Francis S. Collins

When Francis S. Collins stepped down as director of the National Human Genome Research Institute in 2008, he had no idea that one year later he would be tapped to become the next director of its parent agency, the National Institutes of Health.

Best known for his work in genetics and leading a decadelong government initiative to sequence the complete human genome, Collins got his start in science as a chemist. After receiving a Ph.D. in physical chemistry from Yale University, he went to medical school at the University of North Carolina, Chapel Hill.

Collins, 60, first joined NIH in 1993. He left the agency 15 years later to write a book about personalized medicine and to work with the Obama presidential campaign. After a one-year hiatus, he returned to NIH as director and now faces a host of challenges, including implementing programs authorized by the health care reform bill and preventing a stimulus-funding hangover.

Sworn in as the 16th director of NIH on Aug. 17, 2009, Collins oversees 27 institutes and centers and a budget of more than $30 billion per year. He returned to NIH while the agency was handing out an extra $10 billion in grant money, thanks to the American Recovery & Reinvestment Act of 2009, also known as the recovery act or simply the stimulus package. He now worries about what will happen to the success rates of research grant applications when that stimulus money runs out later this year.

Looking to the future, Collins sees opportunities for NIH in translational science—the science that bridges the gap between basic and clinical research. He’s boosting collaborations with other federal agencies, such as the Food & Drug Administration. And he’s confident that academic researchers funded by NIH can collaborate with industry without financial conflicts of interest.

In mid-April, on the day before his 60th birthday, Collins sat down with C&EN Associate Editor Britt E. Erickson to talk about some of his plans for NIH. Despite sore fingers from practicing guitar in preparation for his birthday party, Collins spiritedly discussed some of the biggest challenges and opportunities for biomedical research.

The last time C&EN talked with you, you were about to leave NIH. Did you ever dream that you would come back to NIH as director?

I had no idea. I didn’t really have a plan when I left in 2008. I figured 15 years running the genome project and the genome institute was a pretty good run. But I was getting restless, thinking about what the next chapter might be. I wanted a chance to write a book and get involved in politics by helping with the Obama presidential science committee and ultimately the Obama transition team. These are things that you are not really able to do as a government employee. I did not know where that might lead, but here we are.

How does running a $30 billion multi-institute agency compare with leading just one institute?

The breadth and depth of science you need to have your mind around is really phenomenal, especially now with the pace of discovery going forward at such a breathtaking rate. Previously, I had to know everything there was to know about the genome—how we could understand its function and what its role might be in health and disease. But now I need to also know about things like immunology, neuroscience, and behavioral research—the broad spectrum of what NIH does. That is actually exhilarating, a chance to expand my horizons.

Are you on target to allocate NIH’s share of the recovery act money by the end of September?

It is essentially done. We still have a few requests for applications out on the street for the second year of the recovery act dollars, but we put most of the effort into funding projects during that first year of the two-year allocation window. Getting the money out of the door as quickly as we could manage it, while still sticking to our guns as far as rigorous peer review, was critical. There is only a small amount left that we have not allocated.

What will happen to success rates of grant applications post-stimulus funding?

This is what wakes me up in the middle of the night. NIH had a flat budget from 2003 to 2008, so the biomedical research community was really struggling. Success rates for grant applicants were falling, and inflation was eating away at our buying power. The recovery act was a wonderful break in what had been a real drought as far as the ability to encourage research to go forward in new and innovative ways. And everybody jumped in, in a big way, to take advantage of that opportunity. One example of this is the Challenge Grants. We thought we might get 3,000 or 4,000 applications; we got more than 20,000. Clearly there is a great, pent-up scientific opportunity and lots of energy out there.

We are looking closely to see what happens to our grant application pool that is now beginning to appear for fiscal 2011. Will we see a very large number of applications, or will it drift back to the usual level? We don’t know yet. That will make a big difference in terms of how much of a crunch there is going to be in getting funded.

Are you satisfied with the proposed fiscal 2011 budget for NIH?

The President, in the midst of a serious economic crisis and with a determination to hold overall discretionary funding flat, was willing to make science a very high priority and to allocate an extra $1 billion for NIH. I think that is a wonderfully encouraging sign that this Administration is really serious about the support of science. But that funding boost, despite its generosity, is a 3.2% increase, which is exactly what the inflation index for biomedical research is predicted to be in 2011. So essentially, the budget would be flat in terms of buying power.

Why should the government increase its investment in biomedical research?

I think one can make the case that biomedical research is one of the best investments the government makes in terms of both what it does to enhance human health and, frankly, the way that it stimulates the economy. Every dollar that NIH gives out in a grant returns over $2.00 in investments in terms of economic goods and services that are produced within just one year. There aren’t many things that feed back that quickly into the economy. Also, every grant that NIH gives creates seven high-quality, high-paying jobs that sustain American leadership in science.

How can NIH help scientists better communicate the importance of their work to encourage more investment?

Effective communication is critical. I think most people don’t even know what NIH stands for. The public generally knows what NASA is all about, but NIH, the major supporter of the research that brings hope for new advances in the treatment of cancer, diabetes, and heart disease, has very little name recognition. One of the things that I think we need to do a better job of in the scientific community is getting the word out about what we do and why it matters—and why science is both interesting and challenging.

What is the status of the NIH Roadmap for Medical Research?

The NIH Roadmap has been updated quite extensively since it was launched in 2003. It was the brainchild of my predecessor, Elias Zerhouni, who concluded that some crosscutting opportunities were having a hard time finding a home at NIH because they didn’t fit into the portfolio of one of the 27 institutes and centers. These research projects were broader than any one institute’s portfolio and were also, in some cases, high risk. The NIH Roadmap was initiated as a means of providing funds for such projects and was made permanent through the NIH Reauthorization Act of 2006. It is now referred to as the Common Fund.

What projects are currently supported by the Common Fund?

A major one is the Molecular Libraries program—a real marriage of chemistry and biology. It provides academic biomedical researchers with access to chemical libraries of hundreds of thousands of compounds that they can screen for activity against their favorite target. This has really empowered a whole new approach to therapeutics by putting into the hands of researchers at universities and institutes the kind of technology that previously existed almost entirely in the private sector.

The Common Fund also supports grant awards that specifically require innovation in the application—such as the Pioneer Awards, the New Innovator Awards, and the Transformative R01s. One-third of the budget for the Common Fund goes to those three programs, which we will probably continue for quite some time because they are unearthing a lot of outside-the-box ideas.

Will you keep the balance of NIH’s research portfolio at the current 60% basic research, 25% translational science, and 15% clinical research?

Those numbers depend on definitions that are not entirely consistent. But I think the percentages are unlikely to change dramatically in the course of the next few years. NIH does have as its mission this entire spectrum from very basic research to clinical trials. I do think, however, that this is a moment where the translational opportunities are particularly compelling. While I don’t expect to see a major shift in the proportions, I do think the translational part of our portfolio has some real opportunities for rapid progress.

How can NIH boost its translational science portfolio?

One thing that is stimulating translational science is the ability of academic researchers to get more involved in the small-molecule business to develop promising compounds that are a starting point toward something that ultimately might be appropriate for a clinical trial. We have a program called Therapeutics for Rare & Neglected Diseases that offers the opportunity for compounds that look particularly promising to move into the next phase of preclinical testing and animal toxicology.

The health care reform bill authorizes a new program called Cures Acceleration Network to help speed up new drugs for rare and neglected diseases. What role will NIH have in CAN?

The Cures Acceleration Network, which is authorized but not yet appropriated, would provide an integrated and very rapidly moving DARPA-like effort to stimulate therapeutic development, not just for rare diseases but for all diseases that are currently not getting the attention they deserve in the private sector. NIH will administer the grants for the program.

What is the impact of the health care reform bill’s giving NIH a broader role in translational science?

We are trying to figure out exactly how to organize this translational effort. We are very excited about that opportunity because the time is right to invest in those kinds of translational programs. While I think this is not going to dramatically shift the emphasis as far as where the dollars go across our portfolio, I think the translational part will be particularly interesting to watch in the next few years.

NIH has teamed up with FDA to invest in regulatory science. What questions are researchers hoping to answer through that collaboration?

There are some great projects being proposed by researchers, which should enable FDA to be in a better position to figure out how to deal with some of the most recent developments in therapeutics. Some of the questions being asked include: How do you review clinical trials for very rare diseases when you can’t find hundreds of patients? How do you deal with a therapeutic that needs to be connected with a diagnostic to decide whether it is right for a particular patient with a particular disease? And how do you deal with cell-based therapies? Induced pluripotent stem cells are looking increasingly exciting for therapeutic applications, but there are complex questions about how to assess their safety and efficacy.

With respect to genetic tests that accompany drugs, what can science do to speed up their adoption? For example, a genetic test could help doctors decide how much of the blood thinner warfarin to give a patient, but few doctors are using such a test.

First, you want to have rigorous data to show that having the genotype of an individual really does provide benefit in setting the right dose of the drug. Warfarin is a very dangerous drug. Overdose happens all too frequently and can even be fatal. Clearly, there are two genes that are well worked out that play a role in determining what the right dose is for an individual, and there have been trials suggesting that if you incorporate that genotype information as well as age and gender, which are also important predictors, you can do a better job of getting that dose right. Right now, FDA has put a notice on warfarin that physicians should be aware of the value of genotyping, but it is not required.

Aside from cost, why isn’t there more widespread use of genetic tests that predict drug response?

It is partly the cost, but I think the major barrier is logistics. Right now it is very clunky to try to get that genotyping result in time to influence the decision. You have to, for example, figure out where to send a blood sample. You have to try to get the result back within 48 hours. It is just not well set up.

What will it take to get such tests more widely used?

What is ultimately going to solve this is having the cost of a complete genome sequence for each of us fall below $1,000. At that point, it will become very attractive to put complete sequences into the medical record, with appropriate privacy protections. With the click of a mouse, the physician can figure out whether this is the right dose of the right drug at the right time.

NIH received $400 million in stimulus funds for comparative effectiveness research (CER) to compare how different treatments work. What is NIH’s experience in this area?

We have been doing CER, although we didn’t call it that, for many years. A prime example is the Diabetes Prevention Program, which taught us how best to help susceptible people avoid diabetes. Another program looked at drugs for psychosis, showing that the older ones are just as good as the newer ones. We’ve spent a lot of money and a lot of time on those trials, and they have been very revealing, oftentimes giving surprising results about which alternative works best. Certainly with recovery act dollars we are being asked to do more of this.

What effect will health care reform have on CER?

The health care reform bill has a whole component about CER, setting up a new nonprofit organization, the Patient-Centered Outcomes Research Institute. NIH will sit on its board. That group will be charged with defining CER priorities. It will have a budget, and it will figure out what organization is in the best position to approach those priorities. Oftentimes that will be NIH; other times it may be NIH’s sister agency, the Agency for Healthcare Research & Quality; and other times it may be a third party.

NIH has been under pressure to manage conflicts of interest by extramural grantees. What steps are being taken to do this?

There have been troubling examples of extramural grantees who were receiving large sums of money from pharmaceutical companies or other partners without disclosing the support. This lack of disclosure can cast doubt on whether their resulting publications were fully objective. We cannot take the chance of having the credibility and the integrity of the biomedical research effort damaged by these circumstances.

As a result, NIH is taking this issue quite seriously within the limits of our legal authorities. We are in the process of issuing more strict guidelines to grantee institutions about what kinds of processes they should be following to review potential conflicts by NIH grantees and what they should do about reporting those to us if they are discovered. We hope to have this new plan finalized and in place by late summer.

Should academics stop collaborating with pharmaceutical companies because of concerns about conflict of interest?

Absolutely not. Collaborations are necessary and important. Partnerships are critical for progress to be made, but they need to be done in a way where there is no financial conflict that might cast doubt on the integrity of the conclusions. I think that kind of collaboration is entirely feasible. We have gone through that process in our intramural program and developed a number of models that work quite well in terms of those collaborations being quite successful but without the risks of financial impropriety.

Aside from budget concerns and conflict-of-interest problems, what is the most pressing issue for NIH today?

I think it is the ability to identify all of the resources to push forward phenomenal, unprecedented, historic scientific opportunities—the opportunities to ask and answer questions that we could not have really imagined even a decade ago. But will we have the resources in terms of both budget and talent to make those opportunities happen? That is what I think is our greatest current challenge. There is no shortage of great scientific ideas.

Are you worried about the waning interest in science among young people in the U.S.?

Yes, that is another concern I have. If you look at graduating seniors in U.S. colleges and universities, only 15% of them now major in science and engineering. That has drifted down gradually over the past couple of decades. Other countries are not seeing that trend at all. In China, it’s 50%. In Singapore, it’s 65%. We can’t expect to maintain the remarkable U.S. track record of leadership in science and engineering without continuing to refresh our most critical resource, namely scientific talent.

What changes are planned for NIH this year?

I don’t see any other major structural changes. The leaders of the 27 institutes and centers have a great appreciation of what science can do, and they are very collaborative and interactive. The Common Fund has stepped in to keep projects that just didn’t fit one of those institute’s agendas from falling through the cracks. I think we now have the right structure to make the science go forward in pretty amazing ways.