For America First, Invest in Science and the NIH

This transcript has been edited for clarity.

Robert A. Harrington, MD: Hi. I'm Bob Harrington from Weill Cornell medicine in New York City, and I'm here on theheart.org | Medscape cardiology. What I always try to do is have a conversation with one or two people about something that's topical in cardiovascular medicine. But this time, the topic is so important that I'm having a conversation with three of my colleagues who I think are real experts on this. And the topic is the National Institutes of Health (NIH), and where we're going as a country, as a research community with the NIH, specifically with regard to the direction of funding from the NIH — something that all of us in academic medicine, certainly, but all of us in society should care about.

And I'm going to use the recent publication of a presidential advisory from the American Heart Association (AHA) that talked about the future of biomedical research in the United States and how to optimize research coming from the NIH from the perspective of the Heart Association, the second-leading funder of heart and stroke research in the country. Three of us are co-authors of that paper, and one of us is the leader of a major clinical research institute. I think we'll get some good insights into how people are thinking about the NIH, how people are thinking about the future of biomedical research funding.

So, with that as background, let me introduce my colleagues: First, Dr Svati Shah is a professor of medicine at Duke University, where she's also the associate dean for Translational Science. And Svati is also a member of the AHA board of directors. Next is Adrian Hernandez. Adrian is the executive director of the Duke Clinical Research Institute and a long-time, well-funded NIH investigator who runs a large research institute that is also the recipient of NIH funding in the areas of translational, clinical, and population health science. Finally, my good friend Joe Wu, recent past president of the AHA, professor of medicine and radiology at Stanford University, where he directs the Cardiovascular Research Institute.

So, Svati, Adrian, and Joe, thanks for joining us here on Medscape. Joe, why don't you kick us off? Because you were the president where a lot of these ideas began to emerge, what became the principles of thinking about the NIH and the future of biomedical research. Talk to us about how the paper came to be, how the working group came together, and the big picture ideas.

A Century of AHA Dedication

Joseph Wu, MD, PhD: As you all know, this year, AHA celebrated its 100th anniversary. And I would say, for the past 100 years, our organization has been dedicated to reducing death and disability from cardiovascular diseases. Outside of the NIH, the AHA today is the second-largest funder for cardiovascular research. Since 1949, we funded more than $5.2 billion in this area. So, I think we're tied quite closely to the NIH, which I call ‘Big Brother’.

As the audience knows, there's a lot of mistrust. There are a lot of advice that different parties provide to the NIH about what they should do, what they should not do. We wrote this document mainly to highlight the important role that the NIH has played. And I think that it's important for the audience to understand that the NIH lays the foundation for biomedical research, supports a lot of our young investigators, supports a lot of our mid-career and senior-career investigators. Outside of cardiovascular science, the amount of funding that goes into different areas is very, very important. Our goal was to lay the foundation, inform the audience what NIH is doing and the importance of it.

Harrington: Thanks, Joe, for setting the stage. Svati, let me ask you, because you bring several perspectives to the conversation, one of which is that you're an independent investigator with a long history of securing NIH funding over the years at Duke. You also serve as the associate dean for Translational Science, and then you have a couple of AHA roles, one of which is you're the past chair of the Research Committee, which is an enormous responsibility for helping determine the direction of AHA funding. And you're a member of the AHA board of directors. So put all those hats together, and as you got called by Joe to participate in this paper, what were you thinking we ought to be trying to accomplish?

Svati H. Shah, MD: I'll start first by saying that I personally cannot under-emphasize the importance of the NIH and the funding that comes from the NIH. It fuels science. It fuels research and discovery. It has economic impact. And something that I'm very passionate about is: How do we train the next generation of scientists that are going to take care of the four of us when we're in the hospital? So, the NIH funding is important for those reasons, but in thinking about my role as chair of the AHA Research Committee, it also amplifies the impact of our AHA research dollars. You know, all of us take care of patients, and I'm actually at the hospital today. The NIH funding and our AHA dollars literally influence every interaction that we have with our patients and the way we take care of our patients.

Bob, as you Joe and Adrian know, at the AHA, we've been thinking a lot about our own research processes. How much do we want to fund? How do we give out our funding? How do we measure impact of our funding? And in that light, what impact do we want to have? What are the aspects of public health that we want to help with our research dollars? And so, with that framework of how we've been thinking about it at the AHA, when Joe called me and asked me to be part of this paper, my brain was in this space of, 'Let's think about this in the context of the NIH.' Yes, absolutely. The NIH funding is really important, as I already said, but same as we've been thinking about the AHA: What are areas that we want to help enhance, impact, and provide some guidelines around that so that we can have a continued impact on public health?

Harrington: I'm particularly glad you mentioned training and the principle of training the future. I've always been struck by the statistic that Joe likes to quote a lot — and I think this is right, Svati — that 75% of our research grants at the AHA go to early-career investigators. So, we're there doing it, but we can't do it alone.

Shah: That's correct.

NIH Advances "Innovative" Research

Harrington: Adrian, I'm going to start walking through the principles that were laid out in the document and the first one, I think you'll know why I started with you, because there are also some words in here that are in the Duke Clinical Research Institute (DCRI) mission statement. And the first principle is to prioritize high-quality biomedical research that is innovative and impactful. And certainly one of the things that your research group — my former research group — really tries to strive for is to be innovative and impactful. Do you want to build on that? I think this is a good first principle that we started with from the AHA. But as somebody who runs a research institute, how does this resonate with you?

Adrian F. Hernandez, MD: If you think about the story about NIH and the AHA, over decades, everyone around the world has been jealous of the research ecosystem that we have in the US. It's always been really creative, bringing new ideas from discovery to population health to bear. It's also been important in terms of developing new concepts for treating disease and preventing health problems. And it's really vital that this enterprise that has such a huge impact across the US in every corner is not only robust but actually matches the needs.

As healthcare dollars have gone up, the NIH funding has been largely flat — or actually going down based on inflation-adjusted dollars. And so, if we're going to meet the need to be innovative, we need to make sure that we continue to support the system and also do it efficiently. And so certainly embrace that.

Harrington: Adrian, let me push you a little bit. What do you think of when you think of innovative research —what does innovative mean? You're more on the clinical to population health stage, as opposed to Svati and Joe who are more on the basic to translational stage. Tell me what you mean.

Hernandez: One is being very patient-centered, so meeting the patient where they are, and that means having research be able to go across every corner of the US, not necessarily having people come into our so-called ‘ivory towers’ to access cutting-edge research. We should reach them where they're at and also at the moment they're at.

People are sick, they have problems. Let's fit into their lives. The second thing is bringing all the different disciplines of science together. This panel is exemplary of that. We have a lot of fun working with people who come at the problems from different perspectives, different expertise, and different experiences. It's that kind of team science that can make a huge difference in terms of spurring innovation and actually developing new ideas that translate into everyday health.

Harrington: Joe, let's think about the other word: impact. You're a laboratory scientist, but you also have the vantage point of having been the past president of the AHA and seeing the globe. What do you think we meant in the document by impactful research?

Wu: I think the word impact conveys several meanings. As Adrian mentioned, if you look at this panel, I'm more of a basic scientist. I think Svati is translational and Adrian is more of a clinical scientist. In terms of my own career, I got my very first grant from the AHA. My second grant was a KOA grant from the NHLBI (National Heart, Lung, and Blood Institute). And what we've been doing is trying to understand a lot of the mechanisms of stem cell biology and regenerative medicine and gene therapy and so forth. A lot of those are being translated in other fields into the clinic these days.

This type of research takes a long time to implement, and the foundation that we build from the basic science all the way to clinical, it's not overnight. I think that the NIH should continue to fund all areas, rather than just focus in one particular pot of money dedicated to one particular group of people. I'm a strong proponent of that. I hope that NIH will continue to do that in the future.

Peer Review

Harrington: Svati, I'm going to go to principle number two, which deals with the peer review process. And we wrote that it's to continue to improve efficiency and transparency in its peer review processes. It's not just coincidental that I'm asking you the question, because it pertains to your role overseeing the research committee at AHA. Talk about this one. What's right with peer review? What's wrong with peer review? How would you advise the new leadership of the NIH to think about peer review.

Shah: I'm honored to say that I've given over 15 years of non-indentured servitude to study section at the NIH. We’ve been thinking about this a lot at the AHA and really looking at our peer review process too. We call it study section, right? For those of you who aren't familiar with this, this is where we either get together in person or, more recently, via zoom, and review a portfolio of grants that have had some review before.

Over the years that I've been doing study section, I have seen that there's even greater room for multiple voices, right? There's not a 'single voice' dominating the room, and there's more of an inclusive environment around who's able to make comments around the grants that are in front of us. Our recommendation would be to continue to expand that inclusivity by being more structured in the diversity of those review panels. That means diversity with regards to career stage, age, race, sex, the type of science that's done. Bob, as you know, over the past 30 years, science has gotten more complicated. It's not a grant about a single thing. There's usually many different aspects of science that are embedded in these complex grants. And so, there's really a need for diversity in the type of reviewers who are reviewing these grants.

The second thing that we thought a lot about here at the AHA, as well as our recommendations in this paper to the NIH, is making sure that we're training the reviewers ahead of time. Some of that training is about the specific grant, right? There are certain aspects of the specific grant that you're reviewing that you want to make sure the reviewer is keeping in mind. For example, when we think about these career development awards, part of it is the science, but part of it is: Is this person somebody that we want to keep in science? So, making sure that we're thinking about training our reviewers, you know, ahead of time.

Diversity of Thought

Harrington: Adrian, you may remember that when I was at DCRI, I served on the large trial study section for many years at NHLBI. And one of the things that always struck me about the importance of that was that it was an awesome study section because it was made up of really different individuals: clinicians, clinician scientists, biostatisticians, epidemiologists, data scientists. The diversity of thought in the room was pretty incredible.

But one of the concerns is that the independent study section is going to be done away with, and more of it will be concentrated within the NIH. Part of my brain says, well, maybe that's not so bad because it'll get more efficient, people that really know the process can move things along. But I also worry that there will be some loss of expertise. Maybe there's a balance that should be tested. What's your thinking on this?

Hernandez: Coincidentally, I joined that committee that you were on before and rotated off this past summer as chair. Through that clinical trials committee lens, I saw exactly what you're talking about, these different disciplines coming together across NHLBI to develop the best programs that should move forward in terms of the reviews. It's very impressive in terms of my peers on that committee, in terms of the type of expertise that they're bringing together, and also, importantly, a new addition is operational expertise. We had a project leader on that committee to say: "Even though you all scientifically say, 'this is a great question,' you have a fantastic, innovative trial design, but you have no plan to actually execute."

Now, certainly there are ways to actually streamline the process, because one of the things that comes up is, if people don't get the question right, they don't have an important, impactful question, you could just stop there. Other funding agencies are being pretty ruthless at the LOI (letter of intent) stage saying this is not aligned. It doesn't meet a high impact area, and let people go on their merry way. Instead, we often have people who spend a year, maybe more, developing a grant and then submitting it. Certainly, that's a huge opportunity to streamline the process and make our time as reviewers more efficient to focus on those most likely to have an impact.

Implementation Science and the Valley of Death

Harrington: Joe, I'm going to go to you, and maybe this is less your basic scientist hat and more your recent AHA president hat: As you think about impact into the broader community, principle number three was the NIH, in coordination with others, should play a larger role in the translation of evidence into practice, including more funding for implementation research. What were we trying to get at there?

Wu: I think that's a very important topic. So last night, I was talking to one of the executives at Eli Lilly, and he was telling me that it took Eli Lilly about 20 years to develop the GLP-1 drugs. Most of us think that it was 2 to 3 years, then go to the clinic, and — voila! — New England Journal of Medicine papers. The point I'm trying to get at is all of this takes time. If you have great basic science, but if you don't have people who can implement this in terms of doing a well-designed randomized trial, that figures out the right patient populations, the study cohorts, then whatever basic science and discovery you have cannot be translated.

From my vantage point, there's also a gap in between. In Silicon Valley, we call it the 'Valley of Death,' in which you have a nice basic science discovery, but you don't know how to file the patent. You don't know how to get money from the venture capitalist. You don't know how to get your phase 1 trial, phase 2 trial, or how to attract Big Pharma. The NIH, to its credit, have been trying to do that. The NCATS (National Center for Advancing Translational Sciences) is one example. But then PCORI (Patient-Centered Outcomes Research Institute) and other large organizations are toward the end. But this is a whole ecosystem that we need to line up and learn from each other to deliver the best science to our patients. And this is what we're trying to get at with statement No. 3.

Harrington: Svati, you made the comment earlier in our conversation about how you're on rounds this week, and every interaction, in some ways, is guided by science that NIH, AHA, other funding agencies may have supported. An interesting statistic that I've read recently, that I've been requoting, is that something like 85% of the drugs in the market can trace their origin in some way to an NIH grant, either a pathway discovery, a molecule discovery, a new mechanism of action discovery. What do you think of, Svati, when you think of implementation science?

Shah: As Dr Wu was saying, sometimes you can't predict what's going to be the impactful science, right? Bob Lefkowitz, who's a Nobel Prize winner and who is at Duke University, likes to give a talk to us in cardiology about how to deal with failure and rejection. He has a letter — it's a mimeograph, because it's from a long time ago — that says biased G protein-coupled receptor signaling (GPCR signaling) is not a field you should pursue. That's a dead field. And then you think about all the drugs, right — Some 50% of drugs that are influenced by that discovery. Broadly thinking about the diversity of science is really important, and Dr Wu has emphasized that a couple of times in that space.

However, though, we have these 'Valley of Deaths,' one valley of death is that they say it takes 17 years to take a discovery and have something that can go to a patient. But then there's a second valley of death, when you develop something that can go to a patient, how do we actually get it to our patients? Including patients who may not have access. So to me, implementation science is the study of the methods that it takes to figure out how to get those therapies to the patient — that second 'valley of death' — is that implementation, the actual implementation and dissemination of those therapies, of those risk scores, to our patients, and making sure they're getting to everyone everywhere.

Training the Next Generation of Researchers

Harrington: That's such a great description of the whole process. Adrian, I'm going to go to principal No. 4 with you, because I know that in your leadership role at Duke, you care deeply about training the next generation; and principle No. 4 was that the NIH should continue to build and support the biomedical research workforce with funding and training opportunities. In some ways, that's self-evident, right? We want to support young people, but can you put the emphasis on this for us as you look at where the world is going in regard to the need for the next generation?

Hernandez: Just this week, I was meeting with fellows, and we were talking about what's going on in the world, and one of their worries was: What's going to happen to people like them? They're making choices because there are pathways that NIH and AHA have opened up for research careers that are embedded in healthcare or clinical centers like Duke or Stanford or Cornell. But if there's no pathway, how are they going to take forward their creative energy and interest in clinical research? It's critical to have those training opportunities and support, as well as actually supporting loans that they may take on as part of their medical careers.

"Work Hard, Work Smart, Work Together"

Harrington: That last piece is so important, not just thinking about training for grants, etc., but to help them get to that next stage of their career, which involves some personal things, like paying off educational loans, etc. Joe, I'm not sure I've met anybody as passionate about young people as you. And throughout your tenure as AHA president, you talked about it constantly. When I was at Stanford, my office was across the hall from your laboratories. I would ask your trainees, "What does Joe Wu teach you?" And they have this great saying: it's to work hard, to work smart, and to work together. Talk about that, Joe, and talk about the critical nature of the NIH and supporting all of those young people who were in your lab.

Wu: I pride myself on the trainees. By my last count, we have about 57 trainees who are now PIs (principal investigators). I think it's important to have a pipeline, because sooner or later, I'm going to retire — and then, without the pipeline coming in, who's going to be teaching our future generation how to do science?

My analysis is akin to a karate dojo, and your sensei, your instructor, is a yellow belt. There's a very big difference learning how to do karate, practicing karate from a yellow belt vs a 5th degree black belt. If we don't have a new generation to replace us, then the quality of our research goes down. There's no reason for trainees from throughout the world, Europe, Asia, South America, to come to the US. They might just as well learn at their own place. We lose our preeminence, we lose our dominance in this area, and I think it's going to have a lot of trickle-down effect.

Investment in Biomedical Research

Harrington: Thanks, Joe. You've been a champion of bringing people from around the globe to study with you. That's an important component of how we do science — to take the best from around the world. And one of the great things about the AHA grants, unlike some of the NIH grants, is the AHA will actually support people from around the globe, which is a way that AHA and NIH work well together.

All right, we've got one final principle, and I'm going to give each of you a chance to comment on this. In some ways, this is the 'Mom and apple pie' question. We'll start with you, Svati. Principle No. 5 is that a predictable, robust, and sustained public investment in biomedical research should be a national priority. Svati, make your case for that.

Shah: I'm going to take the lens of training the next generation of workforce. There is attrition in science, as Adrian was talking about. There's attrition in people who want to pursue research careers, whether you're a PhD or an MD, we saw that attrition before our current environment. I think this is a national emergency. This is a critical need. We're going to lose many generations of scientists, and we don't know what kind of incredible discoveries those scientists would have discovered. If we do not have predictable, robust, and sustained public investment, people are not going to pursue research careers.

Harrington: I like the way you said it. I've thought about this since the post-World War II era, as the sort of societal pact among four parties: the NIH, the research universities, industry, and the philanthropists. You put all of that together, and it has created a biomedical research enterprise. I've been using this phrase lately: If you really do care about America First, you should be investing in science, because there's nothing that we are better at than biomedical science. Looks like you're all nodding. So, I've made my point. Adrian, give us your pitch on a sustainable future.

Hernandez: It's also economics. And so, [let's] talk about a sector where America has distinguished itself over decades as the world's leader: People come to America to train with the best, to develop science, and also that actually has a huge impact across the US, economically, every corner of the US. That is a really important area, and that's also why, historically, there's been such great bipartisan support over the years for the NIH and also science in general, because it has an economic impact in every corner of the US.

Harrington: Yeah, we actually mentioned that in the paper. For every dollar of NIH funding, there's a lot of dollars produced [for] economic impact in a community, and that's every community across the country, because there's thousands of investigators. Joe, as the driving force behind this paper, I'll give you the last word on the importance from a national priority perspective.

Wu: This is something, as you know, I feel very, very passionate about. If we don't invest in science, we lose our edge in biomedical research, and once we lose our edge, again, there's no reason for other people to come to the US and do research here, stay here, contribute to our economy, contribute to our science. So, this is a generational threat, and we need to understand that. And I would hope that all of us talk to our congressmen, talk to our donors, our academic leaders, and our friends and relatives to convince them how important this area is.

Harrington: Well, this has been a fantastic conversation. I hope that our viewers will take the opportunity to read "Principles for the Future of Biomedical Research and Optimizing the National Institutes of Health: A Presidential Advisory From the AHA." I want to thank my colleagues, Drs Shah, Wu, and Hernandez. Drs Shah and Hernandez from Duke, Dr Wu from Stanford, and thank you for both contributing to the paper as well as contributing to this dialogue, which I think is going to be an important national dialogue.

Robert A. Harrington, MD, is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, as well as a former president of the American Heart Association. He cares deeply about the generation of evidence to guide clinical practice. When not focusing on medicine, Harrington dreams of being a radio commentator for the Boston Red Sox.