The Story of the Human Body: Evolution, Health, and Disease

Each year, Microsoft Research hosts hundreds of influential speakers from around the world, including leading scientists, renowned experts in technology, book authors, and leading academics, and makes videos of these lectures freely available. Thank you for coming. My name is Kevin Kouts, and I'm here to welcome Daniel Lieberman to the Microsoft Research Visiting Speaker Series. Daniel is here today to discuss his book, The Story of the Human Body: Evolution, Health, and Disease. The human body has undergone numerous changes over millions of years. While all this evolution certainly brings benefits such as greater longevity, it has also helped create conditions our bodies can't handle, like obesity and type 2 diabetes. Daniel Lieberman is professor of human evolutionary biology and the Lerner Professor of Biological Sciences at Harvard. He is well known for his research on the evolution of the human head and on running, especially barefoot running. His research and discoveries have been highlighted widely in the media. Please join me in giving him a warm welcome. Thank you so much. It's a real pleasure to be here. Now, if I stand here, will I be able to— is this OK? OK. And can you— OK, I guess I'm mic'd. OK. So first of all, thank you for inviting me. It's kind of an honor and a pleasure and I kind of— I find it a little bit bizarre to be here at Microsoft, this sort of fabled place. I spend a lot of place where— a lot of time working in parts of the world where computers don't even exist. So it's fun to come to the other extreme. In fact, we try to bring computers every summer to the places we work at in Africa. So it's fun to experience this amazing, amazing place. So I'd like to talk about a question, or actually a pair of questions that have evolved over the last 20 or so years since I've been teaching human evolution. When I first started teaching human evolution, I was pretty much fascinated with and focused on telling the story of the human body in terms of the family tree, you know, who begat whom. Teaching students about Australopithecus afarensis and africanus and Homo habilis and Homo erectus and all that kind of stuff and the dates and who found them. And over the years, I've become more and more interested not so much in that story, but rather the story of how the body itself has changed and also why that's relevant. And to a large extent, that's because of the questions that my students ask. After all, most of them don't become like me, professors. Most of them go on to become doctors or software engineers or whatever. And they're not going to remember the minute differences between one species or another species, but they all have bodies, and they all use their bodies and they all care about how other people's bodies are functioning. And so my book really is an attempt to try to answer two questions which have sort of arisen over the years in my teaching and one is— and my research— which is why is the human body the way it is? And the second is why is that relevant today? Why should we care about that evolutionary history? And I'm going to try to very briefly summarize some of my thoughts. And the first 150 or so pages of the book actually tells the evolutionary story of the body, and obviously there's no way I can do that in a 35-40 minute lecture. Let me just briefly summarize that there are— I see 5 major transformations that really allowed— that really caused our bodies to diverge from essentially a sort of chimpanzee-like creature around 6 million years ago up to the bodies that we have today. And the first one was the origins of bipedalism. So our very first ancestors appear to have been bipeds, but apes. Apes that basically walked on two legs. And then— excuse me— another major shift occurred around 4 million years ago with the genus Australopithecus. So some of you have heard of Lucy, for example. She's a very famous australopith. Excuse me. And she was adapted to more open habitats and to eating diets other than just fruit all day long, because chimps, for example, basically all they do is eat fruit. 90% of their diet is fruit. Then around 2, 2.5, maybe even 3 million years ago, it starts— there is a shift to hunting and gathering, right, with the origins of the genus Homo. Brains get bigger, people start cooperating, they start processing their food, they start running, they start throwing. Modern bodies more or less evolved then, but that wasn't the end of our evolution of our bodies because the descendants of Homo erectus grew even bigger brains and even larger bodies and slowed down their rate of reproduction and probably became fatter and all kinds of other transformations. And the final major shift was actually just a small one from an evolutionary perspective. It's the origins of our own species, right? Homo sapiens. And we're basically very much like Neanderthals and other archaic human cousins, except we differ primarily above the neck. But of course, what happened above the neck in humans, especially in our brains and our ability to communicate through language, had major effects on, of course, the entire world, and still is today. So those are That's like a 5-second— well, maybe a 5-minute intro to everything that happened in human evolution. But now let's move on. Because let's just assume you've read all those chapters, you understand it all. And let's think about the consequences of those shifts. And the important point is that if you stand back from all those 5 transformations, each of which was an improbable event, many of them driven by climate change— if you stand back, what we end up with is a creature like us. That was evolved to be bipedal, slightly fat. So a typical chimpanzee or a typical ape has about 5% or 6% body fat. But even lean human beings, so hunter-gatherers or supermodels, have maybe 10% or 15%, maybe even 20% body fat. So we're a very fat species compared to most mammals. We're furless. We're sweaty. We're big-brained. We're dependent on tools. But of course, the other factors that we're very interested in today is our diet and activity adaptations, right? We're adapted to eat a diet that's very high in fiber and low in carbohydrates, but we're also adapted to crave energy, right? So we love sugar, we love fat, we love starch. We're also adapted to be highly physically active. I'll show you some data of that in a second. But we're also adapted to enjoy comfort and to enjoy rest whenever possible. And it's these transformations, of course, that are very important in today's world. So humans didn't stop evolving when we evolved— when our species evolved around 200,000, 250,000 years ago. Evolution has been continuing and it's even going on today. After all, natural selection is the outcome, it's the emergent property of heritable variation, so variations that you inherit from your parents, and differential reproductive success that's related to those variations. So individuals with variations that cause them to have fewer offspring or more offspring then result in change from one generation to the next in terms of the percentage of those genes. And so it's still going on. There's actually evidence for natural selection going on today. In fact, one of the biggest studies— I was talking to somebody here from Framingham— one of the biggest studies going on today is the Framingham Study, where people are actually documenting selection that's occurring right now in our lifetime. But so although natural selection is still going on, anybody with— you know, if space aliens came to Earth and were to observe us for a while, what they'd most notice about us is our culture. Our cultural behaviors. And there's another form of evolution that's going on that's also incredibly important. It's cultural evolution, right? So culture is essentially what we learn. You also inherit culture from your parents, but you learn it from each other or from the internet or from reading a book or going to a lecture. And cultures change over time. They change very rapidly. Just think about the last 5,000 years or so of changes in text and script, right? It's been an amazing transformation, and a lot of it going on right here in Microsoft is is still being transformed. In fact, probably what makes this such an important company is its role in cultural evolution, if you really think about what the internet age— So it's a very important force. But if you stand back from the details of what's gone on since our species have evolved, I would say there's two really big transformations that sort of stand out. And again, this is very broad brush, right? The first, of course, is the origins of farming, the agricultural revolution, which actually happened 7 times independently. The first incidences of agriculture about 10,000 years ago in the Middle East, also about the same time in China, but elsewhere in different parts of the world. And of course that transformed the world in terms of the food that we eat, right? We get a lot more food, so we have much larger population sizes. But also people start living in cities and towns and surrounding themselves with their own waste products and interacting with animals and getting diseases. So along with more food and more people also came a lot more infectious diseases. And then the other sort of huge transformation was the origins of the industrial revolution as well as modern science, right? Those happened hand in hand. They were interrelated. And through industry, we've been able to generate more food. And of course, there's been incredible population explosion. And at first, as cities started to swell, infectious disease rates went up even more. But then with the invention of sanitation and antibiotics and and various other aspects of modern medicine, we've now become able to combat many of those infectious diseases that were unleashed initially by the Agricultural Revolution and then became even more important during the Industrial Revolution. So arguably, today is the healthiest era in human history. And let me give you a few bits of information to try to convince you of just how good it is today. So one important fact is— or measure of health is infant mortality. So today, uh, in developed countries such as the United States, infant mortality rates are less than 1%, but that's actually very unusual for most of human evolutionary history. We know that during the Paleolithic, infant mortality rates were pretty high. We can measure them in hunter-gatherer populations. We can estimate them, uh, from population size estimates from the fossil record. And when farming evolved, uh, although people had more offspring because they were able to have them more rapidly, infant mortality rates were still extremely high, about 30 to 40% is a reasonable average. Of course, there's a lot of variation around these numbers. And it's only been very recently, again, as I said, really since the invention of penicillin and antibiotics, that infant mortality rates have plunged to the rates we have today. Adult mortality has also changed. So if you survive childhood, it turns out that many people think that hunter-gatherers live horrible, nasty, brutish lives. That's not true. If they survive childhood, actually, they live to be pretty old. They live to be into their 60s to their 80s. And it was with the origins of farming that mortality rates started to plunge precipitously as people then started dying from all kinds of infectious diseases and malnutrition and famine and all those things that affect farmers. And it's only again since the invention of modern medicine and sanitation and various other wonderful things that again mortality rates have climbed back up again. And actually we're not too different from our Paleolithic ancestors. Again, if you discount mortality that occurs during childhood. So the end result of this, of course, is growth in world population, right? So the world was pretty unpopulated until the origins of farming. Then it started to increase very slowly. This is in billions here, by the way. And of course, with the Industrial Revolution, there's been an incredible accelerated increase in population. Today the world has more than 7 billion people. And I guess the best estimates are for by the end of the century, we should have more than 9 billion people on the planet. So all of this, of course, of course, is a result of lots of people having lots of babies who survive. But there are other ways of measuring health. A good one is stature. So all of us have a certain genetic potential to grow to, right? There's many, many genes which influence how tall you're going to be. But not all of us reach that height because of usually insults to our growth, right? So if you have infections or malnutrition or other problems, you don't actually reach your genetic potential. So height actually turns out to be a really useful measure of overall health. And so this is a graph of height of males in Europe. I've actually taken French males, hence the Napoleon and this guy over here. And these are European Paleolithic males. And you can see that during the Ice Age, during the Paleolithic, people were about 5 foot 8 inches in Europe. Then during farming, again, health declined precipitously around the world. People shrank down to about 5 foot 4. And here's Napoleon, who we all know, famous shrimp. And then height started to increase again with the Industrial Revolution. And now, actually, we've not only caught up with, but we've even slightly exceeded, even in France, their Paleolithic ancestors. So the average Frenchman is now 5 foot 10. Is there a difference between Homo erectus versus Homo sapiens? Homo erectus— varied a lot in height depending upon where they were. So Homo erectus is a species that evolved around 2 million years ago and died out— well, went extinct in different parts of the world. They're our ancestors. In Africa, for example, Homo erectus was pretty tall. But there are examples of Homo erectus populations in some parts of the world that really were much shorter. Like, for example, in the Caucasus, they were quite short. So there's a lot of variation in height in the Paleolithic, just as there is today. A lot of that, of course, driven by selection. But the important point is that although health is doing really well today by many markers, we could also clearly be doing a lot better. And the way of— the best way of encapsulating this is what's called the epidemiological transition, and some of you may have heard of this. But if you just stand back from the last few hundred years and look at what has happened recently, we know that there's been an incredible decline in death and illness that comes from infectious diseases as well as malnutrition. So our ancestors were much more likely to die of plague and smallpox and tuberculosis and infectious diseases such as that. So those diseases now— most of us don't even worry about that anymore, right? But what's risen in concert with that is noninfectious diseases. So today we die from cancer and from heart disease and osteoporosis and type 2 diabetes and various autoimmune disorders. These are all on the rise, and there's actually a lot of evidence that they're on the rise. And some of you have seen these famous graphs. I mean, this one is plastered all over the place. It's very hard to go anywhere without seeing graphs about the shifts in obesity around the world, but suffice it to say that during my lifetime, the percentage of people in the United States who are obese has more than doubled. Along with that has been a rise in a whole series of other diseases, such as type 2 diabetes, which is going up in the U.S. and also going up in even faster rates in many— developing countries such as China or India where diabetes rates are climbing at really alarming rates. Breast cancer, the list goes on of non-infectious diseases whose incidence is going up. I'm not talking about death from these diseases, I'm talking about the incidence of these diseases. And there's a whole series of other diseases that people are getting too, like myopia and cavities and lower back pain and flat feet and various mental health issues and acid reflux. We don't have a huge amount of data on some of them, like Alzheimer's, from the Paleolithic, but there's a good bet that most of these diseases are becoming much more prevalent today. And I'll show you some of the evidence for that in a second. So is this just the price of progress? Many people would think, well, of course. If you're not going to die young from smallpox or the plague, we're actually lucky to be able to live to be old and die from cancer or heart disease, right? This is actually a trade-off, right, if you're living longer. And to some extent, that's actually true. For example, think of cancer. Cancer is a disease caused by mutations, right? And mutations accrue with time. So as you live longer, you're more likely to acquire mutations to some extent. But it turns out that if you look at the evidence, that's only a partial explanation because— and one of the major reasons for that is that it's very important not to confuse diseases that are more common as you age with diseases that are actually caused by aging. And so— and the hypothesis from the field of evolutionary medicine— and evolutionary medicine is the field of essentially applying evolutionary theory, Darwinian biology, to medicine and disease. So the evolutionary medicine hypothesis— and if any of you know this wonderful book by Nesse and Williams, "Why We Get Sick," it's really sort of started this field— is that many of the health problems that people encounter today, these noninfectious diseases, diseases, and actually many infectious diseases as well, are what we call mismatch diseases. It's an important term. If there's any term you remember from this lecture, I hope it's mismatch disease. And those are defined as diseases that are more common or more severe because our bodies are inadequately or poorly adapted to novel environmental conditions in which they experience, right? And so I actually, as an experiment, tried to list all the mismatch diseases that I think are common today in our culture, and it was a pretty unpleasant task, let me tell you. And I should mention that this is— I use the word hypothesize for a reason because we lack a lot of good data on hunter-gatherers. So we don't know, for example, about ulcer rates or preeclampsia among hunter-gatherer populations. But there's compelling arguments to believe that many of these diseases are either more common or sometimes even novel because of the environmental conditions in which we live in. And by the way, these are just the non-infectious diseases. Had I put in the infectious diseases that have arisen since the origins of agriculture, this would be a really truly scary and horrible list. And I've left those out, OK? And if you think these diseases are important, the chances are that most of us in this room are actually going to die from mismatched diseases. So the number one cause of death in the United States today is coronary heart disease. It kills about a third of Americans. The evidence shows that coronary heart disease used to be extremely rare to the point of essentially nonexistent among hunter-gatherer populations. Cancers are ancient. They, you know, dinosaurs have cancer and dogs get cancer, et cetera. Cancer is certainly not a novel disease, but the evidence clearly is that cancer rates have been rising, particularly many kinds of cancer around the world. So that's another mismatch disease. And, you know, cirrhosis, type 2 diabetes, metabolic syndrome, hypertension, osteoporosis, these are all common diseases today that are costing us billions but which are mismatched diseases. In fact, if you think about the United States today, we're having this big debate about healthcare. We spend about $2.5 trillion per year on healthcare. The estimates are that about 70% of the disease that we treat in the United States is preventable, and I would argue that almost all of those are mismatched diseases. So we are really confronting an epidemiological transition that's costing us an enormous amount, not only in terms of money but also in terms of misery. So the origin— so why we get sick from these diseases is important. But I think an equally important perspective is what do we do when we get sick from these diseases? And here is where I think the importance of cultural evolution comes in, because how we respond to these diseases is setting up an interesting new dynamic. So many of you may know that I'm interested in running and in barefoot running and in feet. And so I have a bit of a foot fetish. So I'm going to use a foot example to kind of explain this, right? So we obviously evolved to be barefoot. Until recently, shoes didn't exist anywhere on the planet. And when shoes were invented, they were very minimal, right? So our bodies were adapted to be either barefoot or wearing very minimal shoes. Okay? So what happens? Well, we invented all kinds of novel shoes. And looking around the room, I see quite an interesting variety of shoes here. And many of the shoes we invent are cushioned and they're comfortable or they're sexy and they have all kinds of features that we like about them, right? But there's also no question that those shoes cause a variety of problems, including flat feet. So I work with barefoot populations around the world. I can tell you that barefoot people don't get flat feet. It's almost completely nonexistent, right? And we can make a very compelling case that flat feet are caused by shoes, which cause your feet to become weak so you don't develop an arch or your arch collapses, right? So that's a mismatch disease. Not a very serious one, but nonetheless a mismatch disease. So what do we do? Well, we go see a podiatrist who gives us an orthotic. And there's nothing wrong with that. The orthotic basically replaces the natural arch of the foot. It's fine. You can live with a flat foot. In fact, probably about a third of the people in this room have flat feet and are wearing orthotics. Maybe because this is Microsoft, maybe it's a bit more than a third. I don't know. Anyway. But the point is— sorry, that was a cheap dig. The point is, though, that what happens is that sets up a vicious circle. Because we can get away with flat feet, right, we can then continue to have the shoes that cause our feet to be flat and keep the cycle going. So we don't pass on flat feet to our children, although there is a genetic base— there is some genetic proclivity towards flat feet. But those genes aren't novel genes that have swept through our, you know, the United States in the last few generations causing an epidemic of flat feet. What's happened is those are ancient genes that are interacting with modern environments, and then we're basically continuing the cycle. And I think this cycle is so important so vital to think about that I think it deserves a term. Now, I'm not the first person to come up with this idea of this vicious cycle, but I would propose that we call it "dis-evolution"— "dis" for bad and "evolution" for change over time. So another example would be something I work on— I work on heads as well— is that if you eat very soft, processed food, you don't chew very much. Chewing is necessary to grow a proper-sized jaw. If you don't grow a proper-sized jaw, your third molars, your wisdom teeth, can't go in. So they become impacted, so you have to go to an oral surgeon to have them removed, which enables us to continue to eat food all day long that doesn't require much chewing, which keeps the cycle going. And my hypothesis is that this vicious circle, this dynamic, this evolution is a really important cause of the underlying— underlying the epidemiological transition that we're experiencing. And let me try to give you a few bits of criteria by which to judge this. So characteristics of mismatch diseases that generate this kind of feedback loop are first that they're caused by gene-environment interactions. Pretty much all diseases have a genetic basis to some extent to them, right? But what's happened— what's changed is not the genes, it's the environments that have changed, OK? I think that's not a pretty non-controversial statement. Secondly, for most of these diseases, the environmental causes of them are very hard to perceive. They're incremental. They happen step by step, and there's no obvious relationship between cause and effect. Like, all of you folks are sitting very comfortably in these chairs, and yet probably all of you are aware of the data that sitting in chairs ain't good for you, right? But we do it nonetheless. And sitting in a chair for an hour is not going to cause you to die instantly, right? But you keep doing it over and over and over again, hour after hour, day after day, year after year, decade after decade, the problems caused by sitting in chairs accrues very slowly. Third, I don't think anybody's died from sitting in chairs, right? Most of the diseases that we get from this mismatch don't affect reproductive success. They don't tend to occur to us until we've had not only our children but often our grandchildren. So we're already quite old, and so they don't really affect how many offspring you leave who then survive and have offspring. And finally, all of them are based in causes that have trade-offs, right? There are benefits to chairs, for example. They help you sit at a computer, for example. I'm sure people in this room are very interested in that, right? So there's always trade-offs. Everything involves trade-offs. So let's look at 3 different kinds of examples of this vicious circle. And I'll first start with environmental changes that involve too much of a stimulus. Then we'll talk about environmental changes that involve too little of a normal stimulus. And then finally, environmental changes that create too novel a stimulus. So let's start with too much, because that's on everybody's mind today, right? So one of my— one of the major arguments is that we evolved to be sort of gas guzzlers of the primate world. We're a very energy-intensive species, even hunter-gatherers, right? And that actually— that transformation really started around 2, 2.5 million years ago with the origins of the genus Homo. It's when brain size, for example, started really increasing rapidly. And brains are very expensive tissues. If you're sitting here listening to me, you're using about 20% of your body's resting metabolism just to pay to pay for your brain. And if you're dozing off, you're still using about 20% of your metabolism to pay for your brain. Brains are costly tissues guzzling vast amounts of energy all the time. So big brains are very expensive. You have to pay for them. Big brains are costly, but an even more costly aspect of our biology is our reproductive strategy. So we evolved from creatures that were sort of ape-like— well, they were apes, actually, and they probably reproduced about every 6 years. So a chimpanzee, for example, has offspring every 6 years. But hunter-gatherers are able to have offspring every 3 years. So basically they can double the rate at which they pump out babies. And not only do we pump them out faster, which takes a lot of energy, right, because each baby costs a lot of energy, we also grow them more slowly. So here's Prince William, for example, at the age of about 13, and you can see that he's still not even shaving, but if he had been a chimpanzee, he would be an adult. Ready to have, you know, starting to breed, right, and have offspring, right? We have extended our period of— the trajectory of development, slowed it down incredibly by about 50%, adding an enormous amount of cost to raising a child to become reproductive. So we slowed it down, made them more costly with bigger brains and bigger bodies, pumped them out faster, which takes a lot of energy. This is a very energy-intensive system. How did we get the energy to have this kind of biology, right? And the answer is— I've mentioned it before— hunting and gathering. Now hunting and gathering didn't occur sort of all at once like 2 million years ago, like somebody sort of invented it like the computer, right? It evolved probably very slowly, but it involves the combination of a number of important human behaviors— making tools, for example, which really takes off around 2.5 million years ago; food processing, hunting, which didn't really start until around then, endurance running, one of my passions, begins around then, the ability to throw spears, for example, in order to hunt starts around then. We also know there must have been an important division of labor and intense cooperation. All these things combine together to create a novel way of life that enables hunter-gatherers to get more energy than their ancestors probably were able to do. And importantly, the food that that provides that energy were foods that were high in carbohydrates and high in fat— hunting and gathering things like tubers or honey. So we're very dependent and we crave, as a species, carbohydrates and fat. And for millions of years, our ancestors got them through hunting and gathering, but the origins of agriculture transformed our ability to get these resources, right? We started to grow them, right? We— around, you know, the oldest farming is from the Middle East and from China. It's only been around for about 600 generations. That's the number of generations of dogs that have come and gone since the time of Christ, right? Not a lot of generations. And we've transformed what we eat. Pretty much everything we ate today— I had a nice lunch in the cafeteria here at Microsoft and all the food I ate was domesticated. In fact, probably just from a few sources. And of course, in the last few generations, we even created industrialization of food. We grow meat like we build cars. We're able to turn corn into sugar, and that's, of course, further transformed our ability to get carbohydrates and fat in just a few generations. So important examples of this are, for example, how much sugar and fiber we eat. So hunter-gatherers don't get a lot of sugar. Most of the wild fruits that you get out in, say, Africa are about as sweet as a carrot. I can tell you this from a from personal experience, they're not that sweet, right? And they come loaded with a lot of fiber. And the only sort of high-sugar food that hunter-gatherers can get is honey. They don't get as much of it as they would like. So estimates are that Paleolithic hunter-gatherers probably got about 4 to 8 pounds of sugar a year. And we all know that today Americans, well, we grow it by the droves. We turn our corn into sugar. And the average American gets about 100 pounds of sugar a year. Importantly, that sugar we get today is not is— it's been— had its— the sources of sugar have had its fiber removed. So a typical hunter-gatherer eats about 80 pounds of fiber a year. That's normal. Typical American eats about 12 pounds of fiber a year, right? And we think that's normal today, but it isn't. And the reason it's a problem is because of food processing and how that affects the way we metabolize foods. So carbohydrates are broken down into sugars, or we just have the sugar raw, and it enters our body and it gets converted either into glucose or fructose. And glucose goes straight into your bloodstream and that causes an insulin response. And foods that are high in glucose but also low in fiber go very rapidly into the bloodstream, cause a rapid spike in blood sugar levels, which cause then a rapid spike in insulin levels, which then cause a crash in blood sugar levels, which leads to more eating. And also leads to various problems. Fructose has to go to your liver. Your liver can't handle that much sugar that fast because— in the absence of fiber, because fiber slows the rate at which, again, the sugar gets into the bloodstream. So foods that are very high in sugar and low in carbohydrate basically present a kind of double whammy to our bodies, and they create what's called metabolic syndrome, an increase in belly fat and cholesterol and blood pressure and blood sugar rates. If any of you want to read the— there's a wonderful recent book about this called Fat Chance by Robert Lustig, which explains a lot of the biology. So this leads to a variety of diseases, one of them being type 2 diabetes, right? So it's a gene that's caused by interactions between our genes and our environment. There are genes which predispose some people towards being more likely to get type 2 diabetes than others, but it's the environment that really causes these diseases to become much more common. And so, for example, high amounts of central adiposity, belly fat essentially, essentially, is a major risk factor, which leads to insulin resistance, which is when the cells in your body no longer able to sense insulin, which then— which acts to basically take blood sugar— sugar from out of your blood and basically into your cells. So what happens is you set up this vicious circle. You get high levels of blood sugar. Your insulin levels spike because they're trying to get the blood sugar out of your body. Blood sugar, by the way, is very toxic in overly high levels. Eventually, your pancreas essentially wears out. Which means that blood sugar levels remain high and insulin levels remain high, and eventually the whole system crashes. So what do we do about type 2 diabetes? Well, we have two major responses, right? One is through medication, right? There's lots of drugs out there which help treat that, that system I just showed you earlier. But of course, the other thing we prescribe is exercise and good old-fashioned sensible diets. And both of these are important ways to treat type 2 diabetics. The important point to remember, and it's not a— it's a very insightful point, is that medication, of course, doesn't cure anybody of diabetes. It helps mitigate the system symptoms, allows people to live with the disease. But exercise and diet actually can prevent diabetes, and in fact, in extreme cases, it can cause the disease to go into remission. You can actually reverse diabetes with serious exercise and very, very good diet. And of course, there's lots of other benefits from exercise. So I would argue that that because of this feedback loop, when people don't use exercise and diet as much as medication to treat diabetes, it's become a disease of dysevolution, right, where we have a gene-environment interaction in which, yes, there are some genes which predispose some people more to diabetes than to others, but those genes haven't just suddenly swept through human populations. It's environmental shifts that are causing diabetes to become more common. Then the causes of diabetes are very incremental and non-obvious. You know, when you have the orange juice, for eating breakfast, you know, you don't feel the diabetes coming on, you know, just from drinking that orange juice, right, or not going for a run. The disease has little or no effect on reproduction because most people don't get the disease until after they've reproduced, often when they're grandparents. And of course there's a trade-off between the costs and benefits of the environmental shifts that have led to diabetes in the first place. So there are many other examples of diseases of too much, but let's move on to another example of diseases of too little, right? And it's axiomatic in biology that almost every system of our body requires stress to grow properly. And by stress, I don't mean like social stress, like, you know, getting in front of a bunch of people and them not laughing at your jokes, for example. That's very stressful, right? What I mean by stress is environmental stimuli that require your body to have to work harder. And there are many examples. And one example, of course, is your muscle system. We all know that, for example, if you want to grow you know, bigger biceps, you have to lift heavy weights, which causes essentially muscle damage, which then elicits a response so the muscle then hypertrophies and then grows, right? So no strain, no gain, or sometimes people say no pain, no gain, is a real phenomenon. It's necessary to allow capacity to match demand. But also, muscles are very expensive. About 40% of most people's metabolism is used to pay just for the muscle in your body. So if you're not going to be using it, and you're in an environment where energy was limited, which is what was the case for most of human evolution, it's best to get rid of it when you don't need it. So if we don't use our muscles, as our former governor of California experienced, you lose that muscle mass. That's a natural tendency. And that prevents overcapacity. It's evolution's way of matching capacity to demand properly. Well, there's lots of examples of stress that are important. And perhaps none are more important today to talk about than physical activity, which is well known to have a variety of effects on many systems of the body through stress—your cardiovascular system, your muscles, your digestive system, your immune system. In fact, physical activity, it turns out, and the stress it causes is incredibly important for neural—neurobiological health as well, related to Alzheimer's and depression and anxiety and even the ability to learn and remember things. But the important point is that the importance of physical activity in human health is not a coincidence. I would actually argue it's because of our evolutionary history because part of hunting and gathering involves being an athlete. Our ancestors, who were apes, probably didn't walk very much. Typical chimpanzee walks about 2 to 3 kilometers a day and maybe climbs about 100 meters a day in trees. In fact, if you go watch chimpanzees, They kind of spend half the day just putting food in their mouth. That's basically all they do. And then they digest it and then they fill their guts again. They actually spend 50% of their day eating. Again, that's also what used to be normal. Gorillas actually spend even less time moving about. They actually travel about a kilometer a day. But your average hunter-gatherer— this is a worldwide average— average female hunter-gatherer travels 9 kilometers a day. The average male hunter-gatherer travels 15 kilometers a day. So 5 to 10 miles a day. To put that into perspective, your average hunter-gatherer goes at least from LA to Washington walking every year. And they work every day. They do physical activity every day, walking, running, climbing, digging, throwing. There are no bank holidays. There are no weekends. There's no retirement. This is what life was like until extremely recently. And one way to measure that is— there are many ways to measure physical activity. A physical activity level, or a PAL. Physical activity level is just the total amount of energy you spend every day divided by the amount of energy that you need to maintain your body. So basically how much energy you spend if you're in bed basically doing nothing in a perfectly climate-controlled room, right? So most hunter-gatherers have physical activity levels— there's a lot of variation, I'm simplifying horribly here, right? But the average is about 1.9. So that means they spend about as much energy using their bodies as they spend spend maintaining their bodies, so, alright. Subsistence farmers are just a little bit harder working than hunter-gatherers, so they have average about 2, and again, there's a huge amount of variation around these numbers. But people who live sedentary office lives, like me, right, have physical activity levels of about 1.5 to 1.6. That's an enormous reduction. That's a greater than 15% reduction, right? And there are many examples, and one example that I kind of like is Sewing machines, right? So of course, back in the Paleolithic when people sewed, they sewed by hand, right? And then with the Industrial Revolution, people invented this— Singer invented the sewing machine, which had this pedal. My grandmother actually used one of these, right? It has a pedal that moves the motor. And now, of course, we have electric sewing machines. And there is actually a bunch of folks who've actually measured— they put oxygen masks on people using different kinds of sewing machines and actually doing just about everything else you can imagine. And it turns out that a pedal sewing machine costs you about 98 kilocalories an hour. An electric sewing machine, here used by the Mayor of London— actually, I'm not sure if he's really sewing, but anyway— uses about 73 kilocalories an hour. You think, OK, 15 calories an hour, that's like nothing, right? Well, imagine these folks are unionized, right? So they're only working 5 days a week, 8-hour days, 50 weeks a year. That adds up to 52,000 calories a year, which, by the way, is enough energy to run 18 marathons. —right? And that's just putting an electric motor on a sewing machine. Now add in escalators and elevators and shopping carts and all the other conveniences in our lives, we have transformed human work in the last few generations like we've never transformed it before and it has incredible effects. So just think about it. We actually—the estimates are we spend about 300 to 500 calories less per day doing physical activity than our grandparents. That's an amazing, astonishing transformation in human biology. And there are many effects of that physical inactivity. I'm just going to pick out of the hat one of them that I'm very interested in, and that's osteoporosis. So this is a disease that's basically unknown among hunter-gatherers or subsistence farmers, but it's rising around the world at very alarming rates. In the United States now, about 30% of women over the age of 50 and about 10% 10% of men over the age of 50 are now diagnosed with osteoporosis. And this is rising everywhere. This is a very alarming disease. And it's caused by forces affecting growth. So here's the guy who won the US Open this year, Rafael Nadal. And you can see that his left arm is much thicker than his right arm because that's the arm he uses to play tennis with. He holds the racket, right? Now, the genes in his left and right arm are obviously the same, right? I don't think he's a chimera. And he's got a lot more muscle mass in his left arm and he's also got thicker bones because the bones actually respond to loading. We know that bones, again, experience that trade-off just like muscles, right? If you're using your bones a lot, you want them to grow thicker so that they can handle the loads. And if you're not using them very much, you actually— they'll waste away, they grow thinner. And so astronauts, for example, go off into space, essentially get osteoporosis because their bones just waste away in microgravity. So this, this relationship between physical activity and bone growth, however, comes up against a very ancient constraint. And that constraint is that we grow our skeletons when we're young and we lose skeletal mass as we age. That's just the way mammals are. Sorry, there's nothing we can do about it. So most of us hit peak bone mass between about the ages of 20 and 30. And as we discussed before, people who are more active when they're young acquire higher peak bone mass. They, they build better skeletons. And we all lose it as we age, and if you're a woman, you lose it at a faster rate once you go through menopause because of estrogen. Estrogen plays a very protective role for bone health. So individuals who are inactive grow less peak bone mass, and they can also lose their bone at a faster rate than people who are active. And the end result is that inactive people are much more likely to fall below the bone mass threshold that leads to osteoporosis. And so that's why osteoporosis is on the rise. So it's another example of dysevolution, right? It's a disease that's caused by an interaction between genes and our environment. And it's not like genes for osteoporosis have suddenly swept through our culture, our population. It's our environmental changes caused by electric sewing machines and cars and shopping carts and all kinds of other things, right? Every time you use a shopping cart, you don't think, oh my gosh, it's contributing to my osteoporosis. You can't even feel its effects on your bones, right? But the incremental effects add up slowly, slowly, bit by bit over the years. It has no effect on reproduction because most people don't get the disease until they're grandparents. And obviously there are many benefits to cards— cars and shopping carts and elevators. So there's a trade-off for all these things, right? I'm not saying that we should get rid of cars or shopping carts. We have to understand that everything involves costs and benefits that get traded off. Finally, diseases caused by things that are too new. We're all very aware of the fact that our environments are filled with novel stimuli that we never experienced when we were in the old days, like bungee jumping, cars, cigarettes, various kinds of pollutants in our environment. You could add computers, for example, as well. And there's no question that we're not always well adapted to those aspects of our environment. So here's an example. Here's a gentleman, who looks like a perfectly respectable person. Like, we all like to be like this guy, right? Here he is. He's reading. He's sitting in a nice comfy chair. He's wearing shoes. Well, in actual fact, all these things are basically killers, right? Well, I mean, I'm exaggerating a little bit. They're not killers. But they all cause health problems, right? And I'll just pick as an example reading, right? Because it's something that we all care about profoundly, right? So reading is obviously a very recent phenomenon, right? We only started around 3000 BC. And it's only in the 19th century that universal literacy really started to explode. And so now most people read, at least in developed nations. And it's actually around that time that people began to notice something was going on. So here's a quote from James Ware, who was a physician to the Queen's Guard. And he noticed, quote, among the Queen's Guard officers, many were myopic. So these are from the upper classes. Right? While of the 10,000 foot guards who came from the lower classes, less than half a dozen were myopic, were nearsighted, right? And we now know that this is actually well documented all around the world. Less than 3% of hunter-gatherers and subsistence farmers have myopia. This is a very, very recent phenomenon in our environment. And some countries, like in Asia, for example, some countries have about 50% rates of myopia. And it's caused by having an overly long eyeball, right? So what happens is that light from— like photons from me hit your eye, you focus them on your retina, but if your eyeball is too long, you can't focus them even more. Your lens and your cornea can only focus them so much, and so things that are distant are blurry. And there are two interesting mechanisms that cause myopia, and there's a big debate that's going on, but one of them is close work, right? When you stare at something that's up close, right, if you're myopic, you're always doing that all the time. Time, right? And even glasses make everything so up close. You're firing these muscles in your eyes called the ciliary muscles. They attach to these little filaments that hold your lens up. In fact, those filaments have a wonderful name. They're called the zonules of Zinn. I just happen to love that name. It's irrelevant, but the point is that those muscles are always contracting, and that contraction, of course, generates force, which actually increases the pressure in the main cavity of the eyeball, which causes the eyeball to stretch. And it's thought that that's one of the factors that causes overly long eyeballs. And that's why people who spend a lot of time staring into microscopes or doing close work are likely to have their vision worsen. However, it also turns out that that doesn't explain all of myopia. So there's these gruesome experiments that were done back in the old days where they would stitch the eyelids of animals shut, not to study myopia, but they discovered that these animals, who clearly were not reading or doing close work— these eyes were not being used at all— developed myopia. And they developed overly long eyeballs. And it turns out that there are stimuli that are clearly necessary from vision that actually regulate eyeball growth. And if you lack appropriate visual stimuli, your eyeball grows too long. So there's a kind of repressive— repressor mechanism going on. And there are actually a lot of data to support this hypothesis. It turns out that, for example, children who spend more time outdoors, regardless of how much reading they do, are less likely to develop myopia. So the bottom line is that myopia is a complex disease. There's no question it's caused by gene-environment interactions. There are people whose genes make them more likely to get the disease, but obviously it's caused by environmental factors that interact with those genes. Every time you read a book or don't go outside, you don't feel the effects on your eyeball length, right? So it's very hard to figure out what actually even causes myopia. Obviously, it has little or no effect on reproduction, thank God, right? And there's no question that the benefits of reading outweigh the costs, right? I mean, most of us are not going to ban books because it causes myopia, right? Or for that matter, computers or all those other wonderful inventions. We're willing to tolerate them. But nonetheless, it's an example of dysevolution. So what are our solutions? Well, one is let's make our kids play outside more. And that's, I think, a no-brainer. And maybe we can develop books and other visual stimuli that are more dynamic, that are less likely to to cause that problem in the retina. So finally, the last few minutes, I just want to end with some thoughts about how an evolutionary medicine approach, an evolutionary perspective, can help us think about the future of the human body. Because there's a very famous expression by the great geneticist Theodosius Dobzhansky that nothing in biology makes sense except in the light of evolution. And in the field of evolutionary medicine, we would argue that includes medicine. So what's the perspective that we can get about this epidemiological transition that can help us think about how we can decrease the burden of non-infectious diseases as the burden of infectious diseases is declining? Well, if you stand back from the details, I would say there's 4 basic options that are available to us as a species. The first option is to do nothing. Let's just let natural selection solve the problem. A second is to invest more in treatment, basically send NIH more money, which is kind of difficult when the government shuts down, but anyway, that's another story. We can certainly educate people more so they better understand how their bodies work so they can make informed choices. And finally, we can change our environments. And I would argue that of all these, we should do everything except the do nothing, right? That I don't think is an option. For one, even if natural selection could solve these problems, which is very debatable, it would take too long for it to be of any practical use to any of the people that we care about. It would take hundreds, if not thousands, of generations. Generations. Furthermore, there's a lot of reasons why there's no necessary reason to believe that natural selection is going to adapt us to high fructose diets, right? Because that only works if there are heritable variations which actually affect reproductive success. So it's a very iffy statement. I could spend hours talking about 2 and 3, and there's no question we should do that. I think we don't spend enough on treatment. We don't spend enough on education. But from an evolutionary biological perspective, perspective, there's reasons to be skeptical that we can do so much through either, right? One is that a lot of the genes that are important in the gene-environment interactions that we— that were used for pharmaceuticals, for example, those genes tend to be of very small effect and they're very numerous and they also turn out to be very uncommon. So the genes that I may have inherited that make me more susceptible to diabetes would make— are not the genes that, for example, would make you more susceptible to diabetes. And even that— and those genes, it turns out, don't even have a very strong effect. Effect. There's no— there's not going to be— these are diseases that have multiple complex causes and there's not going to be a Pasteur for these diseases, which is why progress in solving many of these non-infectious diseases is going to be very slow and incremental, as it has been, and it's going to remain slow and incremental. I hope I'm proved wrong for some of these diseases, but that's everybody's best guess. Education is also very important, but there's many reasons and many studies which show that education is only so effective. For one, even public service announcements are drowned out by about 27 to 1 by advertisements for foods that are very unhealthy, for example. But even more importantly, even though we may know what's good for us, it's very hard for us to actually make decisions about that's what's good for us. For example, when people are, you know, when there's a stairway next to an escalator, do you know what percentage of people take the stairway as opposed to the escalator? 5%? You guys are good, right? Yeah, it turns out the worldwide average I think is 3%. And when you put a sign up saying, "Please take the stairway," it doubles to about 6%. And you know, that's just human nature. If you were to put an escalator in the Kalahari Desert, the Bushmen there would do the same thing. It's normal because if you're on the threshold of energy balance, it makes sense not to waste energy climbing the stairs, right? Because you can use that energy to reproduce. To hunt, to do something that's going to benefit you. The same thing is true of if you put a piece of cake in front of me and a piece of celery, of course I'm going to eat the cake. I'm evolved to prefer the cake. It makes sense. There's nothing wrong with that, right? So overcoming those urges, those instincts, those primal urges is going to be very difficult. And those of you who are interested in behavioral economics, you may know like Daniel Kahneman's book "Thinking Fast, Thinking Slow." And there's a lot of research on this problem. Problem now and these are very hard to overcome. So education, I think, is only going to do so much, which leaves finally— the final shift is changing our environments, right? If you think about it, as I said before, we evolved to be bipedal and fat and furless and tool-using, but importantly, we evolved to eat high-fiber diets that are low in carbohydrates, but to crave sugar, starch, and fat. We evolved to be very physically active, right, but to enjoy taking it easy when it's possible. So the problem is that we never evolved to make the choices that we now confront in our lives. So if you were able to travel back in a time machine to this Homo erectus family, you would not hear that mother or father telling their kid, "OK, little Thag, don't forget to eat the healthy food today and don't forget to exercise." Little Thag had no choice but to exercise and eat healthy food. There was nothing else for her to do. That was called life. And if you didn't do it, you died. But today we have to nag our children to make the right choices because we're surrounded by labor-saving devices and by calorie-rich food, especially without fiber and filled with sugar that make us sick. So we have this mismatch again between these ancient genes, which we're not going to be able to change, and novel environments which we can change. And so that's where I think our big debate ought to be. Instead of having the debate we're having today about healthcare, which is really about who's going to pay, I think we should also be having a debate about how we can change our environments. And that's missing from the current debate. And there's really two extremes, right? One view is to coerce people, right? Ban trans fats and, you know, ban smoking and ban fast food from children's cafeterias and require coercively physical education, right? That's one approach. The other approach is to respect people's choices but to kind of help them make the choices that they would make that are in their own self-best interest. That's nudging, right? And that would include things like sugar taxes and, you know, signs encouraging people to use the stairs. And Mayor Bloomberg's Big Gulp ban, actually, I would classify as a nudge. It's interesting how people reacted so vigorously against the Big Gulp ban. He wasn't banning soda. He just made it— if you wanted to get, I think it was 36 ounces, if you wanted to get 36 ounces, you had to buy 2 16-ounce sodas, right? I mean, it wasn't— he wasn't banning soda, he was just making it harder to get those large quantities. Anyway, the point is that we have— we need to have a more informed debate about it. And I think where that debate really is probably most obvious is for children because children really can't make rational decisions on their own. We long ago agreed that we have to make decisions on their behalf. To have, right? So nobody debates anymore that we should require seat belts for children or require them to go to school or require immunizations. Well, maybe there are a few people who debate immunizations, but they shouldn't, right? So what about physical activity, right? In Massachusetts, where I'm from, we just— I can tell you it's a miserable state in terms of physical activity. We do— you know, the American College of Sports Medicine and the Surgeon General both agree that children need about an hour of vigorous activity every day to have a healthy body. How many schools give their kids an hour of physical activity a day, right? We view it as a trade-off, so you, you know, they don't have enough physical activity because they need time to study for their exams, but of course it's a false trade-off because physical education actually improves mental health as well. We are doing our children a terrible, unconscionable disservice by not requiring more rigorous and vigorous physical activity in schools. And we also have bans and coercion, right? I mean, who disagrees that children should be banned from smoking or drinking, right? So if that's the case, how is junk food any different? Maybe we should ban junk food from schools as well. So I hope that 10 years from now we look back on this debate and think, "Oh yeah, the junk food tax and the physical education laws, those were no-brainer, they enacted in the 2000, the second generation decade of the 2000s." You know, those were no-brainers just like we think about seatbelts and smoking. The bottom line, though, is that we are not gonna get out of this problem without thinking about evolution. Evolution still matters, right? It helps explain why we are the way we are, it explains why we get sick, and I also think it helps us evaluate the opportunities available to us to make the human body better off in the future. And so with that, I'd like to thank you very much and answer any questions. Thank you. Yes. In your research, how much of a role has culture played into all these environmental choices? Is there a difference, for example, between Eastern culture and what is acceptable, what's not acceptable behavior? Does that play a role in choices you have and how healthy you are as a society? So that's not actually something I work on too much. So the question is, how much do different cultures stress behaviors that have outcomes on health differently? And the answer, of course, is enormously. And we see the differences in health outcomes from one culture to another. But of course, one of the things that's interesting is how fast cultures are changing around the planet, right? As industrialization spreads and as fast food spreads and processed food spreads and urbanization and mechanization spreads, those cultures are changing really rapidly, much more rapidly than ancient cultural traditions. I mean, most cultures— what your grandmother taught you about what's a healthy lifestyle is pretty much universal, I would argue. Get enough sleep, eat lots of vegetables, get lots of exercise. These are kind of no-brainers around the world. People know this. What's changed is our ability to continue to do these. Yes? I guess I got confused with the point with genetic diseases. So when my doctor asked me if my father actually had high blood pressure, that doesn't mean that even if we go further, somebody in the— In the gene, didn't have high blood pressure. So it was developed in the gene during the modern times? So the genes that make people, for example, more susceptible to things like high blood pressure or diabetes, right, they're not novel genes. They're ancient genes. But so maybe your grandfather or your father also had high blood pressure. But if you went back 30, 40 generations, they didn't have high blood pressure, but they had the same genes. So those genes haven't changed. The environments that interact with the genes, that trigger the disease, have changed. And furthermore, the genes that may make you susceptible to high blood pressure are not the genes that may make the person sitting next to you susceptible to high blood pressure, because there are lots of genes and they tend to have all very small effects. And so that makes it very hard to find a gene that causes high blood pressure. There is no gene that causes high blood pressure, and they're not common genes, and they're not genes of large effect. Yes? So you said that life expectancy now and in the Paleolithic was more or less the same, but that the diseases that we have now are very different. So what were the causes of death then, if you know? So what caused people to die in the Paleolithic? Great question. So infant mortality, of course, was high in the Paleolithic, and that was from diarrhea and infectious diseases and things like that. So what people died from in the Paleolithic was violence, and they died from respiratory diseases, and they probably died from accidents. But they didn't die from diabetes or heart disease. So we've done pretty well in many respects, but but not completely. Yes? So if we were able to reduce those non-infectious diseases, like the diabetes and the heart, what would we die of? We'd die of old age. I mean, just think about— we all know people who— I mean, eventually your body does— I mean, everybody who's very old gets hypertension, right? Everybody who's very old does. Sucumb to often to just slow cardiovascular problems, et cetera. But we wouldn't be dying from— but also the other thing that's interesting about people who die, don't die from any of these mismatch diseases, they also have— they tend to die more rapidly. It's called the compression of morbidity. Or rather, what's happening today is what we call the extension of morbidity. So people today are sick for longer at the end of their lives. And they go through very, very long declines. We all know what I'm talking about, right? But if you look at people who are very healthy, for example, there's a very famous study by a guy named Jim Fries who's at Stanford. He's done a number of studies on this, but he's shown that people who basically exercise and eat a healthy diet tend to have— tend to become sick later in life, considerably later in life. And when they do get sick, they get sick for less long. And then they basically die better deaths, for lack of a better term. So we're essentially— we've extended morbidity, illness, and made the process of dying much more costly and there's much more suffering. Yes? So slightly related to her question, but also to the earlier chart that you Sure. It has— compared to mammals, rest of the mammals, human beings lead very long lives. And so given that our population has extended so much, and essentially we're not talking about extinction level scenario right now, but what does having a much longer life do for us as a species? And people don't reproduce at 70, 80 and on. Like, what— how does it How does— So what's the advantages of living longer? Well, there are many. So one of them is actually— it's a wonderful hypothesis called the grandmother effect. So hunter-gatherers— remember, hunter-gatherers are gathering food every day. A hunter-gatherer mother can't get enough food, actually, to pay for her energetic needs on her own, plus her offspring. It's very hard in a day out there in the Kalahari Desert or somewhere else for a mother to get enough food, not only to pay for her own body, but for her infant, who's nursing and her children and her toddlers, et cetera, who are now post-nursing but she still has to feed them. So mothers need help. They get help from fathers, right? But also they get help from grandparents. Grandfathers and grandmothers both provide important surpluses which help pay for their offspring. And it's again only recently that we stopped this system of life, right? So grandparents in the Paleolithic played very important roles in their own reproductive success. And today, in a strange way, we've kind of inverted that, right? Because now grandparents no longer feed their kids, right? Their grandchildren. I mean, my grandmother brought me cookies and stuff like that, and those were always great. But that wasn't necessary. My parents didn't need my grandparents to bring cookies from New York to keep me alive. And you could actually even argue that grandparents now, because of healthcare costs for the aged, are actually sucking up the resources that could go to their grandchildren. That's kind of a macabre thought. You could even make the prediction that there's actually going to be selection against living long today, just because of economic conditions and the cost of health care. I mean, I'm not— that's a facetious argument. I'm not sure if that's really true. And I hope it's not. But so really, longevity evolved a long time ago for the purposes of improving reproduction. Again, natural selection really only acts when it benefits how many offspring you have who then survive to have offspring. Yes? You mentioned the effect of reading on myopia. Now, we must have some statistics on eyeglasses for a very long time now. And of course we know about Gutenberg who got books cheap so mortals could read them without going bankrupt. So has anybody traced what happened when printing spread around Europe like wildfire? Sure, when printing spread, myopia increased, but of course at first it was just among the educated. I mean, you know, when Gutenberg was printing his Bibles, most people couldn't read. So as I said before, the evidence is that prior to the universal literacy, it was really only the very wealthy and the very educated who got myopia. And now it's everywhere, right? Yes? With all of this knowledge and insight, what are the things that you've adopted in your personal life and your, you know, maybe family practice to avoid this problem? Gosh, so how do I avoid being a hypocrite? Well, I mean, I'm no saint. I'm subject to the same cravings as everybody else, but I try to run a lot. I love running. I try to promote physical activity. I try to force my daughter to be physically active and, you know, poor thing. And I'm careful about my diet, pretty much like most people or many people. You know, look, the thing about diet and exercise is that, you know, they're not magic bullets. You know, eating a healthy diet and exercising does not guarantee long life. But not exercising and eating a poor diet certainly increases your risk of being ill and having increases your risk of morbidity. And we're all susceptible to the same problems. And I think our trick is to help each other make the right choices. So I try to use forms of self-coercion. One of the reasons I like marathons is not because I love the marathon so much, but because it forces me to exercise. Because if I know I have a race coming up, it forces me to get there in a horrible— I'm from Boston. It's horrible weather most of the year. I'd rather not get out of bed and do a long run, but I have a race coming up and I promised some friends I'm going to meet them and I have to go out there and do the run. I usually enjoy it afterwards, but I don't love it at first. No, it's self-coercion. How do you force your daughter there? I think I'm not going to answer that on camera. Back in the back here. I wonder if other animals suffer from this evolution. I think like dogs and cats probably have an easier life now than thousands of years ago. Yeah, well, we're perpetrating— I mean, there's a dog obesity epidemic now going on. Absolutely, yeah. Yes? So, I've seen the latest trend in shoes, these running shoes that look like a foot, you know, this minimalist cushion or something. What— how does a body who been wearing other types of shoes for 40 or 50 years, what's the impact of now switching to something— Great question. So the question is, what happens if you've been wearing conventional shoes for most of your life and all of a sudden you switch to minimal shoes? The answer is you get injured, probably, we think, unless you do it— unless you transition carefully. Because to wear a minimal shoe requires more foot strength, probably requires more calf strength. Now, you can develop that strength, but you're not going to get it overnight. And so most of the time when you buy these shoes, if you buy a minimal shoe, it actually comes with warnings saying, you know, don't— transition gradually, transition slowly, build up carefully, don't do it all at once. And I think that's very good advice because you can't suddenly just change from one kind of body to the next. And I think if you do try to use minimal shoes, do so cautiously and carefully and mindfully. If something hurts, don't do it. Pain is an ancient adaptation to tell you you're doing something wrong. When you ignore pain, you're ignoring your biology. Yes? Has there been any conclusive study done about the barefoot running or the minimalist running is better than shoes with thick soles and heels and all that? So the question is, is there any evidence that barefoot running is better for you? Well, I would argue that there never will be such a study because I don't think barefoot running is necessarily better for you. I think that what we can learn about barefoot running is— what I think is important about running is how you run and not what's on your feet. And you can run well in conventional shoes and you can run poorly when you're barefoot. The advantage of being barefoot, however, and by barefoot I mean actually barefoot, not a minimal shoe. I hate the term barefoot shoe. It's an oxymoron. It shouldn't be allowed to be used. But a minimal shoe, when you hit the ground and you hit the ground very hard, it hurts, right? So one of the advantages of incorporating a little bit of barefoot running into your running is that it teaches you not to slam into the ground, which is probably not a good idea. However, simply taking off your shoes doesn't make you a great runner necessarily. I don't know if you've read Chris McDougall's book "Born to Run." A lot of people read that book and they thought, oh my gosh. I'm going to throw in my shoes and I'm going to become perfect, right? And everybody will love me, right? And I'll suddenly be able to run ultramarathons. Of course, that's not true. It takes time and not everybody can do it, certainly not easily. And you can still run poorly barefoot. So I think we have a lot to learn about running from barefoot running. But I think what matters about barefoot running, just like with other aspects of evolution, is that it teaches us something about how our bodies were evolved and so that we can figure out intelligently how to make decisions about how to use our bodies. So you don't have to be barefoot to get the benefits of what we're learning from barefoot running. I think it's kind of fun and I think people should— I think it's fun to try. Most people are afraid to take their shoes off and go running. They think they're going to hurt themselves. And actually, if you run barefoot on a hard surface, your body often switches to forefoot striking and you learn to run in a gentle way. But it doesn't mean you're going to run perfectly and you can still injure yourself. So you have to be very careful. And that's why I'm skeptical of a lot of the paleo diet and these primal movements. Just going back to an old way of life doesn't necessarily guarantee health. After all, hunter-gatherers did not evolve to be healthy. They evolved to be healthy only insofar as it helped them survive to have more offspring. We didn't evolve to be happy either. We evolved to be anxious and to be nervous and to be depressed sometimes. These are all adaptations. It's just that in our world today, they sometimes get out of control. And I think we can learn a lot from biology, about our biology, from studying things like barefoot running or the effects of physical activity, but it doesn't mean we have to just simply analogize our life back to such simple, you know, ancient ways of living. Yes? Are there any scientific proof of connection between on organic food and the kind of disease that you have studied? So the question is the relationship between organic food and disease. I'm not an expert on that, so I'm gonna— I study bodies. I'm not an expert on that, so I wouldn't presume to answer. One last question. One last question. To continue on Gutenberg, It hit a generally unready population in Europe, but it hit the Jewish population of Europe, which was ready to read. And in 1950, it hit the Jews of Yemen by books being imported and by Jews of Yemen emigrating. Has anybody looked at that? I have not looked at those populations. That's a great study population to look at, absolutely. Good idea. All right, well, thank you so much.