Funding the Fundamentals of Biomedical Science: The National Institutes of Health in 2025 and Beyond

In the United States, the aim of the Current Administration is to support something called “gold-standard science.”  Their clear implication is that American scientists have been publishing something less than the gold standard – perhaps silver or bronze, or maybe even brass, when gold is the standard of the day (here and here).  We have discussed the nature of scientific research several times over the past few years; the first post is here.  There is much to criticize in the practice of science these days.  The current disequilibrium has been due to secular trends in the business of science and scientific publishing, particularly with the rise of pay-to-publish open-access “journals” in a publish-and-probably-still-perish academic environment.  Careerism has always presented problems.  The Bayh-Dole Act of 1980 has perverted disinterested biomedical science in the United States, an old and tiresome story.

Whatever the causes of the scientific distemper, neglect of fundamental biomedical science will be the death of all biomedical science in the United States.  What is meant by fundamental?  The more common term is “basic science,” usually in comparison with “clinical science.”  Basic science is the foundation of all biomedical science.  Or in other words, it is impossible to interpret pathobiology without a thorough understanding of the relevant biology.  Nevertheless, the number of basic science papers published with NIH support has been declining for years.  The proposed 40-percent cut to the NIH budget will continue this trend toward oblivion.  The first thing to go as competition among scientists increases further will be basic science.  This is the exact analog of eating the seed corn.

The STAT link above is paywalled, but Dr. Michael S. Lauer has recently published a paper entitled Brief Report: Absolute and Relative Declines in National Institutes of Health (NIH) Funded Basic Science Publications.  Dr. Lauer was Deputy Director of Extramural Research at NIH until he retired in February 2025.  Most of my colleagues received his regular emails about the state of extramural research at NIH until then, so I read this preprint (not yet peer-reviewed but the data and conclusions are straightforward) with interest.  Since the 1950s NIH has been the major source of support for basic research in biochemistry, molecular and cell biology, physiology, and genetics, the biological disciplines necessary for the understanding of pathobiology associated with disease.  Dr. Lauer is an authority on the subject of extramural research funded through NIH.

The most interesting finding in his analysis is that 60% of papers published in 1990 with NIH support were in fundamental, basic science.  That is, there was no explicit connection to any particular disease or condition in the paper.  However, the expectation was that basic biology would eventually provide the understanding of pathobiology. [1] .  In 2024 only 24% of the papers supported by NIH were basic science.  From 2013 to 2024 the number of basic biology papers decreased from 30,000 to 20,000.  According to Dr. Lauer’s summary:

The relative decline in fundamental science publications dates back to at least 1990, when fundamental and mixed mostly fundamental (i.e., including implicit biomedical relevance) accounted for 75% of publications and human-focused science accounted for only 18%.  In 2024, human-focused and mixed mostly human science accounted for 58% of publications, while fundamental and mixed mostly fundamental science accounted for only 42%.  (These patterns are illustrated in Figure 1, p. 9 (pdf), which does not reproduce well but is clear in the pdf).

Scientists, including most physicians, have always appreciated the importance of basic science for human health and wellbeing.  Many others adjacent to the scientific world have, too.  This included at one time the current Director of the National Institutes of Health, Jay Bhattacharya, MD.  Following up on original work by Mikko Packalen (paywall) of the University of Waterloo (Ontario), the then Professor Bhattacharya of the Department of Internal Medicine at Stanford and Packalen published NIH funding and the pursuit of edge science in the Proceedings of the National Academy of Sciences, in 2020.  Packalen and Bhattacharya recognize that:

Innovative research (edge science) is critical to the advancement of biomedicine. The NIH plays a crucial role in fostering innovation.  An empirical assessment of the success of the NIH in this role is an essential step in identifying ways to encourage novel research.  This research introduces a measure of the age of the ideas used in published biomedical research papers and comprehensively evaluates the performance of NIH-supported research relative to non-NIH-supported research, using this measure.

It can be assumed that novel research would represent the “gold standard science” by any measure of Making American Science Great Again.  Packalen and Bhattacharya characterize edge science as follows:

• Papers that build on very recent ideas are funded less often than papers that build on ideas that have had a chance to mature for at least seven years.
• Mostly limited to basic science, and that papers that build on novel clinical ideas are not NIH funded more often than are papers that build on well-established clinical knowledge.
• The tendency to have funded papers that build on the most recent advances has declined over time. In this regard, NIH funding has become more conservative despite initiatives to increase funding for innovative projects.

This is consistent with Dr. Lauer’s current analysis.  One would expect NIH to fund innovative papers in basic science.  Private funding agencies (e.g., American Heart Association and National Cancer Society) are primarily mission driven. [2].  Moreover, their work builds on the foundation of basic science funded by NIH and to a lesser extent NSF.  Neither AHA nor ACS have the resources to build the foundation.  To the extent that funding of basic edge science has declined, this is unsurprising given that publications of basic science supported by NIH have decreased markedly in the past 20-30 years.

It is also no surprise to learn that NIH funding decisions have become more conservative.  As inflation-adjusted research budgets have decreased, the imperative to produce instrumental knowledge “now” has become irresistible to those who are dependent on grant funding for their livelihood.  Politicians also have often derided basic research projects with “funny” names, going back to the late Senator William Proxmire’s “Golden Fleece” awards, which received a lot of attention in his day.  Thus, policy makers have responded with an emphasis on translational research that “connects the lab bench directly to the hospital bedside.”  This is noble but also exceedingly rare, with one recent example of a near-cure of a brain disease proceeding directly from a rodent model to a human patient with essentially no steps in between (CoQ10 precursors described in a recent Coffee Break).  Progress in biology, including biomedical science, is nearly always incremental and admits of very few shortcuts.

Returning to NIH funding and the pursuit of edge science, Packalen and Bhattacharya find that NIH becoming more conservative in funding decisions is consistent with at least three explanations:

1. Review committees have become more cautious in funding the most novel work or that reviewers today are unable to discern which projects are edge science.
2. Ideas generated in the 2000s may have been less fruitful than ideas generated in the 1990s, which is consistent with “empirical evidence” that health advances have become less common and harder to achieve than in the past.
3. It may be possible that some NIH grantees feel locked into their funded research aims…and that lock-in may prevent funded scientists from working on emerging ideas.

Regarding (1), in my 25+ years of experience, review panels are generally cautious about novel work.  Extraordinary claims require extraordinary evidence.  And at NIH and NSF there is a tendency to have applicants “wait their turn,” even though this is seldom acknowledged.  And contrary to what I perceive as the spirit of this paper, review panels are indeed “unable to discern which projects are edge science.”  But this is not because these panels of experienced scientists are unable to identify projects that are likely to succeed in their specific aims with the overarching aim to go beyond the limits of current scientific understanding.  Rather, the problem is that success rates for full research grants are seldom greater than 15% and often less than 10% and there are no objective methods to distinguish among the top third of applications.  Thus, funding decisions are effectively a lottery, and an individual scientist usually has no more than three chances.

Point (2) is not to be taken too seriously.  This comes very near to being a restatement of John Horgan’s The End of Science thesis (1996; 2015).  Sometimes this trope is conflated with the fact that it has become much more difficult to sustain a career as an independent and disinterested scientist. [3]  As for empirical evidence that health advances have become more difficult than in the past, one needs only to consider modern clinical oncology, which has become more effective by the year over the past twenty years due to advances at the level of basic biomedical research.

As for point (3), Packalen and Bhattacharya first concede that while “many NIH grantees do not feel obligated to adhere to their research plans in light of new results,” it may be possible that some scientists feel “locked into their funded research aims.”  Bad scientists are locked in, yes.  But all scientific funding agencies understand the difference between a contract and a grant.  The latter is awarded to answer scientific questions rather than produce a “deliverable.”

About thirty years ago I attended a panel discussion on grant writing at a large international scientific meeting in San Francisco.  This question was asked by a young scientist: “I have a grant, but what should I do if I realize that my hypothesis was naïve or that a different approach would be more likely to work?”  The members of the panel, including several members of the National Academy of Sciences and a Program Director from NIH, responded unanimously that the good scientist would follow her instincts and change directions. [4]

So, what is to be done?  Jay Bhattacharya, MD, has pronounced in colorful terms that the scientific establishment needs to be changed.  He is certainly correct at the margin.  But the proper response cannot be to “tear down the house” because a few rats may have taken up residence in the cellar.  In an excerpt from the paywalled STAT article, Bhattacharya’s coauthor Packalen says, “The best case for using taxpayer dollars to fund scientists is that you want to fund the kind of work that private corporations would never want to fund.”  This applies to basic research and is unlikely to extend to the current Secretary of Health and Human Services in his aspirations to get a handle on chronic disease prevention by the end of the summer, less than two months away.  This is applied research that may eventually Make America Healthy Again if approached seriously (food dyes are unserious, low-hanging fruit that appeases RFKJr and his acolytes).  This research is unlikely to attract much attention or funding from the private sector – probably just the opposite.

Packalen also notes that as the United States has reduced its support for basic research, Chinese institutions have been increasing theirs.  Packalen’s 2019 paper Edge factors: scientific frontier positions of nations (paywall), shows that progress in the United States has been stagnant, while progress in China, South Korea, Ireland, and Taiwan have accelerated.  Six years later, the Chinese have overtaken the U.S. in scientific research.  One anecdotal but useful measure of this can be found in the acknowledgments of the most influential recent Chinese scientific papers.  This research was most often supported by an institution such as the Chinese Academy of Sciences, with no indication that multiple scientists were required to grub for support from various and sundry different agencies, a time sink that is bottomless, to complete the work.

Does this matter for the advancement of scientific knowledge of our world?  No.  It matters not where groundbreaking scientific research is done.  Is this the way to MAGA or MAHA?  No.  Packalen says he still talks to Bhattacharya about this: “I think government is very slow to act on these matters, but I am still hopeful something will happen.  Jay still believes in this edge science concept.”

Perhaps, but that seems doubtful.  Even if it is true, edge science will get left out after a 40% budget cut because edge science generally cannot be identified ex ante.  One should never generalize too much about his or her own necessarily limited personal experience, but as a participant in this process during the past forty years the entire sad story portends an end of American science.  I am biased, however.  My research has always been “basic,” beginning with the mechanisms of bioluminescence in marine invertebrates, continuing through studies of the cell division cycle using Saccharomyces cerevisiae as an experimental model (budding yeast: bread and beer and wine and bourbon), and ending, so far, with studies on the multi-component assemblies required for the origin of animal multicellularity.

The research on bioluminescence revolutionized cell biology.  No one could have predicted this, but it has led to edge science that is otherwise unimaginable.  For example, GFP labels allow therapeutic stem cells to be identified in living organisms by fluorescence when otherwise the cells look exactly like their neighbors.  Research on the cell division cycle began with yeast and the pioneers had no intention of applying their results to cancer biology.  But it turned out the basic molecular mechanisms controlling cell division in yeast and humans are nearly identical at their core. [5]  Fundamental research on the origins of multicellularity may also lead to knowledge that is applicable to cancer biology, since a hallmark of cancer cells is that they “lose their social manners” and become motile free agents that lead to metastases.

Most of this research was supported at a time when NSF and NIH review panels met to decide which grants not to fund, according to those who taught me.  They exaggerated a bit, but it is also true they began their careers in basic/biomedical research in the 1950s and finished around the turn of the twenty-first century, having been supported by NIH and/or NSF the entire time, albeit with a few temporary disruptive interruptions along the way.  They are missed, along with those times, which were the most productive ever for American science, just as Vannevar Bush intended.

Now?  Scientists who have worked their entire professional lives as productive scientists have seen their grant support cancelled with no warning and no explanation other than “we now have different priorities.”  None of this is to imply that the practice of science cannot be improved.  No one who has ever been in this “game” believes our current practice of science is the best of all possible worlds.  But it is imperative that those taking charge of the rules have had experience in the game.  This is not where we are at the moment, and the “beyond” in the title of this essay is unimaginable.

Notes

[1] The National Science Foundation (NSF) is the source of funding for non-biomedical biology, and in the past NSF has not entertained research proposals that were biomedical.  NSF is the source of funding for essentially all of basic science that is not biomedical.  The model for NSF developed by Vannevar Bush after World War II became the blueprint for the expansion of NIH from the 1950s until early 2025.  Given that NSF has also been in the crosshairs since early 2025, one wonders what will happen to this, the first and other crown jewel of American science.

[2] NB: My research group has been funded by both AHA and ACS and I have reviewed basic science research proposals for each, with much more experience with AHA basic science review panels than with ACS.

[3] Sabine Hossenfelder is sometimes a serious science communicator, but one gets the impression that much of her antipathy to the scientific establishment writ large is born of disappointment that she did not get the plum position she desired.  She belongs to a very large club that has included most current scientists at one time or another.

[4] It is not for me to decide whether I have ever been a good scientist, but I once sent a letter asking the same question to my funding agency and the reply can be paraphrased as “Don’t be stupid, and thank you for letting us know you have a better idea.  Good luck.”  My department paid for the equipment necessary for the switch to a different experimental model to answer the same question.  The response of the sponsored programs office of my institution showed they did not understand the difference between a contract and a grant, though.  That caused a bit of lingering trouble.

[5] See Figure 1 of one of my favorite scientific papers (click on the button to download the pdf): An overview of the phylogeny and diversity of eukaryotes.  We animals are on the lower left branch of Opisthokonts with Fungi and choanoflagellates (the model organism for origins of animal multicellularity).  Amoebozoa are our close neighbors.