NIH impacts: Research, public health, and innovation

[00:00:38]

ELENA RENKEN: Hello, everyone, and welcome to SciLine’s media briefing on the impact of the U.S. National Institutes of Health. We’ll give context about the NIH’s role in health research funding and priorities, how it influences biomedical innovation and drug development, and the potential results of reforms and cuts. My name is Elena Renken, and I’m SciLine’s manager of journalism projects and multimedia. A little background about what we do at SciLine. We’re an editorially independent nonprofit based at the American Association for the Advancement of Science. We’re fully funded by philanthropies, so everything we do is free, and our team aims to make it as simple as possible for journalists to use scientific evidence and expertise as you’re reporting. A little scientific research can deepen your stories with evidence and context, whether you’re developing a topic that clearly involves science, like heavy rainfall, or covering something where the science angle is less obvious, like funding for education or national parks. More of our resources are available on sciline.org, including interview opportunities and trainings, and you can always click the blue “I Need An Expert” button if you need to speak with a scientific expert for your story and we’ll look for a source with the right background to answer your questions before deadline. Now a couple of notes before we begin. I’m joined here by two experts who have studied the NIH and health research in the U.S. I’ll let each of them introduce themselves, their topics of research, and their connections to the NIH. Dr. Sampat, would you go ahead?

[00:02:15]

BHAVEN SAMPAT: Hi, good afternoon or good morning, depending on where you are. I’m Bhaven Sampat. I’m an economist by training. I’m a professor at Arizona State University based at the Consortium for Science Policy and Outcomes in Washington, D.C., and I’ve studied over the course of my career the history, politics, and economics of the NIH.

[00:02:35]

ELENA RENKEN: Thank you, and Dr. Ledley, would you introduce yourself?

[00:02:38]

FRED LEDLEY: Hi, I’m Fred Ledley. I’m a professor at Bentley University in the Boston area and director of the Center for Integration of Science and Industry. I’m a medical researcher originally by training, turned biotech entrepreneur, and back to professor where we study the process of innovation and, particularly, the business of innovation.

[00:03:05]

ELENA RENKEN: Thank you. I’ll ask each of our panelists some questions before we start taking audience questions today. Journalists, you can submit those questions at any time during the briefing. Just click the Q&A icon at the bottom of your Zoom screen, and please let us know if you’d like your question directed to a specific panelist. We’ll be posting a recording of this briefing on our website later today, and a transcript will be added in the next few days. With that, let’s begin. Bhaven, what factors shape health research funding priorities, and how does the NIH influence funding and research in the private sector?

[00:03:43]

BHAVEN SAMPAT: Great. Good opening question. Let me step back just for a second before I answer it directly, just to make sure everyone’s on the same page. So the NIH, the National Institutes of Health, plural, is the largest single funder of biomedical research in the world. It’s plural, so there are 27 institutes and centers, and its mission is—there’s a long mission statement, which you can look up on the website, but essentially committed to promoting science and fundamental knowledge about living systems and the application of the knowledge from that to extend a healthy life and reduce burdens of disability and illness. Historically, there’s been kind of this health mission and science mission and, actually, the historical political economy of the NIH, there have been tensions between the health and science aspects of the mission. So then to answer your question, Elena, how research priorities like of this $50 billion budget, the research priorities, how do the research priorities get set, how do we determine as a society what kinds of things get funded, there are essentially two kind of stages of that process. First is through Congress, so Congress makes allocations to each of the individual institutes or centers.

So, and some of those are focused on specific diseases, like the National Cancer Institute, others on particular organs, National Eye Institute, professions, National Institute of Nursing Research, etc. So that’s the first level. Congress is deciding how much to give to each of these individual institutes and centers. Then there’s this bottom-up scientific peer-review process where what are known as, something known as “study sections,” or panels of external scientists, evaluate proposals, typically from scientists and clinicians at universities and colleges in medical schools across the country, evaluating them for their scientific merit, for their significance, and there’s a range of other criterion as well. And you kind of mix and stir those processes and you get essentially this proposal from this institute gets funded, and that determines the total amount that you’ll see funded for a particular disease, for a particular area of science, or for a particular institution. So that, in a nutshell, is the priority-setting process at the NIH.

[00:06:09]

ELENA RENKEN: Great. Thank you. And next, what are indirect costs, and how do they fit into the financing of public health research?

[00:06:18]

BHAVEN SAMPAT: OK. An important question, not such an easy question to answer. So essentially, 80% of the NIH’s budget is spent on what’s called extramural research, and I think literally that means outside the walls of the NIH campus, so it’s spent at universities, colleges, medical schools across the country. Of that, about a quarter is not spent for specific research grants but for the overall fixed costs of research, infrastructure of research, so buildings, IT infrastructure, utilities, administration, things that you can’t—costs that you can’t assign to any specific project but that kind of help support the infrastructure for universities, colleges, medical schools to be involved in NIH research in the first place. And going back to World War II, there’s this recognition that we couldn’t expect universities, colleges, medical schools to be involved in providing what we economists call this “public good” of participating in federally funded academic research unless we funded both the direct costs of research, the specific costs of any individual grant, as well as the indirect costs, or the overhead costs of research. And so today, on average, about a quarter of extramural monies are spent on indirect costs of research, and that’s a topic of some controversy today and a focus of some of the NIH reform that the current administration is talking about, but indeed, it’s been a focus of NIH reform for the last 20, 30 years.

[00:07:58]

ELENA RENKEN: Good to know. Thank you. And what can you share about those issues in NIH reform before current proposals and beyond those?

[00:08:11]

BHAVEN SAMPAT: You mean what are the general types of things that people talk about when they talk about NIH reform? Yeah, so there’s been a number of longstanding issues in NIH reform, some of which relate to my answers to the previous two questions you just asked. First is priority setting. Do we spend enough money on disease X? Do we spend too much money on disease Y relative to disease X? So how we think about prioritizing different diseases, that’s been one. How we prioritize different areas of science, types of science, that’s another priority-setting question that’s been a perennial question, a topic of perennial debate throughout the history of the NIH. Related to that is questions around peer review, the peer-review process I described. Is it effectively identifying the best science, the science most likely to yield breakthroughs? Is it aligned with the health priorities of the nation or of the world, or is it an old boys club that benefits certain areas of science, certain types of institutions more than others. That’s been another area. A third topic related to peer review is just the administrative burdens of research. Is doing science increasingly costly both to the university scientists and to the NIH and other bureaucracies that administer it? That’s a third. More quickly, fourth, fifth, and sixth. The fourth has been organizational structure of the NIH, so I mentioned that there’s 27 institutes and centers. There didn’t used to be. There used to be, actually, just used to be the National Institute of Health, then you had the National Cancer Institute, and then after World War II, you had this growth of disease and organ and categorical institutes.

A big question has been whether you want essentially multiple institutes funding science or you want to kind of consolidate them around certain themes to take advantage of complementarities and synergies amongst those institutes. So the shape of the NIH has been another longstanding issue and target of policy reform. Patent policy, which I suspect we may talk about a little bit, is another. When the federal government funds research, including on drugs, who should own the intellectual property rights or the patent rights? Is it the public sector? Is it the private sector? And if licensed out to the private sector, under what conditions? And then finally, as we just talked about, indirect costs, I think that’s been another major focus of policy reform. Not a ton has happened, actually, over the last 50 years, but that’s been another major focus of policy reform throughout the history of the NIH.

[00:10:52]

ELENA RENKEN: Thank you. And you mentioned that interaction with the private sector. In terms of that priority setting, is there any context you can give us about how the NIH impacts the private sector?

[00:11:04]

BHAVEN SAMPAT: Yeah, and I suspect Dr. Ledley is going to chime in on this point as well. I’ve done, in addition to some of the historical work I do, I’m a quantitative economist by training, so I’ve done some quantitative work suggesting that there’s a large role of NIH funding in drug development, so the vast majority of drugs on the market today, and this is kind of an imperfect science, how you trace the links between NIH funding and products. But to the extent that we can trace it, and there’s now five or six different kinds of studies with different methodologies that get at this, it looks like the vast majority of important drugs have some linkages back to the NIH. In terms of drugs directly coming out of NIH funding, I think that’s a significantly smaller number, maybe one in five important drugs, or something like that, come directly out of NIH labs and then are licensed to the private sector. There’s been other work I’ve done suggesting, that tries to get at the causal impact of NIH funding, so if you increase NIH funding by $10 million, like what will happen to private sector drug development, patenting and whatnot? And suffice it to say that the effects are positive, so to the extent that we can measure it, increases NIH funds in a particular disease area, in a particular science/disease area, lead to more private sector innovation in those same areas. So a big debate among economists is whether public sector funding and private sector funding are substitutes or complements, and the evidence I’ve just summarized for you suggests complements, that more NIH funding in an area kind of crowds in more private sector activity in the same areas.

[00:12:51]

ELENA RENKEN: Very interesting. Thank you.

[00:12:53]

BHAVEN SAMPAT: Thank you.

[00:12:55]

ELENA RENKEN: And to turn to you, Fred, how does the NIH affect drug development regulation and access, and what are some examples of successful drugs developed?

[00:13:07]

FRED LEDLEY: Yes. So thank you. It’s great to follow everything Bhaven said. The NIH work is really the critical groundwork for everything that happens in drug discovery. As Bhaven said, you can trace back from drugs back to the type of work the NIH does, and it’s sometimes hard to explain to people, but the NIH focuses historically about half their budget on basic science, and basic science can be kind of eclectic. It’s sometimes research in worms and snails and things like that, but it creates understandings of biology and it creates mechanisms, it creates understandings of mechanisms of biology that can then be targeted by drugs. So one of my favorite examples is about a third of our cancer drugs now don’t just kill dividing cells. That’s how we used to think about cancer. But they enable those cells to die. It’s a pathway called “apoptosis,” or programmed cell death, that when a lung cancer cell is floating around where it doesn’t belong and it sits down somewhere and starts to grow, we call that a “metastasis,” but those cells should autonomously die. They should be programmed to death. And our understanding of that came from earthworms and how they develop. It’s the strangest research. But that led to discovery of a protein called “Bcl-2,” and a very important drug, venetoclax, which was developed by AbbVie, a biopharmaceutical company, directly targets that gene that was first discovered in that type of research, with a lot of intermediates, a lot of work to find the human protein that’s similar to the one in earthworms to figure out what it does, to see what its structure is.

All that basic science is really what industry primarily starts with when they start to develop drugs, and our work has shown that if you don’t have that mature basis of basic science, it’s virtually impossible to develop targeted therapeutics, and if companies start too early, we know it takes them longer to cross the finish line, so they end up with more years of clinical trials and they end up spending more money. So that’s really the key function of the NIH, and where that handover happens is variable. Some drugs are actually discovered in academic centers, the famous one being a drug called “Xtandi.” It’s the first treatment for prostate cancer, was discovered at UCLA. The very first GLP-1 drug, which is not used very much anymore, was actually discovered at the Bronx Veterans Center with NIH funding. It was a drug called “exenatide,” and it was a precursor of Ozempic and Mounjaro and drugs like that. So that’s the primary function. And then the NIH also has a critical role in just facilitating clinical trials. They don’t pay for a lot of them. They’re not involved in the actual development work. Industry pays for that. But the great cancer centers in our country provide a lot of support services for the data collection, and the patients are already ready to go, and trained nursing and clinical staff. So it just makes this whole process work. And also very importantly, as Bhaven talked about, it’s those discoveries, those aha moments that people get excited about. That’s what stimulates investment.

[00:16:57]

ELENA RENKEN: Thank you. And under proposed funding cuts, how do you expect biological innovation would change?

[00:17:05]

FRED LEDLEY: So we think that there’s a direct relationship to how much basic science one has and the likelihood that a drug can be approved successfully and that anything that reduces the amount of basic science is going to have a significant negative effect on that. You can’t cut corners in basic science. It’s not pretty. It seems disorganized. It seems repetitive. But when someone has that aha moment, it’s just as important that somebody repeats that work and really demonstrates the conditions under which it’s true, or refines it, or has a more detailed picture of the protein that you can use to model. This is just—it’s quantitatively critical in terms of the ability to successfully develop drugs.

[00:18:02]

ELENA RENKEN: Regarding pharmaceuticals specifically, how does the role of the NIH compare to the role of the private sector in the U.S.?

[00:18:09]

FRED LEDLEY: So that’s really a key question and one that people have a lot of opinions about, but the data is pretty clear that they’re really complementary. We see about 90% of the NIH funding that we can connect directly to drugs. So these are publications funded by the NIH where we know the topic, we know what it’s about, and so we know they’re providing either basic science related to that target, to that biological mechanism, or they’re related to the drug itself. We also know that very little of that funding is going to clinical trials, and we’ve tracked that. It’s about 2% or 3%. And industry is really responsible for the clinical development process and also the preclinical, and this is very important for them to control because that’s the part that goes to the regulatory authorities, so that has to be precise. They’re legally responsible for what gets submitted to the FDA, and they usually take the lead in the preclinical and the clinical development and usually the discovery, although the discovery is where that gray zone is, where some drugs are discovered in academia, some are discovered through collaborations with academic scientists, but most of them are actually discovered in industry, and industry certainly wants to own those patents. So it’s really a very complementary handoff. Many academic centers are involved in clinical trials because those trials tend to be performed in the great academic centers, in the great cancer centers, as well as around the world. You can have 100 different sites doing a trial, but while it’s done in the academic centers, it’s typically funded and supported by industry.

[00:20:06]

ELENA RENKEN: Thank you for the reminder of the extent of that research and funding. We’ll now begin asking questions to both scientists here, and I want to remind reporters on the line to please submit your questions using the Q&A box found at the bottom of your Zoom screen. First off, I want to ask both of you about the news coverage you’re seeing on changes at the NIH. What advice do you have for reporters right now?

[00:20:34]

BHAVEN SAMPAT: Want to start, Fred?

[00:20:36]

FRED LEDLEY: Sure. So I’m going to answer really from my background. I’m a physician by training, and my advice would be to focus on what really matters, which is the impacts on health. The discussion may be about indirect costs. It’s certainly about all the people whose careers are being disrupted, but the story that matters the most is the impact on the health of Americans and the world and how does it affect children, how does it affect mothers, how does it affect your parents or grandparents who have Alzheimer’s disease or cancer and who still have unmet medical needs that are likely to be addressed either with public health practices or with medicines. That’s really the story here, is the NIH has a mission to protect and advance the health of our public. Are they able to do that or will health suffer?

[00:21:42]

BHAVEN SAMPAT: I more or less—we didn’t plan this, but I more or less agree with that, but I’ll put a slightly different spin on it in the sense that a lot of the coverage that I see, in fact, does speak to folks at universities, university scientists, folks like Fred and myself. I’d like to see more stories, and it’s actually been quite interesting, if you think about the historical political economy of the NIH, I’d like to hear more about the reactions from patient advocacy groups to a lot of the changes being proposed. I’d like to talk to the pharmaceutical industry and get a sense from the drug industry about what their reactions are to some of these changes. Historically, both of those groups have been strong supporters of NIH funding, and seeing more stories, hearing their points of view on the current changes or proposed changes I think would be useful. The kind of second part to that is, I wouldn’t forget about Congress. Historically, there has been a lot of this sort of tug of war between the executive branch and the legislative branch around NIH reform. Historically, the NIH has had lots of strong congressional allies who have kind of protected the agency, even in previous administrations where there were actually tendencies for cost cutting and things like that, and it’ll be interesting to see if that political economy continues to prevail going forward or if we’re in an entirely different scenario going forward. But more stories thinking about the relevant congressional committees, the congressional champions of the NIH and how they’re thinking about NIH reform would be useful, again, as a complement to some of the coverage right now, which is heavily focused on the administration.

[00:23:52]

ELENA RENKEN: Thank you. And a question here from a reporter at the Boston Business Journal. With the amount of federal funding for research already being cut or attempting to be cut, how long could it be until we see effects in terms of layoffs at colleges or hospitals or at private sector partners?

[00:24:11]

FRED LEDLEY: So clearly, that’s a huge question for the Boston area, as a Boston writer. It’s inevitable that if this funding disappears, there’ll be cuts. Some of the universities, Mass General has already been working on downsizing a little bit. The private philanthropy can’t make this up and university funds cannot make this up. This is too central to the structure of all this, and hospitals’ primary mission is health care. They may or may not have endowments. The big ones do, but that really is designed not just to keep the lights on, but it’s designed to treat people and advance health. So private industry is also going to be cutting if this happens because they’re going to have less to follow. The markets may not be quite the same, and I think this is a real issue for areas where you have big clusters of life science companies and healthcare companies. I think it’s starting already. I don’t think it’s when. I think it’s how much.

[00:25:38]

BHAVEN SAMPAT: An interesting thing that may be an early indicator on the private industry side is just looking at some of the disclosures to investors or public firms. What are they saying about this? I think that might be an interesting angle to dig into as well. I think it might take a little bit of time to affect the private sector because of just the lags between research and private sector investment, but looking at looking at some of the disclosures and some of the public documents from the drug companies and biotech companies, device companies might provide a sort of early signal of how they’re thinking about these changes.

[00:26:16]

ELENA RENKEN: A good place to look. And a question here from a reporter at Fierce Biotech. The NIH recently announced a policy to block access to certain NIH data repositories for institutions in China, Russia, North Korea, and a few other countries. This ban seems to stem from a Biden-era proposal to block commercial transfers of large health datasets to these countries. Does this ban go beyond that proposal, and what are the potential impacts on global scientific research and biomedical innovation?

[00:26:53]

BHAVEN SAMPAT: Fred, I’m going to let you take that one first.

[00:26:56]

FRED LEDLEY: Sure. We’re seeing enormous numbers of datasets disappear. We’re seeing a lot of websites disappear or be changed. The SEER, I don’t know specifically, but this is really a different issue, I think. There have been some strategic issues of what constitutes the intellectual property, not patents, but the know-how and the more public good generated by U.S. taxpayers and being sure that that’s not misused, but this is very different, and the things being taken down are not really strategic in nature.

[00:27:51]

BHAVEN SAMPAT: I don’t have a precise prediction in answer to that question, unfortunately. Suffice it to say that there is empirical research, not by myself, but by others in economics and adjacent fields, suggesting that scientific data is important for facilitating both scientific progress and then downstream innovation and that science is a cumulative process, so science builds upon itself, and so one would worry a little bit if data are being denied to research, productive researchers in the global biomedical ecosystem. There are tradeoffs, of course, and there always have been, including with respect to national security and other geopolitical concerns. I don’t know about this specific policy, and so I don’t want to opine on that other than make the general theoretical point that science is a cumulative process that relies on data-sharing and relatively free data flows to function properly.

[00:28:57]

ELENA RENKEN: Next, a question from a reporter at MassLive in Massachusetts. Could you share your insights on what appears to be a targeted attack on HIV specifically?

[00:29:11]

FRED LEDLEY: So this is particularly unfortunate because this is an ongoing epidemic that’s been very hard to get a handle on over the last 40 years and one where, last year, the end of last year, we were beginning to be somewhat hopeful that some of the new drugs that were coming out truly could block the spread, the ongoing spread of this epidemic disease, particularly the notion of being able to take a shot once a year and prevent people from being infected or even treat people that way and prevent them from being infectious. It’s not the long-promised vaccine, but it’s equivalent in its function.

And I think just as we legitimately thought that we were on the cusp of that kind of advance, there has been a particular attack on these diseases. They’re better controlled in this country than in much of the world. I think that’s part of it. But that’s how it spreads. We know that these pandemic diseases frequently begin overseas with different conditions and less resilient public health systems. I think this AIDS/HIV has long suffered from the perception that it’s restricted to certain population groups and certain behavioral groups. I thought we put that behind us in the late ’80s. It was a problem early on to get people to pay attention to HIV, and I think we remember some of the activism of that era. I hope that that’s not why HIV is being targeted, but I do have concerns.

[00:31:09]

BHAVEN SAMPAT: Just the historical perspective on HIV and then maybe a quantitative piece of evidence as well. Historically, HIV went from being ignored in the early days of the Reagan administration to there was a lot of disease advocacy around AIDS funding at the NIH to the point where, returning back to some of the discussion about priority setting that I started with, there were concerns in the late ’90s, 2000s, early 2000s, that HIV might be overfunded relative to its disease burden because of the strength of its lobbies. And then there was a counter-argument that, yeah, but if you take it into account, not just U.S. disease burden, but also global disease burden and the special nature of infectious diseases that, in fact, maybe not. So it’s always been kind of this interesting object and disease in the recent history of the NIH. In the work that both Fred and I have done and the quantitative work in terms of looking at linkages between NIH-funded research and private sector drug development, in my work, at least, HIV has been a real outlier in the sense of it’s really kind of the shining example of public sector research facilitating a range of really, really, really important game-changing drugs that kind of reversed the course of the epidemic in the U.S. and eventually globally. So it’s there that the links between basic science and even some applied work at the NIH in downstream drug development have been quite strong. So it’s interesting to see it back in the spotlight again.

[00:33:02]

ELENA RENKEN: A question from a freelance reporter for you. What impact will genomic research cuts have on the public at large?

[00:33:13]

FRED LEDLEY: Yeah, so genomic research has really come to define our approach to biology in the last 25 years and even how we discover drugs. It’s both an enormously powerful tool to know the gene sequences of the genome, but more than that, we discovered a lot of elements of biology that we didn’t even know existed before. So we discovered that there are gene sequences that looked like things we knew, but they were a little different and had a little different function, and some of those became very important drugs. Some of our drugs for epilepsy, for example, that have been—not epilepsy, for migraine, come from genes that look like other genes, and if we hadn’t sequenced the entire genome, we wouldn’t have even known it existed, and now it’s really possible to preempt migraines, to take drugs that cut down the number of migraine episodes tremendously as opposed to treating symptoms or using sedatives. So on a mechanistic basis, we have many, many more targets for drug discovery than we had before, and we have more powerful tools for moving from those early stages through the process of drug discovery to know what molecules may work and which ones are worth taking into animals. We can now genetically engineer models of disease to test things that may not be ethical to simply test in a human subject because maybe there’s already a therapy that’s okay, you don’t want to take it away, that would be unethical, but you have something you think might be better, you can begin to do comparisons in animal models.

You can generate vast diversity of protein sequences for making monoclonal antibodies and things like that. So it really has changed how we go about the process of research in biology, but also the steps of drug discovery, and increasingly, it’s becoming a factor in how we even use drugs. More and more drugs are now designed for people who have specific mutations, and what that does, particularly in cancer where this is prevalent, is if you’re going to take toxic drugs and make sure that you have a high probability of responding to that drug, and maybe you don’t give it to people who have a very little probability of responding, as opposed to what we do with other medicines where we give everybody the same dose, and if they don’t respond, then we try something else. So it really has been a fundamentally different approach that’s become the norm in biology.

[00:36:24]

BHAVEN SAMPAT: Just to respond and maybe broaden the aperture a little bit, one of the kind of difficulties in thinking about cuts in general right now is, first, there’s not all that much precise in terms of exactly what’s going to be cut and when, but the second is, where’s the money going to go? And so one could make a case that, and I’m not saying I’m even making this case, but one could make a case—there’s a lot of high-value medical research that kind of needs to be funded, so one could make the case that reducing genomic research by, say, 10% and reallocating that money to studying off-patent drugs that the drug industry isn’t looking at, that that would yield high social returns, and so on the other hand, if the money is just going into the ether, that’s a different question. So I think in general, maybe this gets to what things reporters should be looking at, is thinking about where the purported savings from cuts are going. Are they going back into medical research but just different kinds of medical research, in which case the discussion is about the relative rates of return of different medical research investments, or are they going towards something else that may not have as high rates of return on average?

[00:37:45]

ELENA RENKEN: Thank you. And a question from a freelance reporter. Does the research on the economic benefits of things like HIV research take into account unexpected applications, such as the COVID-19 pivot where people who had been working on the tough problem of HIV vaccine successfully applied their techniques to SARS-CoV-2?

[00:38:06]

BHAVEN SAMPAT: I mean, in a quantitative sense, no. I mean, it should, right? It should, and I think, right, so going back to something I said in answer to the penultimate question, there was an argument from folks comparing funding to disease burden that HIV was overfunded relative to its disease burden. The response back, not from economists, but from disease advocates, but there’s kind of an economic language we could put on top of it is, yeah, but HIV research has lots of spillovers, plausible spillovers to other disease areas, so this kind of body-count budgeting, comparing one disease to another is an insufficient lens to think about how much money a particular area should get. So I would say, based on my read of the literature, typically, those kinds of studies do not take into account those cross-disease spillovers. I think they should. But certainly, as the question alluded to, we can come up with examples like HIV to COVID, like cancer to HIV, etc., where we see these at least exposed. Good question.

[00:39:17]

FRED LEDLEY: Yeah, it’s very real. It’s a great question. We had a paper early in the pandemic where we looked at the NIH investment in vaccine readiness and there were 150 different companies started developing vaccines in the first months of the COVID pandemic, and what they had at their disposal was an armamentarium of technologies of how to make safe and effective vaccines, and we, in particular, looked at 10 different technologies. I won’t go through the details. Happy to follow up if anybody wants.

But we identified about $17 billion of NIH funding related to those technologies of how to make a vaccine that’s safe and effective and a lot of that was from HIV because that’s proven to be a very, very difficult target for vaccines. There still is no vaccine. But that basic research was just on the shelf waiting to be applied to COVID, including mRNA, including lots of adjuvants, which is what makes vaccines stimulate the immune system, the synthetic technologies for making proteins and things like that. So as a direct consequence of all the work that’s gone into a not-yet-successful vaccine target, companies were able to jump directly into COVID vaccines.

[00:40:47]

BHAVEN SAMPAT: And Fred, your answer, if I may, jogged my memory a little bit. Some of the empirical estimates that I cited earlier in terms of the large returns from a causal inference, the causal impact of NIH funding on outcomes, including I’ve got a few papers on this as well that I just recalled when Fred was answering, about to the extent we can measure, and again, it’s not perfect, but 40-ish percent of the outcomes are in disease areas that were not anticipated, so there do seem to be these sort of spillovers, again, subject to the measuring this stuff is kind of hard caveat.

[00:41:27]

FRED LEDLEY: That’s a really important point. We looked at cancer therapies at one point and we asked which institutes did the basic research that led to new cancer therapies and it turns out National Cancer Institute did about half, just under half. It turns out the NIAID, National Institute of Immune—help me here, Immunology—

[00:41:52]

BHAVEN SAMPAT: Allergy, allergic and infectious diseases, right?

[00:41:54]

FRED LEDLEY: Allergic and infectious diseases actually was the second biggest funder, accounted for about 30% or 40% of the research, the basic research related to drugs, and the reason is that, I mentioned already about a third of drugs are helping cells die, but a third of drugs now are trying to get your immune system to attack cancer cells. That’s been, for a long time, the preferred way to treat cancer. These are really foreign cells, ugly cells, and yet somehow the immune system, which eliminates many early-stage cancers that we don’t know about, somehow it stops attacking cancer cells, and if you could turn it back on, you would have very effective therapies for cancer. That’s how the world’s best-selling drug now works, Keytruda, allows the immune system to attack cancer cells. So much of that work was funded by NIAID, not by the Cancer Institute. So it’s not serendipity. There’s a logic to it, but if you didn’t have a deep knowledge of the immune system, then you wouldn’t know how to engineer it to attack cancer cells.

[00:43:09]

ELENA RENKEN: Those are some really helpful caveats for journalists to remember when looking into claims about economic benefit. Thank you. And now a broader question for you both. Taking a step back, can you paint a bigger picture of the vastness of the NIH research landscape, the range of health issues addressed, the scale of funds involved, what health areas tend to get the most funding, and how does that compare to what other countries are doing?

[00:43:37]

BHAVEN SAMPAT: I can answer the last part of the question. The NIH is the big global player. The NIH is the big global player. I don’t know, Fred, if you know the sort of orders of magnitude globally, but it is and it has been for the last 50, 60 years. It funds maybe about a quarter to a third, depending on what year you’re looking at, of total U.S. biomedical research, with the rest coming from the private sector, though as Fred pointed out, there is this division of labor where the NIH and NIH-funded investigators are traditionally, or disproportionately, I should say, focused upstream on basic science, fundamental knowledge, and the private sector more on late-stage discovery and in doing trials. And then within the NIH, maybe the right thing to do is I could point you to a range of papers and datasets that kind of talk about exactly what’s funded and how that’s been changing over time, but that’s the kind of high-level, 30,000 foot overview of the system.

[00:44:51]

FRED LEDLEY: So the impact is enormous. We’ve shown over the years that, I think the number that gets quoted is 99.4% of drugs that get approved you can track back to basic science by the NIH, and that’s before approval, so it’s basic science leading up to approval. Once you start looking at research into how drugs are used, it’s all of them. So without this, there’s very little seed corn for the pharmaceutical industry to use to grow and produce drugs. The NIH, like everyone else, fashions matter a little bit. One of the things we observed with COVID was there was interest. People got grants when SARS was a problem. They got grants again when MERS was a problem, but funding lapsed in between, even though we as a society knew that COVID was among the top 15 pandemic threats on the planet. So it is hard, and this is true for government policy in general. Anticipatory policy is very, very difficult, and it’s not popular. There are enough diseases. We all have enough relatives with things that aren’t adequately treated that we want the NIH to work on things that matter now. And so yes, voters have a lot of say over what the NIH works on, as they should in a democracy.

So, we have a National Institute of Aging, and to a large measure, that reflects our aging population, and it also represents the demographics of voters. We also have a Child Health Institute, which I’m very pleased for, as a pediatrician, which has made amazing impacts on maternal health because we do care about mothers, and we, on the crudest level, we care about maternal mortality, which is still frighteningly high compared to where you’d like it, let alone infant mortality, let alone diseases of children and the types of congenital or genetic things that we still don’t really know how to help these children have normal lives. So there are a lot of competing priorities here and it is difficult to sort through them. We don’t have objective criteria for them. And we’ve been very good at responding to crises. Bhaven talked about the—took a while to get started, but ultimately an amazing response to HIV. Within five years of the disease being discovered, there was a drug. Within six months of COVID, there was a drug, and it was a partnership of government, NIH, and industry as they both were. So this is really what holds it all together. It’s what stimulates new directions, and it’s absolutely critical for what we have currently, which is the United States has long been the leader of developing new products, getting them to market faster than other countries, finding ways to put them in people’s hands, and those are their families and friends, as soon as possible. That doesn’t happen without the NIH.

[00:48:35]

ELENA RENKEN: Can you talk about how underserved populations and their particular needs do or don’t factor into decisions about how to prioritize which diseases to focus funding on?

[00:48:46]

FRED LEDLEY: So we’re aware there are huge disparities in disease outcomes. This is part of the shame of the healthcare system, but also our knowledge. Many diseases have markedly worse outcomes in individuals who identify as black than white, in lower socioeconomic classes versus those with more ample economic resources. We know there are geographic problems. There is a stroke belt across Appalachia where the incidence and death rate of stroke is much higher than in the rest of the country, and these need to be studied. We’ve been involved with a group that’s been studying the stroke. You have racial differences, you have geographic differences, and how do they play out? And how do you make sense out of it? And more importantly, how do you prevent it? And how do you treat it? And this is very much part of the mission. These great epidemiological studies, which I’ve had the good fortune to be involved in over the years, they take 20 years because you don’t walk in and figure it all out with one meeting with patients.

You have to follow those patients for 20 years, and they don’t generate results for a long time sometimes, although once they get going, they can generate thousands of papers and critical insights. The Framingham Heart Study is one of the most famous ones. Everything we know about heart disease, and now dementia and aging, a lot of it comes from Framingham. These have been—a couple of these have been curtailed in the last couple of months, and once you lose contact, once you don’t have the organization, they can’t be reconstructed and they can’t be restarted. So we need these to deal with the disparities in health care. A lot of the burden of disease in the United States is due to these disparities, so if we really care about not just equity, but also economics, if we care about keeping the cost of health care under control, we need to know how to address these disparities. We need to know how to deliver care where across the population people have more favorable outcomes.

[00:51:11]

BHAVEN SAMPAT: Just to chime in on that, going back to the importance of Congress, there was an old joke in the ’50s and ’60s that the NIH funds research affecting old white men because Congress is filled with old white men, and those sort of questions about how different disease groups and constituencies can have unequal voice in shaping the NIH’s portfolio, that’s been a question of perennial interest and perennial tension, I should say. I mentioned HIV/AIDS, but others throughout the history of the NIH. I’ve done some empirical work on this and, somewhat surprisingly, at least based on data I looked at, I last looked at this five or six years ago, there does seem to be a reasonably strong and positive correlation between NIH funding and at least conventional measures of U.S. disease burden, though I’ll say that I stopped looking at it five years ago and this continues to be an area of active research by others.

[00:52:21]

ELENA RENKEN: In that same vein, could you expand, how much do congressional members’ own personal interests and the perceived interests of their local constituents factor into where funding is allocated within the NIH?

[00:52:35]

BHAVEN SAMPAT: So the NIH is interesting, because unlike other science funding agencies, there’s not a ton of sort of hard earmarks in the NIH budget. By that, I mean the NIH should spend X billion dollars on this disease, or has to spend X billion dollars on this disease. Rather, what there is, is a lot of soft earmarking, congressional report language that kind of tries to nudge the agency to prioritize certain areas over others. I’ve done some work, again, with Deepak Hegde at NYU Stern, suggesting that there is this sort of relationship between disease group lobbying of Congress and other influences on Congress and then Congress affecting the research portfolio, mostly through a mechanism in the peer-review process called “request for applications,” or RFAs, but the magnitudes of those effect sizes are actually much smaller than I initially believed they would be.

[00:53:43]

FRED LEDLEY: I think it’s the great champions of research in general have tended to come from districts dominated by our great research universities and our clusters, and that’s serving their constituency. I will say the advocacy groups have been very, very powerful for the best. They have good causes. We spent a lot of time with an amazing woman, Abbey Meyers, who founded the National Organization for Rare Disorders many years ago and made it her life’s mission to get the Orphan Drug Act passed because she had had a child die of a disease that had been untreated, and people matter and advocacy matters, and individuals can make a big difference in our political system, and I think we still see this. We saw ALD come to the top of everyone’s radar screen a couple of years ago because of very powerful advocacy by the ALS community. They really caught the public’s imagination. Cancer in the ’70s, people felt that the war on cancer was strongly influenced by Mary Lasker, who’s a bit of a legend at the NIH, and her champion of an aggressive approach to cancer.

The Biden administration clearly had an interest in cancer that was not only that it’s a major cost of our healthcare system and a cause of disease burden to our population, but also a personal interest. So health is very personal and it always is, and I doubt if many congressmen vote without—or I hope they don’t vote without thinking about the people in their communities who are suffering where the burden of disease gets very personal.

[00:55:42]

BHAVEN SAMPAT: My instinct is that a lot of the advocacy has been about the size of the budget and not the specific allocation of the budget, and the size of the budget for specific institutes, going back to the priority-setting question we started out with, has been a big focus of advocacy more so than lung cancer versus breast cancer and things like that.

[00:56:06]

ELENA RENKEN: Thank you. And now we have one more question which will give our experts a chance to quickly cover the most crucial insights here. First, I want to flag that, journalists, you’ll receive a short email survey when you sign off from this briefing, and if you could take even 30 seconds to give us any feedback you have, it would really help us design our services to give you what you need for your reporting. Now for our final question. In about 30 seconds, what is one key take-home message for reporters covering changes at the NIH?

[00:56:38]

BHAVEN SAMPAT: I could start with that. I’ll say that I’m all for NIH reform. The NIH is an old and sclerotic institution. There’s lots of room for reform, and there’s lots of great ideas for reform between the center-left and center-right around issues of peer review, around indirect costs, around patents, and I think in some sense, spotlighting some of those ideas could be a useful thing. But the available evidence from Fred, from some work that I’ve done, from folks in the communities we travel in, suggests that, despite that, all available evidence suggests that the value of government funding of research and biomedical research is quite large, and as a result, in my view, it’s important to approach reform cautiously, with a scalpel rather than a sledgehammer, to ensure that the historically large benefits of publicly funded biomedical research are preserved.

[00:57:39]

FRED LEDLEY: So I think it’s important to focus on the goals of the NIH and whether that’s a mission the public wants to support, which is to improve the health of the American public, and to me, the answer is unequivocally yes. Is this something we want to downsize and have less? Research into health and the results are very clear. If you have less research, you’ll have less improvement, you’ll have less treatment, you’ll have less prevention. The mechanisms, the details of organization and restructuring, that’s not what’s going on right now. Research is not necessarily efficient the way an assembly line is, but this is incredibly effective. When we track government funding for research, we track $187 billion of research that mattered to the drugs approved in the last decade. That’s about a third of all the funding to the NIH, and that’s awfully efficient, and it’s very hard to get too precise there, but we don’t see this as terribly inefficient. You always want to improve efficiency wherever you can, but that’s not what’s going on at the moment at the NIH.

[00:59:02]

ELENA RENKEN: Great. Thank you. Huge thanks to the panelists here for sharing so much information and wisdom today, especially during the ongoing coverage of shifts at the NIH, when it’s so valuable to convey the nature of the health research landscape in the U.S. And from all of us at SciLine, thanks to all the journalists who logged on today to gain insight and context that will enrich your coverage. I hope we’ll see you at our next briefing. Thank you all.