Taking Bold Bets: NIH and the Future of Biomedical Science

1. 0:00 – 0:59

   Introduction

   1. JBDr. Jay Bhattacharya0:00

      The American people are not stupid. In fact, they're quite smart. And when we talk to them in ways where we show respect for their intelligence with data, allow people to disagree, but then have the evidence right there in front of people, I think people, people will respond with trust where the evidence actually leads. We need kind of that Silicon Valley spirit. We should stop punishing scientists who fail. If they fail productively, let them publish in a journal to explain why they're-- what they, what they learned from it. Like that Silicon Valley spirit, I think needs to come to science a little bit more.

   2. ETErik Torenberg0:34

      Well, Dr. Bhattacharya, th-thank you so much for, for coming on the podcast. We're, we're stoked to have you.

   3. JBDr. Jay Bhattacharya0:37

      I'm, I'm delighted to be here. So good to talk with you. I'm a little jealous I'm not in Menlo Park to be there with you on this, so...

   4. ETErik Torenberg0:42

      [chuckles] Yeah, exactly. And, and we're talking Monday, September twenty-second. Um, there's, there's big news coming out today. Um, you know, the, the Times, uh, piece on, on you just came out, and I want you to reflect on, on that as well. But maybe you can, uh, you can share with us the, the, the big news and, and why it's so impactful.

   5. JBDr. Jay Bhattacharya0:58

      Sure. Uh,

2. 0:59 – 2:01

   Autism Research Initiatives Announced

   1. JBDr. Jay Bhattacharya0:59

      so, uh, six months ago, roughly six months ago, when I first started this job, uh, Secretary Kennedy challenged me to help get answers for families with autistic kids. I mean, with this, uh, the prevalence has been rising for decades, like one in thirty-one kids I think is the CDC's latest numbers on this. That's, that's an incredible number. Um, and we don't have answers. A lot of times families are-- they have these behavioral therapies that don't really work very well for a lot of their kids. Um, we don't know the cause, so we don't know how to prevent it. Um, and so I launched-- worked really hard to launch this new initiative, fifty million new dollars, uh, two hundred and fifty teams applied for, uh, large research grants, and we're gonna announce today that thirteen teams are going to be granted, um, y-you know, these grants, uh, this, for this Autism Data Science Initiative. Um, the other thing, there's two other things that, that, that are gonna get announced today that, that sort of came out of like this process of working with Mehmet Oz at, at the Center for Medicare and Medicaid Services and, and, um, uh, Marty Makary and Secretary Kennedy. Marty Makary is the FDA commissioner. Um, uh, one is a, a drug, a very common old drug called Leucovorin.

3. 2:01 – 4:40

   New Findings: Leucovorin and Tylenol in Pregnancy

   1. JBDr. Jay Bhattacharya2:01

      It's basically like a, it's folinic acid it's called, but it's like, it, it serves almost like a, a, a way to deliver folate to the brain, um, where for when some, when some kids have folate processing diff... Folate is, you know, something you get in vegetables, right? But, um, some kids have this difficulty processing folate. Turns out that a lot of doctors have experience using fol-fol, uh, folinic acid, Leucovorin, um, in treating autistic kids. And, um, um, you know, fol-folk, kids who have this folate deficiency in their brain, so c- that act-- it actually works. In twenty percent of the kids, I think it restores speech. Si- up to sixty percent of the kids, they get much better. Uh, now, not every autistic kid's gonna get better with this. It's, it, you have to have the specific thing that's happening in your brain. Um, so but, but, but, you know, making that more widely available I think is a really good thing. The other one is a, a, a, a sort of a caution on Tylenol, um, and acetaminophen. Um, that, that is a, you know, obviously a very common pain reliever. Um, it's used, it's the only, uh, sort of pain reliever and fever reducer used, recommended during pregnancy. But there's been new, new evidence that's emerged and it w- like actually highlighted by a new study put out by the, uh, the dean of the Harvard School of Public Health, um, just recently actually, uh, that suggests that, that use in pregnancy can correlate with, with subsequent autism diagnoses later on for the kids. Um, now I, I think there's a lot of controversy still over that, uh, in the scientific literature. Um, but it's enough, I think, to say to, uh, to moms, "Look, uh, just be careful." I mean, you know, you don't, don't use it all, all the time. J- use it only, only really when you really need it for high fevers. Uh, just to, just to think prudently about it. I, I don't wanna panic anybody. Uh, that's not, that's not the kind of result that pa- should panic anybody. It's just a reminder that you should use any medicine carefully, especially during pregnancy.

   2. ETErik Torenberg3:48

      Will there be any revised guide- guidelines around the use of acetaminophen in pregnancy to help, um, to help, you know, moms and, and, and parents sort of make a decision or, or have a judgment call on what they should do?

   3. JBDr. Jay Bhattacharya4:01

      There will be, yeah. So that's something that, uh, uh, Dr. Makary, the, the, um, the FDA commissioner is working on. Um, and there'll be also, uh, you know, ch-changes in, in, uh, uh, like how Medicare pays, Medicare, CMS, Medicare and Medicaid pay for, uh, Leucovorin. So it's a cross-agency collaboration for all of that. So both the guidelines for, for parents, uh, as well as sort of payment, uh, for, for the new, new, for drugs. And then we got the, the-- I'm, I'm the most boring part. I just get to launch vast interesting science projects for the, for, uh, [chuckles] over the next, uh, that hopefully will produce answers over the next few years.

   4. VAVineeta Agarwala4:35

      Oh, and the, you're also paying attention to preterm birth, and you've launched

4. 4:40 – 6:10

   Addressing Preterm Birth & Broader Health Concerns

   1. VAVineeta Agarwala4:40

      a really fascinating initiative there to, again, you know, um, launch not only fascinating science projects, hopefully, but also science projects which lead to clinical, um, insight into why that's happening to moms across America. And so, you know, um, that's another really interesting adjacency, if you will, to some of the announcements that you just made today.

   2. JBDr. Jay Bhattacharya5:02

      Yeah. I mean, the preterm birth thing is, it's really interesting. Like we have worse outcomes in the United States than Europe does. Um, and, um, you know, we don't really have great answers for why. Uh, I mean, there's lots of c-contributors to preterm birth. Uh, of course, pr-prenatal care is so important during pregnancy. Um, uh, ma-making sure you have a a-ac-access to that is really important. Um, uh, so that, that's part of it, but it's not the whole answer. And, uh, we have to, we have to f- we need to get answers to families on all these things that concern us, that concern... You know, I've heard from so many people around the b- around the country telling me, asking me, uh, answers to these questions. It's hard without excellent science, and that's, that's my job, is to make sure that we have rigorous excellent science to address these questions. Um, it's hard 'cause, you know, like so- it's scien- science is difficult, right? You get an answer you think is right and then... You know, eggs were bad for me in, when I was eighteen it turns out. Like it tur- but then like later it turns out eggs are great for you and I, you know, I was fearful of eating eggs forever 'cause the science in nineteen eighty-five told me that this, that eggs are bad for you. Um, and of course now eggs are good for you. I, I, I just... You know, it's one of those things where like-Science is difficult,

5. 6:10 – 9:26

   The Replication Crisis in Science

   1. JBDr. Jay Bhattacharya6:10

      but we have to hold ourselves to higher standards. We have to be-- hold-- When we, when we talk about people's-- about science, it has to be rigorous and reproducible. Something I've been focused on, um, really sharply as my time as NIH director is to, like, make sure that we invest in replication. The, the standard for truth in science ought to be replication. Independent teams. You don't-- Just don't believe me just 'cause I have an-- I say something is true. You know, other people independently looking at the same thing should arrive at the same answer. Then we know we're more likely, more, m- we have more confidence that it's true, uh, rather than just, you know, high, high authority says so.

   2. JCJorge Conde6:44

      For, for the lay, for the layperson listening to this, um, w-what's sort of been the cause for the, the, the loss, I'll, I'll say the loss of vigor in science or the lo- or the, or the challenges around being able to replicate science? Like, what is the underlying cause for this trend?

   3. JBDr. Jay Bhattacharya7:02

      I mean, the underlying problem is just that science is hard. I mean, that's [chuckles] really the bottom line. Um, and then the, the, the secondary cause is that there's just a lot of it, a lot more than there was. Like once upon a time, you know, you go back to like nineteen hundred or something, every scientist knew each other or very-- basically knew almost every other scientist, and everyone was checking each other. That was just n-a normal course. Now you have vast fields where it's very specialized and, uh, it's, it's hard to get people to check other people's work. There's no return for it. Like if I, if I spend my career checking other people's work, I'm, I'm not gonna get a professorship at a fancy university. Um, and, uh, and science is hard, right? It's very easy for a scientist to latch onto an idea and say, "This is right. I know this is right." Um, but it may not be right. And so what matters is other people looking at it find the same thing. Uh, uh, but often when other people look at it, they don't find the same thing, but we don't learn about that, right? Uh, there's been-- The last two decades, uh, there's been a replication crisis in science with increasing realization. The standards we hold ourselves to science in determining truth are too low. We basically-- Y-you can get a paper published in a peer review pa- a journal. You know, I've had like a hundred and eighty of them myself, uh, for which I apologize for every one. But, uh -

   4. JCJorge Conde8:16

      [laughs]

   5. JBDr. Jay Bhattacharya8:16

      ... but, but, like the [laughs] but the, but the thing is like the fact that it's published in a journal doesn't mean it's right. It doesn't mean it's true. It's useful. It's like that's my expression of my belief about that scientific idea. I, I think most of my things are true, but every scientist thinks that every-everything they publish is true. Uh, that's not enough. You have to have replication. You have to have other people checking each other's work, 'cause it's so easy to convince yourself in science that you're right. Um, and so it's really those two things. The volume of science means that people are so specialized they don't-- and there's no returns. There's no, like, there's no incentives to check each other's work as much as we ought to. And then the publication standards are too-- Because science is too hard, uh, science is so hard and publication standards are not high, high enough, really. Um, that's, that's really the reason for the replication crisis.

   6. ETErik Torenberg9:03

      Well, first I just wanna, uh, comment. There was a joke going around yesterday, a, a sort of a quote tweet on, on Twitter about, uh, i-in response to sort of any potential reduction in autism that someone said, "This is a, a, a direct attack on Silicon Valley startup productivity." Um, and [chuckles] you know, what will this mean for, for, for startups? But, uh, but yeah.

   7. JBDr. Jay Bhattacharya9:22

      Oh my goodness.

   8. ETErik Torenberg9:24

      E-e-exciting news there. The, um...

6. 9:26 – 12:47

   NIH Funding, Grant Review, and the Silicon Valley Spirit

   1. ETErik Torenberg9:26

      S-say more just in terms of maybe we can zoom out. You mentioned you, you do- you know, took over six months ago. What, what are sort of your reflections so far in terms of your, your activity and ach-achievements to date and, and, and then what you hope to, you know, achieve going forward?

   2. JBDr. Jay Bhattacharya9:39

      Well, I mean, we've done a lot. So, um, like one of the first things I did was, um, w-we looked at, uh, you know, the way we fund foreign collaborations, right? So, um, that's, that was... It turns out that w-we, uh, we fund collab- for-foreign collaborations, but it's very difficult for the NIH to check that the money's going to the right things. Uh, we couldn't audit. Like the Wuhan lab, the NIH had sent money to the [chuckles] Wuhan lab, uh, but we couldn't audit it. Um, so we put in a new system for allow... Uh, like I'm, I mean, I think foreign collaborations are really important, um, for science, but we need to do it in a way where I can look the American people in the eye and say, "We're-- Look, we can, we're, we, we're actually tracking the money. We're, we're checking to make sure things are going to the right place, doing the right thing." I put in a new system. The frustrating thing about that is like we put that in, and all of a sudden I'm seeing reports that I want to end all foreign collaborations, which is [chuckles] which is, I mean, couldn't be further from the truth. I just wanna make sure that we do it in a way that, that's s- that, that's auditable. I can go to, in front of Congress and say, "Yeah, I know where, where, I know we sent money to the Wuhan lab, and here's the lab notebooks that they sent, that they worked on," which we couldn't do under the old system. Um, we've changed the way that we, um, uh, evaluate grants. Uh, so, uh, y- we have a fantastic... At the NIH, we have a great way of evaluating grants called the Center for Scientific Review. It's the world's best peer review organization. Turns out that a bunch of the institutes, there's twenty-seven institutes, a bunch of the institutes were, had their own parallel review system that n- And so we centralized that, made it so that everyone is reviewed the same way. Um, the other thing, actually, this is related to Silicon Valley. It's something we're working on right now. Okay, you, you guys are gonna tell me that I don't know anything about Silicon Valley, even though, uh, ev- 'cause I mean, I've have, didn't work for a16z. But I'll just tell you-

   3. ETErik Torenberg11:20

      [laughs]

   4. JBDr. Jay Bhattacharya11:20

      ... my view of this is, is like the reason why you, you all are so successful is that if you, if you as a, as a, a, a, as a16z, you have a portfolio of fifty projects, and you fund fifty of them, and forty-nine of them fail, and the fiftieth is, you know, Google or something, you view that portfolio as a tremendous success. And the people that, that those, those forty-nine companies, they're gonna get a second chance, especially if their pro- their failure was productive. You don't f- you don't punish failure that much. You, you're willing to have a portfolio where you think big, right? You're, you're w- you're willing... A-and, and that, I think that spirit needs to come to science. Uh, I did published work before the pandemic, um, l- asking how, uh, how, uh, like es- es- essentially d- is w- is s- is the NIH willing to think big? And too often the answer in recent decades has been no. Um, like the, uh, look, if you look at back in the 1980s and 1990s, the NIH was f- was funding ideas that were like zero, one, two years old. Um, the typical scientific project funded by the NIH in the 2000 teens, it was about, or 2000, 2000, early 2000s and 2000 teens was likeSix, seven, eight years old. Um, we just became, uh, too scared of, of trying new ideas out. Um, we need kind of that Silicon Valley spirit so that... And we should stop punishing scientists who fail. If they fail productively, let them publish in a journal to explain why they're-- what they, what they learned from it. Like, that Silicon Valley spirit, I think, needs to come to science a little bit more.

7. 12:47 – 14:26

   Grant and Review Process

   1. JCJorge Conde12:47

      And do you think that the, uh, that the mechanism for reviewing the grants, say, at the NIH, became overly cautious, or did the scientists themselves become overly cautious?

   2. JBDr. Jay Bhattacharya12:57

      Well, I mean, those are closely linked. It's a peer review organization. I mean, I sat on those scientific review panels for a decade, two decades, and I watched what happens, right? So, um, let's suppose a new idea comes in front of me, right? Well, I'm really good at methods, and especially methods related with the old idea that's-- and this new idea is now competing with my idea, right? Um, and so, like, I look at the new idea, I go, "This, there's no way it can work." And I say that to this peer review panel, and everyone says, "Yeah, there's no way it can work." So easy to do, right? I'm sure you face the temptation too at a16z. You get, you get a thing or you look at the thing, you're like, "This is a, this is-- this guy's, uh, obviously a genius, but he has an idea that couldn't possibly work." I mean, that temptation is very strong. And too often in science, we say, "Yeah..." In, in, in scientific funding, we say, "Yeah, we don't wanna give-- We don't wanna try it out." Um, and yeah, most new ideas are going to fail. That's just normal. You expect that to happen. Uh, but if you don't leave room for people to try them out, you're never gonna make big advances. Um, and I think that's what happened to the culture of s- of biomedical science the last few decades. It's, it's too focused on, like, incremental progress, not enough on enormous... Now, of course, there have been big improvements, uh, big, big scientific discoveries, right? That-- I don't wanna downplay that. That's true. But we spend a lot of money, and per dollar we spend, a whole bunch of, like, sci- uh, of economists who have looked at this and the science of science folks who looked at this say that we are getting too few advances per dollar that we spend. That's because the culture is too conservative.

8. 14:26 – 26:23

   Portfolio Management & Allocation at NIH

   1. VAVineeta Agarwala14:26

      Yeah, it's interesting. It's sort of why many great venture partnerships, um, you know, ourselves included, are not consensus driven. You can't drive, you can't require unanimous consent to fund a big, bold idea because someone's gonna say, "Hey, no, no way that's gonna work." Um, and someone has to be willing to take that bet. Um, I'm curious if, if... And correct me if this is kind of not how you think about the, the NIH structurally, but it occurs to me kind of as an outside observer of the organization, you know, again, for listeners, our country's and the world's largest federally funded, you know, federal funder of biomedical research across twenty-seven, seven different institutes, over thirty-five billion in funding. You know, there's a massive organization funding essentially across multiple sub-disease categories, the most important research that we believe will advance our health as a population. And it seems to me that there are two big categories in which the NIH has to get decision-making right. One is allocation and sort of how you decide how much should go to immunology versus infectious disease versus maternal health and, you know, versus autism and behavioral health. And, you know, there's kind of this fundamental values-based, you know, population input-based, you know, citizenship input-based, whatever it might be. There's some, you know, risk return-based methods that you have to do to decide how do you allocate funds across these different areas. And then there's an execution challenge. Okay, once you've decided you're gonna allocate this mac- this quantum of capital in research funding to this area, how do you pick the right investigators? How do you keep them honest? How do you drive data return? How do you measure productivity on an ongoing basis? How do you incentivize ongoing risk-taking in a multiple year project? How do you get your agreement straight with an international, you know, funding, you know, research partner? All of these are sort of all in the bucket of execution. Is that a reasonable way for people to think about the NIH? Like, you gotta nail allocation and then nail execution, and you're in it to reform both?

   2. JBDr. Jay Bhattacharya16:38

      So, okay, first of all, you're, like, uh, you're m- you're very well trained as an economist. That's very, very clear to me because that's exactly the right way how an economist would think about this, right? So-

   3. VAVineeta Agarwala16:45

      It was your class. [laughs]

   4. JBDr. Jay Bhattacharya16:47

      [laughs] I, I love to, yep. I mean, uh, but, but no, I mean, that's exactly right, right? So first there's a decision about where, which diseases should we focus on. That's inha-- It, it's not only a scientific problem, it's also a political problem. Like the... And it, uh, uh, it ought to be a political problem for the reasons you just articulated, right? You, it, it, um, the, the things that we focus on should reflect the, uh, the, the real needs of the people that fund us. If we're just doing science for science's sake, and we're just, uh, wandering around without producing answers or improvements for people's lives, well, the question is, why should they fund us? And the, and it, it's actually Congress that decides this. Congress and the president together in the budget decide where does the money go, you know, h-how much to infectious diseases, how much to heart disease, how much to cancer, how much to pediatric dise- conditions. You know, uh, like, the, there's a whole allocation, um, that reflects the political will of the people as well as the scientific need, uh, opportunities, right? So it's a, it's a, it's a mix of the two that decides that, and I think it's so completely appropriate that, that that be the case 'cause-

   5. VAVineeta Agarwala17:56

      So let me-

   6. JBDr. Jay Bhattacharya17:56

      Um, you know-

   7. VAVineeta Agarwala17:56

      Let me push back on that. Uh, why? Why, why do people know enough about science and our ability to make progress in important disease areas? They may not even know the names of the diseases. They may not know anything about the true prevalence. They may, they, they've-- We've enabled them to be productive in careers entirely outside biomedical science expressly so that the experts can weigh in on where science is going to improve their health on an ongoing basis. And so you may say, "Oh, that's, you know, um, that's an overly paternalistic view," or you could say, "Well, that's what people decided they wanted." They didn't wanna have to worry about exactly what research needed to be done. They decided to offload that cognitive load to you. [laughs] at the NIH, and they, they may not want a voice in that. Or, you know, you know, at least that's kind of one argument I'd make, uh, in response to the idea that allocation should be political. How, how do you-- how would you respond to that?

   8. JBDr. Jay Bhattacharya18:52

      Well, I think... So some of... Let me, let me get to-- back to the second half of your characterization, 'cause that's where the scientific sort of c-c, uh, expertise comes in, right? So within each area, it is absolutely vital that scientists have their say, right? That, that they can, they can say, "Well, this idea for addressing Alzheimer's is promising. This idea for-

   9. VAVineeta Agarwala19:11

      Mm-hmm

   10. JBDr. Jay Bhattacharya19:11

       ... for addressing, you know, autism is promising." And then they can... And, and then scientists can check themselves and say, "Well, is this, is this actually promising," right? So, um, it's... And, and, and, uh, and the NIH's role is to mediate that, ta-take that scientific input, um, and, uh, make portfolio decisions that will actually advance health in those areas, right? That's, that's, that's basically my job. Um, a-and so, so that, I think the scientists have their say. But in the, the question of where should the money go, right? So, um, let me just go back to the HIV epidemic, just to give us some sense of what can go wrong, right? So it, the early rise in HIV did not, was not met with su-a sufficient response by the NIH. Look, we're talking very ear-very early, in the early '80s, of money going to research on this vital topic. And, and it was the political movement of HIV patients coming together saying, "Look, it's really important that we address this," that led to the NIH, uh, actually taking that real public health threat seriously, right? Um, the s- if you leave it to scientists themselves, or our, I should say ourselves, I'll say two things. One is we don't reflect the will of the people. Like, we d- we're not good at mediating between different population groups. I mean, and it's, it's not right, right? There's no philosopher king that can decide, uh, "Well, this much money should go to HIV, this much money sh- sh- uh, should go to cancer, this much money should go to pediatric conditions." It, it's the will of the people. And so really, I don't see any other way to do it. You know, like, what was it? Like, W-Winston Churchill saids- said that democracy is the, is the, is the worst, uh, worst system of government on, on Earth, except for all the others. I mean, w-we don't have a philosopher king. Leaving it to scientists is not an answer. Like, y- the people really should have some say in where, where that allocation happens, I think. Um, the other part of it is that, frankly, I mean, this is something related to the r- the, to the, what we just talked about before. Scientists, if you ask us, we're not actually good at predicting the future of the, of future in terms of, like, our, uh, will this investment result in productivity? I mean, uh, actually, frankly, neither is Silicon Valley, right? The... You can't say, you can't promise me that every single project you pick is gonna work for your portfolio. You cannot, right? Um, and so scientists play a vital role in deciding what scientific opportunities there are, letting us know, and then we can deci- make decisions. But the portfolio decision, that's a, that's, that's not exactly a scientific decision. That's an economic, small, microeconomic, small, small E kind of d-decision. And then the, the macroeconomic decision is where are the disease areas we should go to. It really shouldn't just be scientists that decide that. Of course, there's an interplay, right? So if there's a scientific opportunity in a particular area, I want to be able to reflect back to Congress and say, "Well, this is a great area. You should fund this right now," 'cause, you know, there's huge advances in cell-based therapy for sickle cell disease. We definitely need to fund that, right? And they'll, and then, then Congress can move based on that scientific opportunity. But that's an exchange between, uh, you know, the people and, and the scientists, not just a one-way street.

   11. VAVineeta Agarwala22:20

       No, I like that.

   12. ETErik Torenberg22:21

       So I-

   13. VAVineeta Agarwala22:21

       That's insightful.

   14. ETErik Torenberg22:21

       It's awesome.

   15. JBDr. Jay Bhattacharya22:22

       Yeah.

   16. VAVineeta Agarwala22:22

       Yeah. No, I mean, it seems like a more interdisciplinary approach to allocation and execution, um, that includes an understanding of how much we're spending, how much it costs on a go-forward basis, what the economic impacts might be of getting the research right. Um, no, thanks, thanks for sharing that view. I think it's important for people to understand that you're trying to bring more voices to the allocation question and more rigor to the execution question, but both are not as straightforward as it may seem.

   17. JBDr. Jay Bhattacharya22:56

       Yeah. It's a, it's a, this is a weirdly complicated job. Uh, I thought being professor was complicated, but this turns out this is a little more complicated than that.

   18. VAVineeta Agarwala23:02

       [laughs]

   19. ETErik Torenberg23:03

       Are, are, are there certain areas you feel were under-allocated or over-allocated, if, if you could, uh, you know, just wave a wand?

   20. JBDr. Jay Bhattacharya23:10

       Oh, we're all-- It's e- every area is under-allocated, of course.

   21. ETErik Torenberg23:15

       [laughs]

   22. JBDr. Jay Bhattacharya23:16

       I mean, you almost suspect it's... I, I mean, I think, um, the thing is about the u-under-allocation is I don't know if it's a question of money. Um, but if you look at, uh, the trends in public health over the last decade and a half, w- the United States has seen no increase in life expectancy. Um, we have enormous overhang of, of patients, people with heart disease, ca- uh, with the, the, the r- the... Actually, cancer, we've seen big improvements in, in life expectancy or, or sort of, uh, life expectancy after getting cancer, but, but huge increases in the incidence of cancer. Uh, type one, uh, type two diabetes, autism, we've talked about, a whole host of other chronic conditions. I mean, uh, and we've made big advances in other places, right? So the question is, like, uh, uh, how can we address the biggest health needs of the country, right? It s- it seems like we're really good at, like, at, at, at... and we should be good at, um, so some, s-s-some of the, some, some, some conditions that have lower prevalence. Like, we've made tremendous advances in HIV. That's a huge cause for celebration, right? Uh, we still have f- some way to go. Forty thousand people got HIV last year. We can end the HIV epidemic. We should still invest in that. But at the same time, what about all the people that died of heart attacks? What about all the people that died, d-died of, have, have, you know, type two diabetes, that are suffering from, you know, b-blindness because they're, uh, they, they, you know, 'cause they have, uh, you know, uh, bleeding in their eyes or in their retinas? I mean, like, so you have, uh, what, what about the, the people with kidney failure that, that are, the, the prevalence is rising? What about all... We have to, we have to look at the practical health needs of the countryThat are people are-- where people are suffering and make sure that we a-address our science to those things. It's... And then we-- I, I don't think we've done that as much as we ought to. And if you look at the macroeconomics, you don't have any increase in life expectancy in this country in over a decade. Um, science isn't the only reason why. Like the po- the, the, the fact that the NIH-- I mean, the NIH contributes to that, but, uh, it-- but it's not the only answer. Obviously, it's very complicated. Um, but the NIH ought to contribute to that. Things-- the science we do should translate over to better health for people. And so really those areas where people are suffering the most, uh, that's where I want our, our, our sort of is-- I, I would say is under-allocated.

   23. JCJorge Conde25:18

       I love this idea of, of comparing, uh, or, or analogizing the NIH to almost like a portfolio manager, right? Where... And, you know, similar to what we do as, as venture capitalists in Silicon Valley. And if I really wanted to abuse your analogy, which I, I will if you'll allow me for a second, you know, the people are almost like your limited partners. They're the ones that tell you, "These are the sort of the theses and the fund areas we want you to go after." And you all are the, the investors, the venture capital investors that have to do the portfolio management and picking and all that. You said a few minutes ago that a lot of the grants in the NIH are going to older ideas, and there's, you know, lots of data that shows they're also going to, you know, more established, you know, older scientists, you know, at, at the very high, you know, uh, highly regarded institutions. Um, the equivalent of that would be if we only funded, um, 30-year executives that came out of, you know, large established companies and ignored, you know, the young up-and-comers, you know, coming right out of uni-university or, or dropping out of school or whatever. Um, you've talked a little about, you know, that question. Like, how do you reform the process,

9. 26:23 – 31:23

   The Challenge of Supporting Early Career Investigators

   1. JCJorge Conde26:23

      the, you know, the execution, to use Vineeta's, uh, phrasing, on selecting for the, the innovation that, if you will, bubbles up from the bottom?

   2. JBDr. Jay Bhattacharya26:33

      It's a, it's a hard question, actually. It's something that's at the top of my mind. Um, and actually, the-- what you just described is exactly what we've been doing in science for a long time. So in the n- the, the, the data out of the NIH is that from-- in the 1980s, if you were 35, you actually had a chance of getting a large NIH grant. Like, that was the me- the, the, the median age of the first large NIH grant, you were 35 years old. Now, you're in your mid-40s. We tell young investigators, "You gotta do postdoc one, postdoc two."

   3. JCJorge Conde27:01

      Which, by the way, super young, to be clear. Mid-40s, super young.

   4. JBDr. Jay Bhattacharya27:03

      [laughs]

   5. JCJorge Conde27:03

      Just wanted to be clear about that.

   6. JBDr. Jay Bhattacharya27:04

      Super young. I mean, I'm fift- I'm 57, so like, I don't... I mean, that's all... They all seem like babies to me. But, um, um, but the, but the thing is, you have, um, the, the... Just like as, as in Silicon Valley, the new ideas come from younger, younger investigators, right? So I, I did a study a few years back where I looked at, uh... It turns out that the age of the ideas in your published work ages by every, uh, by, by one year for every year of chron-chronological age. So my ideas get one year older every year [chuckles] that I age. Uh, the, the very best scientists fight like crazy to stop that, so every two years of chronological age for Nobel Prize winners, their ideas and their papers age by a year. If you want the newest ideas, you have to let the, the young people have their, have a try. Um, and we're just, just bad at that. Like, young people, we fund, we fund them, and then they drop out, and they leave for, for other places. Uh, that wasn't true back, uh, like the back, back in the '70s and '80s. The, the culture of biomedicine says you have to have one, two, three postdocs before you have a shot at an assistant professor job. Um, and as a result, the ideas that we, um, support are just, uh, they're just older. I mean, not, not necessarily a bad thing. I mean, of course, you should, in the portfolio, have some support for older ideas that we're, that are still promising. But if you don't also fund, uh, some of the newer ideas, the portfolio is gonna produce fewer advances as a whole than if you, than if you do, right? You have to have a, a... You have to diversify in that sense. Uh, to solve that problem is hard. So the, the NIH has been trying to solve this now for, for two decades, and we made no progress. Um, so first, uh, we have to, we have to, I think, um... I mean, I'll just give you some sense of wh-where we've gone backwards. Uh, you know, uh, we, uh, used to have a, uh, a system of peer review where in order to be a peer reviewer, you had to have a, a large grant. Now think about that. I got a large grant. I'm in my f-50s, and, uh, I see an idea that challenges my 30 years of work.

   7. JCJorge Conde29:08

      [laughs]

   8. JBDr. Jay Bhattacharya29:09

      And, and [chuckles] I'm on this, I'm a reviewer on a panel. It's really hard to, like, me- open your mind and say, "Well, I might've been wrong." Um, that system, uh, now that got changed, but now this-- so that we no longer have that rule. But, like, it's the, it's the mindset. You, you have to allow, um, uh... Now, so what I've done is I've, I've asked the, uh, institute directors, I've given them the authority, essentially, to expand what they can do, uh, in terms of the portfolio. I'm not gonna judge them to make, just like with in Silicon Valley, I'm not gonna judge them to s- uh, on the, uh, does every single grant succeed? I'm gonna judge them on the portfolio as a whole. Does it translate over to better health for the, for the people that they're, for the disease that they're, like, trying to address or the dis-diseases they're trying to address? Does it result in big advances in biological knowledge, right? I'm gonna assess the portfolio as a whole. And then the other thing is I've, is, is that does it match the strategic vision of the insti- the institutes, they have these, like, fantastic strategic plans. Like, you know, you go look at them and say, your, your eyes will say, you, you look at them, and you go like, your eyes will get big with the science that they're proposing. And yet, what they actually end up funding based on their peer review panels is often you'll get 10 great proposals on one part of the strategic plan and, like, nothing on another part of the strategic plan. Um, and so, like, you... I, I'm gonna encourage them to be able to pick the portfolio so that it matches the strategic plan. Um, uh, I'm gonna reward them for a, for rewarding and empowering ear-early career investigators more, right? So, uh, I'm gonna build incentives into the, uh, the decision-making at the end, at the, by the institute directors so that they have incentives to solve these longstanding problems. We have to solve the, the new investigator problem. And I'm gonna start to evaluate, um-Long-established investigators, 'cause I th- I do believe they play a pretty fundamental role still. Uh, but in the, in, in, in like how well do they advance the careers of the early career investigators that work with them, right? So if they're good at that kind of mentorship and at career advances, I'm gonna, I'm gonna reward them, um, in, in the, in their grants. I'm gonna start evaluating the grants for that, for, for that too. So 'cause the, the, the grant portfolio has to be, uh, sustainable in the long run in producing new ideas. I mean, just that's... We should-- We need to just... And if we don't have the early career investigators, uh, sort of getting the support they need, we're, we're gonna start to stagnate.

10. 31:23 – 35:46

    Allocating Grants and Training Under the New Administration

    1. VAVineeta Agarwala31:23

       I love to hear the interest in advancing early career investigators, but we can't have that conversation without talking about the universities from where they tend to come. And so, you know, I was a product of NIH MSTP funding. I did my MD-PhD, um, with the generous support of the NIH, and my peers and colleagues, um, you know, in my class and, you know, decades, um, behind coming up get trained on those grants today. How, how can you work with, um, [lips smack] you know, with the administration to ensure continuity for the training grants that, you know, NIH does believe are going to fuel the pipeline of early career investigators who, as you say, you know, are perhaps most likely to bring change, big ideas, you know, and take big swings.

    2. JBDr. Jay Bhattacharya32:21

       Yeah. I mean, we al- we... As you know, we, uh, you were, you were biophysics, right? So we have, we have a range of, a range of like ways that we support early career investigators, right? There's, so there's, um, there are these awards for pre-docs, pre-docs meaning undergrads. Um, and, uh, that's really important. Like, we wanna make sure that the undergraduate, uh, um, the, the, the very talented undergraduates who are interested in biomedicine and research biomedicine have, have the support to do this. Um, uh, if, if, uh, i- there's also like, uh, support for, uh, for p-postdocs, right? So, uh, uh, for, for, for people who are getting their PhD and then postdocs. Um, I wanna s- it's gonna be hard, but we have to structure things so that, um, uh, that, uh, the, um, uh, the range of investments we make actually translate over to people wanting to stay in biomedicine. I mean, that we have a lot of people who drop out, but I think the main problem isn't th-that, that support for the early... I think we have a lot of portfolios pretty good on, on that. We could do better, but, but that's pr- it's pretty good. The problem is, like, after you've had this career in biomedicine, c- how do you... Like, do y- of, of, of this c- r- research training or do you have support to, like, make the next leap into an assistant professor job? And too often, um, it's too hard to do that. You can't get the support you need to do that. There's k- these K Awards that we have that, uh, it's really difficult to get them. Um, I think we have to do better at that, and we have to reward universities that are better at that. Um, it, it, there's problems all across the system, but I think that miss- that missing-

    3. VAVineeta Agarwala33:51

       Mm-hmm

    4. JBDr. Jay Bhattacharya33:51

       ... link is really the, you know, you finish your MD and your PhD, and then w- can you get that assistant professor job or are you gonna be asked to do 17 different, uh, postdocs before you have a chance? Uh, right now that system is set up to make it difficult.

    5. ETErik Torenberg34:05

       You, you mentioned earlier that we're not making advancements in, in life e-expectancy. Um, w-why are we lagging? W-why, why are some European countries doing better, and, and, um, what are the highest leverage points you think to, to, to get back to improving there?

    6. JBDr. Jay Bhattacharya34:19

       Well, I think, I think the key thing is we have to... A lot of our science is, is, you know, this replication crisis we talked about earlier is very important. Um, we have to solve that. Uh, uh, that, that, that will help a lot. Um, and then this portfolio thing, I think both of, both of those things actually will, will, will, will, will address the sort of, the scientific rigor problem and the sort of conservatism problem. Um, as far as like addressing life expectancy, um, that, that really needs to be... It's in a sense not just a scientific problem. Like we have to, we have to essentially get a message from the people that we want, that, that they want scientists to address those problems. Like, that's, it's just what we talked about earlier, the politic- political, um, nature of, of, of, of that kind of allocation decision. Um, but you know, that's exactly what the Mahabru movement represents. The Mahabru movement is a n- it's basically a cry for help from the American people saying, "Look, all these chronic disease problems, all these problems with our k- uh, that, with our kids, and we're sick. We're much, doing much worse than folks in, in Europe, um, in terms of our health. We just..." I mean, it's, it's, uh... And, and that essentially is a, a call for the NIH to reform itself to address those problems. It's a, uh, and to me, it's a tremendous opportunity. Um, and, uh, you know, this, this is why I a-agreed to take this job. I mean, I was perfectly happy, uh, being a professor, uh, [chuckles] um, but it's, uh, but it's, you know, a once in a lifetime opportunity to make the NIH really work for the American people. Um, s- you know, a-and I think h-having that political movement behind me, behind us is really important for that.

11. 35:46 – 38:34

    Academic Freedom and Scientific Publishing

    1. VAVineeta Agarwala35:46

       Last week you announced, um, some really interesting initiatives around academic freedom, and many folks know your voice kind of reached the national stage, uh, in part because of your ardent, um, [lips smack] desire to see academic freedom respected, protected across the country. And, you know, it sounds like you're looking for ways to improve publishing fundamentally so that people feel freedom at all levels, including early career investigators, um, to share their view on science that they think might be interesting. And we need to figure out, to your point earlier, uh, how to make the point that anything published is not necessarily fact, but it's one opinion backed by one set of data and one set of analysis and one set of perspectives, and you'd like more of those to flourish in the public arena. Say more about, um, the role that you want NIH to play in protecting academic freedom.

    2. JBDr. Jay Bhattacharya36:42

       Of course, at the NIH, um, I found out that a lot of folks at the n- internal investigators at the NIH, in order to publish their work, had to seek-Permission from their supervisors. I changed that. Like, no more, no more permission. You-- If you're an NIH researcher, you have a scientific paper, you don't have to get permission from me. If I... You know, people are gonna publish research that I don't agree with. Uh, that's, uh, it's wonderful. Um, they should be able to do that. Um, also, the, the, the, the, the places that, uh, like the universities, I think, need to be pl- absolutely committed to academic freedom for s- excellent science to happen. Um, and, uh, you know, like, there's been a lot of like, uh, uh, angst over the, the, uh, the administration's actions with the universities over the last, uh, uh, few months, um, uh, regard- holding them to high standards regarding, you know, antisemitism and so on. Um, uh, but there's also been a mis- message that we really do want academic freedom at the universities. Scientists to really be able to say what they think and be, and, and, and explore where they will, uh, or else they're not good environments for research. Um, a-as, as far as journals, that is a complicated question, but there's-- The pr- the problem right now is that the scientific journals, there's essentially a, a, a duopoly. A very, very few number of scienti- uh, co-companies, for-profit companies, control a very large number of journals, and they charge tens of thousand, ten thousand dollars per article for science that they didn't do, that the American people paid for. They, they want... They actually had a, uh, a pr- a, a, a sort of a, um, if you-- uh, a policy where, uh, if a regular person wanted to go find a scientific article, um, they had to go-- There was a paywall where they pay like fifty, a hundred dollars. Uh, we got rid of that paywall for s- NIH-funded research. Um, there's still a lot to do in this area. We need more f- academic freedom. We need more openness in scientific publishing, and I, I'm working on policies to do that.

    3. JCJorge Conde38:29

       So Jay, you know, one of the w- one of the key questions if, you know, for the, for the American

12. 38:34 – 41:57

    Rebuilding Public Trust in Science & Public Health

    1. JCJorge Conde38:34

       public, they're looking for, for better, uh, outcomes, better health. One of the big avenues that, of course, this country uses, and it really had as a gold standard in the past, is, um, you know, having this extraordinary public health infrastructure. But I think what's also true is over the course of the last several years, there's a lot of, of mistrust now in terms of public health. Um, how do you sort of rebuild that trust for the public? Because obviously, you know, if there's no trust, the, the, the, the message can only be so effective. And so how do, how do we build those bridges back, uh, to the extent that you think they need rebuilding?

    2. JBDr. Jay Bhattacharya39:09

       You know, I think the problem with public health, uh, and the lack of trust in it, you have to point to the pandemic. You have no choice, right? If you look at, you just think back to the, the pandemic, and you remember the plexiglass that was everywhere. That's, you know, there's still... Every time there's see a plexiglass, it makes me, fills me with rage, but that's another story. Um, and there was no science mar- behind that, right? There was the, there was like the, you wear a mask when you walk into a restaurant, and you take it off when you sit down. You know, you, uh, again, no science behind it. Um, a whole host of, like, things, and espe- there were really damaging things like closing schools, where, again, the science was so weak that it, it, that, uh, uh, and it, it, it, and yet now kids are, like, years behind in their, in their education as a result, uh, where, and they'll be paying the price for that for years. Um, and so a, a lot of pub- the American people have lost trust in public health for reasons I can completely understand. Um, and so the question then is, what can we do about it? Uh, and to me, the, the key thing is there's two things that have to happen, like two, two very broad things. Like one, um, I, I, I think we have to restore gold-standard science. Like that, that presidential EO on gold-standard science is so important 'cause what it says is it articulates things that we thought a-all science already knew, uh, and, and are committed to. Like replication is really important, uh, f- uh, unbiased peer review, humility in how we talk about the limitations of our scientific findings. Um, there's a whole host of things where you read it and go, "Wow, this is, this is-- I thought science already did that." And, um, so if we actually do that, I think that, that's a b- major part of this. The second thing is we have to, just like we talked about earlier, about the role of the people and the pol- and politics in deciding what scientific priorities to, what, what, like, areas of science to fund, and then scientists to decide what priorities within the science areas to fund in, in the portfolio analysis. Um, w-we have to convey to the pe- to people that the, that we are their partners in scientific investigation and in public health. Um, public health, folks in public health are servants of the people. And too often during the pandemic, it came across like we were, we were sitting above people, right? Telling you what to do, uh, telling you, "If you don't take this vaccine, you can't go to work, you can't get a job." You, you know, I mean, there, there, it was, it was, um, it was heartbreaking to watch because if... Uh, I believe very fundamentally that when science, uh, works as partners with people, like through... And ser- and has this at- this almost servant attitude toward people, you can do a lot of good. You can do a lot of good. Um, but I think really that kind of humility and the return to s- to sort of, uh, gold-standard science, that's the way to solve the problem of trust. It's gonna take a long time, though, um, 'cause I mean, I've talked to so many people around the country, and it's, it's not, um, we're nowhere near solving that public trust problem.

    3. JCJorge Conde41:52

       Yeah, and I think it's, it's an, an especially challenging thing as you look forward, um, uh, and I'd love to hear your

13. 41:57 – 48:58

    Communicating Uncertainty & Scientific Honesty

    1. JCJorge Conde41:57

       thoughts on, you know, how do you convey, uh, you know, uh, recommendations and guidance in the face of uncertainty and incomplete information, right? To, 'cause going back to your point, like in an ideal world, you're always resting on top of gold, of, you know, gold-standard science. You know, but, you know, a lot of times science, i, you know, there's a lot of unknowns in the science. Science is hard, going back to what you were saying earlier. And so how do you communicate to, you know, a population, a nervous, a nervous populace, you know, a sense of, of, of a recommendation or, or even guidance in a, in a world where you yourself have incomplete information?

    2. JBDr. Jay Bhattacharya42:34

       I think you just have to be honest, right? So if I, um, asked a question about, I mean, God forbid there's another pandemic w- uh, during my watch, and then, and then I'm asked, "Okay, how should we manage? Uh, ch- is, is it right to wear a mask or something," right? Um, and I don't-- uh, there's no good scientific evidence. I'm gonna just say that.I, I, you know, the, well, the, if the analogy accurate, I, I was a medical student once. I've done an MD, so like I, I can tell you this from firsthand experience. Your, uh, the first two years of med school, you do a bunch of classwork. The third year, you finally get to see patients, right? So you go walk into a pa-patient room and, uh, you're wearing a white coat and you know nothing or very little. I mean, you know all, you could fill with knowledge about biochemistry. You can like write, you know, chemical equations till your, um, your fingers get tired, but what you can't do is understand what a patient really needs. Um, and so you hear, you sit down in front of the patient. The pa- they tell you their stories, wonderful, like they, they, they put their trust in you. Um, and you are tempted to tell them things, uh, to answer their needs that they're asking you, but you don't know the answer. You just don't 'cause you're a third-year med student. Of course, you don't know the answer. And there's a, there's a, like, y- 'cause you're wearing the white coat and because the, you have someone looking at you wanting the answer, um, putting their trust in you, you feel this urge to like say things you don't know. Uh, you know, you, you start like freelancing. Um, and that's just a terrible mistake, right? As a third-year med student, you learn that you should just say, "I don't know. I'm gonna look it up. I'll look, go look the answer for you. I'll get back to you. Um, I'll consult with people who know more than I do." You have to be humble, and especially in the, in the face of new things, you know, new h- new, new pandemic or new or, or s- genuine scientific uncertainty. We in public health have to be humble and say, "Look, I'm, we're not sure, but here's how we're working to try to get an answer." Um, we're gon- a-and we have to convey that uncertainty, and we can't blame the public. Now I've, I've gone around and talked to lots of folks, uh, in, in public health and science, and they're like, "Well, what we have to do is we have to teach the public more about science and t-make sure they understand that science isn't always perfect and science like moves, w-well, you know, you may have a, a, eggs are great one day and eggs are terrible one-another day. That's because we have new science." To me, that's like blaming the public. It's not the s- the public doesn't understand that science is hard. They understand it fundamentally, like they just, this is not a complicated thing in, in, in the sense of like, um, I mean, every-everyone knows w-within the public that science is hard. The problem is that scientists conveyed certainty about things they had no business conveying certainty about and then changed people's lives for the worse as a result of it during the pandemic.

    3. VAVineeta Agarwala45:12

       I was gonna say, well, uh, I acknowledge that there, you know, that the pandemic was a particular challenge, um, with respect to both communication and certainty in the midst of uncertainty. But how do we acknowledge that challenge and not lose trust in some of the bedrocks of public health advancement that we've made over the last several decades, whether that's newborn vaccinations, you know, HHS held, um, held a listening tour and, uh, an advisory update on Hep B vaccination in, in babies, and it's great that we're looking at all of the data holistically there. But in some of those cases, you know, some folks would argue there is substantially less uncertainty than there was in the wake of a new pandemic with a new virus, with no data, with new, you know, completely new infections, you know, than there is in the context of something like a Hep B. So how do we, you know, and please don't feel the need to respond to that specific, um, vaccine example, but how do we not make it so that even when you do have relative certainty, and you come out and say, "Hey, we really [chuckles] this is not perfect, but we we're pretty darn sure this is a good idea," um, how do you then make it so that people don't say, "Well, you know, last time you said you didn't know, so I don't know"?

    4. JBDr. Jay Bhattacharya46:33

       Right. So I, I, I think, um, "I don't know" is a good answer when you don't know. When, when you have a, a little more evidence, a lot more evidence, like just take the MMR vaccine. Like The, I mean, if you wanna prevent measles, take the MR- MMR vaccine. Re- I mean, it's the best way to prevent measles, and measles can be a deadly disease. Like I vaccinated my kids with MMR. I was really happy I did. Um, uh-

    5. VAVineeta Agarwala46:53

       Me too. [chuckles]

    6. JBDr. Jay Bhattacharya46:54

       And, and I think that that, um, [chuckles] you know, I, I think that that kind of, um, certainty, it, it, you know, it's science, right? So you're, n-nothing is known, like to-tomorrow that someone might come along and they overturn, you know, Newtonian physics, and all of a sudden you're talking about relativity or something, right? That, like, it's po- you'll always leave open that possibility. Um, but some things we do know with certain- with like much more certainty. Um, I, I, I'm a, I'm not saying that we should all have false humility. I think we should have humility for the things we just should actually have humility about, right? Um, uh, but at the same time, when we have an area of more scientific certainty, we have to leave open f- room for academic freedom so that people can have their say, that, that, that, that, that, that think differently. Um, we don't cancel them. We don't, we just, we reason with them and we say, "Look, you, you think, you think, you say X, Y, and Z, but look at all this other evidence for..." MMR is a good example. "Look at this other evidence that, that, um, that, that shows you differently." And they'll just have a public discussion. It's okay. I mean, it's okay to, to have that contradiction. Um, and then, and then, um, and then the, and the, I think what will come across is when there is actual excellent science replicated, um, I, I, I maybe I'm naive, maybe I'm, uh, na- uh, but I don't think so. I, I think that wins scientific debates, and you can look, uh, there's evidence for this, right? So the uptake of MMR in this country, the MMR vaccine is like ninety-five percent of American parents vaccinate their kids for the MMR. The evidence is that, and, and I think it's like thirteen percent of American parents vaccinate their kids for the COVID vaccine. I think that reflects the scientific evidence regarding the relative merits of those vaccines. Uh, the American people are not stupid. In fact, they're quite smart, and when we talk to them in ways where we show respect for, for their, their, their intelligence with d- with data, allow people to disagree, but then have the evidence right there in front of people. I think people, people will respond with trust, uh, w-where the evidence actually leads. Um, I mean, I just, I, yeah, maybe that's just a matter of faith for me, but I, I don't see any other way

14. 48:58 – 54:15

    NIH Priorities: Nutrition, Chronic Disease, and AI

    1. JBDr. Jay Bhattacharya48:58

       forward.

    2. ETErik Torenberg48:58

       You mentioned that the, the three priorities of NIH that you have are nutrition, chronic disease, and integrating AI. May, maybe can you, uh, flesh out a little bit on, on the last two, wh-where what you see as most promising in terms of reducing the disease burden, and then also in terms of integrating AI?

    3. JBDr. Jay Bhattacharya49:14

       I, I've seen some, like, fantastic new ideas regarding, uh, Alzheimer's disease, for instance. A, a colleague of mine at Stanford did a-- had-- has this, like, fantastic paper he pub-pub-- set of papers he published using an old shingles vaccine called Zostavax. Um, found-- he found that, uh, in excellent observational studies that it re- uh, that if you had Zostavax, it reduces the likelihood of developing cognitive decline for Alzheimer's disease by up to twenty percent, thirty percent. I mean, it's pretty substantial for a, a pretty innocuous, safe vaccine that's no longer used, actually, 'ca-''cause it didn't work for shingles. Um, I mean, imagine if you had a very simple, cheap way to prevent thirty percent of Alzheimer's cases or delay Alzheimer's for, for years. There's a-- there's all these, like, uh, huge advances, uh, I've seen, uh, that, that, you know, just need a little bit of scientific love. I, I think we just need to focus on those, have the d- make our portfolios focused on those, be willing to take risks in terms of, like, um, on things that look like they're, they're new ideas. Um, and we're gonna, we're gonna make a lot of progress. And AI, by the way, I think is gonna play a tremendous role in that. I, I just... You know, everyone knows about the protein folding in AlphaFold. That has done an amazing job in, in turbocharging biomedic-- uh, uh, dr-drug development, 'cause now you, you don't need to, like, sit there and wait and, uh, uh, for... And, and you can just do your, your, uh, um, your computations, figure out what the, the-- how the protein folds, what the target sites will look like, and then ask which of these drug products are, like, more likely to actually work, um, without having to do m-very expensive biological-- you know, in, in, you know, lab work. Um, you still have to do the lab work, but it focuses lab work in more promising ways. Um, in, uh, in the way that we deliver medicine, right? So you can have AIs help, uh, radiologists do a better job at, at making sure they catch things, make-- catch everything. Um, uh, uh, even simple things like, you know, you go to your doctor, the doctor sits there looking at the computer the entire time rather than at you because they're, like, filling out their, the electronic health records. Have an AI assistant listen to the conversation, fill, fill out the form for the doctor so they're just checking afterwards. It takes them a couple of minutes, and they're spending all their attention on you, right? Um, uh, all of this needs research, by the way. I mean, does, does this gonna help patients? We have to ask those questions. But to me, that's a tremendous promise. Like, those simple things can transform biomedical research and how patients are treated. Um, so that's why AI is so, so important to me as a, as a potential tool. It does need research. I mean, I don't wanna, uh, we can't have AI hallucinating on us and, and then, then treating patients based on hallucinations. But, uh, you know, that's, uh, that's, that's a matter of research to fix those kind of, uh, those, those kind of problems.

    4. VAVineeta Agarwala51:51

       We heard that HHS, um, rolled out across, you know, agency-wide, um, an enterprise secure version of ChatGPT, which is, um, seems like a, a terrific achievement from the perspective of internal HHS and NIH operations even, right? To be able to look up internally how new is an idea. Um, simple, simple queries and, and data kind of fluidity of that kind seems important. What's the future? Is an AI going to write the institute's strategic roadmap and an AI submit a grant and an AI review panel review the grant? And, you know, where, where are we gonna play a role as scientists?

    5. JBDr. Jay Bhattacharya52:34

       I mean, I, I don't... I... Okay. So [laughs] to that question-

    6. VAVineeta Agarwala52:38

       The answer is no. [laughs]

    7. JBDr. Jay Bhattacharya52:40

       Uh, yeah. I j- I mean, I think AIs are really good at summarizing existing knowledge. Like, the, the training data you give it helps it un-- it g-gets-- it's fantastic at that kind of thing. Um, really developing brand-new ideas that, like, that, that challenge existing paradigms, I, I don't... I mean, I don't your, your experience with AIs, but they're not quite as good at that. Um, it's real- it's, uh... We have-- I've just, uh, put a new policy in place where, um, I'm limiting the number of new public applications you can have. Like, uh, to-- we can have, you know, six a y- six a cycle or something. We have people writing sixty applications, and very clearly AI-generated. And then we have, you know, the-- it's, it, it, it's, I mean-

    8. VAVineeta Agarwala53:20

       Yeah. That's the, that's maybe the present, not the future

    9. JBDr. Jay Bhattacharya53:22

       ... what it does, it overwhelms the system with noise.

    10. VAVineeta Agarwala53:23

        Yep.

    11. JBDr. Jay Bhattacharya53:24

        Yeah. So I mean, I think AI is really important, as I, as I said. I think it's-- But it has to-- we have to do research to understand how it can be used to help people. Um, and I think people, scientists are still gonna [laughs] have a tremendously important role. Um, the, the, uh, the new AI system rollout at NIH is just as exciting. We're actually been working on a new system also at, at-- specific to NIH, again, to protect, uh, in ways that, that protect patient pri-pri-privacy and all that. But a, a, a, uh, uh, rolled out across the NIH so that people can, like, interact with it in s- with, with, uh, uh, in ways that help v- uh, NIH-specific tasks as well. Um, so I, I mean, I think that's all very exciting. But it's an augmentation of capacity rather than a substitution of capacity. Uh, it'll make people way more productive. It'll help us address some of the key problems. But scientists are still gonna... I mean, we [laughs] still, we still have work to do as scientists.

    12. VAVineeta Agarwala54:14

        We

15. 54:15 – 56:37

    Advice for the Next Generation of Scientists

    1. VAVineeta Agarwala54:15

       do. If I could just end on one, one last question. If you had one message for the rising star scientist contemplating a career in science where they can bring the best of their abilities to making science better, smarter, faster, you know, a scientist embarking on a new PhD in a, in a brave new field, um, a scientist thinking about starting a new company to advance the work that they're doing, a scientist at the NIH running a lab, wh-what is your one message to the individual scientist who's out there, um, you know, hoping, hoping to make the, the biggest impact they can?

    2. JBDr. Jay Bhattacharya54:56

       I mean, sci-science is incredible. Like, it has almost limitless capacity to, to advance human well-being. Um, and, uh, it's the, it's the individual scientistsWho believes in their idea, you keeps knocking on the door even when the, the door is closed over and over again until it opens. That's, that's who really makes a big difference in this world. Uh, I would say please stay, stay in science, keep knocking on that door, um, and make-- and, and change the world with it 'cause that's the on- that's only the only way the scientists can, can do that. I, I love the story of Max Perutz. I don't know if you've heard of him. He was a University of Cambridge, uh, researcher in the, I think the fifties, and he had this idea that he could figure out the structure of myoglobin, which sounds like a very geeky kind of thing. It's like, but it's, uh, but back then there was no protein folding field really. I mean, it was like in... And, and he was a student, and all his professors kept telling him, "Pick an easier problem, Max. This is crazy. Why are you spending all your time? You're never gonna finish." And for a decade at the University of Cambridge, he wandered around. Everyone knew he was a genius, but he was like, got nowhere. He's just not just working at it until finally he figured it out, and it's just transformed a, like a whole host of things in biomedicine, um, uh, and, uh, you know, eventually won the Nobel Prize. It's, it's, um, you know, it's the kind of thing where I ask myself, do we have a scientific, uh, sort of infrastructure today that would allow a Max Perutz to do what he did back then? And, and I would love to, that the, to make that happen through the, the, the, the sort of the power of the NIH, to allow the Max Perutz of the world, the, the new ones who are now, uh, uh, sitting there with great ideas to be able to m- to, to ha- to, like, try them out and, and s- m- and change the world with them.

    3. VAVineeta Agarwala56:34

       Fantastic.

    4. JCJorge Conde56:36

       So m-maybe

16. 56:37 – 58:51

    The Role and Limits of AI in Science

    1. JCJorge Conde56:37

       on, on that, on that note, just looking to the future, um, if we, if we end where we started, where, you know, uh, you talked about the NIH's highest ambition is to improve the health of the American people, whether that's measured in life expectancy or, or the, or the, the rate of chronic disease, um, that, that, that Americans suffer from. If you had to guess where we're gonna see the biggest and best gains, d- is that going to come from, you know, how we manage patients, so the management of disease, um, you know, new molecules for treating disease, or modifications in terms of how we all live?

    2. JBDr. Jay Bhattacharya57:14

       Yes. [laughs]

    3. VAVineeta Agarwala57:16

       Yes, yes, yes. [laughs]

    4. JBDr. Jay Bhattacharya57:17

       Yes to all of the above. I mean, you know, I, I, I am a big believer in portfolios when I have uncertainty, so I don't know how to answer your question, uh, because I, I see promising advances in all three of those th- all, all three of those topics, and I think we have to invest in all of the above in order to see where the most promising things go. Like, uh, who would have predicted that the GLP-1s, you know, the, the, would, would... Actually we had, we saw a reduction in average body weight in the, in this country the first time in, you know, decades last year 'cause of a Gelo- Gelo monster molecule that somehow turns out to, you know, when you, if you just do the right biology. [laughs]

    5. VAVineeta Agarwala57:54

       There was a scientist knocking on some kind of door to make that happen, right?

    6. JBDr. Jay Bhattacharya57:58

       Yeah. I, I just, I, I mean, you know, it's a sci- that's the only s- thing about science. It's, it's hard, it's hard to predict where, where the, where the best things are gonna happen, and so you have to, like, have a portfolio. But all of those areas to me sound, look like they're very promising, and as I've gone around the country talking to people, I'm, I'm excited about all of it, so I can't wait to see what we produce.

    7. JCJorge Conde58:15

       Do either of you have a prediction to that question, or is it also, uh, kind of- Well, this is the debate we have every week- [laughs] ... in terms of where we wanna invest, you know, that-

    8. VAVineeta Agarwala58:23

       Our answer is yes, yes, yes too.

    9. JCJorge Conde58:24

       Correct. All of the above. [laughs] Uh, well, that's a great place to, to close. Uh, Dr. Bhattacharya, thank you so much for coming on the podcast.

    10. VAVineeta Agarwala58:32

        Thank you.

    11. JBDr. Jay Bhattacharya58:32

        Thank you so much.

    12. JCJorge Conde58:33

        Thanks for being here.

    13. JBDr. Jay Bhattacharya58:33

        Have a great day. [upbeat music]

Episode duration: 58:59