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Francis Collins: On Recruiting Varmus, Discovering Drugs, the Funding Cliff

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Science  28 May 2010:
Vol. 328, Issue 5982, pp. 1090-1091
DOI: 10.1126/science.328.5982.1090

He may be working a 100-hour week, but human geneticist Francis Collins is clearly enjoying running the National Institutes of Health (NIH). Since he began last August, he has pushed out the door the $10.4 billion that NIH got in last year's stimulus package, fleshed out five strategic themes for NIH (Science, 1 January, p. 36), and put his stamp on the president's proposed 2011 budget.

Collins's passion is to expand NIH's emphasis on translational research. He wants to give basic researchers the tools to convert their discoveries into therapies, he says. He is also an enthusiastic proponent of a new drug-development program at NIH called the Cures Acceleration Network. The program, approved for $500 million a year but not yet funded, was added to the health reform bill by biomedical research champion Senator Arlen Specter (D–PA).

Last week in an interview at NIH with several Science staffers, Collins said he was “grieving” about Specter's loss in the Democratic primary. He discussed NIH's budget prospects for next year and spoke of his role in luring former NIH director Harold Varmus back to Bethesda to head the National Cancer Institute (NCI).

Here are his comments, edited for brevity and clarity. On Science online, this article links to a full transcript.

Q:What has it been like going from directing the genome institute to running the whole NIH?

F.C.:When I ran the genome institute, I felt I could pretty much get my head around most of the major issues that we needed to attend to on any given day. Here, it's quite a stretch. The hours are long; I'm probably working 100 hours a week in an average week.

Q:Regarding the budget and grant funding, you've said that you expect very low success rates in 2011, 15%. What's this going to mean?

F.C.:We don't know what the budget will end up being. Obviously, the signs are not particularly good that the Congress will do better than the president's budget [a 3.2% increase]. Some noises might even indicate that they'll do worse.

We will undoubtedly have to look at draconian things like downward negotiations, which means cutting the budgets of approved grants in order to try to free up dollars to fund more grants. We are trying to protect certain parts of the enterprise. Postdoc training slots, for instance. But I'm sorry, I can't come up with a magic solution here that is going to reduce all of the pain.


Q:Some researchers are worried that your emphasis on translational research and big goals will mean cutting back on investigator-initiated grants.

F.C.:I don't think they should be very worried. Everybody's going to be stressed, so it will be tempting if your grant didn't get funded to look around for some reason other than the fact that it was a tough year budgetarily. The amount of additional funds that might go into focusing on translation are going to be maybe 1% or thereabouts of the overall NIH effort. That shouldn't have a very big effect.

Q:Does that mean 1% less for investigator-initiated research?

F.C.:I would argue that if NIH simply said we're going to keep doing what we've been doing all along, we're not in a very good position then to ask the Administration or the Congress to give us more resources.

The translational goals get a lot of traction with the Congress, with the public. They should. I mean, we're the National Institutes of Health. We are supposed to be coming up with ways to prevent and treat disease.

Q:As part of this, you're investing more and more in drug discovery and development. Why?

F.C.:Let's talk about TRND [Therapeutics for Rare and Neglected Diseases]. In terms of dollars, it's pretty puny. Fiscal year 2010: $24 million. What's in the president's budget for FY '11 is $50 million. On the scale of $31 billion to $32 billion, it is a pretty tiny blip.

It is high-risk for sure. Why should we do it at all? Well, if you're talking about rare diseases, or diseases of the developing world that don't have much of an economic market, if the government doesn't get invested in those therapeutic efforts, they're not going to happen.

We've arrived at the point scientifically where we've discovered the molecular basis of hundreds of diseases, and academic investigators [can] turn that into a high-throughput screen that yields up a small molecule that looks like it might be promising. And what TRND offers is to go one step beyond that into the preclinical phase to take some of those promising compounds and see whether you could get them all the way to FDA approval and a clinical trial. … So all of that I think is very defensible.

Q:Have genomewide association studies (GWAS) paid off?

F.C.:We're approaching 1000 validated genetic variations associated with a common disease. Most of them with very small odds ratios [as a cause of disease]. So probably not of much use for making predictions about future risk.

But I see no reason why there should be any connection at all between the strength of a variant as far as its risk on future illness and whether it is pointing you towards a target that could be very valuable for new drug development. So I think we have 1000 new drug targets sitting in front of us. I get a little bit frustrated when people say, “Oh, GWAS has been a bust.”

Q:Was it hard to persuade Harold Varmus to come back [to NIH]?

F.C.:You know, initially Harold was helping with the search process. Which had to be informal because this was a presidential appointment, but he obviously knew the field and so he and a few others were helping me with the trolling of the landscape. After a couple, three, months, it became more and more clear to all of us that there was a really perfect candidate right there in our midst.

Obviously, this is a big investment for him to come back to NIH, for a guy who loves New York City, and to take this on. But he's got a lot of ideas, a lot of fire in the belly. It's going to be wonderful having him here.

Q:There seems to be paranoia that you and Varmus want to take away the special status of NCI.

F.C.:The [Institute of Medicine] in [a] report back in 2003 concluded that the special status of the NCI has been more of a negative than a positive. So what is it that people are worried about here? That not having the ability to submit the bypass budget is going to have a big effect on cancer research? As far as I can tell, the bypass budget has no effect on anything.

Are they worried that not having a presidentially appointed institute director is going to do damage to the leadership of the institute? Well, look back over time and you decide whether that presidential appointment, which means it becomes a political issue, has been a good thing or not. I think Harold and I have the same view here, that this is a big place with a lot of smart people, and the best outcomes are generally when you don't have walls between parts of the organization that prevent people from learning from each other.

Q:How much time do you get in your own lab?

F.C.:I try to be over there on Monday mornings. I have about 10 people in my lab, three projects: diabetes, progeria, and asthma. It's great for me, it's like a wonderful respite from dealing with lots of other issues to actually look at data and talk to young scientists about where they're going. And I would argue it also makes me a little bit more effective as an NIH director to be anchored in the reality of what science is all about instead of just reading it in journals. It works out. It wouldn't work out if I wasn't willing to work 100 hours a week.

Extended Interview

In a full transcript from this 53-minute interview, Collins touches on proposals to restructure parts of the National Institutes of Health, why new therapies cost so much, the future of human genomics, and why it's so hard to recruit institute directors.

View Abstract

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