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Each week, Health Affairs' Rob Lott brings you in-depth conversations with leading researchers and influencers shaping the big ideas in health policy and the health care industry.
A Health Podyssey goes beyond the pages of the health policy journal Health Affairs to tell stories behind the research and share policy implications. Learn how academics and economists frame their research questions and journey to the intersection of health, health care, and policy. Health policy nerds rejoice! This podcast is for you.
Hello, and welcome to A Health I'm your host, Rob Lott. Friends, it's another one of our very special episodes. As you know, typically on a health odyssey, we feature the authors of recent health affairs articles to dig in on their research and explore their findings. But about once a month, our producer Jeff lets us push the boundaries a bit to bring on a special guest from somewhere perhaps a little more exotic in the health policy universe to talk about their experiences in the field and to reflect on their own understanding of this very strange moment in time. Today, we're so lucky to be here with the one and only Doctor.
Rob Lott:Eric Topol, Director and Founder of the Scripps Research Translational Institute. Doctor. Topol is one of the leading voices for reason, transparency, and optimism as driving forces of the biomedical enterprise. He is a principal investigator of the All of Us Research Program, a huge precision medicine initiative created by Congress and funded by the NIH. He's a practicing cardiologist, and with all of his free time, the author of three bestselling works of nonfiction about health, medicine, and technology.
Rob Lott:Now his fourth book published just this month is titled An Evidence Based Approach to Longevity. Doctor. Eric Topol, welcome to A Health Odyssey.
Eric Topol:Thanks so much. It's great to be with you.
Rob Lott:So in a moment, we'll discuss the new book. But first, you've authored a number of books on precision medicine, AI, the bleeding edges of these technologies. Can you tell us a little bit about your journey from aspiring doctor to sort of leading voice on some of these really cutting edge issues?
Eric Topol:Well, thank you. I mean, I think the thing for me is always to try to take at least my best shot for where are we headed in medicine. And we're in some ways going back to college, I mean, genetics, we weren't quite ready until we could sequence the genome. But that's what led in the 1990s, when I was at Cleveland Clinic to set up the first cardiovascular biobank, where over 10,000 people back then, where we had their gene assays for what got them into the cardiovascular world of health issues. And so basically, what happened was in sequence, I got into genetics again, and then sensors because that was, it's not just the genes, there's a lot more to us than that.
Eric Topol:And then this whole theme of individualized medicine, where the more layers of data on each of us, the better we're going to do in terms of ultimately preventing diseases. That's what the new book is about. But it's basically been a very, for me, a logical building up of first digitizing human beings with these things we're just talking about, then democratizing, because once you have everything digitized, doctors are no longer in control of everything, which is good. And then the book Deep Medicine, that was the last book I wrote was about AI and how that ultimately with new models that we needed and we have now is going to be transformative. So we've got the AI models and now what are we going to do?
Eric Topol:And that's kind of, I think where the excitement lies for me and hopefully the medical community and patients as well.
Rob Lott:So I think one place where all of these different trends come together is the All of Us Research Program, which was created as part of the twenty first Century Cures Act, which believe it or not was nine years ago. And generally, correct me if I'm wrong here, the idea is to collect genetic and health data for upwards of a million participants with the goal of opening the door to potentially new innovations in precision medicine, moving beyond sort of one size fits all approach to clinical trials and the findings of clinical research. Enrollment started in 2017. And here we are a number of years later, a full blown pandemic later. Where do things stand?
Rob Lott:What have you seen change? What have you learned in the last few years from that project?
Eric Topol:Yeah, it's been, I think the biggest commitment for a singular or single project in the history of American medical research billions of dollars. Its real origin was interestingly with then Senator Obama, who pressed for something like this, and then Francis Collins, the NIH director. So it got off the ground just as you said, and now has over 850,000 very diverse participants. About half are not European ancestry. So it's very different than the UK Biobank or other biobanks around the world.
Eric Topol:But what's noteworthy is the majority have had whole genome sequencing and progressively they're getting their data. So that is one layer of data. We've also had sensors in a large proportion. And the intent is going forward, we'll have many other layers of data to help guide these participants to get better health care. The only problem is our funding has gotten substantially reduced.
Eric Topol:The Cures Act, the Congress and whatnot, and our current cuts. So it may not be as quite ambitious as originally laid out. But at least it's a very large population, uniquely diverse, that has rich data, and it's being made to the entire world of medical researchers. So just like the UK Biobank, a lot of good things will come from it and already have.
Rob Lott:Well, that's a great segue. Can you maybe give us an example or two of something exciting or promising that's come out of this project already?
Eric Topol:Well, we've already learned of some new gene variants that account for some of the most important age related diseases, including cancer and cardiovascular or neurodegenerative. And that was critical because previous to the all of us, so many of the studies for genetics were in predominantly white and European ancestry. So this multi ancestry capability made a huge difference. But the, for example, we distributed Fitbits very widely throughout this participant group. And we've learned a lot about sleep health, about physical activity.
Eric Topol:So the outputs from this work will go on for decades ahead, which is really exciting.
Rob Lott:Do you have a sense of the current administration's view on this project beyond just their sort of broad attempts at quote, improving efficiency or reducing costs, are they paying attention to the work of all of us? And if so, what do you think their take is?
Eric Topol:I think it's a great question you're asking. And I'm worried about that because of everything that's been going against diversity and equity, which this whole program was dedicated to trying to counter the prior medical research. Josh Denny, who is in charge of the whole program at NIH, has doing everything he can to work with Congress to preserve its support to augment its support. Because, as you may remember, the Framingham study done many decades ago, was one of the most important contributions of medicine ever. That was for cardiovascular.
Eric Topol:And it was again, also of only one ancestry, essentially. So now we have an opportunity to change the future. And if we don't continue to support this program, then I think just because of it, emphasis on diversity of all things, that would be a tragedy. So I'm hoping that we will be able to marshal new support now that the Cures Act funding is basically expiring. And it does take commitment from Congress and also not the attitude that we're seeing with respect to the administration to somehow discount the importance of multi ancestry work.
Eric Topol:What are
Rob Lott:you most excited about with this project going forward? What do you hope to see in the next couple of years? Funding aside, let's say it's a perfect world and you have all the funding you need. What would you like to see happen in the next few years?
Eric Topol:Well, think it gets to the super agers book. And that is a blueprint for how we can prevent, or at least markedly delay the three big killers, the three big age related diseases, cancer, cardiovascular, and neurodegenerative. Because in order to do that, we have to have all the layers of data for each person, which is what all of us is really geared for. And once you do, that's what's so exciting now, is that you can use AI, multimodal AI, to integrate each person's billions and billions of data points to say you're vulnerable and high risk for this particular condition at this time. Used to be we might say, Oh, your risk is for let's say heart disease.
Eric Topol:But we didn't know if you're it'd be when you're 98, or when you're 58. Now we can very, really fine tune this and say, you know, when it is and what we can do to prevent it. Because the important thing to emphasize is that three these three age related conditions are incubating in us for over twenty years. So we have a lot of time to work with here. And if we don't take advantage of that, then we're really being stupid.
Rob Lott:I wanna hear more about, your experience developing this book, in just a moment. But first, let's take a quick break. And we're back. I'm here with Doctor. Eric Topol, Director of Scripps Research Translational Institute and the author of An Evidence Based Approach to Longevity.
Rob Lott:Doctor. Topol, who is the audience for this book? Who were you thinking about when you wrote it?
Eric Topol:Everyone who'd like to expand their health span, or extend it, that is. I think most people would. We're not talking about longevity really, even though that's in the title, we're really talking about health span, which is the number of years with freedom from the big three age related diseases.
Rob Lott:Great. In your introduction, you described two patients. And I'm wondering if you can describe them briefly for our listeners here who may not have gotten to read the book yet, and explain how their experiences informed your understanding of aging.
Eric Topol:Yeah, so these are two patients of mine. Mrs. LR is 98 years old, and she's never been sick with any of these diseases. And she is noteworthy because all of her relatives, her parents, her siblings, all died at young ages. So she's, you know, the last one standing in her family, age 98, and perfectly healthy.
Eric Topol:So this is not only a gene story, in fact, that plays a very minimal role for healthy aging, as we've learned from her. And she is quite remarkable because she does oil painting and has won awards. She's had a gallery for her painting. She does all these thousand puzzle pieces, assembles them. She plays Remy Cube with seven other women of similar age every week.
Eric Topol:So she's not isolated socially as most people are more as we get older. So she's a very interesting person to learn from. The other patient has been mine for a patient mine for over thirty, thirty five years. He's now 99. He's got another year age in his book.
Eric Topol:I just spoke to him this morning, in fact, he's doing exceedingly well. But unlike the first patient, he's had heart disease since age 65. And he's basically a triumph of our treatments for heart disease, and our ability to have secondary prevention, you know, after bypass surgery, after heart attacks. But in the future, we're gonna have people like him who prevented their heart disease totally. So whereas he's 99 and his wife is planning his one hundredth birthday party, gave me a save the date.
Eric Topol:You know, we're going to see a lot more of these two people in the future if we use the data that we have in our hands now and more to come. It's going to change the natural history and the fulfilling the real excitement of primary prevention. That's been a fantasy of ours in medicine. We never really done it in any meaningful way. But we have the tools through this whole individualized medicine, data rich world to accomplish it.
Rob Lott:You've alluded to this earlier in our conversation, but can you say a little more about what's kept us from fulfilling that goal of primary prevention? Why is that so hard? And why are we only now just starting to move in that direction?
Eric Topol:Well, lots of things here. First, as I mentioned, we've learned now it takes at least twenty years for those three diseases to take root. Secondly, we know the mechanisms of how these diseases progress, and they all have a common thread. They rely on our immune system and inflammation. That is the immune cells such as lymphocytes and neutrophils secreting proteins that rev up inflammation in our body or in our brain in the case of neurodegenerative diseases.
Eric Topol:And also, we've learned so much about how lifestyle factors can help. So not just diet, precision details within the diet, like ultra processed foods, and the amount of protein and all those sorts of things, exercise, fundamental, sleep health, but then many other layers of data such as environmental toxins like microplastics and air pollution, and forever chemicals. So basically, we've learned all these things and added is the thing I mentioned with respect to, we had only a fuzzy idea of being able to say you're at risk for this. And it was basically using this polygenic risk score, pretty primitive. And it didn't say when it just said you're at some risk, and it wasn't very accurate.
Eric Topol:But now we have amazingly accurate ways. We have a protein marker, it's just one protein called p tau two seventeen, a breakthrough, where we can say you are at high risk for Alzheimer's, when, when you're going to have mild cognitive impairment. And if you change these things, predominantly lifestyle factors, and possibly drugs that we have even now to repurpose, we're going to change that whole thing and prevent you from ever manifesting. Alzheimer's, well, that's a dream. So there's been remarkable progress, and most people aren't in touch with that.
Eric Topol:I I recently wrote a a subject in in ground truths about p tau two seventeen, and I was stunned in the poll of it. Thousands of people, they'd never even heard of it. And, you know, a lot of these people have family history of Alzheimer's or have an APOE4 allele that they're worried about, you know, a gene test they've had. So we have new tools now, based on all the things I've been saying to accomplish this very far reaching objective that we've never really done before.
Rob Lott:The subtitle of your book is quote, an evidence based approach to longevity. And as you well know, there's a high quality evidence and low quality evidence and everything in between. Of course, writing a work of non fiction is very different from writing an academic journal article, a meta analysis, systematic review. How did you go about judging which evidence to include and which to leave out when you were developing this book?
Eric Topol:You'll note I had over 1,800 citations in the book. So it's much more like a medical type of report. But I tried to, of course, translate it more for the public that has less grounding in this kind of work with a caveat in the book in the introduction, some of it's kind of dense and just skip over that you get to that point where you'd say, I don't get this. The point being is, I obviously for in working in medical research for forty years now, I have a pretty good sense of high quality by knowing the researchers involved, the journals where it's published, the quality of the work, you know, how so much of it is rigorous, and basically tried to use everything we have to make judgments about, for example, what are the lifestyle factors that we can say are hard evidence? And where is where are the soft spots?
Eric Topol:But basically, your point is so critical, because there's so much pseudoscience out there. There's all these people hawking supplements, longevity clinics, longevity companies, I mean, this is just riddled with all sorts of things with no evidence, and selling and basically predatory, okay? So that was one of the reasons why I thought there was a need for the book. We have books out there where people are saying, get a total body MRI, start taking rapamycin, and all these other things, get all these other tests, and there's no data, no evidence. So what I'm trying to do is set the record straight as best as I possibly can by everything we know.
Eric Topol:And I'm also gratified that since the book was done and went to the printer just a few weeks ago, even more stuff has been coming out to reinforce what I thought where we were headed to really anchor it. So I'm pleased that these major conclusions, these blueprints are gonna be considered, I think by most people quite accurate.
Rob Lott:Great, well, you'll have to start that folder of additional evidence for the second edition.
Eric Topol:Keeping that active adding new things that if I ever do that, or if I just hit on one air at a time, because as you say, every week, there's something coming up to help us in this way.
Rob Lott:So a few months ago, Health Affairs published a paper led by Doctor. Don Berwick, which was part of the National Academy's Vital Directions series, offering an agenda for the next administration. And in that paper, one of the goals for our healthcare system that the authors proposed is quote, an additional decade of healthy birthdays after retirement. And I'm curious how you see that as sort of in alignment or not with your own thesis of this book, and really what steps our nation's leadership should be taking potentially to fulfill that goal. What role really do policymakers have when it comes with a goal like longevity?
Eric Topol:Yes, I mean, I think the world of Don Berwick, and I think what that was getting at is that in the book, I also summarize, we have data that if people have their lifestyle factors in optimum form, they can get seven years more healthy aging right now. The problem is most people don't have the right type of physical activity, the attention to sleep health, and achieving that. And really, you know, very healthy diets, you know, this ability to get people to go to a healthy lifestyle, I think will be much increased when people know that it's specific risk that is for sure. Timing, and know, it isn't like most of us are going to get all these three diseases. Most of us are really vulnerable perhaps for one.
Eric Topol:And so if you start to individualize, that's the whole tenet of precision medicine, And then you'll have a much higher rate of moving towards healthy lifestyles, and eking out, you know, what easily could be a decade of healthy aging. The point is not to live an extra ten years with dementia, or, you know, as a cancer survivor, but with all sorts of complications, but to achieve primary prevention of these conditions so that you can live healthily and you're not frail, you're not compromised. That's what our goal has to be. The sad part is we have an administration who purports to say they want to really bring down chronic disease. But the actions don't be speak that with dramatic reductions of support for the public health agencies, NIH, FDA, CDC.
Eric Topol:If we're gonna really do this, we actually have to increase our support because this isn't gonna happen by accident. We're not gonna be able to do what we're talking about today without dedicated programs that are funded to achieve these goals and harness the opportunity, making it a national priority.
Rob Lott:So longevity and superaging, these concepts are often thought of as sort of success at forestalling death. Now with your previous comment, I think I have a sense of how you think about these goals. But after all, death is a scary thing with all kinds of emotions and anxiety at play. And it also obviously has implications for society as a whole. Now famously back in 2014, Ezekiel Emanuel wrote an article in The Atlantic under, the title, quote, why I hope to die at 75.
Rob Lott:And in that, he wrote that, death is a loss. It deprives us of experiences and milestones of time spent with our spouse and children. It deprives us of all the things we value. But here is a simple truth that many of us seem to resist, that living too long is also a loss. I assume you read that article at the And I'm curious how you thought about it then.
Rob Lott:And now as you've developed this book ten years later, how you might respond.
Eric Topol:Yeah, no, I know Zeke and I totally disagree with him on this. And as I think he approaches 75, he may wanna write a retraction. I think basically he takes this fatalistic approach. And I happen to be an optimist. And basically what I've thought is, there's gotta be a better way than what we have now.
Eric Topol:And I think we're seeing that better way emerge. And yes, if you have a very bad chronic disease and you're debilitated, well, maybe that's living, extending life, that's not the goal. But what we need to do is well beyond age 75, we're talking about the two patients that I present in the book and come back to it many times, aged 98 and 99, we're gonna see a lot more of that. We can do this. So rather than a defeatist attitude, I see us get promote healthy aging because right now people age 65, they have three chronic diseases on average.
Eric Topol:That's not what that's not the kind of population that is gonna be the answer to this. We need to prevent preempt these diseases. And we could start, you know, at age 30 and 40 now we have the means to do that.
Rob Lott:So people have been pursuing longevity for centuries, you know, fountain of youth, it goes all the way back. And, of course, with time, we've seen incredible advances in our knowledge and the technology available to act on that knowledge. I'm curious if you could say just a little bit about this moment and why you're publishing this book now. Is it just that now is the latest step in the march of time forward and progress? Or do you see this as sort of a hinge point in history when it comes to science and health?
Eric Topol:Okay, so the science of aging has advanced and it's remarkable. And the thing that a lot of people are thinking about in the science of aging is we could reverse aging. We could reprogram cells. We could give these synolytic drugs that get rid of senescent cells in our body. We could prolong lengthen our telomeres, or you take NAD plus supplements or rapamycin or a long list, right?
Eric Topol:The problem, each of those carries significant hazard. And what I'm trying to do is say, wait a minute, one of those might work someday to slow body wide aging, But let's not overlook the science of aging has brought us clocks. We never had clocks before. Okay, we have body wide aging clocks, methylation epigenetic clocks, we've got organ clocks, these protein organ clocks. We can clock our immune system.
Eric Topol:We have these proteins, like I mentioned, we have ability to pick up tumor DNA in our plasma at the microscopic level where well before any scan would see it. So we have now these new ways to be on top of our aging process. That's to me, the real excitement about the science of aging. And it's the book is really intended to bring that out, to really highlight these exciting advances in contrast to the hype about all these things and this, you know, the hawking of supplements and the predatory stuff, which is baseless. It doesn't have the evidence in people.
Eric Topol:It's all about rodents, you know? And so if you can reprogram a mouse and make an old mouse into a young mouse, that's great. But it just so happens you also create tumors in the mouse. So, you know, these are elegant science approaches, but the science of aging has brought us something else which we can capitalize on. And the reason that's important is you can use these clocks to see if you're making headway in any given individual, right?
Eric Topol:So if you have a brain organ clock, and it says that you are 65 years old, even though you're really 55 years old, you know, that's serious. That's a problem. We then go on to changing your lifestyle and all sorts of things. And by then all of a sudden, brain organ clock is 45. Well, okay, that's the science of aging at work.
Eric Topol:And so we can do this and it's exciting. And it applies to each of the three major diseases to stay ahead of them, get ahead of them. The earlier we start in life, the better, but there's never a time when it's too late.
Rob Lott:Well, that's such an encouraging note. Before we wrap up, I'm curious if there are any other major themes you want to make sure that our listeners take away from the work you've done on this book?
Eric Topol:Well, the interaction of our lifestyle factors with the ability to prevent these diseases is really quite extraordinary. And it's not just these headings of diet and sleep and exercise, But the details, you know, like ultra processed food, how much protein, caffeine, alcohol, I mean, there's a lot of myths and miscues out there. So I try to set all that straight, but also get into the layers of lifestyle that people haven't previously considered lifestyle. I call it lifestyle plus. And that's these environmental toxins, air pollution, and microplastics and forever chemicals, and the importance of things like social isolation, time in nature, and many other things.
Eric Topol:So the lifestyle factors is the biggest chapter in the book, Because if we really take control of those, both the things that are doing good, and those that are being harmful, that's a real important path towards healthy aging.
Rob Lott:Great. Well, with that, I'm gonna go for a walk in the woods. I hope that could help along the way. Doctor. Eric Topol, thank you so much for taking the time to speak with us today.
Eric Topol:Thank you.
Rob Lott:And to our listeners, please tune in again next week. If you enjoyed this episode, recommend it to a friend, smash the subscribe button and tune in next week. Thanks for listening. If you enjoyed today's episode, I hope you'll tell a friend about a health policy.