An Exit Interview with N.I.H. Director Dr. Francis Collins

Hey there, it’s me, Bapu. Today on the show, we have a special guest for you.

BAPU: What do you prefer to be called? Do you go by your first name? What do you prefer?

COLLINS: Go by first name, please.

That’s Dr. Francis Collins. For just a few more days, he’s the director of the National Institutes of Health. The N.I.H. is the main federal agency funding health-related research in the United States. Each year, the N.I.H. spends about $42 billion in funding for medical research at its own labs and through grants to outside scientists. So, pretty important always, but especially now.

Research funded by the N.I.H. has paved the way for treatments in cancer, heart disease, mental health, H.I.V., rare diseases — the list is practically endless. And of course, the N.I.H. has played a huge role in the fight against Covid-19.

By the way, full disclosure: I have received some N.I.H. awards and grants for my research, and I wouldn’t say no to more.

Anyway, Dr. Collins has been N.I.H. director for 12 years. He’s served under Presidents Obama, Trump, and Biden. That’s pretty rare for a political appointee. In fact, Collins is the longest serving, presidentially appointed, director of the National Institutes of Health.

But, as I mentioned, he’s only got a few days left in the job before he steps down on December 19. So, it seemed like the perfect time to reflect on his career at the N.I.H. and what comes next.

From the Freakonomics Radio Network, this is Freakonomics, M.D.

I’m Bapu Jena. I’m a medical doctor and an economist. And this is a show where I dissect fascinating questions at the sweet spot between health and economics. Usually, I talk to you all about a study or a few studies that answer a question that I want to know the answer to. But sometimes, I have the opportunity to talk one-on-one with someone special.

Today on the show: a conversation with Dr. Francis Collins. We’ll cover everything from what the N.I.H. could copy from the defense department to how we went from waiting five days for a Covid-test result to just 15 minutes.

COLLINS: We set up a shark tank, and essentially invited anybody who had a great idea about a way to detect SARS-CoV-2.

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BAPU: Tell me a little bit about yourself. I can tell you’ve got that Southern accent. I grew up in Richmond, Virginia. When I came up north to college, I used to say things like “high school” instead of “high school.” And “Where are y’all going?” instead of “Where are you all going?” I think you’re from Virginia from what I — from what I recall. But, tell me a little bit about how you grew up, why did you get into medicine, and what was your path to the N.I.H.?

COLLINS: Well, it was very nonlinear, let me tell you. So, I grew up on a small farm in the Shenandoah Valley, Virginia, you got that right.

BAPU: There you go.

COLLINS: Homeschooled by my parents who didn’t trust the local county schools to be as good as they were as educators. And they were probably right. Ultimately ended up in public school, got excited about science because of a chemistry teacher. So, I decided I should be a chemist. I majored in chemistry at the University of Virginia, went off to Yale and got a Ph.D. in physical chemistry and then had this, “Oh!” wakeup call about biology that I’d kind of ignored that maybe it might be interesting too, especially this molecule called D.N.A. Off I went to medical school, University of North Carolina, and really fell in love with the idea of medicine combined with genetics. And that’s kind of what then led me ultimately to the University of Michigan, where as a faculty member, teaching medical students, taking care of patients, and mostly doing research, had the experience of a lot of really interesting and challenging projects, including finding the gene for cystic fibrosis back in 1989, long time ago. The Genome Project was just getting introduced at that point. And I was a big fan of it, but not prepared for that phone call from the N.I.H. director, Bernadine Healy, saying, “I want you to come and lead this.” And that was a tough decision to become a — oh my God — federal employee. But — but how can you say no to the chance to do this? That was 1993, when the project was kind of controversial and probably wasn’t very likely to succeed, but it seemed like it was worth a try.

The Human Genome Project was the international effort to sequence and map all of our genes. All of them. The project was part of the N.I.H. and Collins led the agency’s genome sequencing efforts until 2008.

When the project first started, there were concerns about how the information would be used.But because of the work, scientists now have what Collins calls a “blueprint for building every human cell.” I’ve got to tell you — the implications for disease diagnosis, treatment, and prevention are truly enormous.

Collins became director of the N.I.H. in 2009, which is when I started my intern year in medicine. That brings me to a question I’ve been wanting to ask Dr. Collins for decades.

BAPU: So, when I was a grad student at the University of Chicago, this is probably in, like, the mid-2000s, I remember going to the airport one day. I was stuck in traffic, on a road called the Dan Ryan Expressway — if you’ve ever been to Chicago, it’s like a nightmare.

COLLINS: Oh, yeah.

BAPU: It’s a nightmare. And there was some construction happening, which made it a double nightmare. And all I could think to myself was “Wow, you know, the value of time lost to all of these people on the highway was so incredibly high. Why didn’t the city just pay three or four times what it was paying to get this highway fixed? Perhaps if we quadrupled how much money we spend on getting that road fixed, it could be done faster.” Now, let me tell you why that matters for why we’re talking today. So, also at that time I was starting to study the economic value of improvements in H.I.V. and cancer survival. And some of the work that we were doing was trying to figure out what was the societal return to funding by the N.I.H. for these diseases. And it’s probably not a surprise, but what we were finding was that, you know, survival had increased dramatically, especially in H.I.V., but also cancer survival as well, and the returns — the economic returns to private and public funding in those diseases was also really enormous. That was almost 20 years ago and maybe I’ve waited 20 years to ask you this question: when we think about diseases like cancer and heart disease, which are obviously leading killers, what would happen if we tripled or quadrupled N.I.H. funding on those diseases? Do you think we’d get breakthroughs or cures any faster?

COLLINS: I think we probably could. And people have done that analysis about how much money is being saved every time we drop the deaths from cancer, which we, by the way, are dropping now 1 or 2 percent per year over the last 20 years. It’s one of those things people haven’t maybe paid attention to. I think I read that each 1 percent drop there in terms of economic value is worth something like $500 billion. I mean, it’s a big deal.

BAPU: Yeah, it’s a huge deal. And my sense is that there’s a lot of money or value on the table, obviously from improving survival in these diseases even more so. So, the N.I.H. spends something like $40 billion a year on research. And maybe, to ask the question a little bit differently is you know, how much different would our health and the innovations that we have in medicine look if it’s spent $200 billion a year ?

COLLINS: So, then part of your question is, do we have the capacity to actually utilize those kinds of funds if they were to be doubled, or I guess your example more like multiplied by five? Is there actually a — a workforce out there that could take those funds and put them to good use or, or would this be like, just throwing money at a problem without any good ideas? You know, I think there is a workforce that’s underutilized. If you send us a grant with your really good ideas, it goes through our peer review system. You’ve been through this Bapu, you know. And what’s your chance of getting funded? It’s about 20 percent across the board. So, one out of five.We have looked over the course of time when that success rate has gone up and down a bit. And I would say in a healthy situation, it ought to be a lot better than 20 percent. It’s pretty clear that a grant that scores at the 15th percentile and a grant that scores at the 25th percentile are indistinguishable in terms of their ultimate productivity. So, we are leaving good science on the table by the fact that we can’t fund right now more than one out of five. So, I know if we could take that success rate up tomorrow, to say 30, 35 percent, there’d be a lot more great science happening and that would accelerate advances that would reduce healthcare costs and save lives. And I wish I could make that case to somebody who would actually respond.

BAPU: I know that you’ve been involved in sort of this, maybe I call it a high risk/high rewards approach to grant funding and the idea is that there’s innovations that are incremental and there are innovations that are really dramatic. And those are often high-risk sorts of investments. What is your thought on the role of the N.I.H. in that kind of research?

COLLINS: We need to, I think, have really a broad range of approaches — recognize that most of the advances that happen in biomedical research can’t really be organized in a top-down way. They’re the brilliant insights of investigators who come to us with their ideas. But I think we were concerned going back a couple of decades that the peer review process could tend to be a little conservative. And then especially if you have success rates that are only 20 percent or sometimes less than that, and think of yourself, you’re a peer reviewer, you’ve got this pile of 40 grants you’re supposed to go through. And in there, there’s some amazingly solid, phenomenally well-written grant applications from a highly recognized investigator who’s going to do some really impressive, but frankly kind of incremental research to build on the foundation they already got. And then you’ve got this other grant that doesn’t have much preliminary data, has got kind of a slightly wacky idea, but if it worked, it would be amazing. And you can’t fund both of those. Which one are you going to fund? Well, you know, you tend to fund the one that’s a sure thing. But we don’t want just sure things.  At some point we should talk about ARPA-H as the latest example of a way to put that high risk/high reward into overdrive.

BAPU: Tell me about that. I’m curious.

COLLINS: Ah, well, you know about DARPA, which is the Department of Defense’s high-risk, high-reward research enterprise that over the years has had some pretty remarkable successes. Like, you know, the internet, for instance.

BAPU: I thought that was Al Gore.

COLLINS: I’m sure he was working at DARPA at the time. And you know, they’ve done G.P.S. and self-driving cars had a big role from DARPA. And N.I.H. hasn’t really had something quite like that where you have a division that has a totally different culture, they’re not into the standard peer review at all. You have a director, who’s a visionary, who’s looking across the landscape for really exciting opportunities that would probably never result in a standard N.I.H. grant application. And the director hires a bunch of people who come in for maybe three years to run something big and bold, and they have resources. And they identify interesting targets, like, okay, let’s really jack up cancer vaccines using mRNA and figure out who the partners need to be. Build a collaboration, because they got the resources to throw at it. Hold those folks responsible for reaching milestones and be ready to pull the plug quickly if failure is happening and see what happens. I’m very excited about this. President Biden has been a big proponent of this. The Congress seems pretty interested. They’ve tentatively put down a dollar figure of maybe $3 billion for the first year of this, maybe as soon as a few months from now. We just need some authorizations for the hiring and the contracting, but I think this is probably going to happen. And it’s a very different model of doing medical research, but I must say, a lot of what we’ve done during Covid has had that same attitude of, “We don’t have time to go through the usual slow process of considering what is the peer review outcome of a pile of grants.” We’ve got to do things faster than that.

Coming up after the break: who is better at funding innovation: the private sector, or the government? And what’s been the N.I.H.’s role in fighting Covid-19? This is Freakonomics, M.D., I’m Bapu Jena. My conversation with Dr. Francis Collins continues, right after this.

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COLLINS: My wife is trying to get ready to drive to Michigan. Is it interfering? Oh my gosh. Well, let me close — let me close the door. Hang on.

 That again, is our guest today, Dr. Francis Collins of the National Institutes of Health, dealing with all the “fun” work-from-home challenges all of us are facing.

COLLINS: Okay. I’m back. Hopefully more quiet.

Before the break, Dr. Collins told us about the N.I.H.’s new ARPA-H program. That’s short for Advanced Research Projects Agency for Health and it’s meant to tackle the most pressing medical problems. It hasn’t been officially put in place yet but, as Dr. Collins said, it’s something President Biden wants to do. But I wondered … if this program were in place, how might that have changed our approach to Covid-19 research?

BAPU: So, when I think about Covid-19, obviously the U.S. has done a lot in terms of advancing our understanding of how the disease spreads, the risk factors, the treatments, the epidemiology, but, you know, places like Israel and the U.K. have, I think, had maybe an outsize role compared to what you might’ve expected. And part of the challenge I feel like has been that the way that we conceive up and fund research in this country is a little bit different than we might expect in a situation like this, which is, you know, you almost want like an N.I.H. SWAT team to come in and say, “All right, we need to figure out whether or not opening schools is unsafe for communities. We need to figure out in a randomized trial or multiple, large randomized trials, whether or not masks work.” You’ve got researchers out there doing studies, funding work on their own or from small grants, but the sort of societal implications of the answers to those questions is so enormous, I don’t know why there wasn’t a centralized effort to say, “We want four or five teams focused on the sole question of whether or not opening schools is safe. Four or five teams focused on what are the clinical, the epidemiologic and economic impact of shutdowns. And all of these five groups would be funded simultaneously, and then we look at the results.” I’m curious to get your overall thoughts on that.

COLLINS: Well, those would be really important experiments to do. I think they would have been challenging in the United States when you have local leaders and governors who have their own ideas about what they’re going to allow to have happen. So, you have to sort of figure out how to negotiate that. I take your point. I do think there were areas though, Bapu, where we did organize ourselves in that SWAT team mode, when it came to testing therapeutic agents, and that’s a partnership I want to tell you about, called ACTIV. Or when it came to developing at-home testing, using new technologies that otherwise would still be sitting somewhere in somebody’s lab, that are now out there on the pharmacy shelf, a program called RADx, Rapid Acceleration of Diagnostics, which we pretty much ran like we were a venture capital organization to make that happen. Those were really new and previously untested approaches and they worked. So, can I tell you about RADx?

BAPU: Yeah, please. Absolutely, yeah.

COLLINS: So, we all know we got off to a rough start in the U.S. as far as testing capabilities, the Congress identifying this as a serious issue came to N.I.H. back in April of 2020 and said, “Guys, we got to do something here. We want to see more technologies that are actually reliable and particularly those that are point of care, because look at these turnaround times for testing where you don’t get the result back for five days. And by then, if it’s positive, you’ve already infected other people.” So, we took them at their word. Five days after they gave us a billion dollars, we set up what is basically a venture capital approach, including a shark tank, and essentially invited anybody who had a great idea about a way to detect SARS-CoV-2 to bring that forward in a rather quick application. We figured out which of those had the most promise, hundreds of them, and then threw them into this shark tank with technology experts, engineers, business experts, people who knew about scale-up at manufacturing to see whether they had the real promise. And over the course of what was essentially an innovation funnel approach, we have 34 technologies that otherwise wouldn’t be there, including most of the ones that are now point of care and over the counter, available in your pharmacy. And that has made it possible now for us to have a capacity of about 3 million tests a day. That was just an interesting experience because there was no standard peer review panel. There was an awful lot of decision-making. There were a lot of failures, as you might expect. But we learned a lot along the way about how to do this. I wish we can do more of that with our ARPA-H, and maybe we will get to.

BAPU: So, Francis, let me — let me piggyback off something with the RADx and the testing, so it seems like this is really sort of a public/private partnership. It makes me think of this issue that comes up when we talk about new medical breakthroughs and how much they cost. There’s always this question that comes up of how much of the breakthrough was the result of federal research funding versus investments from the private sector. And I’m curious, you know, what are your thoughts on the role of government in funding innovation versus the private sector? From an economics perspective, I think of the role of government as getting involved in funding and things that have really large spillover effects to society that broaden the base of knowledge, things that any individual private innovator really might not be incentivized to see through. And I think that’s often the rationale for the focus on basic science versus basic science discoveries that are so far from the patient that companies wouldn’t kind of do as much of that.

COLLINS: I’m really glad to talk about this, because this is a bit of a personal passion. First of all, the government contribution for medicine, if you look closely, is incredibly important to what happens. Fred Ledley has done this repeated analysis of what exactly has been the government contribution when you see a new medication that is approved by the F.D.A., and that is in a place where we haven’t had a medicine like that before. And over the course of many years, looking at this, what is the proportion that have N.I.H. fundamental research undergirding it? It’s a 100 percent. So, virtually all drugs that get developed are based upon the basic foundation that then builds into this remarkable ecosystem where drug companies pick it up and carry it forward to a product. That has always seemed to me, over my 12 years as N.I.H. director, as something that we ought to tap into even more effectively, that we ought to be able to find ways in which, in a pre-competitive place, we could work more closely with industry to work on problems together. Out of that came the Accelerating Medicines Partnership, AMP, which I co-founded with Mikael Dolsten, who’s the chief scientist at Pfizer, about eight years ago. And which has now grown to a total of seven projects, diabetes, Alzheimer’s, rheumatoid arthritis, Parkinson’s, schizophrenia — and this is — I don’t think been done before — is we figure out in each of those instances, what is the shared area of science that neither sector can quite do on their own, but we could do better together. It was about 20 companies involved. N.I.H., F.D.A. plays a big role, which is really helpful. Industry has to pay half the cost, so they’ve got skin in the game. And it was that experience of finding out we could do this together and getting to know each other — because relationships matter — that helped us when Covid came along. In just a space of two weeks put together a similar public-private partnership called ACTIV, Accelerating Covid-19 Therapeutic Interventions and Vaccines. Of course, it has to be an acronym. And out of that, we prioritized the ones that needed to get into clinical trials — we designed master protocols. We figured out how to put clinical trial networks together. We put together the plans for vaccines that made it sure that those vaccine trials were going to be well-designed and F.D.A. would be able to evaluate them. And all of that happened in a remarkably quick period of time and continues to this day.

BAPU: So I was gonna say, it’s a good thing you call that ACTIV and not Activa because then they might be a trademark infringement issues on the yogurt. 

COLLINS: No, no. We we stop at V, we don’t go beyond.

BAPU: You’re — you’re retiring soon, is that right?

COLLINS: I’m stepping down as N.I.H. director to go back to my lab, which I’ve been continuing to operate for all this time and is doing amazing things right now in diabetes research and rare disease research. And I’m looking forward to having a little more time with my post-docs and post-baccs and a senior scientist to help us steer that effort, and maybe a time to think and write and try to decide what to do when I grow up.

BAPU: Any particular reason why now?

COLLINS: Well, 12 years is a long time, Bapu, no previous N.I.H. director has served more than one president. I’m working on my third president, and I think organizations like N.I.H. need new visionary leadership to sort of reboot. So, it seemed like time to give the president a chance to appoint somebody else. And you don’t want to do that too late in the term because it gets really hard to make it happen. So, it seems like if I’m not sticking it out for many more years, this was a good year to say, “Okay, I’m going to step away.” And by the end of 2021, I’ll be back in the lab.

BAPU: All right. So, I have one last question. First of all, thank you for sharing this arc of your life. It actually shares a lot of similarity with my own father. He grew up in a very small town in India. But, you know, his parents couldn’t really read or write, so they couldn’t educate him, but he had a chemistry teacher who thought he could do something. And he came to this country years later and became a professor of physics and still going hard. Here’s the question. You’ve done a lot. What was the happiest day of your life?

COLLINS: Wow. You know, there’s been a lot of them in terms of the science part, but we haven’t talked about the personal part. I think the happiest day of my life was probably getting married to Diane, my better half, my soulmate, my best friend, my lover, my just, remarkable enricher of my life. So, yeah, that would be right up there.

BAPU: Okay. I’ll make sure that after this podcast airs, I send this to her directly by email, Snapchat, Instagram. I want to make sure that she sees this and she hears this. All right, well, thank you so much for taking the time to talk with me today. I really appreciate it.

COLLINS: It was nice to talk to you, Bapu.

That was Dr. Francis Collins, the head of the National Institutes of Health who, again, will be leaving his role of director of the N.I.H. in a few days. It was a great conversation and something that I’ve been looking forward to. You know, it’s hard being a researcher, especially starting out as one. One study found that early scientists whose N.I.H. proposals received scores just below the cutoff for funding were more likely to disappear from the N.I.H. system — in other words, they stopped applying for grants — compared to early scientists whose proposals had slightly higher scores. But that same study found that those early losses may have had a silver lining. The research that emerged from those scientists whose grants were rejected ended up being more impactful than the research of those scientists who, by chance really, got funded. I’ll make sure to keep telling myself this every time one of my proposals gets rejected.

In all seriousness though, it’s hard to listen to Dr. Collins and not be hopeful, about science and about a lot of things. Anyway, I hope you enjoyed, and as always feel free to send me your thoughts, questions, comments — anything, really! — to bapu@freakonomics.com. That’s B-A-P-U at freakonomics.com. And if you can, leave a review for Freakonomics, M.D. wherever you get your podcasts. It really helps us out. Thanks for listening.

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Freakonomics, M.D. is part of the Freakonomics Radio Network, which also includes Freakonomics Radio, No Stupid Questions, and People I (Mostly) Admire. This show is produced by Stitcher and Renbud Radio. You can find us on Twitter and Instagram at @drbapupod. Original music composed by Luis Guerra. This episode was produced by Mary Diduch and mixed by Eleanor Osborne. The supervising producer was Tracey Samuelson. Our staff also includes Alison Craiglow, Greg Rippin, Emma Tyrrell, Jasmin Klinger, Lyric Bowditch, Jacob Clemente, and Stephen Dubner. If you like this show, or any other show in the Freakonomics Radio Network, please recommend it to your family and friends. That’s the best way to support the podcasts you love. As always, thanks for listening.

BAPU: So, the name of this show is Freakonomics M.D., based on the podcast and book Freakonomics. Do you think if I sent a hundred applications to ARPA-H, they could help us come up with a better name? No? That won’t work?

COLLINS: Ah, you might need another source for that answer.

BAPU: Exactly, yeah.