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Monday, November 28, 2011

Follow up #1 to Why we must generously fund NIH: Scientists toiling in anonymity

Part 1 of a 3-part follow up

While attending a research symposium at the 2010 American College of Neuropsychopharmacology meeting with a young colleague of mine, he whispered in my ear how moving it was to him that researchers had been, for many years, toiling in relative anonymity studying a part of the brain known as the habenula. The habenula is comprised of two tiny spheres each about the size of a large peppercorn, one on each side of the brain. For many years its role in behavior was not appreciated. However, now it is considered very important to addiction researchers. So much so that the Director of the National Institute on Drug Abuse, Nora Volkow, spent a significant amount of time discussing it this past June in her address to an audience of 500 scientists attending the joint Plenary Session of the College on Problems of Drug Dependence Annual Meeting and the International Narcotics Research Conference.

You see, the habenula seems to act as an inhibitory or counterbalancing force to brain areas long known to process rewarding stimuli, the nucleus accumbens and the ventral tegmental area.  Thus, the habenula seems to play a key role in influencing addiction-related behaviors. Of course, this is only one of the many roles researchers have attributed to the habenula. It also appears to be involved in regulating sleep and circadian rhythms, responses to pain, stress, and anxiety, and in reward-based decision-making, a kind of learning that enables us to select actions that are most favorable to us.

Today’s habenula research likely will lead to new and better treatments for addiction and other brain disorders. However, such research would not have happened had not a broad research foundation been built by many scientists who, over the course of more than 50 years of work, have been quietly yet competently laying key groundwork, much of it funded by the National Institutes of Health, NIH.

In fact, most scientific research takes place in the background. Many scientists toil in relative anonymity.  They slowly and painstakingly add brick by brick to the scientific foundation of knowledge, often not knowing whether their research will make a difference in public health until many years after it has been published. Like fine wine, scientific research typically needs time to develop and mature, and can only do so if other researchers happen to add additional bricks to the foundation. Ultimately, if a critical mass of data results, that can catalyze development of new treatments.

This slow process of knowledge accretion is key to scientific discovery. Alarmingly, the process is in great danger today of being seriously disrupted by the budget challenges we face. With the brief exception of Recovery Act (ARRA) funding period, the NIH budget has been taking hits for a number of years, being maintained at or below the level of inflation since 2004. This year’s NIH budget actually could be reduced for the first time, possibly resulting in the lowest research grant application success rate in NIH’s history.  This would result in fewer grants awarded and fewer dollars awarded per grant. As budgets have shrunk, the system as it is now configured has been forced to focus more heavily on apparently “hot” ideas and “leading” researchers.  It has become less able to support novel projects and the potential for scientific discovery they offer. This trend is squeezing out many talented and productive scientists who don’t happen to have a hot idea or a stellar reputation, at the moment. Additional NIH budget cuts consequent to the apparent failure of the Joint Select Committee on Deficit Reduction to reach agreement could be catastrophic.

Now, at first glance, it seems to make sense to reward hot ideas and people with stellar reputations since those ideas and people tend to provide good returns on investment. However, the problem in science is that it takes many years for the scientific community to identify truly groundbreaking concepts and often, hot ideas and researchers of the moment are just that, flashes in the pan.

The hottest ideas and researchers typically are identified (in the moment) in papers published in premier scientific journals.  The journals include Nature, the New England Journal of Medicine, and Science Magazine. Papers in these journals often end up being the most cited work in a field (resulting in the highest scientific impact factors) and researchers publishing in these journals often become the most successful at securing future NIH funding. However, an analysis of articles in these journals suggests that many published papers ultimately make only a small scientific impact (as measured by the number of times a particular paper actually is cited by others). Thus, having a paper published in a premier journal is predictive of, but does not guarantee, high scientific impact. One of these journals, Nature, even commented on the misuse of publication impact factors, noting that:

“Research assessment rests too heavily on the inflated status of the impact factor… Attempts to quantify the quality of science are always fraught with difficulty, and the journal impact factors are among the few numbers to persist. The result is an overemphasis of what is really a limited metric…we have analysed the citations of individual papers in Nature and found that 89% of last year's [2004] figure was generated by just 25% of our papers… None of this would really matter very much, were it not for the unhealthy reliance on impact factors by administrators and researchers' employers worldwide to assess the scientific quality of nations and institutions, and often even to judge individuals. There is no doubt that impact factors are here to stay. But these figures illustrate why they should be handled with caution.” (Nature 435, 1003-1004, 23 June 2005)

Unfortunately, with fewer dollars available and increasing numbers of grant applications being submitted by more researchers, the NIH grant review system is becoming overwhelmed. There is an increasing tendency for grant reviewers, who judge scientific merit, and NIH Program staff, who, based on reviewers’ merit scores, determine which projects will be funded, to focus on applicant characteristics like past publications and journal impact factors. Applicants without papers in high profile publications likely will fare worse in trying to get their grants funded than those with publications in higher impact factor journals. In addition, grant review committees are requiring more preliminary data than in past to prove that an idea works; such data is very hard to come by before funding is available.

Thus, the barriers to NIH research funding have been elevated. This has been sidelining many good ideas and promising researchers, particularly those working in cutting edge areas, in which few people are well-qualified to review the science. Quite unfortunately, in this funding climate, it seems unlikely that the research we identify today as forming the foundation for our current appreciation of the habenula could be initiated. After all, who would believe without prior evidence that a pair of tiny and seemingly obscure brain structures could play a pivotal role in so many behaviors?

A summary of this article series can be found at:

Part 2 can be found here and Part 3 can be found here.

CPDDBLOG welcomes CPDD member's thoughts on this issue.  

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