The 40th annual meeting of the Society for Neuroscience came to a close on Wednesday, 17 November 2010 at the San Diego Convention Center in San Diego, California. Unusually for this conference, the buzz in the hallways and at the poster sessions was less about the latest hot research and more about the dismal funding scenario unfolding at the National Institute on Aging (NIA). “The meeting was dominated by this dreary feeling that the NIA is in freefall,” Stephen D. Ginsberg, New York University, told ARF. Every researcher ARF interviewed on the subject echoed this sentiment. Most Alzheimer’s disease researchers in the U.S. depend on the NIA to fund at least some of their research. While researchers expected a fall in the 2011 pay line—a measure of which is the percentage of requests funded—the extent of that drop is taking them by surprise. Talk of a 3 percent pay line drew fear and frustration from both junior and well-established investigators.

Researchers worry about funding for their own research and also about the impact on the field as a whole. The concern is that, just when aging research is becoming more important—baby boomers are reaching retirement age and older adults comprise a growing fraction of the population—researchers may be discouraged from starting or continuing to study both Alzheimer’s and aging. Several scientists said they expect colleagues young and old to leave the field in the next two years as their funding dries up. “You could not devise a more efficient way of killing basic aging research,” said Gary Landreth, Case Western Reserve University, Cleveland, Ohio. Landreth has decided not to apply for NIA funding next year. As reported recently in Nature, other researchers, including Karen Duff at Columbia University, New York, are requesting that their NIH grant applications not be funneled through the NIA, because the chances of getting funding are so low.

Program officers at the NIA are aware of the issue and share the concerns. “We are worried that people will turn off aging research exactly at a time when we need more funding for it,” said Marcelle Morrison-Bogorad, outgoing director of the NIA Neuroscience Division, in an interview with ARF. She said that the funding situation is at a point where it cannot be ignored, and that for the last nine months, at least, institute officers have been discussing ways to address the dilemma. On 25 October, NIA director Richard Hodes addressed the research community in an open letter explaining how the situation became so dire and outlining some austerity measures.

How did it come to this? The NIA claims it faces a triple whammy of sorts. Stimulus funds from the American Recovery and Reinvestment Act are running their course, more researchers are applying for more grants, and a bigger slice of the pie has been going to larger projects and non-modular grants, i.e., those over $250,000 per year. It is funding of larger grants that has some researchers particularly upset, as in their view, a majority of funds are finding their way to a minority of investigators. But it is not only large program project grants and clinical trials that are sucking up the dollars, as some researchers claim, but also non-modular grants of over $500,000 per year, explained Morrison-Bogorad. More of these grants have been awarded because the nature of the research has changed. “Because the field has matured and the science has gotten more complicated, the best science is a mixture of approaches, not all of which can be tackled by a single scientist,” she told ARF. “We have encouraged greater collaboration.” She also noted that some of the other NIH institutes have restrictions on funding mechanisms. The NIMH, for example, does not award program project grants, and the NINDS limits them.

Researchers are concerned that the funds for those projects come at the expense of regular rank-and-file researchers. “It is similar to what happens in the economy as a whole. The middle class gets squeezed,” said Ginsberg. Other researchers are not convinced that funding of non-modular grants is to blame for the funding crisis. It is unusual for R01 grants to be far above the modular cutoff of $250,000 per year, said Ilya Bezprozvanny, University of Texas Southwestern Medical Center, Dallas. Modular grants are now being squeezed off, he said, reducing the chances of novel ideas germinating in the AD field. “It is possible that ‘super large R01 grants’ with budgets over $500,000 per year are funding clinical studies and patient observational research, but quantitative information from the NIA is needed to better understand where the bulk of the money is going,” he told ARF.

Terrence Town, University of California, Los Angeles, noted that if these grants are funded over five years or more, then even a small number of them could drain the funding pool. He also lamented the fact that changes to the application process mean that it is harder for researchers to address questions that come up in review. “There is a continuity issue that needs to be addressed,” he told ARF. That’s because the NIH changed their policy and now only allow researchers to revise their submission once, rather than twice. If the study section panel reviewing the revision is different, then they often flag a whole new set of issues, said Town. “If you address an initial laundry list of concerns, and then you get another, you can’t address that and then the grant gets rejected,” he told ARF. This is particularly troubling for young investigators, he said.

Fixing this funding crisis will be neither quick nor painless. The NIA plans to limit funding for larger grants to try to improve the pay line for smaller modular grants (i.e., less than $250,000 per year), said Morrison-Bogorad. Since 2004, the institute has had a policy of an across-the-board cut of 18 percent, meaning every division paid out 18 percent less than study sections recommended. “That worked until people caught on and just asked for more money,” said Morrison-Bogorad. Going forward, the institute plans to take a closer look at requests for funding of higher than $500,000. Investigators have to seek permission from the NIA to apply for these grants. “We can say ‘yes’ or ‘no.’ From now on we’ll be saying ‘no’ more often,” said Morrison-Bogorad. That may limit expenditures on big projects, and it will also leave more of the decision-making process in the hands of NIA administrators rather than study sections.

The NIA will not know exactly what the pay line for big and small grants will be until mid- to late December, when they have a funding meeting. At that point they will model scenarios and decide how many large grants to cut or to skip over. “It is something we hate to do. Hopefully it will be temporary and we can come roaring back,” said Morrison-Bogorad. She stressed that a pay line of 3 percent means that grants scoring in the top three percentile get funded, not that only 3 percent of the grants will get funded. It all depends on how study sections score the grants, she said. A 3 percent pay line could mean that 6 percent of grants get funded.

How long a comeback might take is unclear. In the meantime, it seems unlikely that there will be sufficient funds from other sources to take up the slack. “If it does emerge that there is a 3 percent pay line, that is going to be extremely painful for the field,” said Bill Thies, Chief Medical and Scientific Officer at the Alzheimer’s Association, one of the large funders of Alzheimer’s research outside the NIH. “The likelihood that we could step in and make up for a shortfall is pretty small,” said Thies. Over the last few years, the Association has been struggling with its own funding issues since a major part of its donor base is particularly sensitive to swings in the real estate and the stock markets.

Researchers charge that more federal funding is required for aging research and for Alzheimer’s in particular, which is projected to affect 16 million Americans by 2050, according to some estimates. In Congress, the Alzheimer’s Breakthrough Act is languishing in Committee. “The most frustrating point of this is that the federal government is going to be stuck with the bill one way or the other,” said Thies. “They can pay that up front, but they are unable, or are deciding not to deal with the long-term threat. People will pay attention in 2048, but at that point it is going to be too late.” Ginsberg agreed. “Leadership has to come up with better answers,” he told ARF. He said that the NIH needs to make a greater commitment to AD, and if they split AD from the aging institute to do it, so be it. “It is beyond reason to expect progress in the face of the baby boom generation reaching the age of onset for dementia when funding AD research is pennies on the dollar.”—Tom Fagan.

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  1. "...the NIH needs to make a greater commitment to AD, and if they split AD from the aging institute to do it, so be it." Of course they should. It makes no more sense to look at "aging" processes when doing research on Alzheimer's disease "because AD occurs mainly in the old" than it would have to look at "maturation" processes when doing research on measles "because measles occurs mainly in the young."

    I bear a grudge against "aging" because, in the 1970s, when I started the research that eventually came to be instrumental in the cloning of PSEN1 (1), nobody would pay for Alzheimer's research; I managed to get a small INSERM grant under the "aging" mask: When, at mid-term, I showed the steering committee my first results about the formal genetics of AD, they cut my grant. The way to do research on "senile dementia" was to look for means to modify the Hayflick phenomenon. I suspect that much the same thing is occurring now in the U.S. as it did when I briefly visited Bethesda in the 1980s, with strife between NIA and NINCDS benefiting nobody, and least of all AD research.

    References:

    . Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995 Jun 29;375(6534):754-60. PubMed.

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External Citations

  1. Nature
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  3. Alzheimer’s Breakthrough Act

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