The Questions That Shape the Future of Medicine

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On this episode of The Fundamentals, we talked to Dr. Thomas J. Wang, dean of the University of Michigan Medical School, about the fundamental questions that have shaped his career and continue to drive biomedical research.

Dean Wang discusses his work in cardiovascular research, the enduring impact of the Framingham Heart Study, the potential of AI and emerging health data, and the importance of collaboration between academia and industry. He also shares advice for the next generation of scientists and physicians and explains why sustained investment in biomedical research is essential to improving human health.

Transcript

Kelly Malcom:

Welcome to The Fundamentals, a podcast where we explore biomedical research here at Michigan Medicine. Research is fundamental to University of Michigan's mission to improve the world. On each episode, we'll meet the people behind the research, learn more about their fields and the fundamental questions they are trying to answer. I'm Kelly Malcolm, a science writer and communication strategist for the University of Michigan Medical School. This season, we'll start by explaining a little bit of the history behind the questions our experts are asking and get a glimpse into the future of healthcare. In September of 2025, Dr. Thomas J. Wang became the 18th Dean in the history of the University of Michigan Medical School. Dean Wang was also appointed as the Josiah Macy Jr. Endowed Professor of Medical Education and a professor with tenure in the Department of Internal Medicine.

Kelly Malcom:

But before he was our Dean, Dr. Wang was professor and chair of the Department of Internal Medicine at University of Texas Southwestern Medical Center, and prior on the faculty of Massachusetts General Hospital and Harvard Medical School from 2003 to 2013. From 2013 to 2020, he served as director of the Division of Cardiovascular Medicine and Physician-in-Chief of the Vanderbilt Heart and Vascular Institute. Dean Wang is also a scientist whose research focuses on the natriuretic peptide system, cardiovascular biomarkers, and prevention, including insights from the famed Framingham Heart Study. Okay, welcome to the show, Dean Wang.

Tommy Wang:

Thanks.

Kelly Malcom:

It's so great to have you here.

Tommy Wang:

Great to be here.

Kelly Malcom:

I'm really interested in what drove your interest in cardiovascular disease.

Tommy Wang:

Yeah, I would say there are two things that motivated me. One was sort of the public health question. As a economist, epidemiologist, I sort of recognize what kills us. It's heart disease. It's the most common cause of death, actually by far. And so it was attractive to think about a problem and work on a problem that actually affected a lot of people, obviously made a lot of difference. The second thing is that there's a lot of evidence in cardiovascular disease. So there are, of course, a lot of things that are really important to us health-wise. There's dementia, there's stroke, there's cancer, of course. But in terms of areas of medicine where we can really make a difference, cardiovascular disease, when I was in training, felt like that was one of those areas.

Tommy Wang:

Not to say that we're not making huge differences and huge strides in other areas, but in many cases, heart disease is very immediate. And I would say the last thing is that I've always been interested in cardiovascular physiology, just how the heart works, how it pumps blood to the rest of the body, how the electrical system works. There's just a logic to it that really appealed to me. So I would say those are the things that were in my mind when I was thinking about what I was going to do the rest of my career.

Kelly Malcom:

And I think we all know someone with heart disease, unfortunately, so ...

Tommy Wang:

Yeah. I think we don't really realize how common it is. Good data from the Framingham Heart Study where I spent a fair amount of my time in training suggests that about one in two men and one in three women have heart disease sometime during their adult lives, which is really a shockingly high number when you think about it. And we often forget it because of course there are lots of other things we're understandably concerned about or afraid of or can be more dramatic, but sometimes heart disease can be silent for a while and then sneak up on you or you can live with heart disease a long time. So it's not necessarily something at the top of mind, but when you just look at it epidemiologically and in terms of population impact, there's really nothing else that impacts such an individual and societal burden.

Kelly Malcom:

So when I was researching, getting ready for this episode, I was looking through your long list of publications. One of the things that popped up, and I had no idea what this is, I'm going to try to say it, natriuretic peptide.

Tommy Wang:

Yes.

Kelly Malcom:

Can you explain what that is-

Tommy Wang:

Yes.

Kelly Malcom:

... and why it's important?

Tommy Wang:

Yeah, for sure. And you're right, the first sort of 10 years or so of my investigative career, I really spent a lot of time thinking about these, and these are important molecules, and I'll try to put them in a little bit of context. So for most people, the heart has a primary function. It pumps blood to the rest of the body so that the rest of the tissues in your body can get oxygen. And that certainly is the principle thing that the heart does physiologically. But it turns out that the heart does a lot of other things and affects the body in a lot of other ways and also receives signals from the body that it can respond to. And so the question is, how are these signals received or transmitted? And one way is through the nervous system. There are nerves that flow through the body and connect the heart to other parts of the body, and that's been understood for a while.

Tommy Wang:

The relatively new area though is that there are actually molecules in the body that go through the bloodstream by which the heart can signal to other parts of the body. And these are the natriuretic peptides. And so natriuretic peptides are actually hormones, and so we think of hormones like insulin or cortisol, which is the stress hormone, or thyroid, which is the hormone that comes from the heart that allows one organ to signal to the other. Well, up until a couple of decades ago, people didn't realize that the heart was also a source of hormones. So the heart can make hormones that signal to the rest of the body. And again, these hormones are the natriuretic peptides. And so that recognition was really only becoming apparent when I was a medical student in training. In fact, when I was in medical school, the textbooks barely mentioned these molecules.

Tommy Wang:

A decade or so later when I was in training, they were actually becoming an area of quite a bit of interest. And so when I finished training and started the research segment of my career, they were a very interesting thing to study. They continue to be. And the usefulness of understanding what these hormones do really crosses multiple areas. And so for instance, in the hospital, they're one of the most commonly used blood tests now that we test to look at the heart. We of course look at cholesterol and other markers that tell you whether someone's having a heart attack. But when someone comes in with heart failure, for instance, which is one of the most common causes of hospitalization in adults, the thing that you test for that are natriuretic peptides. It's a blood test that you can use.

Tommy Wang:

The levels of the hormones in the blood give you an idea of whether they're in heart failure or not. And they can also be used as a therapy. And so administering drugs that alter levels of these hormones can also be beneficial for heart failure, for instance. So in short, that is what the field is all about. It's relatively new and was certainly an interest that I was focused on when I was early on in my career.

Kelly Malcom:

So you mentioned the Framingham Heart Study, and I think some people have heard ... I've definitely heard of it. It's one of the most famous longitudinal studies of all time. Why is so important to this day? Is it still ongoing?

Tommy Wang:

It is still ongoing. The original cohort, meaning the people who are originally rolled into the Framingham study in the late '40s, unfortunately no one is surviving from that original cohort, but they have subsequently enrolled the children of those individuals and then the grandchildren of those individuals. So the children and grandchildren are still being followed-

Kelly Malcom:

Oh, wow.

Tommy Wang:

... in the study. Yeah. But the original Framingham participants, that cohort no longer exists. I would say there are a number of ways to think about why the Framingham study is important. One is the historical context, and the second is what are actually things that we do today in medicine that were impacted by the Framingham Heart Study? So I'll start first with the historical context. Why do we have the Framingham Heart Study? And it actually goes back to our longest serving president, Franklin Delano Roosevelt. And so as some people might be aware, FDR died of cardiovascular disease. He actually died of a stroke, and the cause of the stroke was incredibly high blood pressure. When he died, the last recorded blood pressure that he had, the systolic number was over 300, which is dramatically high. We consider 140-ish for that top number to be at the edge of the normal range.

Tommy Wang:

And so back then, people didn't realize that having really, really high blood pressure could be so bad for you. And so after FDR died, his successor, Harry Truman, championed the funding of an institute that eventually became the National, Heart, Lung, Blood Institute, which was the institute that funded the Framingham study. In fact, one of the first things that the Institute funded was to set up this epidemiologic study in Framingham, Massachusetts. And so it really had its origins in sort of the immediate post-war period, late 1940s, when there really wasn't a whole lot of recognition about the importance of heart disease and what the causes of heart disease were. And so if you scroll forward seven decades or so, we now know, as I mentioned, that it is the most common cause of death in the United States. And we actually have a lot better understanding of the factors that put you at risk for heart disease, and that leads back to what are some of the findings?

Tommy Wang:

And so as an epidemiologic cohort that followed people who were middle-aged adults at the time, over decades, they found that people with high blood pressure, high cholesterol, diabetes who smoked were at significantly higher risk of developing heart disease, which nowadays seem like obvious pieces of understanding. But back then it wasn't. As I said with FDR, it wasn't fully appreciated that having those high blood pressures were so bad for you.

Kelly Malcom:

Do you think it's still important to follow groups of people over time like this?

Tommy Wang:

Yeah, that's a really good question because there are other ways of collecting data now from people that didn't exist back then. Of course, everyone who comes to a hospital virtually nowadays has information entered into the electronic medical record. And so we have all these electronic databases. There are all sorts of other data that are collected even just in daily life that back then weren't available. And so the only way you could collect data was, as you said, to take a bunch of people and enroll them into a study and follow them manually over time. I think there is still value in that way of doing things. One of the limitations of the electronic or ambient collection of data is that a lot of those data occur in settings that are very selected or forced. In other words, you're not going to get data into an electronic medical record unless you show up at a hospital or a clinic for a particular reason.

Tommy Wang:

And so you wouldn't necessarily have the ability to study people just in their natural environment. And that is one of the advantages of, again, the manual collection through a cohort. Now, will that change over time? Again, as the avenues of collecting data from people get broader and broader, it may eventually be that the manual collection wouldn't be considered a very efficient way of getting the information, but I still think there's a role for these studies in the current day.

Kelly Malcom:

So you mentioned data, and I love to talk about data in this era of AI. How do you think the incorporation of data from different sources will change research? So we've got smartwatches and other ways of monitoring health that people use just for fun or for their own interests. How do you think that can help with the research into some of these conditions?

Tommy Wang:

Yeah. In my mind, there's no doubt that this is a transformative time because of the availability of data from multiple sources. I would preface that by saying there are still issues about privacy and confidentiality and security of those data which need to be worked out and are being worked out. But if we, for the moment, assume that those issues can be addressed, of course it's going to be very valuable to have data from large groups of people and collected longitudinally over time. There's no question about that. You can only think about how large data collections like large language models have transformed other areas technologically. It was really the scaling up of data that allowed these models that learned and iterated on themselves to really produce these emergent results. And of course, the hope is that a similar phenomenon will happen in healthcare. I think there are obviously a lot of analytic issues that still come into play.

Tommy Wang:

And for that, I would go back to some simple principles, which is that when data are collected, there can be bias in epidemiology. We think about things like selection bias or information bias or recall bias. And so as an example, if you were to look at a large data set and say, are people on a cholesterol drug or people not on a cholesterol drug? You would find almost certainly the people who are on a cholesterol drug are at higher risk of developing heart disease than people who aren't on a cholesterol drug. And so if you were to just blindly look at that association, you might conclude it's bad to be on a cholesterol drug.

Kelly Malcom:

Right.

Tommy Wang:

But of course they're on that cholesterol drug for a reason. They were placed on the cholesterol drug actively by a physician who made that decision. And so the interpretability of those data is very important to think about and how to think about analyzing data and understanding it in the correct way rather than the immediate opposite way.

Kelly Malcom:

Mm-hmm. No, that's a great example. One of the best things about working here at Michigan Medicine is just the breadth of research that goes on here. And I know that a lot of our faculty are engaged with partnerships, with industry, and that's something that we want to do more of. In your opinion, what is the ideal partnership between an academic medical center and industry look like?

Tommy Wang:

Yeah, great question. First off, I think it's critical. Medicine will advance because of productive relationships between academia and industry. For a variety of reasons, medicine will not easily advance if we just have one or the other, or if they're not working productively together. And the reason for that is because the different entities are positioned better to do different things in part at different phases in translating, understanding the therapies. And so on average, it takes about three decades between a scientific discovery and the drug based on that scientific discovery to get FDA approved. If you're a private company, for-profit company with shareholders, you don't have three decades to wait for that return on investment. Academia though is well-positioned to make some of these fundamental discoveries and observations and bring them to a phase that industry would then find it worthwhile to take it up and move it forward.

Tommy Wang:

By the same token, the scale of studies and the scale of an investment needed to take a promising molecule to widespread therapy and FDA approval. It's just not possible in academia. We're talking about hundreds literally of millions of dollars, if not billions of dollars of R&D and clinical trials, especially when you talk about things like heart disease. It requires studying a lot of people. Again, that's an area where industry is well-positioned to make those investments, not academia. Now, I'm not saying there aren't specific examples of where the trial was actually led by a university or where the fundamental discovery was made in a drug company. Those things happen. But again, by and large, in many of these therapies that are approved, there was a collaboration between academia and industry across that translational spectrum.

Kelly Malcom:

So you are still relatively new to University of Michigan. What excites you most about the research enterprise here?

Tommy Wang:

Yeah. Well, as you mentioned earlier, it is incredibly strong across multiple areas. I know that we like to talk about Michigan about how we have such excellence at scale. 19 schools and colleges, all of which are legitimately national leaders in those areas. That's definitely true. And it's definitely incredibly helpful in an area like biomedical research and medicine, which is so multidisciplinary. And so being on the same campus as a world-class engineering school, world-class school of public health, world-class school of nursing, the Institute for Social Research, LSNA, which has all the strength in the basic sciences, and even the humanities, which is relevant to medicine, that creates an incredible environment to make advances. I would say at the same time, if we were honest with ourselves, we haven't fully taken advantage of that environment just because it's hard. People and entities, whether that's schools or departments, they get focused on their own thing. And so figuring out how to take advantage of these synergies I think is one of the things that leaders at the institution should think actively about.

Kelly Malcom:

Okay. So what message would you have for our trainee basic and clinical scientists? I know it's sort of a tough time right now, but what message would you have for them?

Tommy Wang:

Yeah, I'll give them the overarching message and then I'll think specifically about what would I tell basic trainees and what would I tell clinical trainees? The overarching message is that this is an exciting time to be in medicine. With all our advances in biomedical, understanding biomedical research, understanding the fundamental mechanisms of disease, coupled with all the technologies that we have available, the likelihood that we can make incredible impact on disease and expand and extend health in the coming decades is really, really high. It's never been higher in our history. I think that is a non-controversial statement. And so this is a great time to be in training and emerging into these fields where you can contribute to this impact. I recognize that there are headwinds. There are challenges. There's uncertainty in funding for research. There are many other uncertainties. No question about that. There have been uncertainties at other time in medicine.

Tommy Wang:

This is not the first time that there have been challenges or funding or uncertainty about how healthcare is going to get paid for, concerns about the cost of healthcare. A lot of these are strands throughout the history of healthcare, at least in the past couple decades. And so those things won't go away. But I think that trainees, especially at a place like Michigan in our peer institutions, can be assured that these institutions are well-positioned to address these headwinds and to sustain this enterprise through difficult times. And they will be able to come out the other side. But of course it requires some persistence and some element of faith that we will be able to navigate these difficult times.

Tommy Wang:

So in terms of specific advice for people who are studying basic science or trainees in clinical departments, I would say if you're doing clinical training, especially if you are interested in a career in academic medicine, especially if you're interested in a career that involves research, one of the pieces of advice that I was given early in my career, which I think is very useful, is to train one level more basic than you think you're going to end up. And what that means is that even if you think you're going to be studying humans doing clinical trials in the future, it does help to have a little bit of an understanding of basic research or the basic mechanisms when you do that, even if you don't think you're ever going to have a career in wet lab research.

Tommy Wang:

And very little of my research in my career has actually been in a basic laboratory, but being able to understand it and work closely with individuals who are basic investigators has really expanded my ability to do research. For the basic trainees, the complimentary piece of advice is relevant, which is to really try to understand the clinical context. Now, that is sometimes interpreted to mean if you're a basic investigator, you should only work on things that have a direct human application. That's not quite what I mean. Sometimes when you study things that are basic, the applicability to a human drug or future human therapy is not immediately apparent.

Tommy Wang:

It sometimes takes a generation of findings before the application to humans becomes relevant. But that being said, I think grounding your work in some question that has some link to human disease or health is a useful place to start 'cause there are a lot of things to study in biology and biomedical science. And the one example that I would give is that at my last institution at UT Southwestern in Dallas, two of our faculty members, Mike Brown and Joe Goldstein, had spent their careers studying very basic mechanisms of regulation of cholesterol. But the reason they studied these basic mechanisms of regulation of cholesterol is because they were fascinated by a human genetic disease that caused high cholesterol, familial hyperlipidemia.

Tommy Wang:

They started these studies in the 1970s, again, very interested in this human disease, even though the research was very basic and they won the Nobel Prize in the 1980s for their advances in the understanding of this. And eventually it led to drugs like statins and other drugs that have transformed the way we treat heart disease. But again, they didn't start these studies with a direct idea of saying we're going to develop drugs.

Kelly Malcom:

Right.

Tommy Wang:

They started to understand basic biology.

Kelly Malcom:

Yeah. So you really never know where the science is going to take you.

Tommy Wang:

Yeah.

Kelly Malcom:

And what would be your message to policymakers and the overall public about the future of biomedical research?

Tommy Wang:

Yeah. The message is simple that we need to invest in biomedical research. It's what's put us in the position that we are today and it will help the world by allowing people to live longer and healthier lives. There's no question about that. There's no question that every dollar invested in biomedical research has incredible return in human health and has economic return as well because longer and healthier lives lead to lower economic burdens on society in the future and greater flow of economic benefits. A more specific message for policymakers is just think about these investments as long-term investments. The idea that if you invest a certain amount of funds, that you're going to get some immediate return in a year or a couple of years in terms of an FDA approved therapy or something. That short-term thinking generally is not helpful for biomedical research.

Tommy Wang:

For the reasons I mentioned, again, the average drug takes three decades from the scientific discovery to the drug. And so our funders need to have some idea of that horizon so that their expectations are appropriate. But if they are, the returns are enormous and immense. The other thing that I would say, and I think this has come up a lot even in the last decade with the COVID pandemic and other things, is that people may have the idea that science moves in a monotonic way, that it just moves forward. You build discovery on discovery, but it actually moves in a very herky-jerky way. You go forward, you go back, there's a lot of interruption along the way. Some things that you find don't end up being true, and it takes more work to disprove those things, but that work is valuable as well.

Tommy Wang:

And so I think the public and the funders of our research should understand that science is not linear. It goes in a series of jagged lines, but the ultimate direction is in a positive direction. That's always been the case historically. And so that, again, that ties back to the horizon. With a long enough horizon, we'll see that all of the directionality of our discoveries is it leads to better health.

Kelly Malcom:

That's a great way to end this. Is there anything else that you wanted to add as we close out?

Tommy Wang:

No. Again, incredibly privileged and honored to be at a place like the University of Michigan, Michigan Medicine. I think it's an incredible place for biomedical discovery and doing the things that advance the health of people in the state and people around the world. So hopefully my colleagues, the faculty, the learners, and staff also appreciate that opportunity.

Kelly Malcom:

Thank you so much, Dean Wang.

Tommy Wang:

Thanks.

Kelly Malcom:

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