Patrick O'Shaughnessy

[REPLAY] Peter Attia, M.D. - How to Live a Longer, Higher Quality Life - [Invest Like the Best, EP.27]

Patrick O'Shaughnessy

[REPLAY] My guest this week is Peter Attia, M.D., whose mission is to understand and improve human lifespan and healthspan (or quality of life). Reading Peter’s research, you find that there are many similarities between health and investing—ideas like compounding—which we explore in detail. We spend a lot of time on mind, body, spirit and performance as it relates to living a better life. Of particular interest is the strategic problem that we face when studying longevity. As Peter puts it in our conversation: we are the species of interest, but we can’t conduct the kinds of experiments on humans—randomized trials, with control groups—that we apply to solve other big problems. So we have to back our way into a better understanding of longevity and quality of life. To that end, we discuss what we can learn from studying centenarians, the problem of progress in science, a drug called Rapamycin (which Peter believes could be revolutionary), eating, the importance of muscle mass, and the idea of distressed tolerance. We emerge with a framework for thinking about health and well-being which can hopefully help us all live longer, better lives. Please enjoy! For comprehensive show notes on this episode go to http://investorfieldguide.com/attia For more episodes go to InvestorFieldGuide.com/podcast.

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Published Nov 6, 2018
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0:00-2:21

I know firsthand how complex the tech stack is for asset managers, and seemingly every new tool and data source makes the problem even worse, adding more complexity, more headcount, and more risk. Ridgeline offers a better way forward, one unified platform that automates away all that complexity across portfolio accounting, reconciliation, reporting, trading, compliance, and more, all at scale. Ridgeline is revolutionizing investment management, helping ambitious firms scale faster, operate smarter, and stay ahead of the curve. See what Ridgeline can unlock for your firm. Schedule a demo at ridgelineapps.com. Hello and welcome, everyone. I'm Patrick O'Shaughnessy, and this is Invest Like the Best. This show is an open-ended exploration of markets, ideas, methods, stories, and of strategies that will help you better invest both your time and your money. You can learn more and stay up to date at investorfieldguide.com. Patrick O'Shaughnessy is a principal and portfolio manager at O'Shaughnessy Asset Management. All opinions expressed by Patrick and podcast guests are solely their own opinions and do not reflect the opinion of O'Shaughnessy Asset Management. This podcast is for informational purposes only and should not be relied upon as a basis for investment decisions. Clients of O'Shaughnessy Asset Management may maintain positions in the securities discussed in this podcast. If you, like me, like to do deep research, you know the thrill of finding ideas and people who have arrived at unique or contrarian solutions to common problems. This episode is not about weight loss, but I mention it because it was by finding and devouring the work of this week's guest, Peter Atiyah, MD, that I reframed the way I think about health, period. Now, usually I would describe someone's career chronologically. Instead, what I'll say about Peter is that he is obsessed with mastery, a topic which we will discuss in detail. He has applied his pursuit of mastery to the fields of medicine, surgery, performance athletics, mathematics, mechanical engineering, racing, swimming, and many other areas. Peter's mission and the topic of our conversation is to understand and improve our lifespan and what he calls our health span. Health span, which is a proxy for quality of life, is where we spend a lot of our time during our conversation, specifically in the areas of mind, body, spirit, and performance.

2:21-4:42

We discuss what we can learn from studying centenarians, the problem of progress in science, a drug called rapamycin, which Peter thinks may be revolutionary, eating, the importance of muscle mass, the idea of distress tolerance, and the many similarities between health and investing. I went into this conversation hoping to emerge with a framework for thinking about health and well-being that I could share with you. Peter delivers in spades. I'm going to re-listen to this one several times to pull out ideas which I can put into practice. I hope you get as much out of this talk as I did. Please enjoy this awesome conversation with Peter Attia. Oh, and one more thing. Be sure to check out the show notes for this episode, which you can find at InvestorFieldGuide.com forward slash Attia, A-T-T-I-A. I've included several links to great thought-provoking videos and articles on the topics we cover. Okay, off we go. I'd love to start with this idea of And I start with wealth instead of health because I think that obviously health is going to be an important precursor for happiness and wealth. But I'd love to hear first if you had to define the very concept of wealth, how you would do it, and maybe a bit about how the answer to that question might have evolved for you in the course of your career. It's actually kind of funny you ask this question. It makes me feel like you've been listening in on my private conversations over the past month because I've thought about this quite a bit. I was having a discussion with a close friend a week ago. And I said, I have the interesting distinction of every time I've been at a fork in the road in my life where I had to choose between a financial opportunity that had bigger upside and then another opportunity that had more bliss. I always went down the path of bliss. And unfortunately, those things aren't mutually exclusive, of course. But in the situations I was always faced with, it was do X or do Y. bigger payoff why will probably be more blissful and I just always sort of followed the bliss bliss bliss so at the end of you know because of the compounding nature of things at the end of 20 years you look back and you go gosh there's a lot less money in the bank than would have if I had done such and such and then I sort of had this epiphany which actually ended up tweeting I think I sent out a tweet about it which might even be now that I'm thinking about it might be that maybe you saw that tweet maybe that's what made you think this

4:42-6:32

which was what if you totally changed the way you define wealth and didn't define it by, you know, anything sort of that had to do with money or success or even satisfaction, but simply define it by the number of great people in your life. And I thought of this metric and I was like, well, what's the big, you know, we use this term, like I'd take a bullet for that person, but what does that really mean? And I thought in practical terms that I understand, it might be, would you donate a kidney to somebody? Because, you know, I've been, I used to. do those operations. And I know what it's like to take a kidney out of somebody and put it into another. And it's not an entirely benign procedure. I mean, the donors in those procedures can die. And so that's a pretty high bar sacrifice. So I thought sort of thinking through my own mind, how many people would I give a kidney to? And my guess is there are some people who wouldn't give a kidney to anybody. And so maybe those people, despite how much money they have, don't actually have that much wealth. Begs the question, how do you increase that number? So have you thought about strategies for that? You know, I haven't really because I don't know that you can game it, right? I mean, I think there's a bit of vulnerability that's required to do that. And there's a bit of, you know, I think you have to be willing to care about somebody a lot. You have to be willing to, in a sense, at least in a moment, almost care about somebody as much as you care about yourself, which, you know, for... for sort of high achieving successful people. I mean, if you really are forced to confront reality, we can be pretty selfish. So, so I think there's a little bit of that. And I mean, look, I mean, anybody who's had a child, I think could immediately understand what that means. Because if you ask most people, how many, you know, who would you donate a kidney to that? You know, certainly first on that list would be your children. Most people would, if you don't say that, maybe you have to examine your relationship with your kids. You know, maybe your spouse, maybe some siblings, but if you take. flesh and blood out of the equation and then say, how many non-family members would you do that for? I just think that that's sort of, I feel fortunate that I look back at different phases of my life, whether it be high school, college, med school, residency.

6:32-8:32

I managed to collect an unbelievable group of people that I, there are people in each of those chapters of my life that I would actually say that for. It's a neat, I like this, the spin that it's not take a bullet for because until I had kids, I didn't, I didn't really know what that felt like. And now obviously I do, but that's a very, it's a very small list. So the kidney is a neat litmus test. I find that the, maybe the only way. certainly not to game it, but at least to think about it a little bit differently, is to change the mindset from sort of a zero-sum competitive edge to one that's more about abundance, where if there's more selflessness in the equation, then perhaps you can, by giving, actually build that list, which is, it takes a really long time to get yourself convinced of that idea, but it really seems to work. So with that in mind, and the strength of relationships being a key component of wealth, but probably also of health. Maybe we can shift there. There's a chart that you drew from a recent post that I cannot get out of my mind that shows the relationship between health span and lifespan, which I will link to in the show notes. But it'd be great if you could describe that chart because it can be a jump off point for quite a number of interesting things to talk about. Yeah. So, you know, I first think that, so it's hard for me to explain what I do because I don't have a one sentence answer, but. And the one-sentence answer sounds so glib and silly that I'm usually too ashamed to say it. But if forced, I would say, you know, I'm a physician and my interest is in maximizing human longevity. But then you have to define that because maybe people don't really know what that means. And so... I think the simplest definition I have for longevity is lifespan and healthspan. It's a product of those things. Now, whether it's an exact dot product or not, I mean, it's irrelevant, but it's a mathematical function that could be described by those things. Now, lifespan is easy to explain. So if you draw an X and Y coordinate, the X coordinate would be time, and therefore lifespan is how long you live. And then the Y axis would be some measure of that quality of life. And so I call sort of that Y axis the healthspan axis.

8:32-10:43

And the function then starts at, you know, zero and say one, right? So times zero and one, meaning, you know, maximum health span. And as you move through your life, the, you know, the curve moves to the right and more or less monotonically decreases with a couple of features, right? So if you just think averages, the average Americans. probably going to live to about 80 right now. You could argue I'll divide that by socioeconomic lattice, but just keep it really simple. 80 is when the curve will cross the x-axis, meaning lifespan ends. At about 40 is when it starts to take its first noticeable dip. So most people are kind of doing pretty well till 40. For example, when you turn 40, it's when you start to... without doing something very deliberate about it, lose about 1% of your muscle mass a year. That's highly associated with many of the things that result in a decline of health span. The other point to notice is assuming we stick to this number of about 80 being when it ends, by the time you hit 70, you're generally about halfway down the y-axis. So if we started at like a unity of 1, you're at now 0.5. So that means that... you'll spend 70 years declining to half of your capacity, and then in 10 years, you'll sort of really unwind. So with those things in mind, the question becomes, how would you make that better? And I think one of my mentors was a great thinker, and he was very disciplined about the following. He said, never try to solve a complicated problem without... explicitly being able to state your objective, your strategy and your tactics. And that's, it turns out that is, I haven't met many people for whom that is a natural thing to do. That takes work and a lot of discipline because I think as humans with our little monkey brains, we just want to jump into tactics. It's the only thing people want to talk about. And so you have to lift yourself out of that. So, so the objective, then this graph helps you define the objective. The objective is to shift that curve up and to the right. So you want more lifespan. You want to live longer, but you want more health span. And you, if you want to alter the shape of that curve so that it's not just,

10:43-12:51

a stretch of the exact curve, which means you still have that decline over that same period of time. The chart looks like the upside down version of every non-log investing chart you ever see, which is the compound growth. This is negative compound growth. So you get that crazy tail off at the end. And just like investing, all the best investing advice is fairly straightforward and very boring because it just needs time to work, right? And all the fun comes at the latter half. So everyone uses the example that Buffett wasn't a billionaire until he was 65 and now he's 80 billion. or whatever it is because of compounding. And it's so hard when it comes to health to convince yourself of that because it's so easy to eat a cookie or do whatever you're doing today. And especially when you're young, really feel no ill effects from that, maybe a racing heart or something like that. But really what struck me about that chart is that, and I think about it a lot now as I'm making day-to-day decisions. That curve getting pushed up and to the right is all about simple daily decisions. And there's a lot of different dimensions that can cause that phase shift for that curve. So maybe we could explore some of those. How many different dimensions to this do you think about? Are there sort of several key categories that you focus on, whether it be with patients or with people reading at large, that are most important for that shift in health span? So before answering that question, I would sort of latch on to something you said, because it's not often I get to have a discussion with somebody that immediately appreciates. the nuance that usually i try to bring to the discussion which is the importance of compounding now it's probably because my background is in engineering and mathematics and so i think the beauty of compounding is a tiny bit more intuitive to me though i think for no human can it be truly intuitive because it's just so non-linear. Sometimes I have to actually put a little Excel spreadsheet together just to prove something to myself, because I can't believe it could actually move this way. If I could reduce the fees on this investment account by 1%, look what it does in 30 years. It's unbelievable. To me, the analogy of health and wealth has this other layer of compounding, and that's exactly what it is.

12:51-15:06

is the most biologically important manifestation of compounding. And we tend to think a lot of things that go wrong and it appears suddenly. So-and-so died of a heart attack. Oh, so-and-so got cancer and within a year they were dead. And as tragic as those things are, we have to remember none of those things happened in a moment. Nobody just has a heart attack or just gets heart disease or even just gets cancer. These things are occurring for generations before. So actually, probably the first paper I ever worked on in my life as a medical student was a review article. You know, we ended up, I don't even think it got published, but I spent a year writing it. It was on the entire mathematical literature of tumor growth rates. And so it turns out there are many different models to model how cancer grows, but they all had one thing in common, which is a cancer spends more than 80% of its life undetectable because it is just simply so small. You know, your cancer needs to get to about half a centimeter in diameter before you'd even have a chance of knowing that it's clinically relevant. And by that point, it's already been 80% in existence. You know, heart disease begins at birth, right? So we saw these autopsy studies in the kids that came back from Vietnam. Kids were killed, and even at the age of 18, they had clinically relevant atherosclerosis. That experiment was repeated a decade ago, or less than a decade ago, actually, with the veterans from Iraq and Afghanistan, and the same thing was seen, albeit slightly to a lesser extent, presumably due to less smoking. But the point is, you know, these things matter, and you have to sort of make these adjustments. So that's kind of the first thing. The second thing I want to do is just go back and define healthspan, because to get into what you do, The lifespan part's really easy to understand because it's not dying. But the healthspan part, everybody might have a different definition of it. So I can only share mine. But my definition is three things. The sort of glib would be, you know, the top line would be sort of mind, body, and spirit. But I would define them this way. So mind I would think of as cognition. And I use cognition because it's measurable. And, you know, neurologists and neuroscience know how to study that. So cognition we measure by three features, which is executive function.

15:06-17:13

processing speed and short-term memory. And so we can test those things and we know how to mark those things. And most people would agree that though those things aren't mutually exclusive and collectively exhaustive, they encompass a good variant of that. And again, I think most people would agree when cognition starts to decline, quality of life starts to decline. And then the second being body, you know, my definition of that is maintenance of muscle mass for reasons we can talk about later, the ability to carry out functional movement and freedom from pain. And again, when you start to think about what are the things that decline a person's quality of life, it usually is some erosion of those things. And then the final thing is sense of purpose and social support. So I'm sure you've been around a lot of people who, from a financial perspective, have everything that they could ever want. They have more money than they could ever spend, and yet they're not really happy. And when you start to dig down into it, at least in my experience and with my patients, that tends to be one of the first things that plops up. Something in their social support network sucks, right? They're in an unhappy marriage. They have a strained relationship with their kids, like something. And or they really don't have a sense of purpose that goes beyond themselves, which actually kind of gets back to the question. Yeah, the kidney thing. So with all that said, if the objective is to increase that, I'll spare your listeners the strategy for how you do that, because that's in and of itself a really long discussion. What you're really asking now are what are the tactics? And it's basically. anything and everything that you can manipulate that can move that those levers and in my view it really comes down to everything about how you eat so that means how you eat when you eat what you eat how you sleep how you exercise how you manage external stress what drugs you take what hormones you take what supplements etc and learning the ability to avoid harmful behaviors because When you go back to the arc of longevity and lifespan, about 80% of people, if they make it to the age of 40 and they're not smokers and they're not suicidal, they're going to die from three disease processes, which are cardiovascular and cerebrovascular disease, cancer and neurodegenerative disease. But there's still 20% of diseases outside of that. And the next leading one is accidents.

17:13-19:14

There are certain actual behaviors you can learn to combat that will minimize your risk of dying of accidental deaths. So those things constitute all of what I think of as the levers. Those are the things you can pull to manipulate to affect that change. So without going, we don't have to go too deep into strategy, but I always find that level a bit more interesting. As do I. It's the only thing I ever want to talk about. Then, you know, don't eat this specific thing. But maybe you could give us a high level of what you mean by the difference between, so I'll call not eating sugar a tactic. That's right. So maybe an example or two of what you mean by strategy without having to flesh out the entire framework. So the strategy is basically predicated on having to solve for a complicated issue, which is we are the species of interest. And yet we can't do the experiments we want on the species of interest. So in science, we love to use experiments. The experimental method has given us something remarkable. And so if you have a theory about how. a certain particle behaves in quantum physics, you can test the hypothesis. Go smash it. That's right. You can build an accelerator. You can smash the particles. You can measure. And you can compare the result of the measurement to the hypothesis. I mean, there's a beautiful clip we should actually link to in the notes of Feynman explaining the scientific method more elegantly than Francis Bacon. And that's basically it, right? And if the measurement doesn't fit your hypothesis, your hypothesis is wrong. When it comes to everything with longevity, we don't get to do that. So instead, you have to triangulate on three things that are not what you want. What you want is give me 100,000 babies born today. Let's randomize them into N groups and put them in an environment where we can perfectly monitor every one of the tactical changes we make and follow them indefinitely and find out who lives longer. Okay, that's never going to happen. So I triangulate from three separate things. The first is... effectively epidemiology and ecology and the understanding of centenarians. Centenarians are obviously a rare subset of the population. About 0.4% of people live to be 100 or longer.

19:14-21:32

But we've learned some really interesting things from them. The first thing we've learned, which anyone listening to this who knows a centenarian or has them in their family will probably tell you, is they don't actually do anything better or worse than anybody else. On average, they're just as likely to smoke or not smoke or exercise or not exercise. So they clearly have a set of genetic advantages. And a group of scientists up at Albert Einstein here in New York have actually done a lot of work at identifying what those genetic advantages are. And they basically fall into a handful of categories. hypoactive genes that result in sort of less of something called APOC3, less growth hormone and growth hormone receptor and lower IGF. In addition to having, they're more likely to have certain genes that code for proteins like APOE2 versus APOE4, for example. The listener may say, well, I don't know what the hell any of that means. And that's okay. The point is each of those genes, remember genes just code for proteins. Proteins do things in the body. They have genes that code for proteins. that offer them protection from every one of those diseases I mentioned. So APOC3, deficiency of APOC3 gives you protection from heart disease. Having an APOE2 versus a 3 or 4 offers protection from Alzheimer's disease. And having lower GHR or IGF offers protection from cancer. So miraculously, the same diseases we spend all our time thinking about because they're going to kill 80% of us, these guys got a whole bunch of genes that just give them protection from those things. The second thing to triangulate on. is looking at the species where we can do experiments, which is every species but us. And so we typically in science will divide the world into sort of four buckets. We'll go from the most simple, which would be yeast, to flies, worms, and mammals. And that's an interesting sort of spectrum because that spans a couple of billion years across evolution. And it's pretty easy to find things that work well in one of those populations or even one species. And that could be interesting. But when you find something that works across that entire spectrum, it's really interesting. So at least to my surveying the literature, there are really only three things that are common across those billions of years of evolution. The first is that some combination of caloric restriction and dietary restriction seems to offer benefit.

21:32-23:49

The nuance around that is so important that it probably doesn't warrant a discussion now only due to time. But for those listening and interested, the answer is not caloric restriction. I'm very confident saying that the answer is not just eat 60% or 70% of your required calories for the rest of your life and that's going to do it. Though that has worked in some animal models, I'm completely convinced it does not work in the real world for a number of reasons that... are absent in the control animals and secondly frankly i think most people would be too miserable that even if it did work it would probably not be a viable option but cyclic fasting might right so there's four different types of intermittent fastings and we can maybe talk about yeah can you describe those because i think that this is a really interesting topic yeah so so we can think of caloric restriction as outright caloric restriction versus things that mimic caloric restriction so we call those things cr memetics so the cr memetics i put into a couple of different categories one is daily intermittent fasting which means if there's 24 hours in a day you will not eat for 16 or 18 of them is typically what you would do so i typically do that almost every day So, you know, I won't eat my first meal today till three, maybe four, but usually no earlier than one. And then I'll, you know, sort of wrap it up within six to eight hours. So 16-8 and 18-6 would be kind of two popular formats of that. Then you have fasting regimens like that of, you know, Walter Longo, where he's promoting something called a 525. So for five days a month, you consume a very hypocaloric diet. It's 750 calories the first day, then 500 calories a day for days two, three, four, five. And then days six through 30, you're consuming ad lib, meaning you consume what you want. There's a 5-2 protocol where you consume two days a week, you fast five days a week, you consume ad lib, et cetera. That's the sort of the CR world. The DR world says you don't actually have to consume any, you don't have to restrict the number of calories, you have to restrict subsets of calories. And so perhaps the most important experiment in all of caloric restriction and dietary restriction is the largest and most long-running experiment on this topic, which was done, two experiments, one done at the NIH, one done at the University of Wisconsin, using rhesus monkeys. So this was an 18-year experiment.

23:49-26:05

I'm actually probably going to write a blog post about this because I think it's so important that people understand. Because even the scientific community, I think, still gets the answer wrong when they look at this. And my view, I'll just give you the punchline, is that if we learned anything from that experiment, it's that caloric restriction probably works best when your baseline diet is abysmal. So the monkeys that were on a very high sugar diet probably saw the most benefit from just reducing the total number of calories. potentially because they were reducing crappy calories. When you took the monkeys that were on the better diet, which was like the real monkey diet, they didn't have like the monkey shakes, they did not experience a benefit to caloric restriction. And that, again, when you get into the sub-sub-sub analysis suggests to me that DR could be just as powerful as CR. So that's point one on all of animals. Point two on all of animals is there's only one drug that has extended life across all four of those models. So there's only one drug that works across a couple billion years of evolution to almost without exception uniformly extend life. And that drug is rapamycin, which again, probably one of my favorite stories of all time, which I won't get into. Although Tim Ferriss and David Sabatini, Nav Chandel and I went to Easter Island last year, sort of as a pilgrimage to see Easter Island being the place where Streptomyces hydrocophagus was discovered in 1964. That was the bacteria that ultimately became rapamycin. Oh, Rapa Nui. Yes, Rapa Nui. Yes. I have a Rapa Nui flag in my house now. Cool. Yes, yes, yes. That's a Rapa Nui, the name for Easter Island. That's right. That's what the locals call it. So the compound was named Rapa Mycin in honor of that. And in my own biased way, I would argue it's probably one of the single most important drug discoveries of all time, certainly in terms of our understanding of longevity and nutrient sensing, which sits at the heart of it. Why rapamycin is important really comes down to something called TOR, the target of rapamycin, or mTOR, the mechanistic target of rapamycin, which sits at the heart of how our body decides when it is time to grow versus repair. So the third and final part of what I think is common to all of the animal literature is across all of those different organisms and species, what are the genes?

26:05-28:20

that when manipulated, produce a favorable longevity phenotype. So I'll give you one example. Cynthia Kenyon, who is at UCSF now, is at Calico, the sort of Google company that is working on longevity, did some elegant work with a very commonly studied organism called C. elegans, which is a worm. And noticed, so this is a worm that normally does the following. It lives for seven days. And the first four days, it's a rock star. And then the last three days, it shrivels up, becomes really slow, can't move, and then it dies. So actually, if you picture our curve, it does that curve in seven days and in about the same distribution. So they took this gene called the DAF2 gene. And if they knock it out completely, the worm doesn't survive. But if they perturbed it in a way that it was just less effective, the worm lived for two weeks. and looked amazing for about 13 and a half of those 14 days so which is anybody who's really forced to think about that that's kind of your dream right like wouldn't you love to push in that curve yeah you just you you want to create an area of one under that curve right um and you just die in your sleep having you know just finished a marathon or something right i was at a swim meet once a master swim meet where a guy died in the pool and as tragic as it was and as sad as it was you know the guy was you know probably in his 70s or something like that But I couldn't help but feel a little jealous because I thought, like, this guy showed up to race today. He got on the blocks. There's some, you know, 50-year-old guy next to him, and he jumps in the water to just give it all he's got, and that was his last stroke. And I don't know. I think that's not an unreasonable way to go. So it turns out that that DAF2 gene is analogous to genes in humans for IGF. So what we see with GHR and IGF in humans is very similar to what DAF2 shows us in C. elegans. And that's one example, but the point remains that all of the genes that seem to offer longevity to humans through these centenarian studies have analogs in the animals that do the same thing. So the third piece of the strategy then is at the molecular and basic scientific level, which is what does it really mean to age?

28:20-30:26

Like, why is it that I now have these gray hairs in my beard? Like, what is that? Why does my skin not look the way it looked when I was 20? And, you know, part of that may actually be senescence. Part of it may be progenitor failure. And so when I think about sort of the next frontier in this whole space, it's What can we do strategically or tactically rather to target those things? Is there anything that we can do when we look at how the nutrient sensing pathways work? Are the things we can do deliberately that will target those? For example, a drug called metformin that some of your listeners may have already heard of because it's certainly in the past few years gaining some traction outside of its common use, which is to treat type 2 diabetes. really understand how these mechanistic pathways work, you start to then think, well, that drug, which would normally be used to treat condition X, if dosed a different way, might actually hit something in that system and offer us something different. You mentioned this idea of growth versus repair, which is a really interesting topic because of fasting. And again, just to delve into tactics for a second. Maybe the two most important things, and I should probably say how I came across Peter's work. This was probably five years ago or so. I was just married a year or two into my marriage and had gotten kind of fat and happy. Fat for the first time in my life and was trying to figure things out. And the standard party line about low fat, et cetera, caloric restriction just wasn't making a dent. So I discovered this idea of paleo and CrossFit, just like everyone else does, right? Kind of went through the normal motions here in New York City. But the two things, the two tactics that... that were by far the highest rate of return or the greatest bang for the buck were the elimination of sugars and glutens and maybe probably most important beyond just weight, but just how I felt was intermittent fasting. Basically never eat breakfast, still don't, and you get used to it and it's the most powerful thing that I think I've done. And from what I understand, and obviously you know way better than me, so I'd love to hear if I'm right on this, is that it's all about repair, that the body takes a certain amount of time.

30:26-32:39

in metabolism just to get through your last meal. And it's only after that's complete that the repair can begin. So like investing, a lot of the best things you can do are negative, meaning things you remove from the equation rather than things you're trying to add into it. So am I thinking about that right? That the growth repair that you talked about with rapamycin and mTOR, there's a similar sort of strategy or idea behind fasting and intermittent fasting? Yeah. I mean, I think the word that is necessary to have the discussion a little more completely as autophagy. So autophagy, as its name suggests, autophagy. So auto-self and phagy. So phagocytosis is when, you know, one cell eats another cell. So just last year, actually, in the fall of 2016, the Nobel Prize in Medicine and Physiology was actually awarded to the Japanese scientist who, you know, basically created the genetic underpinning and understanding of how autophagy works. But it basically comes down to this. So first of all, from an evolutionary perspective, most people would, if thinking about it for more than three seconds, realize that nothing about our world today mimics, from a nutrient standpoint, what it would have been like a million years ago. Because today we can very easily never be hungry. And again, that's a relatively recent phenomenon. So in previous lives, we would have been, you know, basically alternating between fast and famine. Pardon me, between, yeah, feast and famine, I'm sorry. And so feast is, you know, cellular building, right? And then so what's happening during the famine is the body has to be more efficient and the body has to say, well, look, I've got, and I'm overly simplifying, but, you know, I've got all these cells here and they're not all great. you know, some of these guys aren't that good anymore. Well, why am I wasting any energy on them? I have a better idea. Why don't we eat them, recycle their constitutive elements, which are valuable. Maybe this guy's mitochondria is okay. Maybe this guy's got a reasonable Golgi apparatus and we can recycle those. But for the most part, we'll take those guys out of the game. So it's very Darwinian. And then when you refeed me, I'm going to selectively just replenish the good cells. And so that's effectively what we're all trying to hack into. Now, what I can't tell you,

32:39-34:57

I'll tell you in a moment why I can't tell you this is, do you optimize that by doing, you know, what Valter does, which is say five hypocaloric days, 25 full feeding days. Do you do it by doing, you know, 16 hours every day of not eating or 18 hours of every day, not eating, or I actually spent six months only eating one meal a day. So basically 23 hours a day of not eating at all. And then one hour of gorging. And the answer is we don't have a goddamn clue. because we don't have a tool to measure autophagy in humans. So we can measure autophagy in animals by sacrificing them in the lab and measuring a bunch of proteins, but we don't have what I like to describe as a metabolic signature for autophagy. And so what I'd love to have, and I've talked about it with a number of scientists who agree this would be an amazing thing, but nobody's really interested enough to sort of put funding into it, is Wouldn't you be great to draw a tube of blood out of your arm and be able to measure the proteome, the small, meaning like what are the large proteins? What are the changes in proteins, the changes in small molecules that tell us when you're in and out of that state maximally? And so it's certainly one of my hopes that, you know, in the next decade, I can convince somebody to put a few dollars into that project because that would actually allow me, that would give me much more comfort as I pursue these different sort of tricks around eating. taking these drugs and that drugs and All the things that I think I'm doing to optimize that system, I'd love one more layer of assurance that I'm doing it maximum. If you invest well, at least you get a return. And here we don't get to see the final return until the end. Right. It's such an interesting problem that we know, for example, maybe there's like a Pascal's wager for sugar, right? That obviously it's enjoyable to eat sugar, or at least it is when you're still eating it. If you haven't eaten it for a while and you go back to it, it's not nearly as enjoyable. But there are a suite of things. that we're pretty sure, like I haven't seen any studies that sugar is good for you. Maybe one exists, but I certainly haven't found it. The sugar industry has several. They've got some good ones to roll out. Yeah, well, I was just reading about, I'm reading Barbarians at the Gates right now about the fantastic book and gets a lot into the history of the tobacco industry. And in 1960, there's a stat in there, 60% of adult males smoked.

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And obviously that numbers come way down, but a lot of people still smoke and Philip Morris is I think at all time highs. So I was very interested. to see if there was some propaganda campaign, maybe that's the wrong word for it since it's a good thing, but what the style was to get public awareness around tobacco and its link to lung cancer, where I was interested to find that the Germans, pre-Nazi Germans found it, but then that was tainted. Anything, any science that had come out of Germany post-World War II was tainted, so there was like a lag. Which, by the way, as an interesting footnote, Gary Taubes has written extensively about this, but in many ways that sort of happened in nutrition. as well, right? So prior to World War II, much of the best research in physiology was out of Germany. Really? In fact, German was the Linge Frank of science prior to World War II. Anything that was going to be published meaningful in science was going to be published in German. And then, of course, World War II created a complete divide where only physics immediately came to English, right? Because obviously the best physicists had also then migrated to the United States during the Manhattan Project. But interestingly, there was this lag in what was going to happen in physiology. And so post-World War II, you had this totally new school of thought around the understanding of adiposity, obesity, and things like that. And it went from being treated the way I think it should be treated, which is as an endocrine disorder to a behavioral disorder. And that's actually one of the other... lovely remnants we have of world war ii if all of the other things that happened in world war ii weren't bad enough that that might be yet another one so where i was going with the sugar thing is to spend some time on Thomas Kuhn's idea of the structure of scientific revolutions, barriers to change in fields like nutrition, science, whatever. There's a great book called The Diffusion of Innovation. If listeners haven't read that one, that is a fantastic book that just shows you how long it can take for something that seems obvious, whether it's curing scurvy or what have you, to take hold in the public consciousness.

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Let's say we're 50, 60, 70 years from now. What major things, whether it be in, let's focus on nutrition maybe and the second one, body or movement. What major things do you think will look as absurd to us as the fact that 60% of adult males smoked in 1960 looks absurd today? Will it be sugar? Will it be other things? What do you think? I'd certainly like to believe that in 60 years, we will view it as absurd that. all calories are created equal. And again, I think that, I don't know how many people truly believe that anymore. At a policy level, it's even that sort of shifting. I mean, I think you see even the food pyramid certainly wouldn't suggest all calories are equal from a nutritional standpoint, although it would still suggest all calories are equal from a fat standpoint, meaning from an adiposity standpoint. So I'd want to believe that that's the case. From an exercise standpoint, I would hope, but again, I'm just projecting my own biases. I would hope that in 60 years it is so universally accepted that if you can only do one thing in life, whether you're a man, a woman, whether you're athletic, whether you're not athletic, whether you have an aspiration to do anything, whether you want to be a couch potato your whole life, that everybody understands the importance of maintaining muscle mass and that everybody is lifting weights. And whether they want to do what Mark Ripito does and do incredibly heavy squats and deadlifts, great. Or whether they just want to adopt a super slow protocol. you know, lift weights 30 minutes twice a week, but everybody sort of gets it in their mind that this notion of like my exercise is going to the gym today and standing on the treadmill while I watch CNBC, like that doesn't count. That's you can do that if you want, but that doesn't count as your exercise. That would be, that would be interesting. Are there, are there benefits to weightlifting and muscle mass? Let's just ask it in general. What, what are the primary benefits?

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beyond the obvious feeling and looking good that probably drives most people to the gym. What's the physiology underneath that that makes it so important? So I divide them into two categories. And I don't work with performance athletes anymore, not out of any moral reason. I just don't find it interesting anymore, and I find it very difficult to serve two masters. When my goal in life was to be the best whatever I was being that I could be, meaning I was never going to be the best at anything in the world. But when I wanted to be the best cyclist I could be or when I wanted to be the best swimmer I could be, the things I had to do came at the expense of my health. My best cycling physique is a brutal physique. It's like a emaciated, completely unhealthy, hunched over in the shoulder physique. So the two things that I think about from exercise have nothing to do with performance. And the first has to do with the metabolic benefit of exercise. The second has to do with the structural or orthopedic benefit of exercise. So from that standpoint, we'll start with the latter. Maintenance of muscle mass, preserving bone density, the ability to move, the ability to move without pain, all contributes to that health span axis. And people like you and I are not old enough yet to understand what it means to break your hip and why that can end your life. It can end your life literally in the moment. For example, if you have a fat embolism from the marrow in the hip. immediately lodging in your lungs. But more typically, you know, a devastating orthopedic injury later in life results in, you know, a complete loss of mobility and a relatively precipitous decline. So there's no way around it, but if you want to avoid that, you need a strong chassis. I mean, we can putz around all we want, but in the end, your bones have to have... as much density as possible. Your muscles need to be long. They need to be strong. They need to be able to act on the levers that they're designed to act on. The metabolic benefits of exercise and why I particularly think strength training is important really comes down to glucose disposal. Sort of one of my underlying tenets of...

41:05-43:14

living as long as you possibly can is maintaining the lowest average glucose you can and the smallest standard deviation. So, you know, I wear a continuous glucose monitor. So it's a device that, you know, my phone tells me every 30 seconds what my glucose level is. And every time I hit report, it shows me for the last 14 days, what was my average glucose and what was my standard deviation. Which of those two is more important, the level of the standard deviation? Both, actually. So for example, if you have an average glucose of 100, which is reasonable, that's a pretty good average glucose 24-7 over two weeks, and the standard deviation is 10, that might actually produce a lower insulin AUC area under curve than having an average glucose of 80 with a standard deviation of 30. Because what I really care about, So I'm not sure that there's much difference between an average glucose of 80 versus 85 or 85 versus 90. There might not be that much of a difference. But if you have enormous excursion up and down and up and down, you're seeing spike insulin in, insulin out, insulin in, insulin out. That might actually be more problematic. average and standard deviation of glucose becomes a proxy to measure something that is clinically impossible to measure, which is the area under the curve of insulin over a 24-hour period. Can you define a couple of those ideas? So maybe what it might look like, you can just do it for yourself, what you're eating to produce something around, let's say it's an 80 and 110 or some high level, like what kind of diet might be associated? Well, before I do that, I have to answer the question you actually asked me, which is why does exercise fit into this? And what... You know, glucose homeostasis is kind of just one of those miracles of life, right? So if I drew your blood right now, took a tube of blood out of your arm and measured your glucose level, let's assume just to make the math easy, it was 100 milligrams per deciliter. We would call that a pretty normal, it'd be an elevated fasting glucose, but you know, so let me assume it's a little lower. And then, so if I looked at how much blood you have in your body, the total volume of blood in your body, we have about five liters. That means that

43:14-45:24

I can calculate how many grams of glucose you have in your bloodstream. And that number, even whether it be 100 or 200, 200 would be a diabetic. If your fasting glucose was 200, you have diabetes. If it's 100, you're normal. But that difference is only a difference of about five grams of glucose, right, which is like a bite of an apple. So the difference between the person with diabetes and not diabetes is... tiny with respect to how much glucose they are able to balance in their circulation. So everything comes down to how much can your liver buffer glucose into and out of that circulation. And when enormous amounts of glucose enter your system, which is basically anytime you eat a meal, how quickly can you get it out? And you, in the moment's notice, only have two places you put glucose, the liver and the muscle. And the liver has a relatively small and finite capacity for glucose. The muscle has a much larger capacity, and it's probably the greatest difference across people. It's certainly the greatest difference between... fit and unfit people. And so there's a test I do in all of my patients where, you know, measure their glucose and insulin level, give them a nasty amount of huge quantities of glucose, and then continue serially to measure glucose and insulin level. And as old school as that test is, it's called an oral glucose tolerance test. It's been around forever. It still strikes me as one of the five most important tests any human should have done because in that test, I learn everything I want to know about a person's ability to dispose of glucose efficiently. And failure to do that is problematic. So the canary in the coal mine is the person who can dispose of glucose, but they need very high insulin to do it. So the best response is you... Despite how much glucose you ram at somebody, they have virtually no bump in it, and they require very little insulin to dispose of it. So that's the curve you're talking about, being below that curve. Okay, so muscle, then, is all about disposal. So you've got an input and an output here. Exactly. You control the input, which is what you eat, and you control the output, which, contrary to what people think, isn't how many calories you burn on a treadmill or doing your dancer size. It's...

45:24-47:38

how much of a reservoir you have in the muscles to suck that glucose out of circulation. One of the most amazing things about this whole area of dispelling what I think is a myth of calories in, calories out as like the simple equation for health was in Good Calories, Bad Calories in Gary Taub's book. And I just found it amazing that... How quickly your body changes, how different you feel, your mood changes so much, your energy levels change so much. If you change the way that you're eating, even if it's, in fact, probably more calories than I used to for performance reasons and things like that. But just such a simple tweak. And that makes me think back to this Thomas Kuhn idea. I want to hear your issues, maybe some solutions with the scientific community. Because to sum up Kuhn's idea. Progress in whatever field is made a death or a retirement at a time, meaning people rise to prominence. They tend to get there for good reason, probably usually. And unfortunately, then they are less adaptable because they've kind of got this idea that they're known for or what have you. And they're the eminent professor or whatever. And I love this idea that creativity, people always think about the lone genius idea of creativity, which is total bull. Creativity is the person, yes, of course. It's the field in which they're working. But maybe most importantly and most interesting when it comes to Kuhn is it's the field of people who are going to judge. So you've got creatives that weren't known until centuries after they're dead, but I don't think most people want that. People want to be known in their field. So the field that is judging is incredibly important to the progress we make or don't make. So what is the state, in your opinion, of progress in the scientific community? And you can pick. That's a very broad question, and I think, as you probably know, science is niched, right? So you've got, are we talking metabolism? Are we talking basic science within metabolism? Are we talking the clinical application of endocrinology? So that's a hard question to answer. So I don't know who actually first said it, but I've heard it attributed to so many people.

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I actually did spend like an hour once trying to find out who said it. Maybe one of your readers or listeners will know. But I think Max Planck is the one that I ultimately felt most confident probably said that progress in science comes one funeral at a time. But the sentiment is important. There might be one exception. So I agree with it, by the way. I think that is a fair sentiment. There might be one exception to it in this era, which is if we care about science, just as an intellectual exercise for its purity that's one thing but if we care about science as a strategy going back to objective strategy tactics well if you care about science only as a strategy to drive policy and behavioral change which creates a new set of tactics which drives a different objective for example a more healthy population than we have today maybe it doesn't actually matter right so maybe companies can basically impart their views on a population with far greater penetrance than waiting for the traditional approach, which is scientific consensus drives policy change, drives market change, drives adoption. Right. So let's look at smoking for an example, right? Like what happened there? Right. So, so in 1963, I believe, if my memory serves me correctly, it was actually January of 1963. The surgeon general finally said smoking causes lung cancer. And as you pointed out at that point in time, 59, 60% of Americans over the age of 18 smoked cigarettes. Okay. So let's fast forward to the end of the sixties. what percent of Americans are still smoking? And the answer is, I believe, 56%. So the knowledge, just the knowledge, if you accept that people thought that the Surgeon General saying something mattered, and maybe that didn't, but I think at that time it meant more than it would have meant today. Just the knowledge that this was harmful only had a trivial reduction in the harmful behavior. Today, about 18% of Americans smoke. So how did we get from 56% to 18%? It turned out to be a whole bunch of things that

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changed something I called the default environment. So it used to be that smoking was the default. You just smoked. If you didn't want to smoke, that's fine, but you had to opt out of smoking. But smoking was everywhere. If you and I were having this discussion in the 60s, you would have had cigarettes sitting here in a little ashtray between us, right? So the first major thing that happened was the tobacco companies actually voluntarily withdrew from advertising because of a law. that stated anytime a tobacco commercial was on tv an anti-tobacco commercial had to follow it and it turned out the anti-tobacco commercials were so much more compelling than the tobacco commercials that every time you got your pairing of this juxtaposition they were getting share eaten they were losing losing losing so they said piss on this we're out we're never going to go on tv again fine fine so advertising changed the the next thing that changed was really, I mean, it gets a little more complicated, but, and without walking you through the entire timeline, basically the two major other things that changed were obviously the economics of it changed. So once you, you start to play a higher and higher excise tax on tobacco. And then of course you had all of the, like, Within the advertising realm, there became product placement and things like that. It became harder to get cigarettes, frankly. And then the final, I think, nail in the coffin came in 1989 when the airlines basically said, you can't smoke on planes now because of secondhand smoke, which then really paved the way for what we saw in cities like D.C., Toronto, New York, San Francisco, where sort of early adopters of smoke-free restaurants and smoke-free bars. And lo and behold, if you live in New York today and you want to smoke, which you can still do much more easily than you could in San Francisco, Francisco, it's still kind of a pain in the ass. Like you can't be sitting at a restaurant with your friends smoking. You got to go stand on the curb. And if it's cold, that sort of sucks. So it basically, it's really not even about the science anymore is my point, right? It really became about other forces in the market that drove the change. And so as we sit here contemplating your question about, well, you know, if we're sitting here at the peak of poor health, which you could argue we are in terms of relative to.

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what we have at our disposal to be healthy. Certainly not relative to all humanity when we've had much worse health. I'm not sure we need the scientific community a whole heck of a lot, especially for these no-brainers out there, the things that I consider no-brainers. I think any carbohydrate that comes in a package, anything that's highly refined, anything your grandmother couldn't have eaten 100 years ago, it's really hard to make the case that that's an amazing food for you. I don't think anybody thinks potato chips are good for them. I don't think anybody thinks cookies are good for them. So I'm not sure we actually need the scientific community to come out and say those things are bad so that the USDA would regulate them or the FDA would put a different label on the thing. I'm just not sure that that matters as much as I used to think it mattered. How do you personally guard against... Getting too attached to old beliefs, to things that you were doing research on 20 years ago or 10 years ago that you found new evidence for. And it's so easy to say, well, when the evidence changes, my opinion changes. But that's just not how, at least in my experience, it's hard. It's hard to change your opinion. So do you have any personal strategies? Because so much of that compounding that we started with, I think, is the ability to shed old things and replace them with the new. blocks of compounding growth. So do you have any personal strategies for keeping yourself honest and not getting too attached to old ideas? I mean, I certainly do in a large setting. I think on a personal level, I can only take credit for something that, I'm sorry, I can't take credit for it, but I can acknowledge a gift that I was given, which is science I don't think is entirely natural, just as I don't think investing is probably not. I don't know that there are many people that come out of the womb knowing everything. I mean, even, you know, obviously, you know, Warren Buffett will credit Ben Graham for so much of creating his thinking. And so I think your mentors matter. And I just happen to be mentored by, you know, one of the greatest scientists in the world. Who's that? Steve Rosenberg. Okay. You know, certainly one of the fathers of immunotherapy. And so.

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You know, when I first read Steve's book, when I was in medical school, like I kind of dropped everything I was doing and realized like, this is the guy I have to be with. And so I went out there when I was in medical school, worked with him. And then, you know, in my residency, then, you know, went and did my postdoc with him at NIH. And I just think that was like probably one of the most valuable experiences of my life. And I, to this day, will say that Steve's probably one of the most important people in my life as far as shaping who I am and how I think. You see the example of what it means to be agnostic. You see what it means to kill your babies, which was the expression we used all the time in the lab. You have to be willing to kill your babies. So I think culture matters in that sense. And being around everybody who emanates from that level of thinking just makes it that much easier to go forward. And I think part of it is also just how you talk. I'm very comfortable saying I don't know. I don't, I mean, I think that's, again, another thing I just learned from him. Like, I don't know the answer, you know, does sugar cause cancer? I don't know. I mean, I really don't know. It's hard for me to believe it helps. Right. But I, but I, I can't, you know, I don't, I don't, I don't know. I don't know a lot of things. I don't know most things actually. So if you're, if you can be, if you can be wed to that, I think it's safer. The other piece of this is whether we all want to admit it or not, our egos do matter. Right. So the question is, at least for me, What do you anchor your ego to? If you anchor your ego to being right, which isn't a totally fair and reasonable thing to anchor your ego to, I think you're hosed in this regard. Because facts have half-lives. That's right. And so if you're anchored to being right, you might be better off in politics or, I don't know, like there's another career for you, but it's not science. It cannot be science. I think if you want to do science. Or investing. Yeah, exactly, right? I mean, you have to be willing to shed things when the data speak different. So I think, so again, I'm not going to sit here and try to represent myself as egoless, because I'm not. I mean, I have a huge ego, I think. I think my ego is around knowing as much as possible. That's where I get off, right? That's what I want. I want to be the guy that knows the most. And if you want to be the guy that knows the most,

56:25-58:49

You actually have to be willing to get rid of things that are wrong. So I think that's sort of my personal trick. That's a great one. What a neat little reframing of, of being right versus known the most, which again, I'm sure there's a smarter Buddha guy out there who has no ego. He says it's the opposite. Yeah. But, but I'm just, I mean, that's just how I think about it. One of the things I struggle the most with is in the pursuit of, we'll call it, I like Sam Harris's term wellbeing instead of happiness, which kind of is all encompassing for everything that we've talked about is how much of that is growth versus I won't say fixed, but actually subtraction, where if you go east, and this is what I studied in school, it's all about subtraction and less, less, less, less, focusing on a couple major small things and completely destroying ego. So well-being becomes all about having zero ego whatsoever. But at the same time, there's something about that that just feels wrong, that in the pursuit of growth, like the times that I've felt, and I want to get to things like racing and swimming and cycling, the times that I felt most alive have been in flow states. And flow states seem to come during. wanting to know the most, wanting to be the best performance in general. So maybe we could turn there. Maybe we could go to performance. And we didn't get much into your background because I can handle all that in the introduction. But one of the things that you're known for is insane feats of physical performance. Maybe you could just first, before we get into the topic, describe. your history, sort of the timeline of the things that you were doing, whether it be swimming, cycling, what have you? I mean, it's fine. I don't think anything I've done is really that heroic, but I think you always put yourself to the people that are the truth. To me it is. Yeah, yeah. I think what it comes down to, whether it be a flow state or otherwise, for me it's mastery. Mastery is my crack. I have to be mastering something. And so I think in my professional life, there has always been something that has obsessed me and i don't know how to do anything in moderation like swim team six years ago made t-shirts called you know moderation the only thing worth doing in moderation for me you know the whole team ended up getting these shirts for me so so whether it was you know engineering and mathematics or you know when i was i used to build credit risk models when i was at mckinsey and company and i you know when i was like really interested like i just wanted to

58:49-1:00:38

I just wanted to know everything. And I really take huge pleasure in the top of the curve. Most emphasis is on how can you put 20% of the work in to get 80% of the benefit. And I think that's great. I actually don't find that nearly as interesting as how can I put in the last 80% to get the last 20%. I find that much more interesting to me. So I think in my personal life, because I'm so addicted to that junk. I have to come up with things to try to master that don't really matter to anybody but me. And so for me, I think, you know, anything athletic fits into that bucket because when last I checked, I've never made a dollar due to any sport I've ever played and never will. So nobody actually cares. I was once having this discussion with somebody and I said, I promise you my wife would not be able to tell you my best 10K or 20K time trial, like within 50%. And they were like, that's impossible. She would have to know that. I was like. Called her up right there. I was like, hey, Jill, what's my best 20K time trial? And she said something so idiotic. And I was like, God bless her. Like, nobody cares. Nobody cares. But I do. I care so much. And if there's, like, one way that if I learn a new way that I could lean into this corner and, like, hold my arms this way on the bike instead of this way. Like, I used to have models. Every single day I would go home from my training sessions and take my power meter, like the computer, and plug it into my model. Because in time trialing, which is why I think I liked it so much, it's very mathematical. It's all about. how many watts you can put out, and what your CDA is. So coefficient of drag times frontal surface area. So my model would look at what the air temperature was, what the humidity was, what my frontal surface area was, my drag coefficient, and how many watts I could put out. And I don't have any control over the temperature and the humidity, but I have control over the other things. And the endless obsessing I could do over that was crazy, and I don't know why.

1:00:38-1:02:31

But, but that, so anyway, so, so I think every physical goofy thing I've ever done has basically come down to wanting to master something. And I think the one people find most interesting is swimming because I didn't learn how to swim growing up. Where'd you grow up? I grew up in Toronto. Okay. So you did one thing when you grew up was played hockey, right? That was kind of like, that was your church and that was your sport and that was your school and your religion, whatever. But, you know, I went to medical school at Stanford and my roommate was an unbelievable swimmer in college and he swam all through medical school and. you know, once or twice I went to the pool and like, I could swim a lap, but that was like it. And I was actually at the time, you know, pretty good shape doing other things like cycling. But I remember thinking like, this is unbelievable. Like, how is it that all of the fitness I have in all of these other areas of my life, like it doesn't translate at all to the pool. So fast forward a few years, I'm 31 years old. I'm in residency at this point. And I read this book and at the book, I had never heard of the Catalina Channel before, which is the, technically it's the San Pedro Channel, which is the space of water between Catalina Island and Los Angeles. And I read about this woman who swam the Catalina Channel. And I was like, this is incredible. And I read the story of the first person who ever swam the Catalina Channel. His name was George Young in 1927. It's an amazing story, by the way. And I was like, you know, I want to do that. And I was like, there's just one problem. Like, I can't swim. So conceptually, I want that, but I can't do that. So the punchline of the story is I took swimming lessons and I just went apeshit on this problem. And 18 months later, I swam the Catalina Channel, which is about 21 miles. You know, then became completely obsessed with marathon swimming and wanted to do more and more of this sort of thing. How do you think performance, especially that sort of extreme performance, which there's, I mean, I've never experienced more of a flow state than like deep into a long run.

1:02:31-1:04:42

I've also read quite a bit that that may be bad for health span, that the kind of strain that I'm putting on myself, and I feel it, you know, I'm only 31, but I feel it in my knees and my hips and things like that. So how does performance relate to health span? Well, I think if you're being really honest with yourself, for most people, and I think there are outliers, people who can get away with being at such a high level performance-wise without suffering any of the sort of deleterious effects, but... I think for most people, they come at a cost. And I don't think they're purely anti-parallel, but they're approaching orthogonal. For me, it was a very clear decision I made two and a half years ago. And I'm not entirely sure why I made it so abruptly, but I just decided I'm done. I don't care anymore about, I'm never going to do another race. And again, I think there might be someone listening to this that says, oh, that's horrible. Like, that's so sad. No, it's like, Done. Like my identity is no longer going to be wrapped up in that. Now I needed a new junk. So the minute I stopped doing that, I picked up auto racing because I had to get that mastery itch somewhere else. And I figured I might as well do it in something that's not going to be as physically demanding. Although. Anyone who's raced a car will tell you it's physically demanding, but not, it's not the same as like sub threshold efforts for two hours. And frankly, it's even more, it's more, it's as technically demanding as surgery. Um, it's really incredible. And so I get, you know, can you tell me about the first great racing experience you had? Oh boy. I think, I don't know about the first great one, but I think certainly one of the most amazing experiences I had was So, so, you know, I wanted to like get my license first, right? So you have to go to like a racing school and get your license. And I remember, and I think all racing schools do this, whether it's Bondurant or Skip Barber or whatever, but they want to make a point to you as the student, because most of us come in, we love cars. Like, you know, it's not like I just decided I wanted to race because I've never, you know, I've always loved cars. Like since I was a kid, I was an engineer. Like, you know, we just, we love these things, but you sort of have this impression that like, you know,

1:04:42-1:06:45

You go as fast as the car goes and you don't realize like the driver is everything. And so what they do to get you to realize this is they stick all the students in a van and it's like some crappy Ford Eco Liner that is like it looks like it might be able to go 40 miles an hour. And they put the instructor in and he takes us for a lap or two in this track at speeds that if you put me in a race car, I couldn't keep up. And you think you're going to die. Like you're like, because the car is just coming off its side wheels and you smell the brakes from how hard he's braking and how late he's braking. And you realize, oh my God, like there's, there's just, there's something totally different. This is completely foreign. And what's foreign to anybody who's never raced before is. Racing is all about being at the limit of the tire. So the tire is the only thing that's in contact between the car and the surface. So you have all this engine that produces all of this power. You have a chassis that allows you to channel that power. But the tire is the contact point. And you have an angle of slip, which is the difference between the direction the tire is going and the direction between the vehicle is going. And when you're on the road, that angle of slip is always zero. They're always going in the same direction. And you're never near the limit. And usually if you are, something really bad happens and you spin out and you don't even know what happened. But when you're looking at the best of the best, what you realize is, first of all, straight line speed means nothing. Races are won and lost in corners because that's the place where skill matters the most. And secondly, the best are the people who know how to always be at the limit. And so that really became, that stark example became. Like everything I've ever thought about. Right. Which is now whenever I'm racing and I spend most of my time in a simulator because, you know, racing is shockingly expensive and time consuming. So, you know, I might only spend 10 days, eight to 10 days a year actually in race cars on race tracks. Most of the time I'm in a simulator, but it's such a good simulator that it actually allows me to.

1:06:45-1:09:04

reproduce every effect of being in a car are you racing the same car when you're doing the 10 days on the track no usually a couple different cars you are so yeah i mean i'm um i would think that'd be very hard depending on how different they're different they're different and and again there are sort of four things that determine how fast you go right there's the engine the chassis the tires and the driver so i'm the only thing that's staying the same and and usually you can preserve tires across cars like if you're going from say an e 30 m3 you know an e30 bmw to an e46 bmw you can put the same tires on those cars but now totally different engine totally different chassis and so yep There, you know, that's part of it. But, but part of it is also like this beautiful evolution. Like there's a dream car that I want to be able to really race fast one day. And so in my mind, I've just with my coach built a curriculum of what is it going to take? What's that car? It's called a formula Renault 2000. Okay. FR 2000, which is, you know, to put this in perspective for anyone who. cares about this sort of stuff. So, so the Laguna Seca is probably one of the most famous tracks in the United States. Um, it's just outside of Monterey. Now Laguna Seca is kind of one of the places where they benchmark all cars. So there's only been one production car that has ever broken a minute 30 at Laguna Seca. And it isn't really a production car. It's a Porsche 918 Spyder. So, you know, it's hard to be a $2 million production car, but it went one minute, 29 seconds, 0.89. So 11 one hundredths under a minute 30 is how fast the 918 Spyder went. Even the McLaren P1, which is one of the other three hypercars, the three hypercars being the 918 Spyder, the P1, and the Ferrari LaFerrari. Even the McLaren P1 didn't go under 130. So you got the best driver and the best street car. Same driver. Yep, same driver. And you can do it. I mean, in the simulator, which tracks within about a second to the performance, I'm like a minute 23 in the FR 2000. You know, my coach is like a minute 19 high. So open wheel formula cars, totally different animal. I mean, totally different animal. This car is tiny. It's like 180 horsepower, a thousand pounds. So even at a power to weight ratio, it's not that impressive. But you've got tires this wide, completely slick, downforce aero.

1:09:04-1:11:11

I mean, it's just a different level of joy. It's on my, in pursuit of flow states, it's on my short bucket list of things that I want to at least try soon. Another strange one for me is skeet shooting. Have you ever done much skeet or trap shooting? No, but actually it's funny you bring this up. So Tim Ferriss, who's one of my best friends, has got me into archery. archery so i'm actually in the process of now developing yet another idiotic pastime that serves no purpose in my life but pleasure but yeah incredible pleasure which is like you know buying these ridiculous compound bows and arrows and turning my entire backyard into like a you know an enormous archery infrastructure yeah so so you said something earlier which I'm so glad I didn't go one direction with our conversation today because the temptation for someone that's kind of dabbled and knows about so many things is to say, okay, give me the 20 that gives me the 80, right? Give me the little power law that makes me efficient. But now what is so much more interesting for the rest of our talk for the next 10, 20 minutes is that upper part of the curve. And I'd love to talk about your medical practice if you're comfortable, just in general terms, about... The type of people you work with performance less from a physical standpoint than from a career, mental, family, overall performance. And whether there are common things you are honing in on or have found in your own experience that help you explore the upper part of that curve. And this may come back full circle. I think it will to some extent to compounding because I think that everyone I've ever met who. I love my, I said this the other day on Twitter that my favorite compounding idea is the overnight 10 years becoming an overnight success, right? Because everyone, everyone perceives that everyone perceives the last change, which they think, cause we just think linearly everyone perceives the last change without realizing the, the, the boring, slow part of the curve that creates the mastery in the end. Yeah. I mean the day Facebook IPO, it was like an overnight success. Yeah, of course. And, and so.

1:11:11-1:13:06

my view is that you have to break it into things that you're willing to do and enjoy doing daily. So you have to completely throw out, like, I don't like goals. For example, you have to throw out trying to achieve something because like you said earlier, you just can't, we just can't perceive compounding. It's just so. freaking hard to understand compounding and feel it. So with people that you're working with. And it's really hard in this case because this is like actually quasi-hyperbolic discounting. Right, exactly. I think the real mathematical way to describe this problem is that way. That's right. So when you are working with other people, obviously you do this for yourself as well, but when you're working for other people. What is the focus? Is it on mastery? Whether that be mastery of health could be one way of thinking about it or mastery of something else that they're doing. Is it holistic? Are you... Are you compartmentalizing things or is it just sort of trying to improve everything all at once with a set of practices? So it's actually different for every patient. And even for a patient, it will vary over their life. So I agree with you wholeheartedly, right? I'm not remotely interested in how extreme someone can be at any set of behavior changes for a relatively short period of time. That doesn't interest me. And I tend to actually get a little concerned when patients go. like completely on board everything they think I'd ever want them to do. Because somewhere in the back of my mind is this, like, where does this go, right? When does this person snap and immediately revert back to everything else? So that said, part of it is how I try to explain what I do to my patients, which is, first of all, I'm really open and vulnerable about how much I screw up and how much I suck and how I can't do even everything that I want to do. If I can show you the menu of everything that I believe you could do to live longer, I can't do it all. I mean, no way I can't, you know, I did spend three years of my life in the most rigid, strict state of nutritional ketosis experienced.

1:13:06-1:15:12

probably the most remarkable benefits of any human who's ever lived in ketosis because to do it for that long, I think your mitochondria change. I mean, I think everything inside your body changes. And by the way, I think some people just don't respond well to ketosis at all. I happen to respond very well to it and then to be able to do it for so long. And the reality of it is I can't do it anymore. Like I cannot, I couldn't fathom going back to being that restrictive in my eating anymore. Would it extend my life? I don't know, but I just know that it's not like, I don't want to. not eat a piece of fruit after dinner i don't want to not like eat a cookie if my kid makes it even though they usually taste like crap i just don't want to do i don't want to not like nibble on her french fries at the you know when she finishes you know when she can't finish them like i there's just little things i'm going to do and so i would argue that if my you know baseline diet you know six years ago seven eight years ago rather was you know a five out of ten and I then spent three years at a 10 out of 10. I'm probably like a seven out of 10, eight out of 10 these days. I mean, I just rarely can creep up into 10 out of 10 territory, which frankly is for me why I've become a little more interested in fasting as a trick. Can I use fasting mimicry to offset some of my inability? More CR, less DR. That's right. More CR, less DR. An area where I think I've also fallen very short and I'm very open with my patients is sleep. I mean, I think I know I've learned. harder lessons than virtually any human about the perils of poor sleep. I mean, when I finished residency, I basically spent five years sleeping an average of four hours a night, meaning like we slept about, I slept about 28 hours of sleep a week for five years. And I saw every downside of that, right? Complete incapacity. You know, could not consolidate a new memory to save my life. Had the testosterone of a 13-year-old girl by the time I finished residency because you can't really make hormones when you're not sleeping. So I got to see all of that firsthand. And yet I find myself, especially when I'm in New York, I just prioritize other things over sleeping. You know, part of it is I'm just busier when I'm in New York. I have more patients here.

1:15:12-1:16:54

I have friends here. I have more friends in New York than I have in San Diego. And I just, I'm like, you know what? I'm going to sleep five or six hours a night when I'm here instead. I don't think it's, I know it's not good for me, but it's just an idiotic choice I make. And I usually end up paying the fiddler because I'll get sick or I'll feel like crap and my workouts won't be as good or, you know, whatever. So the first thing is sort of bringing it to a point where people can understand that they're in this for the long haul. So whatever we do has to be reasonable. But I also say you have to try. Right. So nothing seems reasonable if you've never done it. Right. So if you tell somebody, you know, it'd be great if you could reduce your added sugar intake from 80 grams a day to 20 grams per day. Well, that's going to seem unreasonable, but you still have to try it. Right. Because I feel strongly enough that eating 80 grams of sugar a day, which is what the average American consumes, is not a good thing. Getting people to switch exercise is a real, you know, people come in pretty with. Really fixed views about what they want to do or not do. Some people who just say, I hate exercise. So how do you come up with the minimum effective dose for those folks? The other thing is, at least for me, on sort of the softer side, especially with really high-performing people, is this notion of distress tolerance. So one of my best friends is a psychiatrist. His name is Paul Conti. one of my best friends in medical school as well. And to this day, we're very close. And he, when I came out to New York to start practicing, I told him he had to come with me. So he lives in Portland most of the time. But so now he spends every third week here and we share an office. And I've learned so much from him about this idea because I don't really love the term like stress management because I don't really know what that means. I know what stress is and I sort of understand what you would do to manage it, but that doesn't mean anything to me. So I have a completely different model for how I think about this, which is.

1:16:54-1:18:59

You know, we have a certain amount of tolerance to distress and that varies as a function of what is going on physiologically, psychologically, emotionally in our lives. So, and anybody can relate to this, right? So you can be in the exact same situation under, you know, different time periods and have completely different reactions. In other words, I can be sitting at the dinner table and my daughter can like spill her milk and I can think it's the funniest thing in the world or I can like yell at her. Why? She did the exact same thing. Why would I respond differently? It's this, right? If my distress tolerance is this thick, I'm lifting my hands above the table, creating a huge buffer of tolerance to distress. It doesn't faze me. When it's here, anything will set me off. Why is it that if somebody cuts me off on the freeway, sometimes I don't even notice? Or if I notice, I'm like, whatever. And sometimes I honk. Why? What could that difference be? So for me, this notion of how do you increase distress tolerance? And again, this language comes from Paul because that to me has been by far the most useful model for how I think about this problem. So now I don't think of it as like one size fits all solution. For me, meditation is simply a tool to increase my distress tolerance. I don't have any spiritual affiliation. You know, I don't, I don't, I don't view this as like a religious necessity in my life. It's just a trick. It's just a hack that allows me to increase that. And so is sleep. And so is exercise and slow as eating correctly. And so is, you know, being emotionally honest and like all of these things that, you know, we can sit here and talk about optimization problem, you know, exactly. Yeah. 24 hours in the deck. So I've got a couple of closing questions that I ask everybody, which always yield interesting stories. The first is to hear the most memorable individual day of your career. I know you have kids, so I won't ask life because that would be my answer. So of your career, the individual day that is the most memorable and to hear a little bit about that.

1:19:01-1:21:05

I remember November 15th, 2007 pretty well because of its significance on the broader stage. But so basically at the time I was working at McKinsey and my I had over time become sort of one of the guys who was building a lot of the credit risk models. And so our work started out on Basel, too, when that came into effect. When we're doing the Basel II, we sort of noticed that some of the numbers didn't make sense. And then that sort of led into credit losses on mortgages. And so in the spring of 07, we shifted our focus from economic capital to these credit losses. And all of a sudden noticed that, well, even the banks noticed that their models weren't predicting losses correctly anymore. And they used relatively simple models. They used a model that was a dot product of a PD model and an LGD model. So a probability of default model and a loss given default model. And they just stopped working. And to make a very, very long story short, over the next six months, I led a team in San Francisco. I had a counterpart in India that led a team there. And we basically redid everything, came up with new models. So we realized that even no regression model was going to answer this question, which is what they were typically relying on. So you had to use like some mathematical adjustments on regression models. Plus you had to develop things called like run rate models, momentum models, vintage models. So use different data, different models, and then find out where did the triangulate. And November 15th, 2007 was the day we presented basically the answer to the leadership of one of the largest banks in the United States. Anybody who's listening who knows the hierarchy at the firm, you've got the most senior partner, the director, and then boom, boom, boom. And I'm the guy called the engagement manager. So on the ground, I'm the guy who's leading the team. But for a meeting of that stature, you would never...

1:21:05-1:23:11

Like have me do the presentation. But going into that meeting, the boss boss, who's called the engagement manager, pardon me, the head of the engagement, he says, you know, Peter, you should present today to the board. And I said, why? And he said, well, two reasons. One, it's such a technical topic and you built the models and or, you know. you built one of the models and you oversaw the teams that built the other, like, you know, technically. And he said, but this is the funny part. He said, you know, but also you used to, you know, take care of patients with cancer and you're used to delivering bad news. So I think you'll have more empathy when you tell them what you're about to tell them. And so... You can sort of see where the story is going. So kind of delivered the bad news, but in a relatively unemotional and just fact, right? So the vintage model says this is how much is going to be lost and blah, blah, blah. And the head of that bank, who obviously a very smart, thoughtful person, really just wanted the punchline after a while, which was like, how much money are we going to lose? And I said something to the effect of, you will lose more in the next two years than your entire EBITDA for the last 10. And the response was something to the effect of that is impossible. Get the F out. They were a little kinder than that, but it was like, that's. Thank you. I can't believe we just paid McKinsey all this money to do all this nonsense. We were wrong, by the way. We underpredicted that 30% was lost. So that stands out, I think, again, not because the day was that interesting or remarkable, but when I think about what a privilege it was to have seen something so important, I think, on the arc of my life's history, to be alive during something we'll tell our kids about. You wouldn't believe what happened in 2008 and not. And to know that I had that little insight into what that problem looked like on the inside was pretty interesting. It's a taste of the deep work and the mastery that we've talked a lot about. So last question, and my favorite that has yielded fascinating answers, is the kindest thing that anyone has ever done for you.

1:23:20-1:25:46

Not including parents, family sort of thing? Yeah, let's steer clear of that. I'm not thinking this hard because there haven't been many kind things done to me. You want to think like, am I missing the kindest? Because I have not received a kidney yet. But I'm not in the market. I don't know that this is the kindest, but it's certainly something that moved me because of how thoughtful and how subtle it was. So I, in August of 2003, I met a woman who had come to the National Cancer Institute for an experimental surgical procedure. She had a rare type of melanoma called an oculomelanoma. So it's a melanoma that originates in the back of the eye. And almost without exception, these things spread to the liver. And they're fatal. They're uniformly fatal. You don't, you'll die very quickly. But we had this procedure where we would do this crazy operation where we would do an, we'd basically take their liver out, hook it up to a whole bunch of cannulas, perfuse it for like six hours with a chemotherapeutic agent that we could isolate from the rest of the body because it was so toxic and then put the liver back in. And, you know, we were basically asking the question, like, does this extend your life beyond a couple of months? Because that's sort of what the life expectancy would have been. And it's a huge operation. The operation itself has probably a 5% chance of killing you. And so she survived the operation and, you know, sort of taking care of her in the hospital over the next couple of weeks because it's a big recovery. But I got to know her and really, you know, like any of my patients, I just really, really liked her. And I don't know how it came up because I don't even remember. But I told her how much I missed San Francisco. You know, obviously living in D.C., which was a nice place to live, I still pined for the Bay Area. And I think I must have told her one day like how much I love the Golden Gate Bridge because I think as an engineer, it's just hard to not appreciate suspension bridges in general. But anybody who stepped foot on the Golden Gate Bridge realizes like it's gorgeous. And I used to go there once a week in medical school, at least twice a month, but preferably, you know, once a week. So she lived for another year.

1:25:46-1:27:43

And her family was incredibly kind and grateful and thankful, and I stayed in touch with them, actually. But about a year after she died, her husband sent me this big model of a Golden Gate Bridge that was sort of an artistic rendition of this brass model that she had. And said to him, she wanted him to send to me, which I thought was very kind. Incredible, incredible story. And a hell of a place to end. This has given me one of the, I think about leadership a lot. And I am fairly confident that the pull version of leadership versus the push is far more powerful. That by setting an example, you can do a lot more than by telling people what to do. And this conversation for me has been a great example of that, of I'm leaving it wanting to go do better at a lot of the dimensions of health span that we talked about. So obviously all the content is fantastic and I really appreciate it. But above all else, I appreciate the example being set. So thank you for your time and hope to see you again soon. Thanks so much for having me. Hey everyone, Patrick here again. To find more episodes of Invest Like the Best, go to InvestorFieldGuide.com forward slash podcast. If you're a book lover, you can also sign up for my book club at InvestorFieldGuide.com forward slash book club. After you sign up, you'll receive a full investor curriculum right away and then three to four suggestions of new books every month. You can also follow me on Twitter at Patrick underscore Oshag, O-S-H-A-G. If you enjoy the show, please leave a quick review for us on iTunes, which will help more people discover Invest Like the Best. Thanks so much for listening.

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