. As a rank-and-file scientist, I never appreciated the importance of really looking at multiple sides of a question before talking about it publicly. I think I've matured a lot in this job.

Along with the challenge of the job also comes a unique view of what really makes research go—from grassroots politics to Washington politics to institutional politics—and, most important, what is really happening across fields of science and among scientists.

C&EN: One of the difficulties of the job has to be ensuring that all of NIH's institutes and centers are properly funded. Since the goal of doubling the budget was reached in 2003, funding increases have dropped below the inflation rate. How are you handling this budget slowdown?

Zerhouni: It's interesting. People are interpreting this in different ways. I tend to be very analytical and quantitative, a bit like a chemist. So what I've done since I came to NIH is to collect data to truly forecast what was going to happen after the doubling and take some steps to deal with it.

However, if we keep going below inflation for too long a time, then we are really going to damage the partnership that we have established between the federal government and institutions that have invested in young talent and new buildings. This historic partnership is what's made us the strongest country in terms of life sciences, and it needs to be maintained. This is the point that I've made in my testimony to Congress recently. I've been very aggressive this year, almost too aggressive I'm told, but I want to convince Congress that the return on investment at NIH has been stupendous. That cannot be overstated.

After all, one of the reasons for the tension right now with the budget is that universities and scientists have responded to the call to join the scientific enterprise, to help fight disease, to help understand health and health care. Now we are pulling the rug out from under them. That's the point I'm trying to convey to everyone: This relationship between the private sector and the government is a long-term policy issue that cannot be underestimated.

C&EN: Unlike NIH's budget request for 2007, significant gains are slated for several physical science agencies—specifically, the National Science Foundation, the Department of Energy, and the National Institute of Standards & Technology. With resources being very limited, do you think the focus on physical science research is the best use of funds?

Zerhouni: I'm a very strong supporter of the interaction between physical and biological sciences. In fact, we cannot see success in what we do without strong physical sciences. Our investment in the physical sciences is something that we consider very important, whether it be computer sciences or chemistry or engineering. NIH funds almost $2 billion of research a year in physical sciences—almost 40 or 50% of the total funding in this area. And people don't realize, but for several areas of chemistry we've become the number one funder of basic chemical research.

It's obviously a lot easier to say, "We've invested in biological sciences; now we'll invest in physical sciences." But my view is that I don't think you should rob Peter to pay Paul. I've always said you need a balanced investment across all fields of science. It is especially important to include physical sciences now that we have built huge capacity in the biological sciences that includes the physical sciences.

C&EN: Perhaps the biggest criticism from the biomedical community (including the chemistry community) involves the NIH Roadmap for Medical Research. Have you been surprised that it has drawn such controversy?

Zerhouni: Yes, very surprised, because it comes three years after the fact. We rolled out the NIH Roadmap in 2003. I'm amazed actually at the amount of misinformation about it. The criticisms are either uninformed or worse. But that's what happens when you want to provoke change. Perhaps what the critics would have liked is a silent director who doesn't do anything new or who doesn't change anything.

Despite all the controversy, I still haven't heard a scientific criticism of the NIH Roadmap. Instead, most of the criticism is about the perception that money is being taken away from research project grants, which is not true.

One interesting result of the NIH Roadmap development process came when we surveyed scientists to find out what the stumbling blocks for biological sciences were. The number one stumbling block turned out to be synthetic organic chemistry. I was shocked because I thought the limiting factor was computational biology. So the NIH Roadmap really changed my view of the importance of chemistry and chemical engineering.

C&EN: Why do you feel the Roadmap is important to NIH?

Zerhouni: I'm very proud of what NIH does. It is terrific to have a decentralized structure of institutes. But by what mechanism are you going to ensure that NIH continues to be bold and continues to experiment with leading-edge issues? The NIH Roadmap provides such a mechanism. It's a strategic framework for not one initiative, but for a process by which NIH examines itself, serves emerging areas of science, and incubates research concepts through pilot programs. For an agency as large as NIH not to have this experimental space is ridiculous.

I'm actually amazed that people don't realize the importance of the NIH Roadmap. In our conversations with Congress in 2004 and 2005, if it wasn't for the Roadmap, we would not have gotten any funding increases. The Roadmap allowed us to show Congress and the Administration that we had a strategy for continued growth after the budget doubling.

C&EN: So the NIH Roadmap is important for the future of biomedical research?

Zerhouni: Yes. I don't think we should just continue to do business as usual, especially now that scientific disciplines are converging at the fundamental level. To me, it's important to understand that molecular recognition issues, molecular engineering issues, and single-molecule imaging are the frontiers. You need to do this research in the context of very complex molecular networks. If you don't do that, you're not really addressing anything. Biological data have to go from what I call qualitative and observational data to quantitative and spatially and temporally resolved data collected on a high-throughput scale.

In this experimental space, for example, we are piloting the Director's Pioneer Awards as a new way of doing grant review. We are testing the multiple principal investigator (PI) approach as a new way of seeing if we can solve complex scientific problems more efficiently. We have also developed PubChem as a database to store biological data of small molecules.

C&EN: One of the criticisms of the NIH Roadmap has been that it comes at a cost to research program grants, specifically research project grants (R01s). What is the true cost of the Roadmap?

Zerhouni: People think it's a giant initiative. For example, in fiscal 2005, the Roadmap budget was $237 million—that's less than 1% of NIH's total 2005 budget. It supported 345 grants at 133 institutions in 33 states. So, even if we eliminated the Roadmap tomorrow, it wouldn't solve difficulties with getting grants because the demand for grants has doubled.

C&EN: Is this doubling in grant demands the reason for the drop in success rates for NIH research program grants—which, for example, for new R01s has fallen from nearly 25% in 2003 to less than 18% in 2005—or is there another cause?

Zerhouni: What people don't appreciate is that the increase in demand for grants has been greater in the two years after the budget doubling than during the total five years of the doubling. Why? It's because we've expanded our research capacity. Institutions have partnered with us, and they built buildings and recruited people. They've done what we wanted them to do.

One principle I tell directors is that we need to manage the real cause of the pain, not what people think the cause is. The real cause is demand and supply between grant applications and the number of available grants. Actually, if you look at the drop in success rate between 2003 and 2006, 85% of the drop is not due to smaller budgets; it's due to increased demand. Only 15% of the drop is due to the limited budget. In fact, in 2007, even if we have a completely flat budget, I plan to increase by 3% the number of competing grants to help keep pace with the growing demand.

C&EN: In addition to success rates falling, the average age of faculty when they get their first NIH research project grant has been climbing; it's now over 40 years. You are concerned about helping young faculty get started, so does the growing age of researchers receiving their first R01 grants concern you?

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Credit: PHOTO BY PETER CUTTS
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Credit: PHOTO BY PETER CUTTS

Zerhouni: I was very fortunate because I started my research when I was 30 years old and had my first independent grant when I was 36 or 37. If I hadn't gotten that at that time, I would have probably left science. My experience told me that if we didn't really address the rising age of first-time competitive grant investigators, we would have a problem. In fact, at one of the first meetings of my advisory committee, I made this point and told them we need to be concerned about it.

People think the problem is that NIH is funding older people, not younger people. But the cause is not NIH. Demographic forces are at play here. You can see it in the statistics. People came into science in the 1960s and 1970s in great numbers, and they are staying much longer than expected. That means that the exit number of established scientists is not equal to the entrance number of new scientists.

When I met Marshall Nirenberg, who won the Nobel Prize for Physiology or Medicine in 1968 for discovering the key to deciphering the genetic code and is a researcher at NIH, I went over his history. He started his independent research when he was 27 or 28 years old. At the time, he was unknown. Nobody thought that he had a prayer to crack the code, but he did it four or five years later. He got the Nobel when he was in his mid-to-late 30s. The punch line is that today he'd get his Nobel Prize before he'd get his first R01.

C&EN: This concern for retaining young faculty members is an important issue for you, isn't it?

Zerhouni: Yes, how not to lose new investigators is my main concern. This is why I am pushing the Pathway to Independence Awards, which is an innovative initiative that allows us to grant R01-equivalent funding earlier in the career path of postdocs. We're going to reserve 150 to 200 grants a year for postdocs who are finishing their training in any discipline. We're going to guarantee them three years of initial funding at the R01 level if they get a tenure-track position. This program would put the institutions and NIH in partnership to retain as many new investigators as we can.

People don't appreciate how bold this is. I'm amazed that no one is saying that this is really revolutionary, because most institutions don't allow postdocs to apply for R01 grants. So I'm opening up the door to a younger cohort and saying: "If you have a bright idea, and you're that good, compete in your own right. If you get it, more power to you." This concept of engaging and encouraging risk-taking is something I've espoused with as much energy as I can.

C&EN: Scientists have also raised concern about the balance of basic and applied research at NIH. Should NIH focus solely on basic biomedical research? What do you believe is the proper balance?

Zerhouni: People are always going to want more basic research. But unfortunately, that's a naive view that I myself used to hold. The reason NIH is so appealing to the public is because we strive to balance the portfolios with 60% basic, 25% translational, and 15% clinical research.

So I believe NIH should have a balanced portfolio, with the largest part of it being investigator-initiated basic research. Industry has an inverse structure whereby they invest little in basic, more in translational, and much more in clinical applications. But because NIH has some translational and clinical research capacity, we can work in research areas that industry doesn't pick up.

If you look at research on "orphan" diseases, for example, should NIH not support these areas of research because they are beyond basic research? Industry isn't going to pick them up. So if we stop working in these areas, no one will address them, and that would be irresponsible. I think the balance of NIH's research portfolio should stay where it is.

C&EN: You noted that one of the NIH Roadmap initiatives deals with multidisciplinary research. What barriers do you see to doing this cross-discipline, team-based research, and what is NIH doing to overcome these barriers?

Zerhouni: I worry about what I call sclerosis: crystallization of silos and barriers that are artificially created between disciplines. Disciplines are created as a means of doing science, and then they become an end in themselves.

This is why in the NIH Roadmap, we said: "Let's do an experiment. Let's try new models of interacting and not dictate how scientists should interact." Some people have interpreted this as if we're going to be the engineers putting teams together. That's shortsighted. What we want to occur is the natural self-assembly of bright people who want to work with each other.

We're piloting this so-called multiple PI approach, which, by the way, is also revolutionary and very bold because the single-PI concept has always been the mainstay. I'm sure I'm going to take a lot of arrows for it, but I don't mind.

When you look historically into why there has been a single PI, it was really an administrative thing. It started in an era when our information systems were not what they are today, and we wanted to allocate accountability to one person. In those days, science was pretty much done in small groups—one professor and a few assistants.

But today, a growing number of scientific problems are really multidisciplinary. For example, systems biology is a challenge. How are all of these systems integrated? How do you really keep track of a thousand genes expressed over multiple observational periods against millions of compounds? How do you do that research with the old model? You don't.

Credit: PHOTO BY PETER CUTTS
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Credit: PHOTO BY PETER CUTTS

C&EN: During your tenure as the director of NIH, you have faced a number of congressional inquiries. One of those inquiries focused on the validity of peer-reviewed grants. Do you worry that Congress is overstepping its authority by trying to reverse peer-reviewed decisions to fund grants on subjects it believes are inappropriate?

Zerhouni: I have to say, this issue has loomed big in my four years at NIH. I have had 150 letters from members of Congress criticizing NIH for funding such projects as HIV transmission and other sexuality issues. This basically was an attack on the peer review system.

I have been fighting tooth and nail to keep Congress from harming the peer review system. In a letter to Congress, I forcefully defended the agency on every one of the questioned grants. This was an unprecedented action because never before has an NIH director written a letter to the entire Congress on issues of science and public health.

Because of that letter to Congress in 2004, the peer review issue is dead in the water. That is an amazing result because in the political atmosphere of Washington, it could have been a very potent issue. If it were not for the way we forcefully defended the agency, right now you'd see a collapse of peer review; you would see legislative language, so-called earmarks, telling us what research we should and should not support. We prevented the politicization of NIH, but nobody gives us any credit for that.

C&EN: Another issue that has been a focus of congressional inquiries is conflict of interest. It's been more than a year since the initial conflict-of-interest rules, which banned outside consulting activities of NIH scientists with drug and biotech companies, were put in place. After the tweaking of these rules last August, are they working as you had hoped?

Zerhouni: In many ways, this issue of conflict of interest was probably more dangerous than any other issue because it risked destroying the trust of Congress in the agency and it risked destroying the public's trust in the agency.

There was a lot of cleanup to do. Some people interpreted my approach as being too harsh and shortsighted. I disagree. I think that in the end we achieved a balanced set of rules. It was the right way to do it, I'm convinced, because I see the dangers of not being clear and transparent about this.

To me, the mark of success in dealing with the conflict-of-interest issue is that Congress no longer raises the issue with us. Congress feels that we've been more clear, forthcoming, and balanced and that we have done what we needed to do. We've maybe been more proactive than people would have liked. For the scientists who lost consulting jobs or were forced to sell stock, I empathize with them. But we have built good safeguards and good ways of getting awards, getting trips, and getting lecture fees that don't conflict with the mission of NIH.

C&EN: Do you feel interactions between government scientists and industry are important?

Zerhouni: I think there is great merit to industry relationships with government and academic scientists. But in the context of the federal agencies, we must be more careful than universities because we can't have private gain from official duty. But more important, there is a need for government scientists to be involved with industry. I support that, but it has to be done transparently. It cannot be done within a culture of permissiveness; that has led us to trouble.

But here's the issue. There are two kinds of interactions. There is the delicious apple whereby the interaction is designed to create a public good: new knowledge, a new treatment, a new understanding, a new technology, or basically something that wasn't there before. We need to find a way to continue to encourage that interaction, even for government scientists. Eventually we will get there, if we have a good system of management.

And then there are interactions that I call toxic oranges, where what you see is scientists really doing marketing and promotional activities. Here you see scientists really not being transparent about their inherent conflict in something that relates to human experimentation or clinical trials.

C&EN: Was it difficult to enact these safeguards?

Zerhouni: It was a no-win situation for me as director. If you want to be popular with your scientists by not taking strong actions to manage outside activities, then you destroy the institution. If you want to be protective of the institution and put in safeguards, then you become unpopular with your scientists.

But this is where leadership comes in. First and foremost is the integrity of our institution and the ability for us to have scientists whom no one can question. Anytime NIH is considered a so-so institution with questionable integrity, we've lost the game.

C&EN: An issue that is gaining congressional interest is public access. NIH has had a policy in place since May of last year that asks researchers it supports to voluntarily post resulting journal articles on PubMed Central as soon as possible, but no longer than one year after publication. Legislation has been introduced in the Senate that would make public access mandatory after six months. Is it possible to find a balance that will satisfy supporters who want tax-payer-funded research available for free as quickly as possible and publishers who worry that making publications free too quickly will hurt their ability to recoup the costs of publishing the journals?

Zerhouni: Absolutely, there's a need to find that sweet spot. What I've found with this issue is paralysis. You have the zealots on one side who are hammering for open access right away. And then on the other side, you have the zealots who say that open access is absolutely not right. In the middle is the taxpayers' interest.

I'm not driven by what the popular thing to do is; I'm driven by what's right. I believe that, number one, NIH needs a database of the research it funds so that it can have accountability and the ability to analyze its own portfolio. Our scientists must also have access to our portfolio of research so they can see what we've funded. So there's an internal need and an external need for accountability.

It is also important that at some point the public, which pays for 99.5% of this research, is not prevented from having access to it. But this access should not be done at the expense and viability of peer-reviewed scientific publishing—whether it be nonprofit or for profit.

I believe very strongly that a happy medium can be found. But if the happy medium causes a loss of viability in being able to produce good articles and good journals, it won't work.

C&EN: Another issue that drew congressional action in the form of appropriation report language was PubChem, a small-molecule database that is part of the NIH Roadmap. The controversy, however, was really between NIH and the American Chemical Society (which publishes C&EN). ACS was concerned that PubChem duplicates ACS's Chemical Abstracts Services Registry. Where does that stand?

Zerhouni: I have to commend your society and give credit where credit is due. Our interactions relative to PubChem started on a bad note and ended on a good note, which showed leadership. We do not want to harm in any way the ability of ACS to continue successfully doing what it is doing. And that's why we said we will not overlap content to the extent possible. We are committed to that, and we're watching it carefully.

C&EN: What have you learned during your tenure about how scientists interact with government officials and the public? What can scientists do to help their cause?

Zerhouni: First, scientists have to communicate much better and much more with their local public. My concern is if you look at polls, 85% of the public supports medical research. However, when I became director, only 6% of the public knew about NIH. I'm proud to say that now almost 12% know about us. So, there's been some improvement, but it's just not enough.

Institutions and their scientists are not communicating effectively and making apparent the connection between what they are doing and what the public sees as beneficial. Unless we do this and better demonstrate the value of the investment at NIH, it's going to be very difficult for us to go forward and to sustain our research. I need help from everybody to educate the public in that regard because I can't do it alone.

C&EN: Do you miss academic medicine? Do you want to return to academics once your tenure at NIH is complete?

Zerhouni: I do. I miss my research. It's really painful not to have the time to do it. These are stormy times. I've spent an enormous amount of time—more time than I thought I would have to—in managing NIH, the relationships within the Administration, and the relationships with Congress.

I have great ideas that I never really had a chance to explore. The more time passes, the more I feel attracted to go back.

 
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