Francis Collins’ “Five Themes” for the NIH

One of the advantages of hanging out around home on the proverbial staycation is that, instead of actually paying more attention to the news, I’ve paid less attention to the news. That’s why I didn’t notice some stories from earlier this week about what the new director of the NIH, Francis Collins, plans to do.

Regular readers probably know that, other than the occasional snarky comment on other people’s blogs, I haven’t (much) engaged in the blogospheric kerfuffle over Collins’ religion and the (in my opinion) vastly overblown fear in some quarters that he would inject his religion into his job as NIH director or somehow restrain investigation into areas that might conflict with his religion. Indeed, I was particularly disturbed at, of all people, Michael Shermer’s argument that his evangelical religion in essence disqualifies him because of what his beliefs entail, writing that “”there is a nontrivial chance that his religious convictions will influence his decisions as a policy maker for science” without providing in his article one shred of evidence that Dr. Collins’ religious convictions have ever influenced his decisions as a federal policymaker for science. This post surprised me because Shermer is usually less dogmatic than that. In any case, the problem with Shermer’s criticism is pretty much the same problem with every critic of of Collins, with Sam Harris characteristically being the worst. They speculate on what Collins might do based on his religion, rather than looking at his 30 year track record of what he has done, which, to my reading, has shown no evidence that he’s ever let his religious beliefs influence his decisions as a major maker and implementer of science policy. It would be different if Collins didn’t have such a long and detailed track record in leadership positions in the NIH and elsewhere to examine, but he does, and nothing in that track record suggests that the fears of Michael Shermer, Sam Harris, P.Z. Myers, and other influential atheists are warranted or even realistic, which is one reason why these criticisms strike me as far more about being against religion than they are for being for good science.

Be that as it may (and now that I’ve managed a brief venting that could have been the topic of an Orac-ian epic post a few weeks ago if I had been in the mood then to enter a fray that I’ve become tired of), what interested me more than this non-issue (again, as far as I’m concerned) is what Francis Collins will do as director of the NIH. That is becoming more clear with an article that appeared on Monday, in which Collins lays out five themes that he plans on pursuing.

First, I agree 100% with Collins’ first order of business:

Collins said that “job one” is dealing with what happens when the $10.4 billion that NIH received as part of this year’s stimulus package runs out in 2011. NIH faces “a perfect storm,” he said, partly driven by a flood of more than 20,000 applications for stimulus-funded grants, that could bring record-low success rates if the agency’s budget doesn’t rise above the current $30.6 billion. He will argue for more funding by telling Congress that NIH funding stimulates local economies and by emphasizing “themes that clearly resonate.” He noted that $40 billion, which some groups are pushing for, is “within [the] envelope” of what NIH would need to restore losses to inflation since 2003.

Indeed. If you think things have been bad as far as paylines go over the last three or four years, wait and see what happens once the share of Obama stimulus money doled out to the NIH runs out. It’s going to get even uglier than it was from 2005 to 2009 if something isn’t done, regardless of who is NIH director.

Collins also tried to allay one big fear of mine (and many others), namely that he is so enamored of “big science” that he will shortchange the individual investigator and cut back on funding of individual R01 grants:

He assured his audience that “the mainstay” will be the individual investigator; anybody who thinks otherwise “need look no further” than the genome institute’s intramural program, where research is “driven by ideas” and where he will keep his lab.

I’m not reassured, for reasons that I will discuss shortly. For one thing, the intramural program is a lot different than the extramural program, and being in the intramural program as the director of the NIH is a lot different than being in the intramural program as almost anyone else. Competition for extramural grants is a lot more cut-throat these days, for one thing. I once sat through a talk by Dr. John Niederhuber, the head of the National Cancer Institute, in which he tried to tell us that he knew how tough it was out there keeping a lab going. As an example, he mentioned that he understood how some labs might not be able to hire that extra postdoc or technician. My reaction? I couldn’t believe how completely out of touch he was. Sure, for big-time researchers like him, difficulty getting grants may mean that he has only two R01s instead of three, but for most of the rest of us it can easily mean the difference between having a lab and not having a lab anymore, not between having ten postdocs and having eight postdocs. I truly hope that Collins is not as out of touch as Niederhuber is.

So on to Collins’ themes:

1. “…large biology projects are one of Collins’s five priorities. He will promote high-throughput technologies in areas that are “poised for this kind of approach,” such as gene transcription and autism studies.” I’ve heard no word yet from Collins on how he will reconcile his claim that the individual investigator will be the mainstay with his emphasis in large biology projects. Unless more money is made available, something’s going to have to give, and my guess is that it won’t be one of Collins’ five themes. Notice how he didn’t include support of individual investigators as one of those themes. In any case, large biology projects have their role. They do their best when the challenges are primarily technological, methodological, and analytical, as they were for the Human Genome Project. After all, we knew that there was a definite answer. The human genome has a sequence, and that sequence was clearly knowable; all it took were the resources and improvements in technology and methodology necessary to achieve it. Such projects have a less successful track record when it comes to more open-ended questions, where we don’t know what genes will be important for various diseases or in what combinations. We’ve been doing this sort of thing for cancer for a decade now, and, although there have been lots of interesting observations, treatments based on those observations have been precious few. Which brings us to…

2. Translational research. Every NIH director I can remember has said that translational research is a priority. This is happy speak that is expected of every director. It’s meaningless. After all, translational research is the NIH’s raison d’être. It’s why the U.S. government is willing to fund the NIH to the tune of approximately $30 billion a year. My one concern, though, is that, like so many NIH directors before, Collins may be overselling the promise of genomic medicine and translational research. Indeed, in an article 10 years ago, Collins wrote in Scientific American:

Within 20 years, novel drugs will be available that derive from a detailed molecular understanding of common illnesses such as diabetes and high blood pressure. The drugs will target molecules logically and therefore be potent without significant side effects.

Ten years on, I’m not sure we’re that much closer to such an understanding. Moreover, as Neil Greenspan points out:

This statement is surprising, and was so at its publication, regardless of the effectiveness of genomics in identifying genes associated with diseases. The notion of drugs without side-effects (even a single drug!), is scientifically dubious if not preposterous. Molecules can never be absolutely specific for other molecules (4) and even if molecular interactions were absolutely precise, the inhibition or activation of one cellular or physiological process frequently affects functionally linked processes not intentionally targeted by the therapy. Even those with no special training in or knowledge of biology or medicine should be skeptical of such a prediction if only because every drug they have ever taken or heard about has been associated with significant side effects at some doses in some people.

If anything, over the years, Dr. Collins’ enthusiasm for genomic medicine and “personalized medicine” (which falls under theme #1) is undiminished and may have grown. In any case, the danger in overselling genomic medicine and translational research is that, when results don’t come as fast as predicted, it will become harder to persuade lawmakers to maintain and increase the NIH budget. That is a political reality. I’ve argued in the past that a robust pipeline of basic science discoveries is absolutely essential to a credible translational research effort, because it is basic science upon which translational science is built. But the process is slow. As I’ve pointed out before, it not infrequently takes decades to translate a basic science discovery into an actual treatment. It’s worthwhile to try to speed up that cycle, but it is potentially risky to oversell how fast investments in research, basic or translational, are likely to pay off.

3. Health care reform, including research comparing treatments. I’ve been skeptical of comparative effectiveness research, not because I don’t think it’s a potentially good idea but rather because (1) it’s about as scientifically uninteresting research as I can imagine (for instance, comparing one existing drug against another), which means that a lot of incentives will be necessary to entice researchers to do it, and (2) it’s also oversold. Look at it this way. Clinical trials often take between 3-10 years to complete. For studies of cancer survival in tumors where differences in 10 year survival are important (like breast cancer), often it’s even longer. By the time a study comparing two or three different treatments is complete and ready for publication, it’s not uncommon for one, two, or all of the treatments under study to be obsolete. Don’t get me wrong, I’m not saying that CER isn’t a useful thing. It most certainly is and, where appropriate, it should be pursued. It’s being oversold, because in a health care environment envisioned by Dr. Collins, where new treatments are being rapidly discovered through genomic medicine, or even in our current health care environment, CER moves too slowly, its often fatal limitation. Also, if more money isn’t forthcoming, CER will end up doing what the big science projects will do: Sucking money away from individual researchers.

4. Global health. Good luck to Dr. Collins selling that one. I mean it. I hope he can pull it off, because global health impacts health right here in the USA. Politically, however, this will be a hard sell.

5. “…empower[ing] the biomedical research community,” which he said includes sustained funding, encouraging young investigators, and funding innovative research.” I’m not sure what this means. Every NIH director I can remember has promised to encourage young investigators and fund innovative research. Moreover, funding innovative research is difficult, as I have said before, because it’s only clear in retrospect which innovative, “risky” ideas panned out. At the time such ideas are being proposed, it’s not at all obvious how to choose between them.

In the end, I don’t give the proverbial rodential posterior what Francis Collins’ religious views are, as long as they don’t directly impact NIH science policy, and I see no evidence from his track record that there’s any reason to be concerned that he’ll be somehow injecting them into the NIH or using them to determine policy or funding priorities. Personally, I find that whole line of criticism to be a huge distraction over what is far more important in a new NIH director, namely his policy priorities. On that score, there are several valid criticisms of Collins, some of which I agree with, such as Collins’ infatuation with big science and overselling of genomics. Moreover, Collins’ “five themes” appear to be a mixed bag of priorities, most of which are worthy but many of which will also likely be in direct competition with each other for resources and attention. Big science projects, which can be highly useful when used for the right kind of project but which can also breed a scientific conservatism and groupthink given how much money and how many people are involved, will compete with encouraging innovative research and supporting young investigators, as well as CER, which, as useful as it may be for choosing which existing treatment is best, is about anything but innovative ideas, given that CER is by definition testing existing validated treatments against each other. All of these will be competing for resources, which will be very slim if more funding is not forthcoming after FY 2011. How Francis Collins balances these priorities and if he can reinvigorate the biomedical research enterprise funded by the federal government will determine his effectiveness and success, not his religious beliefs.