129. How to Fix Medical Research

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My guest today, Monica Bertignoli, is a surgeon by training and the former head of the National Cancer Institute.

Currently, she heads the National Institutes of Health.

The NIH, as it's called, is the biggest funder of basic medical research in the world.

There are so many possibilities that basic research has turned up.

There are so many new directions that we can take, even drugs that are already marketed today.

But we really do have a logjam when it comes to the ability to conduct clinical research, particularly randomized clinical trials.

Welcome to People I Mostly Admire with Steve Levitt.

It's a long way from the operating room to the boardroom managing a $50 billion budget.

And I'm curious to hear about both those sides of my guest today.

My My challenge will be that people who hold political positions, they often feel constrained about what they can say.

And I'm hoping we can at least talk about some important topics like how the NIH funds research, Big Pharma, and how she deals with the current politicized atmosphere.

You grew up on a cattle ranch in Wyoming, and I've looked at the map.

It must be one of the most isolated places in the United States.

It was, to me, the best place in the world to grow up.

It's at 9,000 feet in elevation in the Winderver Mountains.

From the house, it was 18 miles of dirt road just to get to a highway and 98 miles from the nearest town.

And when we got to be school age, my mother would move down to the town of Rock Springs in southwestern Wyoming.

And that's where we went to school.

The few kids I've known who grew up on a family farm have described their youth as harder work than they've ever done at any other point in their life.

Was that your existence or were you allowed to be a kid?

Well, a little of both.

The thing about growing up in an agricultural family is that your mother and father's job, which in my case was raising sheep and then cattle, is your job too.

Everyone in the family is responsible for doing the work that earned our living.

Although my favorite favorite was when it rained,

because if it rained, it meant I could stay inside and read books instead of be out working.

What was work for a kid on a ranch?

When I was growing up, it was mostly sheep, so there were small lambs to take care of.

The sheep were moved in different locations across the country.

There were times a year when they would be branded and vaccinated.

I guess that was my first medical job.

My job was to vaccinate all the young lambs.

how old were you when you became the designated vaccinator oh i must have been about nine or ten now your parents were first generation immigrants you lived in the middle of nowhere how in the world did you end up at princeton for college i was planning to go to the university of wyoming i had a scholarship full-ride scholarship But then in the fall of my senior year in high school, I got a phone call from Princeton University, from the admissions department.

And at the time, they had a goal that they wanted to have two freshmen from every state in the Union.

And so I was one in Wyoming that they called up and they said, Would you like to apply?

So I applied.

I never interviewed.

I never visited.

January of that year, I got a fat envelope saying I'd been admitted to Princeton by early decision.

Wow.

This is the first time in my entire life that I've ever heard of a non-athlete be recruited by a university that way.

So after college, you went to med school and you became a surgeon.

Now, how many women were in your med school class?

That was pretty unusual, right?

I went to University of Utah.

I think there were less than 10 women in a class of 100.

And so it was unusual and more unusual still to decide that surgery was the career I wanted to pursue.

I think I was the only woman who went into surgery after leaving medical school.

This was 1985.

Now I'm very pleased to say that most surgery training programs are 50% women.

It's amazing the transformation in medicine in general.

If you go back, the numbers you said, I think are representative of the U.S.

And within a very short amount of time, the composition of newly minted physicians went from 10 or 15% to 25% to, I think now, over 50%.

Did it seem natural for you to go to med school and to become a surgeon?

Oh, definitely.

Were you fighting a kind of feminist fight or it just was the thing that seemed fun to you?

It was what I loved.

It was what I wanted to do.

So that part was easy.

It was challenging being different.

Women were scrutinized.

You were questioned.

Why do you want to be a surgeon?

And coming up with an answer that made sense to people who really didn't necessarily think that being a woman was consistent with being a surgeon, could be very challenging.

I will also say that I trained in the days when there were senior people who would say to me, you're taking a spot that belongs to a man because after you finish training in a surgery, you're just going to get married and have kids.

And so, why would we give such a precious spot to someone like you?

What would you say back?

Not much I could say back to that.

I usually just kept my silence.

But what got me through that, number one, was

great determination that this is what I loved, this is what I belonged doing.

And then there really were wonderful supporters at every step that I could also turn to for encouragement.

The surgeons I know love surgery.

You hear them talk about it and there's nothing they'd rather be doing.

Was that true for you?

And if so, was it hard to move out of the operating room into the boardroom, essentially, as you progressed in your career?

Oh, very hard.

Surgeons are born, not made.

I still can remember what it felt like the first day I entered an operating room.

I didn't think I wanted to be a surgeon.

I was really interested in science, and I thought I wanted to do internal medicine and spend most of my days in the laboratory.

And when you get to be a third-year medical student, you have a rotation through every single discipline of medicine.

And I decided to do surgery first because I just wanted to get it out of the way.

And then the minute I walked into that operating room for the first time, I just realized that was the place for me.

I didn't look back after that.

So now you do run the National Institutes for Health, the NIH as it's often called.

Can you provide a broad overview of what the NIH does for the uninitiated?

It is the largest biomedical research institute in the world.

It has 27 institutes and centers that really cover every single aspect of biomedical research from the basic laboratory to understand the molecular and cellular nature of disease, all the way through to research that is directed at understanding what individual communities

need to achieve better health.

So you can imagine the scope of that enterprise is really tremendous.

It's still a little bit surreal to have this job.

You know, the NIH, the people there have always been my heroes.

So many Nobel laureates, so many champions who produced the very first insights into disease and transformative therapies.

And the fact that I'm there as the coordinator of this activity is the opportunity of a lifetime.

Now, it's a massive organization.

a budget of nearly $50 billion, almost 20,000 employees.

And these numbers seem big until you compare them to the overall healthcare spending in the United States, which is estimated to be about $4.5 trillion.

So the NIH budget is roughly 1% of total healthcare spending.

I think private pharma companies maybe spend $100 billion on R ⁇ D.

So combined, all of this biomedical research adds up to about 3% of healthcare spending.

Obviously, it has an outsized impact on the future of healthcare.

Now, I suspect you make that point when you lobby Congress for more NIH funding all the time about how cheap healthcare research is relative to the actual practice of healthcare.

Yes, that's a very important point.

But the other aspect of NIH that I think is important is that about 10% of the NIH budget actually stays within the virtual walls of NIH, the clinical centers, the programs at NIH itself.

90% of the budget goes out to the broader research community, academic institutions and organizations across the nation and even the world.

And there it becomes a part of all biomedical research that is done.

There's a lot of hand-wringing about the high and rising cost of healthcare in the USA.

Healthcare costs were 6% of GDP in 1970.

Now we spend about 17%

of our GDP on healthcare.

Now much of that cost increase is driven by new innovations.

So here's a question I've pondered.

As doctors and scientists pursue new ways to fight disease, it doesn't seem like they put much emphasis on finding solutions that are cheap to implement.

If anything, I think market incentives might bias innovation towards new technologies that you can charge a lot of money for.

So given that R D is a tiny share of healthcare spending, but it has this huge impact on future healthcare spending, when it comes to making NIH grants, is there any consideration given to whether the research is likely to generate a cheap solution versus an expensive one?

It's an economist way of looking at the world.

I suspect it's not very prevalent within medicine.

So, first of all, I'm sure you're very well aware that the United States spends far more per capita than any other nation in the world for healthcare.

I'm sure you're also aware that when you look at probably the most important indicator of the health of our people, life expectancy, we're far behind and unfortunately for the past decade have lost progress instead of gained progress.

We're spending a lot of money on things that are not really driving health.

Now, the trick is how do we figure out how to fix that?

How do we figure out where we are spending our money inefficiently and how to drive those resources toward things that bring better benefits for health?

This is a really big focus of what NIH is attempting to understand and to implement because

this is the wonderful thing about being a part of the government.

We have one goal, to improve the health of people.

The aim of our research does not need to make money.

The aim of our research is to improve health.

Completely consistent with that goal, you are probably funding the ideas that seem most promising, the ones that look like breakthroughs.

But I suspect that there's not a line in the NIH grant when an academic applies where they

have to specify whether if this works, it's going to cost 25 cents per dose or $20 million per dose.

And I think from an economic perspective, that would be an interesting piece to add into the decision making.

What's your reaction to that kind of thinking?

We are here to improve health, irrespective of economics.

I'll give you one example right now.

We are thrilled that we see two really transformative new treatments for sickle cell disease, a terrible disease causing a lifetime of pain and disability for the people who inherit both genes.

But they are incredibly expensive when we look at what these treatments require of an individual and the cost that has been placed on these treatments, it's between two and three million dollars for the treatment itself.

I can tell you that the researchers at NIH who are working feverishly to develop a cure for sickle cell disease were not worried about how much it was going to cost when they got done.

They were intensely focused on finding that cure.

Now that we have it though, we have to figure out how to make it affordable and accessible to the people who need it.

That's the secondary downstream part that needs to happen.

We don't set the costs at NIH of any treatments or any procedures, but what we can do is provide the data saying, here's the outcome we're looking at.

There might be three ways or more of achieving that outcome.

And then the private sector can then decide where the dollars need to be spent.

We'll be right back with more of my conversation with Monica Bertignoli, director of the NIH, after this short break.

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I've had a few guests on this show over the years who have complained about a lack of innovation in the new therapies that are being developed.

Their claim was that pharma companies in particular have financial incentives to make incremental tweaks to existing compounds or to push combinations of existing compounds rather than go after more speculative but perhaps more revolutionary innovations.

I don't know, though.

It seems like there have been a whole series of really remarkable breakthroughs in recent years.

You talked about the CRISPR-based therapy for sickle cell, the new mRNA technology that powered the COVID vaccines, the GLP-1 weight loss drugs, or Zempic and others.

It seems to me like we're actually making a ton of progress.

Sure, we are.

I mean, it's more exciting than it ever has been.

It has come from decades of investment in fundamental science from the federal government through the NIH and other agencies.

Fundamental science is what is leading to these major innovations in treatment that are then taken on by the pharmaceutical industry.

I won't say that companies aren't contributing to this, but I think the real core that has produced the environment that we are in today has come from federal funding.

Now, I've heard you use an analogy of a fire hose versus a garden hose, referring to the chasm between basic research and then what's actively being tested in clinical trials.

Could you talk a bit about that?

There are so many possibilities that basic research has turned up.

There are so many new directions that we can take, even drugs that are already marketed today.

But we really do have a log jam when it comes to the ability to conduct clinical research, particularly randomized clinical trials.

A lot of it has to do with funding.

A great deal of it, which we are certainly making inroads on, has to do with the structure and conduct of clinical trials research.

But we still suffer from a real lack of overall funding support for the clinical trials end of what we do.

So when you say funding, obviously the pharma companies fund things if they think they can get a private return.

You're talking about something different, right?

You're talking about funding for projects that may or may not be lucrative for pharma companies.

Exactly.

And if you look at the funding that has powered clinical research over the last two decades, the percentage of clinical trials that are funded by pharma have dramatically increased.

The percentage of clinical trials funded by the government have remained completely static.

They're exactly the same or maybe even a little bit lower than they were a decade ago.

The clinical trials that are done now are driven by pharma, which is fine because they are producing amazing, successful products for us, but they also have a pharma focus behind them.

And that means that we're leaving behind a lot of the key questions that aren't necessarily attractive to pharma.

I think what I'm hearing you say is there are all sorts of medical practitioners out there who would like to be doing randomized trials on new compounds and they're being constrained because there isn't funding there.

Is that right?

Or is it something deeper that nobody really wants to run these trials because they're not valued enough within the medical profession or they're too hard or they always fail?

Definitely not the latter.

Our physicians nationwide are clamoring for more clinical research.

Let me give you an example that comes from direct experience that I had at the National Cancer Institute.

There are two components of the clinical trials infrastructure for cancer funded by the government.

One of them is the National Clinical Trials Network, and another is a program known as the NCORE or National Community Oncology Research Program.

And the NCOR are doctors in private practice.

throughout the entire nation who aren't even part of academic institutions but really look for clinical trials as a way of bringing quality and needed innovation to their own practices because they know their patients need them and want them the capacity meaning patients and doctors willing to do the research is much much much greater than the capacity we have for the funding to be able to deliver the trials for them without a doubt we could dramatically expand our clinical trials throughput it just takes new funding You're in charge of the NIH.

It sounds like you think this is important.

In principle, you could shift money around to do more of this.

Now, I know from working with big companies in the private sector, that's actually really hard.

People at the top have much less control over what happens than you might expect, right?

The CEO can issue an edict, but usually nothing happens when the CEO issues an edict.

I'm curious, what is your experience at the NIH?

To what extent are you able to make things happen that you'd like to happen?

It's really important for everyone to understand the way that funding works at NIH.

Our budget, over $47 billion last year, is completely spent, by and large, completely spent every year.

All of that money that we receive from Congress, the lion's share of it, is committed to research projects that are ongoing and fairly long term.

Without new money to put into rapidly expanding clinical trials, where am I going to take it from?

Do we reduce our investment in fundamental and basic science?

Do we reduce our investment in genomics and precision medicine?

So, fueling new directions and fueling increased work generally needs to happen with new money.

Now, one innovation you've been trying to push at NIH is what's called a learning health system.

Can you describe what you mean by that?

So many times during my career, a patient would tell me, Doctor, I really hope that something about my experience as a patient will benefit someone else.

It's a wonderful sentiment, but I didn't have a way of making that possible.

We didn't have a way of acquiring data from every patient who wanted to participate.

We didn't have a way of tying together the entire system of US healthcare to gather information, analyze those data, and then return it to the care providers.

Now that we have a nearly universal electronic health record, we do have the ability to use that data collection tool as a way of gathering information that can allow us to do research that can inform healthcare, that can be much more dynamic than what we've had in the past, and can be a continual feedback loop, being able to provide information that can guide care.

Before, it's been mostly a linear path.

Doctors will learn about new discoveries at a meeting or in a journal article, and they will take those and apply those in the clinic.

But what happens downstream of that, the learning that comes back, it's that feedback loop that we haven't had.

This reminds me of what the Cystic Fibrosis foundation did, I think, a few decades ago.

I believe they created a national clearinghouse for all cystic fibrosis patients and research and treatment.

And I suspect it's not a coincidence that amazing breakthroughs have happened since then.

Cystic fibrosis used to be the death sentence, a life expectancy of maybe five or ten years.

And now I was reading recently that with proper treatment, life expectancies are almost the same as for the general population.

It was years ago that I read about this, but it really seemed like that research community used data in a way that was brilliant and shocking at the time.

Am I capturing what you have in mind?

This is a great example.

We also need to make it possible for many of the core conditions that really drive health overall.

We need to be able to understand if we're going to prevent Alzheimer's or other dementias, for instance, what are the factors that influence brain aging that might begin when someone's in their teens or 20s or 30s?

We can start to understand people along their entire lifespan in ways that allow us to start to address some of these fundamental issues we have in health.

I have a friend, an economist, Sendal Muldanatan, and maybe five years ago, over lunch, we got to talking about one of his ideas, which is, he says, so many data are collected in healthcare, and then they're actually just thrown away.

He says, if you go to the hospital, the machines are beeping and recording things, and they're thrown away when you leave.

And we had this idea for a business, which is we would work with hospitals and just start keeping them, not even knowing what we would do with them, but just building up an enormous store of data that over time might yield resources.

Now, in the end, we're academics.

We never managed to do what it would take to make that happen.

But I think the principle that you're talking about is so powerful.

And as our tools for data analysis of large data sets get better and better, it really does seem to me to be the future.

But I suspect that many people within medicine don't see it like this because it's too new and it's too different.

Is it an easy fight or a hard fight to get this going?

There are many, many large efforts actually undergoing to take in data from large patient populations and analyze them.

One of the things we need to do though, if we're really going to follow an individual over their lifespan and understand

their medical condition and their data in a deep way that allows us to produce results that are really meaningful and can translate to other people, we have to engage those people directly in the research.

And I think this has been one of the greatest impediments to the work.

We haven't had a really effective way of getting people's permission and understanding and bringing them into the research process.

We're starting to see justifiably people raising concern, you know, why should anybody have my health data?

I didn't say yes to that.

I didn't give my permission.

We need to do it in a way that allows people to give permission for their health data use and also allows us to continue to interact with people in ways that are meaningful to them.

So, for example, one of the things that I hope to achieve is a way, literally nationwide, where anyone could say, I want my data to be used for health research.

And if something becomes relevant to me that I should know about, I want you to be able to contact me.

That would be transformative in our our ability to really bring people to research and research to people.

But there are certain people that this approach would have a really hard time serving.

There are people who don't trust in medicine right now and so would just say no.

There are also people who have certain conditions where they feel there's some stigma with them.

It could be someone who's got a substance abuse issue or somebody with HIV or some of these conditions where they'd be really concerned about privacy and protection.

So we're also working really hard on programs that will allow it to be done very safely and very inclusively so that people don't get left out.

If you can provide them benefits to providing their data, I think people are often eager to do it.

It's just that in many commercial settings, people feel like they're not getting the benefit.

Meta is getting the benefit.

Meta is getting all the advertising revenue when my data is being used to then sell ads to me.

And I think both in that private sector setting and in this setting, the key is finding ways to let people see the direct benefits, exactly like you're talking about.

How do you link data provision to then better services, better outcomes for them?

It's funny, you haven't mentioned the words HIPAA, but HIPAA are the set of rules around sharing of healthcare data.

But my God, I have felt like in my own research and my attempts to make social change that HIPAA has become such an obstacle.

It was put in, I think, with good intentions to protect privacy, but now there is such a terror.

And I know you're a public servant and you probably are not allowed to say anything bad about HIPAA, but do you know what I'm saying when I talk about HIPAA that way?

I think you've hit exactly the issue.

It's not that HIPAA's bad, it's that people interpret it as being risky, as putting responsibility on them.

It really is this need for security on an institutional level that can inhibit research.

I'll give you another example for this world that we are working to create where people can give their permission to use their data for research.

They can give their permission for us to contact them.

Think about this.

If you were somebody who had a rare disease or if you were the parent of a child with muscular dystrophy, I think most would say, yes, please take my child's record.

And if there's some new treatment for muscular dystrophy, please contact us.

We want to know.

We want to take part.

But in order to do that, not only do we have to have the data, we have to have their identity.

We have to be able to link back to them to find them.

We do now have systems, data algorithms that can allow us to mask people's identity, but complete anonymity could never be entirely assured.

I think you're right.

People will do if they understand how it can benefit them.

One of the things that I really love to do is to get together with patient advocacy groups and uniformly they are demanding that we use their data and they're demanding that we communicate the results back to them.

So if we listen to our patients, this is what we're going to be doing.

If we listen, frankly, to the lawyers in our institutions who are worried about being sued because, oops, there was a data breach, then we say no.

So somehow we need to put the proper safeguards in place.

Now, given that you run the NIH, every word you say is highly scrutinized.

And I imagine there are all sorts of things that you think that you believe that you can't ever say out loud, at least publicly, for fear of triggering a controversy.

Is that hard on you?

Well, let's see.

Well, you know, you got to self-censor your answer, too.

Oh, boy, people who know me know that self-censoring is not one of my strong suits.

I do try as much as possible to think about the person who's affected by what we're trying to fix.

So if I'm going to say something,

my first concern is not what a legislator is going to think, or my first concern is not what a commentator is going to think.

My first concern is what is a patient with sickle cell disease going to think if I'm talking about a program that we're designing to help them.

Because that's who we're here to serve.

Now, one would hope that the NIH, despite being a government agency, would be largely immune from politics because it's about science.

It's about truth.

Are you able to speak with any candor on the subject of how politicized the NIH is?

Someone has said to me once, how are you going to make all those people who don't believe in vaccination understand that's not the the right thing for their health?

I'm not here to try to dictate to someone what they should believe or how they should think.

What I'm here to do is to meet them where they are, tell them what our science tells us is the best approach to say, okay, what do you need?

What are your concerns?

What do you think we should do to help address your health needs?

And so meet them where they are.

This is the kind of small politics in the way we meet people person by person.

And that I think is a big focus for us and something that we are going to work very hard on because at the end of the day, NIH absolutely has to be here for everyone.

You're listening to People I Mostly Admire with Steve Levitt and his conversation with Monica Bertignoli.

After this short break, they'll return to talk about President Biden's cancer moonshot initiative.

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A while back, President Biden launched a cancer moonshot initiative, but I barely hear it talked about in the media.

I'd love to hear Monica's impression of how the project is going.

And on a much more personal note, Monica, who spent her career studying cancer, was diagnosed with breast cancer a few years back.

Now, my understanding is that health-wise, she's doing great now, but I wonder how her experience studying cancer has affected her experience as a patient and how being a patient affected her views as a researcher.

Now, President Biden has a cancer moonshot initiative, the goal of which is to reduce cancer mortality by 50% within the next 25 years.

Now, it's hard to disagree with that goal, but what do you think?

Completely unrealistic, possible, likely?

If you had to bet on it, what do you think would happen?

Possible, but difficult.

And just to be clear, that's age-adjusted cancer mortality.

That's very important because we do have an aging population.

So the percentage of our population with cancers will continue to go up significantly as the population ages.

But dropping age-adjusted cancer mortality by 50% is an achievable goal.

We did an analysis about a year ago when I was still at the National Cancer Institute, and we would need to make a great deal of progress in delivering the very best standard of care to everyone.

In other words, eliminate disparities in cancer care so that all people had the best result that we can deliver today.

Unfortunately, still not true.

We still need to make significant progress toward further reducing smoking.

Alcohol use has an effect on cancer.

Obesity has a significant effect on cancer.

And then finally, we still have to find some better treatments.

Now, if we continue the trajectory that we've been on so far, exactly matching the reductions we've seen every year so far, we're not going to be able to do it.

We have to kick it up to be able to achieve that 50% reduction in 25 years.

What's interesting as you describe that is what my intuition would tell me, which is that the real lever here is lifestyle.

It's the prevention of cancer through things that doctors and research won't help very much with.

It's about people's own choices.

If you could deal with that, you could make a ton of progress.

And then overlaying on that, great treatments once you have cancer.

But the biggest bang for the buck, really, because it doesn't have to be expensive either, is just getting people to live lives that don't facilitate cancer.

I think that's fair.

It's not going to do it all, though.

It's really going to take progress on all fronts.

It was actually encouraging that our current approach is a really good one in that I don't think we can afford at NIH to pick any one area to solely concentrate on.

We have to keep up our focus on fundamental science, on prevention and early disease detection, and on treatment of advanced disease.

And then finally, on being able to understand how to best deliver care.

We've got to go across all of those fronts.

You aren't just someone who studies cancer, you're also a cancer survivor.

Just a few months after taking over as director of the National Cancer Institute, you were diagnosed with early stage breast cancer.

And I'm sure that's been incredibly hard, but all in all, it seems like things are going pretty well with that fight.

Yeah, that was a nasty surprise.

I am very lucky.

My disease was diagnosed early.

Very effective treatments were available to me.

What

really was brought to mind was when I sat down and looked at the treatment I received and realized for the first time, frankly, as a cancer researcher who did lots of clinical trials, that there were more than 100,000 women who participated in clinical trials, just the key ones, one for each treatment I received, to produce that treatment.

Really, if I tried to add up the numbers, it would be millions of women who agreed to participate in a clinical trial to have somebody flip a coin and decide what treatment they were going to get.

The altruism, the bravery of all the women who did that, and who was the beneficiary of all that?

It was me.

When anybody gets an initial diagnosis of cancer, I'm sure it's shocking and jarring.

Do you think for yourself, because you were so knowledgeable about cancer, did that make it easier or harder to get that news?

I could really see it going either way.

Gee, I don't know.

It's so individual and it affects everyone differently.

I will say that by nature, I'm an optimist.

I think all surgeons are optimists.

I don't think you could be a surgeon if you weren't an optimist.

And so when I look at what were the the expected outcomes of a cancer diagnosis, I was more of a glass half full than a glass half empty type of view.

I think that really helps when you do have something like this happen.

In our society, I think especially in older generations, there has been this sense that illness cancer should be very private.

Just to give you one example, my father, who just retired his physician, he had cancer for a year or two before my mom even found out.

He's still married to her.

He had kept it secret from her and she only found out from a message on the telephone.

I have no idea what motivates that kind of secrecy, but I'm curious, in a strange way, because you were leading the National Cancer Institute at the time that your cancer was diagnosed, it turned a potentially very private experience into a more public experience.

There was a press release that announced that you had been diagnosed and described your precise cancer, hormone receptor positive, HCR2, negative breast cancer.

Was it natural for you to be public about this or something you had to do given your job?

It was very natural, frankly, because I felt I owed it to everyone who had this disease that I wouldn't hide it.

You know, I felt like the best way I can support.

all women out there who also have a diagnosis like this is to be very public about it.

And I did get some notes from people and they thanked me for being so public about it and making it very clear to all that a cancer survivor can be even stronger than before.

Maybe you're not allowed to pick favorites, but I'm just wondering if you have a hunch about any breakthrough technologies that could be game-changing in the way that, say, mRNA technology was on vaccines.

Is there some approach which maybe isn't yet there, but you can see that maybe it would just be game-changing?

I can give you a couple of examples.

One of them is a new approach to combating disease and also doing drug discovery, tiny little proteins called nanobodies.

You've heard of antibodies, right?

Antibodies are things that our plasma cells make in order to respond and identify cells that can be targeted by the immune system.

Well, it turns out that camels and sharks have a different version of antibodies that are a tiny little fraction of something that acts like an antibodies.

They're called nanobodies.

And they fit into tiny little grooves in cells and proteins and are able to bind cells in different ways and are a really interesting, interesting new possible tool

in being able to control and target immune behavior and target drug delivery.

And part of the reason why I think that's an example of something that could be transformative is the immune system governs so much of what happens in health.

Inflammation, a driver of so many of the diseases that disable us.

Ability to fight tumors, the development of neurodegenerative diseases, and finally, the ability to combat infection.

Many of these are related to immune function and immune dysregulation.

So, this technology has the chance of perhaps being able to be a driver of therapies and interventions directed at immune responses.

That's really exciting.

I think there's another really interesting new result relevant to women's health.

Women have much more autoimmune disease.

Again, it's an immune effect.

You can tell I was an immunologist in my original training because these are all the things that capture my attention most.

We've always wondered why do women have so much more autoimmune disease than men?

75% of autoimmune diseases affect women.

And there's some really interesting results from a group of researchers at Stanford showing how when the X chromosome, you know, a man has an X and a Y, woman have two X's, there are many important proteins coded on that X chromosome, but having two X chromosomes fully expressing all of those proteins is harmful.

So what happens is a woman, one of her X chromosomes is silenced.

There are certain mechanisms that allow the genes there not to be fully expressed.

Well, this group has found that there are some proteins that participate in this silencing of the X chromosome that drive the immune response.

And they were able to prove principle of it by taking these proteins, introducing them into male animals, and they produced autoimmune disease in the male animals.

Wow, that's great.

Now, the wonderful thing there is not only do we have

a new identification of why women were different than men, now we have new targets for what we can use to help silence the immune system when it produces autoimmune disease.

I've given you two examples.

I could give you 200.

This is exactly why I say to you, I think it's a fire hose down to a garden hose, because all of these brilliant ideas that are coming out of basic science are really ripe for translation into new therapies.

And I think we could do that faster.

So in my mind, I was demonizing Pharma in various ways, you know, the way people always do.

But then I was just thinking, so let's say that somebody does a clinical trial and they show that some particular therapy works, there's still this problem that if nobody commercializes it, it won't exist.

That's another interesting gap.

It's not really your problem, but I wonder whether there isn't a social need

for an entity that takes the job of taking medical compounds that have immense social value, but that can't put enough money into the pockets of the the pharma company to make it worthwhile and nonetheless make those available.

I don't know if such an entity exists, but it seems like, given what you're saying, we really need something like that.

Well, you've just described the challenge we have with rare diseases.

In some ways, we're back to the sickle cell issue.

Not that it's terribly rare, but it's not as common as other things.

And you see the tremendous price tag on that.

Those price tags sometimes have to do with just the ability to also provide a return to the commercialization partner.

Yeah, I've actually read about that.

And so the pharma companies that have the sickle cell treatments, they say somewhat reasonably, look, it costs $2 million,

but to live a life with sickle cell is even more costly to the system than $2 million.

So we're actually a bargain relative to the existing treatment.

Great example.

And it's not a crazy argument.

Research done at NIH really needs to engage with pharma to be able to succeed in delivery to the people who need it.

The Accelerating Medicines Partnership program allows NIH to work directly with pharma partners on issues like this, on development of gene therapy, and on conquering some of these fundamental challenges we have.

We also have a small business innovation project.

that takes a fairly substantial portion of the NIH budget, which provides support for early development to be able to get these promising treatments into clinical development.

So this is one of the major focus areas for the intramural program at the NIH.

What we do at Home Base, largely it's about these kinds of things, the areas that industry alone is not going to grab and run with.

I sure hope that Monica's optimism about the future of medical research is warranted.

Having spent my career as an academic economist, I have to say, I've become somewhat jaded.

It's kind of sad, but at some basic level, economists collectively know that what we do doesn't matter very much.

It's just rare that an economist comes up with an innovation that has a first-order effect on people's lives.

Academic economics always feels a little bit like a game to me.

And when I think of medical researchers, I assume they aren't so different than economists, which makes me worry.

Maybe though, the combination of working on problems that really matter and the huge profit opportunities if you succeed brings some discipline to medical research that economics lacks.

It's certainly hard to argue with the speed with which COVID vaccines were developed.

Let's hope the Cancer Moonshot Initiative has the same outcome.

Now is the moment in the show where I invite Morgan, my producer, on, to take a listener question.

Hi, Hi, Steve.

Recently, you were on John Hartley's podcast.

The podcast is called Capital and Freedom in the 21st Century, and I thought you were pretty good.

Yeah, John was one of my all-time favorite undergraduate students, and he's now getting a PhD at Stanford in economics.

And honestly, I just went on it because I was looking forward to the chance to catch up with John after all these years.

I'm shocked that it actually went kind of viral.

Tyler Cowen, who has a podcast, but also a blog called Marginal Revolution, about the episode, he said this is quite simply one of the best podcasts ever.

I've never said that about a PEMA episode.

I think it's just further evidence that I'm better at being interviewed than actually doing interviews.

Well, what was interesting for me is I thought I knew a lot about you, but even I learned something.

And that is that you're retiring.

You're going emeritus in June this year.

Yeah, I didn't think anyone would care.

For years on this podcast, I've been saying how I'm not interested in doing academic research.

And so by going emeritus, all I'm really doing is assuaging the guilt I have about being part of an economics department and doing nothing that any of my colleagues care about.

But all the stuff I actually myself am interested in, the center I run at the University of Chicago or this podcast, none of that's changing.

So for me, it was a mere formality.

I I did find out the hard way, though, that there are a lot of people who expect to be told firsthand that you're retiring rather than finding it out in a podcast.

So, apart from all the praise you had for that episode, The Economist magazine did something a little different.

A lot of the content from the Hartley podcast was used in a rather snarky article that the magazine published.

The title of the article is Why Freakonomics Failed to Transform Economics.

I know you have a really thick skin and a lot doesn't bother you, but were you a little miffed by this?

I was, because of all the media outlets that you would think might like me and what I do, you'd think it'd be the economist.

And so when I heard they were writing a piece about me on my retirement, I thought, wow, this is going to be really exciting.

And when I read it, it was nothing but negative.

And I don't get mad about very many things, but this is one thing that actually made me angry.

It's really dismissive of your abortion and crime research.

Yeah, and it's not the first time.

I went back and looked.

And three or four times over the last 20 years, The Economist has taken this negative, dismissive stance towards the research on abortion and crime.

And it's so frustrating to me because the criticisms are just based so loosely on the evidence, and they completely ignore the fact that not only did we write the original paper 20 years ago, but in an opportunity that almost never arises in academic economics, we made predictions in that first paper about what would happen over the next 20 years.

And having waited 20 years, we went back to the data and we analyzed what has happened.

And amazingly, in some sense, the results over the last 20 years, every single prediction that we made, there were six or seven of them, turned out to be as true or truer in the last 20 years of data as they they were in the initial data we used in that first paper.

With evidence that strong, it seems to me just so unscientific that an outlet like The Economist will dismiss our results based on critiques made 20 years ago that we successfully rebutted then and show no interest in trying to update their thinking as our own research has been updated.

So that does get me mad.

So we had a few listeners write to us to defend you, and I think they'll be happy to know that you and John Donahue, your co-author on the abortion and crime work, wrote a rebuttal for The Economist that recently was published.

Given how negative the article was, I was surprised that The Economist was so receptive to actually let us write a rebuttal.

John and I were given the space to tell our side of the story, and I was glad to do that.

I've never actually sat down and in one succinct piece tried to explain why I think people should take the abortion and crime argument seriously.

And it was a fun exercise to do, and I'm glad we now have that on record.

What I thought was interesting was your rebuttal with John Donahue only focuses on the complaints against the abortion and crime work.

You chose to let all the other points The Economist makes about Freakonomics just fall by the wayside.

The main argument the article makes is that freakonomics is a failure because it didn't change economics.

But that premise is so absurd, I wasn't sure it deserved rebutting because freakonomics is a book written for a popular audience.

It's my academic papers turned into interesting stories working with Stephen Devner.

We never intended for it to change economics.

It is impossible, inconceivable that it ever would have changed economics.

And maybe you give the writer of that article the benefit of the doubt.

And when he uses the word freakonomics, he doesn't mean the book itself, but more the approach that I take to economics.

But the thing is, I don't have a unique approach to economics.

My academic papers are motivated simply by, can you learn something interesting about the world by looking at the data?

And that is what a huge swath of economists do.

And I'm a very small bit player in that exercise.

And if there's any question about whether that approach generally is having an impact on economics, all you have to do is look at the most recent Nobel Prize winners.

That approach to learning about the world has been taking down Nobel Prizes left or right.

So that critique in The Economist was completely silly, but it didn't get under my skin the way that the comments about abortion and crime did.

Trevor Burrus, Jr.: We will include a link to John Hartley's podcast, the original Economist magazine article, and your rebuttal with John Donahue in the show notes.

Listeners, if you have a question for us, our email is pima at freeconomics.com.

That's p-im-m-a at freeconomics.com.

We read every email that's sent, and we look forward to reading yours.

In two weeks, we're back with a brand new episode featuring Joseph Stiglitz.

He's a Nobel Prize-winning economist, but also one of the most prominent voices criticizing unfettered markets.

As always, thanks for listening and we'll see you back soon.

People I mostly admire is part of the Freakonomics Radio Network, which also includes Freakonomics Radio, No Stupid Questions, and the Economics of Everyday Things.

All our shows are produced by Stitcher and Renbud Radio.

This episode was produced by Morgan Levy with help from Lyric Vowdich and mixed by Jasmine Klinger.

We had research assistance from Daniel Moritz Rabson.

Our theme music was composed by Luis Guerra.

We can be reached at Pima at freakonomics.com.

That's P-I-M-A at freakonomics.com.

Thanks for listening.

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