Behaviors That Alter Your Genes to Improve Your Health & Performance | Dr. Melissa Ilardo

0:00 Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday [Music] life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest today is Dr. Melissa Ardo, professor of biomedical informatics at the University of Utah. Dr. Allardo is a world-renowned expert in human genetics and epigenetics. She conducts pioneering studies on how our behavior and the environment can modify our gene expression. Today marks the first time on the Hubberman Lab podcast that we really explore human genetics, epigenetics, and how behavior shapes gene expression across generations. We talk about the inheritance of physical traits like eye color. And we dive deep into fascinating mechanisms such as the

0:46 mamalian dive reflex, a physiological reaction to breath holding in cold water that, as Dr. Ardo explains can dramatically alter the physiology of your spleen to allow significant increases in red blood cell count and oxygen availability to your brain and body. And by the way, the mamalian dive reflex can be activated outside of free diving and you can even do it at home. We also explore how mate preference and selection in humans relates to the immune system. That is if you were given a choice of many many different mates as most people are. The mate you would select is the mate who has the immune system composition that is most different from yours. And you would know that on the basis of their smell and how attractive their smell is to you compared to the smell of other people. We also talk about how differences in

1:32 external traits signal important variations in organ function, hormone levels, and even brain physiology. Toward the end of our conversation, we discuss the current state and ethical considerations of gene editing in humans, something that's apt to be an increasingly important topic in the years to come. Because gene editing in humans is now possible and is happening, as you'll soon learn, Dr. Aardo does incredible realworld experiments that reveal the remarkable interplay between genes and behavior. And she's an absolutely phenomenal teacher who makes complex genetic concepts accessible and practical. The conversation is sure to change the way that you think about mate selection, your parents, their parents, and what you can do to optimize your physiology and health through behavioral practices that influence gene expression. Before we begin, I'd like to

2:18 emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zerocost to consumer information about science and science related tools to the general public. In keeping with that theme, this episode does include sponsors. And now for my discussion with Dr. for Melissa Ardo. Dr. Melissa Eardo, welcome. Thank you. Nature versus nurture. Super big question that we all wonder about. You know, how much of our capabilities and potential and just general themes of life. Everything from how we look to what we're capable of doing or not doing in the moment or where we might be able to improve or not improve. We hear some of its nature, some of its nurture. So if

3:03 we take a step back and we just ask a big question about human genetics, how much of our DNA is modifiable by our environment and what we do, what we choose to do in particular, because that's most of what we're going to emphasize today. I think that's something we're still understanding at this point. I mean, I think every day we're getting more and more information about the ways that we can actually modify gene expression and these things that we thought were totally predetermined in the past. Um, and so yeah, I think we're still learning with epigenetics and all of these new fields just how much we can actually change things. Um, there are of course things that are kind of written in our genes, but um, I think we're learning that there's a lot more that we can change. Most of us at some point in high school um, learn Mandelian

3:50 genetics, right? Mendle the monk and his peas in his garden. Um, most people probably don't remember the details of that, but we also learn about eye color. You know, it it's uh, you know, common place for people to understand that if both your parents have dark eyes, with very rare exception, it's unlikely that you're going to get light eyes as a child, but it's possible. But if you have one lighteyed parent and one darkeyed parent, then you start to enter the probability game. And then at some point, your parents dictate a lot of your appearance, your phenotype. uh and yet that there are aspects of our parents that are not seen in us at all and vice versa. And so I think for most people when we think about genes, we

4:35 think about heritability. But your work focuses a lot on the aspects of genetic expression that are subject to change based on what people choose to do or are forced to do in order to survive, something we call selection. So could you tell us about selection in terms of how quickly a given behavior, for example, can change our gene expression? I'm not aware of any way to change one's eye color without putting in like a colored contact lens. Now, there's some esoteric things showing up online about people using these bizarre treatments to change their eye color, but for the most part, people accept that you're not going to change your eye color by behaving differently. But what are some examples where we can change our gene expression quickly or relatively quickly by doing something differently? Yeah. Um, just going back to eye color because

5:22 this is just one of my favorite genetics um, facts. So, everyone with blue eyes descends from the same person. Um, so at one point in human history, one person had a change in their eye color. And it's just like amazing to imagine this person who had blue eyes for the first time. um and then through many generations probably because that was a very attractive and interesting feature in that individual you know that spread throughout human populations as we know them. So I always just find that to be fun about blue eyes. So there was a blue-eyed F1 as we say the first um let's stay on eye color for a moment because I uh before we get into how genes can be modified by behavior. Um I've been told that the green eye phenotype is one of the more rare eye colors. Is that true? I think that's

6:08 right. Yeah, I think it's the most rare. Okay. So, and can we assume that there was an original F1 browneyed person that gave rise to the entire lineage of brown eyes subsequently? Yeah, I think in the history of humans as a species, I think that was our original eye color. Um, and so then, yeah, having these other eye colors um arise in the population um created these events. I think green eyes, if I'm not mistaken, there were multiple people, you know, that comes from different genes from different individuals in the history of humans. Um, but yeah, blue eyes is just this one individual. I realize I'm slightly remiss on the statement about eye color not being subject to behavior. We know that as you get more sunlight exposure, in particular ultraviolet light exposure, that eyes will darken. Is that right? Regardless of where they start. Interesting. So like a blue-eyed baby will have much bluer eyes at birth than

6:55 it will at age 15 at age 80 for instance. And we believe that's due to uh changes in pigmentation because of of UV exposure. That's really interesting. I'd like to take a quick break and thank our sponsor, JWVE. JWV makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, it is the incredible impact that light can have on our biology. Now, in addition to sunlight, red light and near infrared light sources have been shown to have positive effects on improving numerous aspects of cellar and organ health, including faster muscle recovery, improved skin health and wound healing, improvements in acne, reduced pain and inflammation, even mitochondrial function, and improving vision itself. What sets tube lights apart and why they're my preferred red

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10:00 falling back asleep should you wake up in the middle of the night. It's an extremely powerful tool that anyone can benefit from the first time and every time. If you'd like to try eight, go to eight.com/huberman to get up to $350 off the new Pod 5. Eight ships to many countries worldwide, including Mexico and the UAE. Again, that's eight.comhuberman to save up to $350. Thank you for that because I think that uh most everyone um is interested in eyes and and eye color. Uh what are the um sort of examples that come to mind when you think of rapid changes in gene expression in any organ? Could be at the surface of the body or it could be internally uh that are governed by some change in behavior. Yeah. So I mean our our genes are constantly changing

10:46 how they're expressing based on um you know what environmental stimulus is coming in. Um so we have you know these changes that happen on the order of you know minutes or hours or things like that. Then there's also changes that we're finding out are happening kind of over generations. So we now know that um there can be epigenetic changes. So these are changes you know little modifications to the genome um that happen by things actually molecules actually attaching to the genome and changing how genes express um that can be passed down. So this is really interesting from a the perspective of things like trauma. Um you know we know that you know refugee populations actually have some of these changes that they've inherited from their parents even if they weren't you know victims of the of the event that caused them to be refugees. Excuse me for interrupting, but are those changes that are passed

11:32 down, are they adaptive? Are they making subsequent populations more resilient or less resilient? Yeah, that's a very good question. Um, you know, in the case of of trauma and refugees, I'm not sure. I do know in terms of starvation, that's been something that's been studied as well. So, there was a famine um that affected Dutch people several hundred years ago, I think. And uh and that was actually also kind of recorded in these in these epigenetic changes. And so presumably that's a change that is helping that population to better survive that famine. So in that way it's resilient. But then you know you think about in a contemporary situation where um you know food is abundant maybe that is no longer beneficial even though at one point it was. Um and so then we have this other kind of order of change which

12:17 is um you know actual changes in the genes themselves that either arise from mutations in you know these single base pairs um or at many different sites or things like variation that's already present in the population at a certain amount that then you know increases in frequency throughout the population. And this is where a lot of my work has focused. Um, and these are changes that until recently we thought would take, you know, 5,000 years, 10,000 years, um, uh, at least. And now we're starting to understand that maybe that can happen in as short as a thousand years, 2,000 years. This might be slightly, uh, out of line with what we're talking about right now. But I really fascinated by this concept of hybrid vigor. Uh I was taught I don't know if the data still hold up that if you give mice a choice

13:04 of other mice to mate with to produce off offspring with that they will select a mouse whose um major hystocompatibility complex which is a reflection of diversity of of uh immune genes so to speak. They'll pick the the mouse whose immune system is most different from theirs. Presumably the just so story because we're making stuff up about why they do this, right? Nobody really knows. The the just so story is that they do this in order to produce offspring that have a much broader array of immune genes to be able to combat a much broader array of potential pathogens. Is that true in mice still? And is it true in humans as well? Do people elect to produce offspring, if given a choice, produce offspring with people that are more different from them

13:50 as opposed to similar to them? So they did a very similar study in humans and humans also are drawn to other humans that have these differences. So it's interesting um especially with the immune system. There was a study where I think they had people smell sweaty t-shirts of you know members of the opposite sex if they were heterosexual um to see if you know how attracted they felt to the person just based on the smell of their sweaty t-shirt. Um, and people were more drawn to people who had very different immune systems than their own. Um, so I think this is something, you know, we we see it in mice and it's easy to say, "Oh, you know, it's they're animals. Of course, they do that." But we do it as humans, too. And it'd be interesting to know to what extent that's influencing our choice of mates and spouses. Super interesting. So,

14:36 they're given a choice of sweaty clothing from the opposite sex potential partner. or I guess they're I don't know if they were, you know, sent out on dates after the uh the experiment, but they're and they're smelling let's say 10 different t-shirts that are sweaty and then they're saying and then they rank order them and the one they like the most. If you go and look at the genome of the person whose sweat was on that clothing and specifically the immune system that you're talking about, you know, the um what is it? Histo major compatibility complex. Yeah. The the more different they were in that um the more attracted they were to that smell. It's kind of amazing, right? Like that smell, which we just think of as I like this body odor. I don't like this body odor. I love this body odor is um kind of a proxy for gene expression related

15:23 to the immune system of the offspring that you haven't even had yet with this smelly t-shirt owning person. It's kind of wild. So, I think it speaks to smell and these aren't really pheromone effects, but it speaks to smell as uh a pretty powerful driver of mate selection. Yeah. I mean it I think it could be um it's also interesting you know we have you know when you're talking about hybrid compatibility or hybrid I I called it hybrid vigor based on no particular knowledge of the correct term that it's the term I use because it makes sense to me. Yeah yeah something like that uh you know we're having with globalization people um meeting each other you know across cultures across continents for the first time. So, we're getting genetic combinations that have never been possible in the history of humans. Um, and that's creating some

16:10 interesting both kind of resilience and then also disease because you have, you know, combinations of genetic variants that have never been in the same individual before um that are now showing up together. I find this super interesting um for a couple of reasons. First of all, I I'll turn 50 in September, and I remember a time not that long ago where it was very unusual, for instance, to see an interracial couple in a television show when I was growing up. Now, that's changed, right? And I think that's reflective of a number of things. I mean, there's cause and effect directionality here that we could get into, but that's a different podcast. uh but that yes people are um intermaring andor producing children with people that whose backgrounds genetic backgrounds are very different than their own. Um and if we take the

16:57 opposite extreme, it makes perfect sense as to why this hybrid vigor thing would exist. And and the opposite extreme is a very uncomfortable thing. But if you think about incest, incest has been discouraged in populations for a very long time without anyone understanding genetics like the the mechanisms of genetics per se. It's been well understood that in small villages that people shouldn't mate with their siblings, shouldn't mate with their cousins, shouldn't mate, and ideally not even with second cousins because of the potential for disease. So I've always been fascinated by the idea that nature punishes reproducing with people that are too close to you, right? And then of course there's the moral and ethical and all all that aspect. But but mother nature actually punishes individuals that do

17:44 this through mutation. Yeah. When you have two individuals um who are closely related, you know, that dramatically increases the chance that they're both carrying um you know a variant that has a negative uh impact on on the offspring. So, you know, when you have people kind of mixing more outside their families, then it's very likely that even if you're carrying this delletterious variation, um it's going to be kind of watered down by outside uh genetic material. But yeah, as soon as you have people too closely related to each other, you know, those things are ending up together um and creating disease. Yeah. So, it's definitely nature has a system built in that says don't do that. Yeah. I I find it amazing that these things are operating below the level of conscious decision making to influence preference like this smell

18:30 or that smell, right? And we've established you you've told us that that the smells that reflect the most distant immune system are the most attractive smells which is really wild. Um, so is it fair to say that humans are continuing to evolve, uh, given that people are traveling further, meeting people from further away, having children with people from origin populations that presumably have never mixed before in the course of human evolution? Yeah, absolutely. I think sometimes people kind of, you know, think we're done. We've reached this, you know, ultimate uh, point of evolution. You know, it's we've finished evolving. Um, but as long as there are things that are affecting our ability to reproduce, we're going to continue to evolve. Um, and you know, especially once you have this introduction of new

19:15 genetic variation, um, I mean, some of the greatest adaptations in the history of humans have come from the introduction of new genetic material. So like, um, the Tibetan high altitude adaptation is actually believed to have arisen from the crossing of humans with another, um, early homminid group called Denise. So we essentially stole the advantageous genes from this other group. And so maybe you'll start to see that happening again, you know, as you have a more globalized population where, you know, different groups of humans are are creating these interesting phenotypes um through the mixing of their genes that maybe will lead us to be more resilient as our planet is changing around us. How long ago did the uh did this gene that affords uh better

20:01 abilities at altitude or ability to survive at altitude enter the human population? You know, I'm going to get myself in trouble because I don't remember exactly how long,000 more than 10,000 years ago, but it only became advantageous when the ancestral population um of Tibetans moved into these extremely high altitudes. So they kind of, you know, was just sitting there waiting for a chance to be really advantageous. And then as soon as they went to these high altitudes, people carrying that genetic variation were at a huge advantage. Um, and so they, you know, pass that along to their to their children and their children's children and so on. Okay. So does that mean that at some point the species we know as homo sapiens was able to reproduce with a species that was not homo sapiens? they

20:47 gave and that's how the gene entered the homo sapien population. That's exactly right. So yeah, it happened we see that happening with um Neanderthalss as well. Um but also these this other population of they call archaic hominids. Um Denise um so these are a population that were found uh in areas of Asia. Um and their genes were introed we say um so essentially you know inserted into the human genome. So individuals from that region tend to have a higher ancestry coming from that homminid group. But that meant that a homo sapien mated with this other species of primate. Yes. And the offspring had this gene incorporated into it. Right. Exactly. And then that that offspring at some point mated with another homo sapiens and so on and so forth. Correct. Yes. Okay. Yeah. I'm not

21:33 trying to paint more color on it so that people uh I'm not trying to be salacious here. I just I think that sometimes um we forget um that in the primate lineage that there there were other primates with whom homo sapiens were capable of reproducing with. That's right. Yeah. And there's actually some extraordinary work from Fonte Pabo um who works a lot with ancient DNA where they found an individual who was a first generation mix. I think it might have been with Neanderl. Um I forget now at this point. But um it's so it was it was a first generation halfh human half whatever archaic comet it was. Um which shows you I mean if they found this the chances that they would find this one you know mixed individual um are so slim that it suggests that this was something that was actually happening a lot um for them to happen to find it. So in the diagram

22:20 that everyone has seen of a of a quadriped animal like walking on all fours and then gradually evolving into the upright form that we know as homo sapiens which is the uh primate right before it with which by the way being slightly hunched forward in a slightly C-shaped position looks a lot more like homo sapiens nowadays who are on their phones all the time. That's a separate point. That's an editorial point. But was there a kind of final primate step before homo sapiens like one or was it a collection of a bunch of different primate species and then we got homo sapiens? Yeah. Um I mean it definitely you know we have an ancestor. I don't remember exactly the name off the top of my head but I have an issue with this diagram. Um because it's you know it's the classic depiction of evolution,

23:06 right? But it really suggests kind of like I was saying before this trajectory um and we are the pinnacle of it. You know we've achieved this thing. And I think it also fits with this, you know, concept of survival of the fittest. Um, which I think is, you know, also a little bit misleading in that, you know, it's not about the most fit, it's about the best fit. So evolution doesn't care how fit you are in the way we think of fitness. It only cares how you fit with your environment. Um, so, you know, the idea that evolution is driving any species, but especially ours, towards some optimum, um, I think is inherently flawed. I had a colleague at Harvard, he's still there, although I think he closed his lab, who once said, "It takes a lot of generations of

23:51 offspring to evolve a given trait, but it takes very few to devolve a trait." That's right. Like you can create immense problems in all sorts of things from, you know, pancreas function to uh mobility to vision with a delterious mutation. Mhm. But it takes a very long time to create an advantage for a given species through the accumulation of new uh combinations of genes. Is that true? Yeah. Yeah. I mean it's um most mutations are delotterious. Most mutations cause problems. Um and so we actually don't even see most mutations because they kill essentially the offspring before, you know, it's even becomes a fetus. So most mutations are happening in a way where that we're not

24:36 even seeing them. Um so to wait for something that comes up that's actually beneficial um can take forever um because you know you have to have exactly the right thing the genome's huge um so when those changes are happening for it to not only happen in the right place but to not cause problems takes a really long time. So some of the faster examples that we know of of evolution, especially in humans, come from when there's variation that's just already there. And you know, it's not particularly advantageous um like I mentioned with uh Tibetans until you move into a particular environment or until you start practicing a certain activity like breathold diving. Um and so you know we have we call it standing variation just there's all these differences between all of us humans on Earth. And so when you have variation

25:21 that's beneficial in the right environment, um, then evolution can happen a lot faster. Got it. Okay. So, I'm obsessed with the X-Men. Yes. I love that series. I've probably watched it five different times. I mean, for a biologist who's interested in all animals, but the human animal perhaps most, you know, it's uh it's like the perfect form of entertainment for me, right? uh different individuals who have mutations that afford them specific gifts or abilities, but it creates some uh let's just say some social tension between those that have and those that don't. And it's about learning these to use these mutations for good versus evil. And it gets into all sorts of interesting human psychology. you work on the actual uh real life

26:08 version of what I think of X-Men and as you'll tell us today women as well which is as you just told us there's variation in all of our genomes and occasionally by virtue of the needs of a particular group or individual those mutations afford them an incredible ability to do incredible things. So, if you would could you tell us about uh these underwater free divers that you've studied? Uh this is a collection of studies, I realize, but maybe the first study uh because I find this to be one of the more incredible examples of behavior shaping what we think of are fixed properties of the human body. And um please just tell us about it. It's such a wonderful story. Yeah, absolutely. And I also love the X-Men.

26:54 Although if you ever want to ruin a perfectly good sci-fi movie, watch it with an evolutionary biologist or Okay. Noted. No. Um uh yeah. So there are these these incredible people um well really all around the world, but I started u my work in Indonesia um called the Bajjo. Um they are a group of what's called cenomads. Um so comads are they're these people who spend their whole lives essentially at sea traditionally. Um they live on houseboats. Um, and everything they need they get from the sea. And they do this through fishing, of course, and other things like that. Um, but also through an incredible amount of breathold diving. So, they're extremely good at this. They can hold their breath for many minutes at a time. They dive to incredible depths. Um, a lot of them wear these uh jewelry made of black

27:39 coral. Black coral only starts growing at about 100 feet deep. So, that tells you how deep they're diving. So, those are trophies. They're actually meant for to protect them from uh evil spirits and things like that. How long are their breath holds on record? I've heard you talk about this before. It's a little debatable, but the number I heard from you in a lecture, I went, "Whoa." Yeah. So, I was told, and I always emphasize that I was told, I did not see this. I did not record it. I was told 13 minutes. Um, and this was by the father of a diver who I worked with in Indonesia. That's got to be in in the neighborhood of world record stuff. It is. Yeah. I'm trying to remember what the current world record is, but it's also I mean, you have to think about if you see them diving, like it's incredibly active. Um, so a lot of the

28:25 breathold records that we think of are people floating in a pool. They're not moving. Um, they're not expending any, you know, energy. They're not using up that oxygen as quickly. Um, and these these cenomads are when they're underwater, they look like hunters on land. They go deep enough that they're not floating anymore. And so they're walking on the on the surface of, you know, the the bottom of the ocean with their spear guns and they they look like hunters. It's incredible to see. Amazing. So even if it's not 13 minutes, let's say it's half that, it's still super impressive. It's very impressive. Yeah. So do they grow up doing this? They do. Yeah. And they, in fact, they spend so much time traditionally on these houseboats and so little time on land that a lot of the children actually learn to swim before they learn how to walk. Um, so one of the divers, uh, when

29:11 I was when I was out there, one of my colleagues noticed that one of the divers's feet was very soft. And we realized that it's because he's never really walking. He's just always in the water. So his feet don't develop the same kind of calluses that ours do because he's not using them like we do. Amazing. So h how did you find this population and what sorts of questions did you start to ask? Yeah. So, I was actually um diving as part of a coral genomics project in Thailand um escaping Danish winter uh because that's where I was doing my PhD. And I I heard about a population called the Mochin. Um so that's another group of these cenomads and heard about you know their incredible underwater diving. Um started looking into it and saw um a study that I think you've seen that um that showed that children mochin children could actually see underwater better than uh

29:57 European children. um and started thinking about, you know, I mean, free diving is really dangerous. Um and so I was thinking that this could actually be something that's driving selection in this population that's causing this population to evolve. In other words, just to put this in um everyday terms for people, if you don't get good at this, you die. Yeah. Exactly. If you die young enough, you don't reproduce. Exactly. If you get good enough at this, uh, you can live long enough to reproduce and your children will presumably inherit whatever mutation or or genetic variants afford this ability. Exactly. Yeah. Yeah. And, you know, I mean, we see with competitive breathold divers, um, you know, I I've never actually been to one of these competitions, but I've read about them. People pass out underwater all the time,

30:42 um, and they're, you know, pulled to the surface and revived. But if you're a cenomad diving in the middle of the ocean with no one nearby, nobody's going to pull you out of that water. And so you've just removed yourself from the gene pool completely. Whereas someone who maybe has a variation or has genetic variation that's making them safer at diving um might survive that. And in this case, the safety at diving comes from being able to stay under longer. We can talk about that, but as long as we're on this point and because some people will be tempted to uh to go test their breath holding uh time, which please don't do it. Um just I'm just going to do it across the board. Just don't do it. But learn from an expert. If you're going to learn to free dive, learn from somebody who's truly expert under the right conditions. I'll put a link to a couple folks I know that I have no business relation to. Uh Mark

31:28 Healey and some other people that teach this on land first. Actually, you know what? I'll just tell you. You know what they told me was the first step, right? In one of these uh free diving classes, I chose not to do it. Is to do not do this, but I was told here's the first step. You're going to hold your breath on land and force yourself to not breathe when the gas reflex hits until you pass out. Yes. And I was like, I you know what? I'm not going to take this course. Yeah. So, this is exactly what gets people in trouble because Yeah. Like, you know, we don't have a reliable sensor for when our our oxygen is low. And so that happens to people underwater because that feeling that wanting to breathe is a buildup of carbon dioxide. Um, and so yeah, people teach themselves to overcome it like they're suggesting you do there. And then you know you're underwater and you pass out and that's it. I've been told that you go from

32:14 feeling that gas reflex. You learn to ride that like a bump. Mhm. Um the same way you might stay in a cold plunge or something a little bit longer than your impulse would have you stay in. But in this case, you're underwater and then it passes and then you're you're swimming freely about and you're uh you feel good, you're relaxed, you're doing slow exhales to let off that carbon dioxide, whatever carbon dioxide is left, and then it's just lights out. That there's no there's no flickering. Uh, it just goes to complete blackout, right? Like curtains as they call it, and then you're dead. Yeah. Unless somebody pulls you up to the surface. Exactly. Yeah. Yeah. So hopefully we sufficiently scared people into into doing this. Okay. So this population presumably is not thinking about carbon dioxide thresholds for the gas reflex, areas of the brain stem that are measuring carbon

32:59 dioxide. They presumably learn through experience that if you do the right things, you live and reproduce. Your family eats. You do the wrong things, you die. Right. Yeah. there's so much um cultural knowledge that's integrated into the practice and that's passed on from you know generation to generation because a lot of times they're doing this in family units. Um you know the one of the divers that I worked with his dad used to be the most famous diver in the village now he's the most famous diver in the village and and so there's a lot of that tradition and that traditional knowledge that's passed on despite it maybe not looking like what we would read in a textbook. when you say the um one of the most revered or expert divers, I'm very curious as to uh how this weaves back to an earlier part of our conversation is prowess at diving based on how long someone can stay under

33:46 and is prowess at diving because it correlates with the ability to secure resources is that um somehow correlated with des like desirable mate. Do these people tend to have more offspring than people that are not as good at diving? And of course there are confounds here like you can imagine differences in hormone levels to begin with. Uh eating more during uh puberty and growing you know stronger or whatever it is. Um or more or smarter and not just smarter but do you see this like are the people who are great divers in the village do they tend to be the ones with more um uh more children to be direct? You know it would be interesting to count that. I think now um you know things are changing for the for the Bajjo at least the community that I worked with where a lot of people

34:31 are moving away from traditional diving and into other kinds of fishing practices. Um and so I think at this point you know this prowess this respect for these you know these divers is more respect for the fact that they're keeping the tradition alive and they're continuing this tradition even though it's a very hard thing to do. Um but yeah it would be really interesting. I know actually the one the one diver came from a very big family and that was something that the Bajjo actually asked me about was why why do the Bajjo have so many children and so it would be interesting to see if yeah diving success correlates with reproductive success because you could imagine that it would I mean they're they're diving for things that they're eating so why wouldn't that um increase your success on that just out of curiosity um and uh because I like seafood um what what are they fishing for they dive for it

35:18 depends on where they are um they're spearing a lot of fish. Everything is delicious. Um they dive for shellfish. Um they also harvest seaweed sometimes. Um and they they actually collect a lot of sea cucumbers which they dry out in the sun and then eat later. It's like pure protein. Yeah. Yeah. Yeah. Very interesting. So what did you study in the in this group? Yeah. So we started thinking about okay you know for natural selection to act in this population it needs some kind of physical trait to act on. um which got us looking at the you know the dive reflex or the mamalian dive reflex. So this is if anyone um and again I hesitate to to tell people to do this but if you hold your breath and put your face in a bowl full of cold water your body responds as if you're diving um and and what that means is that um

36:05 your your heart rate slows down um your blood vessels and your extremities constrict uh because you know your fingers will be okay with a little bit less oxygen but your brain really needs that oxygen. So, it's keeping the blood central where you need it the most. Um, and then your spleen contracts. And so, the spleen certainly wasn't the first organ that I thought about when thinking about diving. Um, but the spleen is a reservoir. I mean, it spleen does many things, but one of the things that it does is it's a reservoir for red blood cells that are carrying oxygen. And so, through that contraction, those oxygen rich red blood cells are now pushed into circulation, and you get an oxygen boost. How significant is that oxygen boost? It's about 10% in in most of us. That's pretty impressive. Exactly. Yeah. Yeah. It's I mean it's enough to to make

36:50 a difference. Yeah. By comparison, you know, there are um a lot of discussions online about you know if you finish your exercise, resistance training or cardiovascular exercise with a brief sauna session. So going slightly hypothermic, right? This you have to hydrate, etc. But it actually works even better as long as we're talking about dangerous practices. It works even better if you're slightly dehydrated. You get an overp production of red blood cells in the subsequent days. And this is used for a performance-enhancing effect in elite athletes mainly. Um you have to again avoid dehydration, death etc. But this is done and there someone will correct me but the the shift in uh available oxygen is in the low percentages like one or two%. Okay. So this is what people are fighting for

37:35 using these kind of uh baroque protocols. You're talking about a 10% increase in available oxygen through a contraction of the spleen. I didn't even know this the spleen could contract. Yeah, that's right. Um just when you put your face into colder than ambient temperature water. Uh yeah, usually in um like lab protocols, we do it at about 10° C or 50° Fahrenheit. So quite a bit colder. For how long? Um well, depends on how long you can hold your breath. Oh, right. Um yeah. So the but you know the extent to which like how long the contraction actually takes. I think we have room to to learn more about that. Um but one thing that's that's slightly different from what you're talking about is that after you stop holding your breath your spleen takes that oxygen back um essentially. So that's it

38:21 refills with red blood cells and that oxygen is no that extra boost is no longer in circulation. Ah so it's only during the breath hold. That's right. Only when you need it the most. Interesting. What an incredible adaptation of the human body. Yeah. What are some other functions of the of the spleen just for this is the first time the spleen has ever been discussed on this podcast I think. Um we don't think about spleens too often. Um well you can live without one so it seems like how important could it be but um well in this population it sounds like it might be critical. You you'll tell us. Yeah. What are some other things that it does? It's um it's involved in the immune response to certain bacteria. Um and uh actually I'm trying to think of what else it does, but that's you know the main role is immunological. One thing I in anticipation of this

39:08 episode I did a little reading about it and it's it gets very heavy neural intervation which is interesting. We don't normally think about our peripheral organs besides our heart as getting a lot of neural intervation. Of course the gut has neural intervation etc. But the spleen gets very heavy neural intervation which makes me think that maybe there's the opportunity for more perhaps even conscious control of the spleen. Does this population um communicate about any sense that they they can like switch this thing on or is this just all kind of um unconscious genius related to their their behavior? Yeah, as far as I know, it's all unconscious. It's not something that they talk about. And you know, most of them, you know, when I was explaining what the spleen was, it wasn't something that they had ever thought about. Um, or, you know, experienced any kind of sensation in the area where the spleen

39:53 is found. Um, yeah, but who knows? I mean, it's, uh, encapsulated in smooth muscle, I think, the spleen, and that's what controls that contraction. So, yeah, maybe there could be some way to, um, you know, to consciously contract your spleen. We also, our spleens contract when we exercise to a lesser extent. Um, and this is why like horses and apparently greyhounds, um, someone wrote to me after the study came out, have massive spleens. Um, as do seals who do a lot of deep diving, but that makes a little more sense. Interesting. Horses, I don't I don't think about horses being underwater very often or greyhounds for that matter. Yeah. But I wonder if they incorporate breath holds as a way to deploy red blood cells. Yeah, it could be that. Yeah, something in the kind of breath holding aspect of

40:39 extreme bouts of exercise is also contributing to uh to that contraction. Like when uh when one becomes a bit hypoxic because you just can't keep up with whatever exertion like you just can't breathe in enough oxygen, dump enough carbon dioxide to keep up with your physical activity. Is there any that is that one of the conditions under which it sort of mimics a breathold or do you need this cold? There seems to be something about the face being cold. Yeah, there's um it's stimulation of the veagal nerve that is in part triggering this response which you know runs through your face. And so that's why the you know the facial immersion is is crucial um to triggering the response. But there is I think a component of if you're just holding your breath where that also kind of triggers it. So um but yeah, it's really amazing

41:25 to think that as mammals this evolved sometimes so long ago that it's in it's even in mice. They've done a study where they actually trained mice to dive and they could measure the mamalian dive reflex in mice. Wild. Yeah. So, you sort of answered my next question, which was uh why do we have a dive reflex? I mean, we're not a harp seal, right? And we're not a diving bird. Why do we why do we have this? Yeah. I mean, it's a great question and I don't think we really know. Um there's a some people talk about something called the aquatic ape hypothesis. um that says that one of our ancestors sorry I'm trying not to interrupt but I just someone I've heard of the stone date hypothesis you know all the psychonauts love the stone date hypothesis which is that psychedelics what are what led to new ideas and

42:11 daytime dreams that led to our evolution and uh anyway forgive me for interrupting it was it was an interruption of of of the stone ape um so that the aquatic ape was right there alongside the stone ape but I think I think that you know given the fact that it's present throughout all mammals. I think it's much more likely that it was some very long ago ancestral, you know, protomamal that was doing some kind of diving. And because of that, this response is present to varying degrees in all modern mammals. As many of you know, I've been taking AG1 daily for more than 13 years. However, I've now found an even better vitamin, mineral, probiotic drink. That new and better drink is the new and improved AG1, which just launched this

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46:02 questions that are hopefully springing to people's minds here and there. Uh, I've seen these videos of babies being born into a swimming pool and they can and that you could on their belly. It looks like the nirvana cover and you know, they're they seem perfectly happy to be underwater shortly after birth, which makes intuitive sense. They were in the womb. they were floating in the amniotic sack and they're underwater, so to speak. Um, do we come into this world knowing how to dive and be underwater because of our experience during pregnancy? I mean, it it seems like it. I mean, I've seen, you know, if you take babies, and I'm not recommending anyone do this, but like blowing their face, you know, they they instinctively hold their breath and can be put underwater. And uh and actually bajou people told me and I don't know if this is something they actually do but that the test of a

46:48 bajjo is as a baby they pass the baby under the canoe and if the baby comes out the other side then it's a bajjo because it has held its breath like it will for the rest of its life. What's the alternative? Yeah I don't that's why I said I don't know if they actually do this but um it was just something that they told me. Um but yeah I think there is some innate uh response where we know even as babies to to hold our breath. That's fascinating. So what did you discover in this uh group of incredible divers? So we discovered that they have larger spleens. Um so you know I mentioned the spleen's role in diving. Um it's it's increasing your they sometimes people call it a biological scuba tank. You know it's increasing the amount of oxygen available to you. So you know our hypothesis was that they would have larger spleens because a larger spleen presumably means longer

47:35 diving, safer diving. Um, and so we compared them to a nearby population living in a very similar environment but with a history of farming. So these are people who live right next to the ocean but aren't really interacting with it. So you know Bajjo children are in the water from the moment they're born almost. Um, and then children in this other village didn't know how to swim. Um, and so we found that compared to that village um, the Bajjo had significantly larger spleens. So their spleens were about 50% larger on average. Um, and this was true for divers and non-divers. So that showed us that it was very likely to be something genetic rather than, you know, the fact that you're diving increases the size of your spleen. But does diving increase the size of the spleen? This is a question that I think is still open because in both of the populations where

48:21 I've measured this, divers and non-divers have the same size spleen. However, other people have shown that um you know, when you train if you train people, if you recruit people to a study and train them in breathold diving, their spleens increase in size. Um, so I don't know if it's just that the populations that I've worked with have some kind of genetic factors that override that change. Um, but yeah, open question I would say. I know you've done some work parsing which genes are different in this population and developing some animal models for that and that some of this converges on thyroid hormone. Um, could you tell us the relationship between thyroid hormone levels that people are fascinated by thyroid hormone? It seems everyone either thinks they have a thyroid deficiency or an overprouction of thyroid or they want to increase their

49:07 thyroid. What is the relationship between thyroid hormone and spleen function as it relates to the production of these additional red blood cells? The gene that we found that was evolving in the population um correlates with higher than average thyroid hormone levels. Um so not you know like clinically hyperyroid but higher than average and this is actually also true for Europeans who are carrying the same genetic variant. um you know we showed in another group of individuals that if you have this gene variant um you have higher thyroid hormone levels and you have a larger spleen um so it's not just something that's true in the cenomads um and so what we think is going on potentially and this relates to the work that we did with mice as well is that um because of these higher I hesitate to say elevated because that's a clinical term higher than average thyroid hormone

49:53 levels um people are prod or the you know the mice the humans whoever it is are producing more red blood cells Um and so now whether that's kind of stretching the spleen um you know because the spleens that we saw in the mice were larger but less dense um or you know if there's some other mechanism we're not completely sure yet but yeah it seems like these higher than average thyroid hormone levels at least when the genetic cause was um was what we saw in the cenomads increase the size of the spleen increase hemoglobin increase hematocrit um increase red blood cell count. I can think of two general scenarios where having a nice big spleen would be advantageous. One is in the performance enhancement context. Your runner, maybe there's a way, I'm not suggesting this as a protocol that you

50:40 know like getting your face into some cold water, holding your breath could afford you a kind of a boost. So instead of the scuba tank boost underwater, you're getting the above ground boost in endurance or strength output. You said you have to be holding your breath at the at the same time in order to take advantage of that deployment of red blood cells, which is a little confusing to me because I imagine if this if the spleen contracts and the red blood cells are deployed into the body that those are available whether or not your mouth is open or not. Yeah. Yeah. And we don't I don't think know how quickly the spleen reuptakes those red blood cells, but it does do that eventually. So maybe this is something that would be advantageous for a short burst or something like that. I mean, I think there's a lot that we don't know about the performance-enhancing aspect of this, but that's really interesting because um the work that we did in the

51:25 mice where we replicated what we saw in these divers um they had larger spleens, they had higher red blood cell count, but they did not have any change in ariththropoin, which is how we normally think about um changes in red blood cell count. This is a drug that was really popular with cyclists for a while. um people would self-dose with ariththropotin and it would increase their red blood cell count dramatically to improve their performance. Um so this is like an ariththropotin independent mechanism of increasing your blood red blood cell count that could have an advantage in performance. I I think fascinating and then the other scenario is for uh robustness of one's immune system. I for one don't like being sick. And if there's anything I can do to

52:10 increase the function of my immune system, including sleep, exercise, sunlight, all those things, uh, but in particular, if I feel like I'm traveling in an additional amount or not sleeping as well, I'd be willing to do pretty much anything within the realm of reason to improve my immune system vigor, right? Yeah, absolutely. Uh, and if sticking my face in a bowl of cold water, 50° for I guess as long as I can hold my breath in the morning is going to potentially afford that advantage. I'm willing to be the the idiot that uh is doing this thing without any specific clinical trial yet, but I'd love to see a clinical trial on this. Oh, absolutely. Has anything been done to explore how that particular behavior or that is uh generating the dive reflex can afford any uh enhancement in immune

52:58 system function. I haven't seen any studies that look at that. But it would be really interesting um because yeah, I mean like you I also would do anything to not get sick and we do see in these populations um a lot of older people who are continuing to dive um and and there is a seeming health and robustness that I wonder if it's related to the activity of diving itself. We have a family friend who's 94. My mom just told me 94 and my mom said over the phone, "She swims four miles a day." And I'm like, "There's no way." And she goes, "No, wait. She swims a mile a day, four days a week." Um, which is still pretty impressive. Yeah. Swimming a mile is uh Yeah, that's quite impressive. Four days a week at 94. Mhm. Presumably that's not backstroke. At least some of it's uh

53:44 Yeah, I think that like is there something to being in water that just generally is good for us? I would imagine I shower, I bathe. But, you know, is there something good about swimming or floating or diving just for our general human physiology that we're aware of? Yeah. I mean, it's it's so low impact and and such a natural way to, you know, to to move to exercise that um I yeah, I think especially as we age, it would be a really wonderful way to to stay fit and healthy. has the size of spleens, or rather the genes related to um what you're talking about, um has that been correlated with whether or not people evolved from coastal versus more um central regions of of continents? That's a really good question. We haven't looked at that, but it would be really interesting to see because I

54:30 mean, you know, the oceans are an incredible resource in terms of food availability, especially to early humans. Um, so you would imagine that anyone living near a coast anywhere would take advantage of this resource. Um, so it would be interesting to see if maybe coastal populations are more likely to carry the genetic variation um that enables this behavior. Although there are actually skeletons that have been found in various parts of the world near river systems that also suggest that those people have been diving. Um, so maybe it's just being near water anywhere in the world. I don't think of humans as an underwater species, but you're changing my view of this. I feel like we need to think about humans as some some humans in the past and now spend a lot of time underwater. Yeah. Without a scuba tank. It seems to be that way. Yeah. All over the world.

55:15 That's super interesting. So, this isn't the only population you've studied. um if you would could you tell us about the the recent work um uh the women study on women partic in particular uh and I'm very interested in how this relates to cardiovascular health. Yeah. So, um, you know, speaking of older divers, um, there's a group in Korea on an island called Jju. Um, these are all female divers. Um, they're called the Henyo. Um, which just means sea women. And, uh, and I, the average age of the Henyo currently is around 70 years old. Um, so that's when I think of robustness with age, I think of the Henyo. Um, but this all female diving population has likely been diving in that region for thousands of years. Um,

56:02 and what's really extraordinary about the Henyo, there's a few things. First of all, they're diving in extremely cold water, especially compared to the Bajjo in Indonesia. No wet suits. No wet suit. Well, now they wear wet suits. Up until the 80s, they were diving in these cotton bodysuits that you can see provide zero thermal protection. I mean, it's just cotton cotton swimsuit essentially. Um, so you know, diving with no protection in extremely cold water. And um, and as women, they're diving throughout pregnancy. So, they're diving up until the day they give birth sometimes. Um, and and then they're back in the water a few days later. So, this has really shaped this population in really interesting ways. I was wondering how deep do they dive? This is a really good question I get asked a lot. How deep do any of these populations dive? Um, and there's just like not really

56:47 data. So, we don't really know. Um, you know, now we're starting to see, you know, we're looking at, um, the henoy. We actually tracked some of their diving

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