Respectful Insolence

NIH grant funding in crisis

I was going to blog about this a couple of days ago, but the Scientific Activist beat me to it, leading to a heads-up from PZ Myers. Never let it be said that a little thing like that stopped me from putting my two cents in. Besides, I think I bring a certain perspective that hasn’t been addressed thus far about this subject, namely the declining success rates for applications for R01 grants from the NIH. For one thing, I have an R01. I’m about a year and a half into a five year grant, which means that I have about two and a half years or so before I have to go for renewal. Consequently, I can bring the perspective of a first time grant holder. For another thing, I’m also a clinician, which means that I have to devote a significant chunk of my time to the care of patients, which decreases the amount of time I can spend on science compared to basic scientists.

First, I should explain just what an R01 grant is. It’s the gold standard of NIH grants, an unsolicited investigator-initiated grant that can be about whatever the applicant wants it to be about. In other words, it’s not a grant program that calls for research proposals on specific topics. As the NIH explains:

The NIH awards R01 grants to organizations of all types (universities, colleges, small businesses, for-profit, foreign and domestic, faith-based, etc.) and the R01 mechanism allows an investigator to define the scientific focus or objective of the research based on a particular area of interest and competence. Although the Principal Investigator writes the grant application and is responsible for conducting the research, the applicant is the research organization.

The R01 grant mechanism has been an incredibly successful program, because it allows any scientist with an idea and enough preliminary data to apply for funding. Robert Weinberg, at his address at the AACR meeting last spring, emphasized just how much the R01 grant mechanism has contributed to the success of the U.S. biomedical research effort, because traditionally, it has been individual researchers pursuing new ideas that generate the basis for new treatments. If the idea is judged worthy by the reviewers in the study section that covers the topic of the grant, an R01 can provide for up to five years of uninterrupted funding, including salary support and indirect costs to the institution. A typical R01 grant these days funds approximately $125,000 to $250,000 per year in direct costs. It is difficult to overemphasize the importance of this stable source of funding to biomedical scientists. Other grant mechanisms don’t last as long or provide as much money, forcing scientists to reapply every couple of years, rather than every five years. Indeed, the R01 is the “gold standard” grant mechanism for individual investigators. In the basic biomedical sciences, an investigator is unlikely to achieve tenure without having obtained an R01. In fact, to earn an R01 is a key milestone in an academic scientist’s career, a key sign that a young scientist has “arrived,” and renewing that R01 for the first time is a milestone that indicates that the researcher has become established. Consequently, the chances for investigators to obtain a new R01 for a new idea and to keep an R01 once they’ve gotten it are of great concern.

In last week’s Science, H. George Mendel and Elliot Veseli published a letter in which they described the findings of their analysis of the success rates of R01 applications. The results, as anyone who is struggling to get or keep an R01, are not encouraging:

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Nick and PZ are dwelling on how much the success rates have dropped so much during the Bush administration. True, there is plenty of blame there, particularly for the last two fiscal years, in which the NIH budget has gone from flat to decreasing in real numbers. However, the story is a bit more complicated than their simple Bush-bashing would lead you to believe, as richly deserving as the Bush administration may be of bashing because of its science policies. Notice that the steepest decline actually began in fiscal year 2002 and accelerated in 2003. I would point out that fiscal years 2002 and 2003 were the last two years of the much vaunted doubling of the NIH budget over five years that began during the Clinton administration and concluded during the Bush administration. In fact, the success rate of new R01 applications actually fell from 20.1% to 15.4% during four years when the NIH budget was climbing by some 15-20% per year and resubmissions fell from 55.1% to 45% during the very five years that the NIH budget was doubling. In fact, it’s very telling that, during the exact years the NIH budget was in the process of doubling (fiscal year 1999 to 2003), the funding devoted to R01 grants only increased between 10-15% at best. One has to wonder where all that extra money went, as most of it clearly didn’t go for funding R01s. Then, when the doubling of the NIH budget ended in 2004 to be replaced by flat or declining budgets, R01 success rates went into a free fall. This is not that surprising, given that, thanks to the flat to declining NIH budget and commitments from grants funded during the period of the budget doubling (which will continue through fiscal year 2008), the 2007 NIH budget will have 11% less purchasing power adjusted for inflation than it did in 2003.

Clearly, though, something else has been going on here, in addition to a flat or declining budget. Nick’s linking the decline to 2001, the year Bush took office, is far too simplistic. What could it be? For one thing, as suggested by this Inside Higher Ed article, the doubling of the NIH budget encouraged universities to build and hire new investigators, leading to more applications and driving the success rate down. It is thus possible that smaller budget increases sustained over a longer period of time could have avoided the boom and bust cycle, the “bust” part of which we are presently suffering through until the grants funded during the doubling period work their way through the system and political pressure builds to increase NIH funding again. Another complaint comes from the aforementioned Robert Weinberg, who, while lamenting the fact that the average age of investigators getting their first R01 has increased from 34 to 42 over the last generation, pointed out that another part of the problem is that the NIH has shifted its priorities to emphasize “big science” projects involving many investigators and collaborators over grants to individual investigators:

As a consequence, American biomedical research is increasingly reverting to models of researchorganization that have held back scientific progress in many other parts of the world. In these models, researchers acquire their scientific independence only when in their 40s and even 50s, long after the peak of their scientific creativity has passed.

The failure to recognize and halt this trend is compounded by another problem. As time goes on, ever larger proportions of NIH funds are diverted to funding research collaboratives of various sizes to the detriment of small, investigator-initiated projects. Perhaps those in power have been influenced by the obvious successes of the Human Genome Sequencing Project and the bounty of useful information that it has yielded. Those who control the scientific purse strings seem to have lost sight of the fact that this undoubted success does not provide a useful template for how most discovery research is conducted. In the case of the National Cancer Institute, this vision of grand projects and their utility has caused this particular Institute to invest large amounts of funds in proteomics, nanotechnology, and a massive software development program that aspires to make the data systems of American research hospitals intercompatible. Implied in the launching of these large-scale projects is the notion that if small scale projects yield relatively small advances, much larger projects will yield proportionately more.

[...]

As a consequence of these trends, small-scale discovery research is under siege, yet it is precisely such small-scale science that attracts the best and the brightest of our young people. Many of those who are training for careers in research do not look forward to working as members of large research consortia, in which they will only serve as small cogs in very large wheels.

I agree with most of this, except for one part. Given that I’m in my 40’s right now, I take a bit of offense at the suggestion that the height of my scientific creativity has passed, but maybe I’m deluding myself. In any case, Mandel and Vesell appear to echo Weinberg here, although they do not put it in quite so stark terms:

Particularly surprising and regrettable is the continuing erosion in the allocation for total R01 annual funding of new unamended applications. This decreased from $510 million in FY 2002 for type-1 grants to $351 million in FY 2005 (see table). These dollar figures represent less than 1% of the entire NIH budget. Of similar concern is the 38% decrease in total number of unamended R01 applications awarded during this period for new applicants (type-1), even though submissions increased 24%. Major reductions are also evident in renewal applications for competing ongoing investigations (type-2).

What they left out is that the emphasis of what the NIH is looking to fund has also shifted to emphasize more bioterrorism defense projects, further exacerbating the problem. They did, however, point to a more pernicious effect when paylines decrease to only 9%:

Peer review cannot discriminate among and accurately select only 1 of 11 meritorious applications. FY 2006 data are not yet available, but because the total NIH allocation for that period has been less than the biomedical inflation index, a trend toward further diminished support of R01 applications is evident.

When paylines become this tight, politics, personal biases, and conservatism become the order of the day in the decisions over who gets funded because, while it is relatively easy to distinguish a proposal that is in the top 20-30% from one that is in the top 10%, it is very difficult to differentiate and rank proposals that are in the top 5-10%. They’re all excellent. In such a climate, reviewers become much more conservative and much less likely to fund riskier research projects and more likely to let their personal biases dictate what is funded. After all, each R01 funds between about $750,000 to $1.5 million when you count indirect costs, and reviewers will be reluctant to take a chance when so few projects can be funded and you also want to make sure that science you like gets one of them. The science supported by the NIH will likely become more and more conservative and risk-averse, just as it did in the early 1990’s, the last time pay lines fell this low. Anecdotal reports from colleagues on study sections already suggest that this is already happening.

I can also tell you from personal experience that it’s even worse than that. In an attempt to keep the number of R01s from plummeting even more precipitously than it is, the NIH has been cutting the funding of new grants. For example, the budget of my R01 was cut a cool 22% right off the top before I ever saw a cent. I can barely afford to pay my postdoc and technician now. Worse, their salaries are mandated to increase by 4% a year, but my grant doesn’t a dime. Each year, I have less and less to pay for supplies. I’ve calculated that, if I do not somehow obtain more funding by the fourth year of my grant, I could easily have no money for supplies, putting me in the strange position of having an R01 but being desperately resource-poor, so much so that I would have to dip into the remnants of my laboratory startup funds, which would only get me through maybe another year, or let someone go. On top of that, the NIH has been cutting noncompeting renewals (the second, third, fourth, and fifth years) of R01s. My second year was cut by 3%, and the NIH cut a month from the end of my last year. I have no idea what they will do for my third year. It would be so much easier if I just gave up the lab and became a clinician, but I won’t do that without a fight. My basic science colleagues do not have that option. If they lose their funding, they lose their labs and, if not tenured, their jobs.

So what to do? Throwing more money at the NIH won’t necessarily correct this problem if present NIH priorities remain the same, although increasing the NIH budget so that it at least keeps up with the rate of biomedical inflation would certainly help. In that, the Bush Administrating is being penny wise and pound foolish, saving an insignificant amount of money over the last two years (in the $2.3 trillion federal budget, the total NIH budget is around $28.6 billion, or around 1.2%) at the potential cost of a degradation of our biomedical research enterprise that will be difficult and expensive to reverse. This is exacerbated by the shifting priorities of the NIH away from funding R01 grants. True, the NIH is funding more small grants (R21s, for example) for one or two years that are designed to fund riskier pilot projects, and this is a good thing, but these cannot make up for the decrease in R01s, which provide stable funding. What is more critical is to halt or reverse the decrease in the funds devoted to funding investigator-initiated R01 research grants. Big science can yield dramatic results, as the Human Genome Project has shown, but it is individual projects where riskier ideas are likely to be first explored. I’m not sure I’m as pessimistic as Robert Weinberg, but I will leave you with his warning:

Compounding this is the current deplorable state of funding investigator-iinitiated research: pay lines in which only 10% of submitted grant applications are funded constitute profound disincentives for researchers. Why should a young person invest in the laborious task of writing an NIH grant application that has only a minimal chance of being funded?

These factors, when taken together, have made careers in biomedical research increasingly unattractive for many young people. Imagine the prospects of predoctoral students starting out in their early 20s, who confront a wait of two decades until they can procure their first R01 grant, become scientifically independent, and flex their scientific muscles for the first time. Increasingly, these factors dictate that the best and the brightest are not entering our ranks. As a consequence, those of us who conduct discovery research are confronting the prospect of a lost generation, a wide gap in our ranks, as bright young people look elsewhere to discover their career paths. The marvelous engine of American biomedical research that was constructed during the last half of the 20th century is being taken apart, piece by piece. We will all pay for this destruction for decades to come.

When Dr. Weinberg finished his address the AACR, which served as the basis of his editorial in Cell which I have quoted, he received a prolonged, standing ovation from a packed lecture hall.

Comments

  1. #1 Nick Anthis
    September 13, 2006

    Thanks for the detailed thoughts on the issue, which are especially valuable from someone who actually has an R01 grant. Oversimplification is the name of the game in politics, unfortunately, so I fall prey to that as much as anyone else, but I think the trend is, regardless, pretty striking. Regardless of cause, it is still up to the current administration and others in the federal government to respond to this crisis by upping funding levels, especially considering that so much money is wasted on other arguably less worthy endeavors (like the war in Iraq, as so many of my readers have pointed out).

  2. #2 Sir Oolius
    September 13, 2006

    It seems like these days more NIH money is being allocated for the smaller grants: NRSA, K-awards, etc. to keep the younger generation “hooked” until funding improves.

    Either way, this problem probably wouldn’t have been as severe had NIH budgets increased by their “normal” pre-doubling amount (7%) after the doubling was complete. Anything less than a 7% increase is likely equivalent to a decrease in funding (b/c of “biomedical inflation”). If this doesn’t change, in a few years it’ll feel as if the doubling had never occurred because the 7% increase line will have intersected the 0% increase line; except of course that we’ve trained a bunch of folks to be scientists who’ll not be able to pursue academic careers because the money won’t be there.

    Currently, the House of Representatives is primarily the culprit since both the Administration and Senate have grudginly come ’round to accepting 7% increases (or thereabouts).

  3. #3 Pinko Punko
    September 13, 2006

    The problem is with NRSA and K awards, the NIH is basically funding positions in other scientists’ labs. Without the posibility of an R01, indentured servitude essentially continues and being a scientist and going through the usual life milestones (kids, god forbid- a house) becomes less and less of an option, especially if you are doing your science at a research center here funds will stay concentrated the longest (Boston, Bay Area, etc.) where the cost of living is enormous.

  4. #4 Theodore Price
    September 13, 2006

    Sir Oolius,

    The data on F32s (postdoc NRSA) shows the number of awards have decreased from 1998 to 2003. F31s (predoctoral) have increased slightly. K awards look like they have been fairly steady.

    Orac, maybe (almost certainly not actually) you didn’t mean it this way, but your line about paying your postdoc vs. having money for supplies is very troubling. As a postdoc, i am very tired of hearing the problem framed this way. While I can understand that it is true (choice of salary vs. money for research), shouldn’t we be able to understand that having to even acknowledge such an issue is ludicrous? Moreover, I have heard next to nothing about how the fall in funding for R01s affects postdocs. The research performed and the preliminary data is largely gathered by them. Also, who is really chosing who in this game? I would argue that the postdoc is choosing the PI they wish to work with more than the PI is choosing the postdoc. When funding falls through it can be a career ender for all involved.

  5. #5 DrM
    September 13, 2006

    The effect if this on junior scientists across the country may be devestating. Most universities are more grant-conscious than they’ve ever been in the past and receipt of nationally funded grants are more or less required for tenure at just about all research universities now (in the not too distant past, getting a grant was “money” for tenure at most universities, but legitimate attempts to get funding were often almost as good as success). As the numbers indicate, the opportunity to receive such grants are plummeting and younger faculty are less likely to receive an R01 than ever before.

    Universities have largely taken the mindset of “the budget has doubled, we need to get a bigger piece of the pie” without recognizing that although the pie is larger, fewer slices are being cut from it. The fat are gorging themselves and the thin are starting to starve (I don’t have the details but I just heard one panel recently decided to allocate $58 million to a total of 3 projects). By the time universities adjust to the new economics (if ever) we may have lost a generation of young scientists (perhaps some slight hyperbole, but still…).

  6. #6 PhysioProf
    September 13, 2006

    Excellent description of the current situation. I am also a tenure-track assistant professor at a medical school, and just recieved my first R01. I have no MD, and am mostly focused on basic research.

    Another adverse consequence of the extraordinarily tight funding situation at NIH is a shift in resources away from basic research–studies directed at
    elucidating fundamental biological principles, rather than understanding
    or curing a particular illness–in favor of more “applied” studies.

    While superficially this might seem like a reasonable idea when money is tight, it is actually counterproductive, as basic research provides the
    information necessary to guide applied biomedical studies into fruitful
    directions. In addition, unlike applied research, basic research can
    lead to completely unexpected discoveries that open up otherwise
    unimaginable possibilities for applied advances.

    Basic research supplies the intellectual pipeline that ultimately leads
    to therapies and cures. If we starve the basic research enterprise now,
    in 5-10 years, the pipeline will run dry.

    In relation to resumbissions: I have generated a PDF graph of the numbers of new (Type 1) R01 applications funded every fiscal year from 1972 to 2006 (as of this past May), broken down by initial submission, first resubmission, and second resubmission. I generated this graph based on data extracted from the public NIH CRISP database. I would be happy to e-mail it to someone who could post it. (I do not have easy access to a Web site where I could post it myself.)

  7. #7 Orac
    September 13, 2006

    E-mail it to me. I’ll be happy to post it on ScienceBlogs with your permission.

  8. #8 Orac
    September 13, 2006

    Theodore,

    I’ll probably answer you tomorrow.

  9. #9 Sid Schwab
    September 13, 2006

    The combination of an administration with a distain for science, along with an economic priority of tax-cuts above all else makes for a near-fatal environment for research in academic institutions.

  10. #10 Mouth of the Yellow River
    September 13, 2006

    Ni Hao! Kannichi Wa!

    Two media announcements representative of the problem, throwing money at “big wasteful” assembly line production science rather than small teams of hypothesis-driven researchers as described by Weinberg, emerged recently that have not been noted much in the blogosphere.

    One is the superproject to “knockout” every gene in the mouse. Although each mouse may be of utility to some R01 researcher as a model, the exercise has potentially no end with ever increasing cost to prepare and phenotype and varies how and where the gene was disrupted to complete excision to complete replacement.

    Another is based on a publication wrongly interpreted by the media and the big science powers that be as reason to expand the so-called Human Cancer Genome Project, or filling of the Human Cancer Genome Atlas (for more, Google “Cancer Genome Atlas).

    The latter project is endless given the constant relatively rapid evolution of cancer genomes in respect to type of cancer, individual host, time in progression down to every individual cell that collectively comprises a cancer sample.

    The recent Science paper from the Vogelstein laboratory essentially confirms these predictions (CANCER: First Pass at Cancer Genome Reveals Complex Landscape, Science 8 September 2006: 1370, DOI: 10.1126/science.313.5792.1370). However, except for a few voices crying out in the wilderness like Harvard cell biologist Steve Elledge in favor of R01 driven studies in cancer functional genomics, the results have generally been spun to favor moving forward with more and more, endless sequencing of diverse cancer genomes hoping that some unifying pattern of mutations will emerge.

    There is no end to the sequencing because no unifying pattern will emerge for a general understanding and approach to cancer prevention and treatment. The lack of a clear conclusion will call for more and more data through sequencing.

    Yet every product of an altered gene is a “druggable target” even before it is shown that the alteration has relevance to phenotype at the moment, and can even be temporarily effected before still more random mutations bypass the given drug treatment (drug resistance). Pharma will have a mind boggling array of choices to commit to, few of which are likely to be of general utility, if any utility at all. Quite a dilemma.

    There is no end to this or a valid rationale for it other than it is a good exercise to improve speed and reduce cost of sequencing genomes. It is an example of endless, largely mindless assembly line-fueled worker data production to the limit. A data production mill for a potentially useless product fueled by valuable resources that should be going into R01-funded functional studies.

    Even though small team hypothesis-driven research may result in many false hypotheses at least the collective resources will yield collective insight into the biological nature of a rapidly evolving alien entity called a cancer. This might have a chance of eventual trace back to a common “big bang” error like by-pass of a normally lethal aneuploid event and cell death surveillance mechanism at the single mitotic event that sets off the evolutionary process of constant change and adaptation.

    MOTYR

  11. #11 PhysioProf
    September 14, 2006

    Orac, what’s your e-mail address?

  12. #12 Orac
    September 14, 2006

    It’s in the “Contact” information, a link to which is on the menu bar right under the title.

  13. #13 Andrew Dodds
    September 14, 2006

    Hmmm, perhaps you need some new definitions:

    Bacteria – Foriegn micro-invasive terrorists.

    Cancer Cells – Domestic home grown micro-invasive terrorists.

    Surgery – Precise internal terrorist invasion rectification.

    And let’s fact it, money spend on medical research will save far more americans than any number of homeland security projects in States that have no coast or foriegn border ($788 million.. Orac! I think I’ve found your grant money!).

    The scary thing is, this is entirely consistant with Neo-Con budget priority. Anything military gets big rises regardless of usefulness, anything involving middle class professionals (ie those based in reality, who are likely to be disloyal if told to lie) gets ground down.

  14. #14 tgibbs
    September 14, 2006

    One consequence that I’ve observed is that my university is far more reluctant to hire Assistant Professors fresh out of a postdoc with no funding. When NIH was funding at a reasonable level, the university were willing to take a chance on somebody with exciting ideas and a strong graduate and postdoctoral publication record. But with funding this tight, even talented researchers are taking much longer to get funded, if they get funded at all. This translates into financial risk for the university, because if the university shells out a startup package only to have the faculty member fail to get funded, and leave for industry or some other endeavor, they have little to show for their investment. So these days the university is looking to hire more senior researchers, preferably those with an ongoing grant that they can bring with them. I’m sure this is why NIH has recently started a program to allow postdocs to apply for independent, portable grants. Such a grant would increase an applicant’s attractiveness, but there is still going to be uncertainty–even if he is successful in getting one of these entry-level grants, will he be able to take the next step of getting an R01 as a faculty member.

  15. #15 David Bruggeman
    September 15, 2006

    “basic research provides the information necessary to guide applied biomedical studies into fruitful directions. In addition, unlike applied research, basic research can lead to completely unexpected discoveries that open up otherwise unimaginable possibilities for applied advances.”

    The linear model rises up once again. This presumes only one model of knowledge creation, which I’m skeptical about. It’s tricky, since this kind of discussion can be diverted into debates over definitions, but I would suggest that research with an eye toward application can provide foundational knowledge, and can certainly lead to completely unexpected discoveries or applications.

  16. #16 Rob
    September 20, 2006

    Great post Orac! This is almost entirely my point of view; i’ve discussed it briefly on my blog but not this detailed and I lacked the Weinburg reference. Great job on getting your R01, at least you will have a chance for competing renewal. Here’s another issue. I know I’m not the best and brightest recent PhD, but only 3% of first time investigators get funded, and as you noted the average age is now 42. At 32, I just started my postdoc. In most places, 5 years is the max. I’ll be 37 by the time that occurs. I’ll have to get a faculty job or give up on trying to get funding; here only faculty can apply for funding. So what would I do for the 5-6 years in between the time I’m expected to land my first R01 and trying to apply for faculty positions? Essentially my probability of ever gettign this high is so remote that I probably won’t bother, unless my postdoc career gets much better (and I’m pretty good, but not spectacular).

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