A bold vision

When Dr. Elias Zerhouni became the Director of the NIH in 2002, he filled a position that had been vacant since December 1999. Within four months, he had visited nearly half of the 27 institutes and centers, and by June 2003, he had put together an action plan called the ‘road map’ to promote cross-institutional collaboration. Julia Puppe spoke with the 15th Director of the NIH about breaking down bureaucratic barriers and creating a bold vision.

Born in Nedroma, Algeria, Dr. Elias Zerhouni came to the US in 1975, when he was 24. With a medical degree from the University of Algiers School of Medicine, but little knowledge of English and limited resources to afford his stay, he did not have his future mapped out. He certainly did not intend to become the Director of the National Institutes of Health (NIH).

“I had a background in maths, physics and engineering,” Zerhouni recalls. One of his earliest jobs was with a construction laboratory, where he tested the strength and durability of concrete and discovered that concrete castings were cracking because the builders weren’t using enough fine-grain sand. “Then, through medical school, I was seeking a way to combine physics and engineering with biology and medicine, and I decided to become a radiologist, primarily a researcher in imaging.”

In addition, he taught himself English to be able to come to the US, where, three years after his arrival, he became chief resident in radiology at the Johns Hopkins University School of Medicine. One year on, in 1979, he was made an assistant professor.

Between 1981 and 1985, Zerhouni was in the department of radiology at Eastern Virginia Medical School and its affiliated DePaul Hospital. He returned to Johns Hopkins as an associate professor in 1985. In 1988, he was appointed Director of the MRI division. He was promoted to full professor of radiology in 1992 and of biomedical engineering in 1995. In 1996, he was named chairman of the radiology department. In May 2002, President George W. Bush named Zerhouni to serve as the 15th Director of the NIH.

What prepared him for the job? Absolutely nothing, he answers. “I wasn’t intending to have this job; you can’t prepare for it. It’s your life experience that makes you able or not to do these kinds of jobs. I remember the first day I was called to consider the position, and I thought it was a mistaken call, that somebody had given the wrong number because traditionally, NIH directors come from biology. They don’t come from quantitative or imaging sciences in general. These are new sciences that are really interdisciplinary.

“Typically you get someone who’s been a microbiologist, or an internal medicine doctor. But what was needed at the NIH was a new look and a different approach to how science was organized, and how to stimulate science in a large organization. I had done that at Hopkins, so I guess that’s what qualified me for it.”

His first day in the office, Zerhouni describes, was a “whirlwind” experience and very confusing. A lot of people, he recalls, were looking forward to a new director. Staff were very welcoming, though puzzled at the same time. “They were thinking ‘Who is this guy?’ There was a period of a few weeks of getting to know each other.”

A world wonder
Government, Zerhouni explains, is a very different organization, and the NIH even more so. “NIH is extraordinary. It’s probably the best government agency anywhere in the world. People talk about the seven wonders of the world, like the pyramids and the Taj Mahal; I think if we had a listing of the seven best institutions in the world, the NIH would probably be in that list.”

The reason, he says, is the incredible amount of knowledge accumulated in one organization, with academic standards of excellence and pursuit of new knowledge. “This is a hybrid that I don’t think exists anywhere. You have a combination of academic freedom and a sort of hierarchical, top-down government structure. What drives this is the search for something unpredictable, while at the same time you are accountable to Congress and, of course, the public. My first day was marked by complexity and the realization that I was dealing with a completely different beast, if you will.”

The “beast” comprises of 27 research institutes and centers, as well as 18,000 employees. The NIH’s institutes have a long tradition of science advances, with 122 Nobel Prize winners, both from people trained at or funded by the NIH. But how does Zerhouni keep on top of the research that is going on anywhere within the NIH? “There is a tremendous interaction between the institutes in the scientific world, so that frankly, if you want to know anything about any topic, you can pick up the phone and within five minutes find someone at NIH who knows the person who’s doing the research anywhere in the world.”

In addition, Zerhouni says, the most important advances that have occurred in the past three months are regularly reported via an internal communication system. And there are also workshops to review any emerging field of science. But it’s hard work, Zerhouni admits. “When organizations grow, they become more complex. You don’t realize this but complexity prevents communication. In other words, people just stay in their silos, they interact as much because the things have gotten too big. My action has been to streamline the way NIH is governed, so I created the steering committee. I streamlined the number of committees that you had to go through, and I also tried to introduce a philosophy of communication and collaboration across institutes.”

Under Zerhouni, the NIH practice of allowing each of the 27 centers to have a say in all major matters came to an end. He eliminated some 60 committees to establish a top-level steering committee of only 11 members, and appointed six working groups with rotating memberships.

His biggest focus has been on breaking down bureaucratic barriers. The natural tendency of any organization is to become bureaucratic and rule-bound, Zerhouni says. “This is more so in an organization where you have government rules. I’ve been trying to break that down, and second, to encourage institutes and the sciences there to take a chance on new investigators, bring new blood to the scientific enterprise. I’ve created programs to encourage new and early-career investigators. And I’ve promoted the idea of risk-taking. I have a very simple saying: ‘The greatest risk in science is to stop taking risks’. I keep repeating this.”

The road map
To break down bureaucratic barriers, Zerhouni launched a program called the road map. The idea, he elaborates, was to bring the NIH’s employees together. “I said, ‘Let’s get together and let’s identify what are the major roadblocks, and what are the major opportunities?’ Throughout that discussion, it became obvious that complex science requires multiple disciplines to come together. You need to have a physicist work with a biologist, work with an engineer or a computer scientist, but our grant mechanism only allows one principal investigator.”

This rule, which favored individual institutions rather than cross-institutional collaboration, had been in effect for over 45 years. Under Zerhouni, it took the NIH two years to change it. “We changed the law in the federal government to allow so called multi-principal investigator projects. It sounds simple, but it has tremendous impact in that now, if you have a project and you want to come to NIH to work with someone in physics at Berkeley and someone in biology at Harvard, you can do it – you can do it transparently.”

The NIH road map, which was introduced in 2003, has been organized around three major priorities: new pathways to discovery, which contains 12 initiatives, including several to create molecular libraries; research teams of the future, which includes nine initiatives focused on high-risk research, interdisciplinary research and public-private partnerships; and reengineering clinical research, which includes seven initiatives to facilitate clinical studies.

Resources
Not everyone appreciated Zerhouni’s reform efforts. With the flatlining of the NIH budget after 2003, critics, amongst them local groups, patients organizations and scientists unions, voiced their concerns that the project would take away from their own valuable resources. “This was probably 90 percent of the criticism because no one had a scientific reason to criticize it. They were just saying, ‘Is this the right time? Should we invest in this sort of project when we are suffering in terms of our regular grant program?’ It was the typical conflict between the here and now and the future – the uncertain future of science. My view is that there is no wrong time to do the right thing.”

Zerhouni was also criticized for what many believed to be a top-down way of doing science that was controlled by the director rather than initiated be the investigator. “The criticism has gone by the wayside because in practice, it’s really a bottom-up exercise, not a top-down exercise. We don’t decide what the topics are, but we certainly want to take the lead in making sure that it happens.”

A good example, Zerhouni says, is nanotechnology. When he became the NIH Director in 2002, $30 million out of the NIH’s $26 billion budget was spent on nanotechnology. “Everyone said this was insufficient because nanotechnology was clearly going to have a huge impact on medicine. So when you start a program like the road map, some people will say that you are taking money away from them. But as leaders, we had to make these early, risky investments, and we did. Today, this effort has really paid off. We have companies that are now marketing products that came out of this effort for diagnostic purposes in cancer. There’s even one company that just had its FDA approval.”

Achievements
One of the biggest achievements of the NIH road map, Zerhouni believes, is that it has created a space where scientists can take risks and incubate new ideas, even in times of constrained budgets. “It has liberated directors and scientists to think outside of the box and try new things that they wouldn’t otherwise try at that stage. Number two, the road map forces conversation and consultations across many fields of science to see where the gaps are and where the opportunities are.

Thirdly, Zerhouni continues to say, it has created new, experimental ways of doing science. “For example, the Pioneer Award. This is something many people opposed. It’s the idea of blue-sky science. Typically, in federal agencies people are risk adverse. They want to be sure that a project is going to work. That isn’t always a good thing. We’ve also launched a program called the New Innovator Awards for young early-career people, to encourage them to take a flyer, take a real chance outside of the beaten path.

Another example is the Clinical and Translational Science Initiative, designed to spur the transformation of clinical and translational research in the US so that new treatments can be developed more efficiently and delivered more quickly to patients. “If you ask people in the academic centers, they’ll tell you that this has probably been the most game-changing initiative NIH has taken in years. We pretty much phased out a program that was 60 years old and changed it into a program that is really adapted to modern translational science.”

It is great, Zerhouni adds, to have fundamental discoveries in the lab but they need to be translated into real health benefits. “It’s a challenge. All of these discoveries are going to be studied in the human population, but we need to scale that up. And we need to understand it better. When you look at a population, for example, like diabetes, we now know that diabetes is not just one type of disease. There are probably 15, 20 subtypes of diabetes at the molecular level. Those studies need to be done in animal models, but also in human populations. And that’s the challenge right now.”

Personalized medicine, Zerhouni explains, means that over the next 20 years, we are going see the first reclassification of diseases that affect people based on their molecular pathway, not on their clinical manifestation. The NIH is encouraging scientists to do exactly that through the clinical and translational science centers that have been created around the country.

Budget
Research, Zerhouni is convinced, is the basis of virtually every improvement in health and medicine. Advances in science and technology, however, cost money. On December 26, 2007, President Bush signed off an NIH appropriation of $29.229 billion, an increase of $329 million (1.1 percent) over FY 2007. The final appropriation also includes a $196 million increase from 2007 to 2008 in the transfer from NIH to the Global HIV/AIDS Fund, which results in a program level for NIH of $28.942 billion, an increase of $133 million (0.46 percent) over FY 2007.

“The most optimistic proposal for the budget was $1.1 billion over 2007, which would have covered inflation,” says Zerhouni, adding: “Anytime the NIH budget goes below inflation, there’s a real pain in managing that. You have to make difficult choices in terms of priority. I was hoping that Congress and the administration would get together and give us at least the inflation number. Barring that, what we have to do is readjust our programs and really fund the top priorities that every institute has.”

In 2008, one of Zerhouni’s top priorities is to encourage and support new investigators early in their career. “If we don’t encourage young people to stay in the sciences now, what we’ll face is a downstream situation, where all of a sudden you don’t have the scientists with their programs and their new ideas.”

His second priority, he continues to say, is to ensure that the NIH does not become risk adverse, and that the institution keeps funding emerging areas as well as traditional areas of science.

Vision
Leading a complex organization, Zerhouni is convinced, requires a bold vision that is communicated to everyone in the institution. “If you don’t do that, people don’t know where you stand. Here’s where I stand: the life sciences are going to be the key to progress in this century. Sciences are going to do well because health care costs are going to be unsustainable – they already are – and you need to transform medicine.

“People are very focused on how we deliver health services in medicine. I’m more focused on what it is we deliver. My point is that we need to transform health from a curative type of medicine to a preemptive one. We need to do this in the next 20 years by being more predictive and more personalized, and changing the paradigm. We need to transform what we do from intervening after the disease strikes the patient to intervening before the disease strikes the patient.”

The NIH, Zerhouni emphasizes, is an investment in the future across all sciences, including, for example, physical sciences. “They are going to be key in the progress in medicine and health. I’m an example of that. I’m not a biological scientist. Originally, I became a biomedical engineer. If I hadn’t brought mathematics and physics to imaging, I don’t think imaging would have done as well. We need to continue to encourage that.”

While Zerhouni is committed to educating Congress about the importance of the NIH’s vision, there are still countervailing forces. In the FY 2009 President’s Budget, NIH proposes to increase support for research centers to $2,963 million, a 0.7% increase above the FY 2008 Enacted Level. This request level will continue to provide program growth for the Clinical and Translational Science Awards.

In the past 40 years, NIH funded research has successfully reduced the mortality and morbidity of once acute and lethal conditions by finding ways to improve treatment. Based on the progress and discoveries made through NIH-supported research just in the last few years, NIH can foresee its vision of a future and transformative era of medicine and health care that is increasingly predictive, personalized and preemptive. A vision that, without a doubt, is worth all the support it can possibly get.

Dr. Elias A. Zerhouni, who is the Director of the NIH, leads the nation’s medical research agency and oversees the NIH’s 27 institutes and centers with more than 18,000 employees and a fiscal year 2007 budget of $29.2 billion. A world renowned leader in the field of radiology and medicine, he has spent his career providing clinical, scientific and administrative leadership.

In his own words
EHM. What do you consider to be the NIH’s main achievements historically?
EZ. Historically, the NIH has been the incubator of the generation of scientists that you now see making progress in the various fields they engage in. Since the 1940s and ‘50s, the NIH has been their training ground and an enabling ground. It would be very hard to imagine all the progress that has been made without it.

The second merit is that NIH, unlike any other government agency in the world, is driven by its peer review process, which is independent, quality-based peer review. Every time I go overseas, I get asked this question about NIH: ‘How did you manage to keep your peer review independent of politics and earmarks?’ The answer is simple: it’s inscribed in law, and that we don’t want to change.

Another point is that it’s investigator-initiated. 75 percent of our funding goes to projects that were generated by the investigators themselves. That freedom is probably the most important factor that has made US science so powerful, in addition to the amount of resources.

EHM. How have you helped shape the organization more recently?
EZ. More recently, the accomplishments of NIH include the war against AIDS. If you really think about the ability to develop drugs against HIV/AIDS, it traces directly back to NIH. The drug was developed at the National Cancer Institute. The science behind retroviral biology was developed at the NIH. The first trials were done at the NIH. The collaboration with industry to accelerate drug development was stimulated, supported and directed by NIH. That’s a 15-year achievement.

Another achievement is the push for human genomics – the completion of the human genome and the understanding of how to utilize genomic technologies, how to promote them, so that you can understand the biology of disease. It’s happening right in front of our eyes. When I became director, there was one gene that was known to be of influence in diabetes. This year, I have received reports of relevant genes almost every week for hundreds of diseases. We now have 12 genes that are relevant for diabetes. This is an enormous turnaround because 10 years ago, when you tried to figure out a theory of disease for any one of the many diseases that we know, you were hard pressed to find one molecular pathway or target that you knew had something to do with it.

Today it’s the opposite. Every day we find that there is a molecular connection between a particular disease process through these genomic findings. For example last week, we had a finding on autism, chromosome 7 and chromosome 16. This would not have been possible five years ago, period. There has been a real explosion in genomics, and NIH has really led the world there.

Budget

• The NIH invests over $29 billion annually in medical research for the American people.
• More than 80% of the NIH’s funding is awarded through almost 50,000 competitive grants to more than 325,000 researchers at over 3000 universities, medical schools, and other research institutions in every state and around the world.
• About 10% of the NIH’s budget supports projects conducted by nearly 6000 scientists in its own laboratories, most of which are on the NIH campus in Bethesda, Maryland.