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

Episode Date: May 26, 2025

My guest is Dr. Melissa Ilardo, Ph.D., professor of biomedical informatics at the University of Utah. We discuss the interplay between genes and behaviors, including the immune system–related reasons people find the smells of potential mates attractive—or not. We also explore how physical and psychological traits are passed from one generation to the next, and the specific behaviors that can influence gene expression to improve health and performance. Melissa explains her lab’s pioneering research on breath-hold training and how activation of the dive reflex through breath holding can significantly improve oxygen availability by changing spleen size and function. We also delve into the medical uses and ethics of gene editing to cure disease in both babies and adults. For those interested in genes and inheritance, human performance, immune system function, and natural selection, this episode illustrates the remarkable interplay between human nature and nurture. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Joovv: https://joovv.com/huberman Eight Sleep: https://eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman Function: https://functionhealth.com/huberman Timestamps 00:00:00 Melissa Ilardo 00:02:35 Nature vs Nurture, Gene Expression, Eye Color 00:07:06 Sponsors: Joovv & Eight Sleep 00:10:24 Epigenetics, Trauma, Mutations; Hybrid Vigor, Mate Attraction 00:15:47 Globalization; Homo Sapiens, Mating & Evolution; Mutations 00:25:28 Sea Nomads, Bajau & Moken Groups; Free Diving, Dangers & Gasp Reflex 00:32:52 Cultural Traditions, Free Diving & Families; Fishing 00:35:36 Mammalian Dive Reflex, Oxygen, Spleen, Cold Water & Face; Exercise 00:42:43 Sponsors: AG1 & LMNT 00:46:00 Free Diving, Spleen, Thyroid Hormone, Performance Enhancement 00:52:00 Dive Reflex, Immune System; Swimming & Health; Coastal Regions & Genetics 00:55:17 Female Free Divers, Haenyeo, Cold Water, Age, Protein 01:03:20 Human Evolution & Diet, Lactase, Fat 01:05:07 Korean Female Free Divers & Adaptations, Cardiovascular, Pregnancy 01:10:13 Miscarriages & Genetic Selection; Bajau, External Appearance, Mate Selection 01:17:15 Sponsor: Function 01:19:03 Free Diving, Underwater Vision; Super-Performers & Genetics 01:25:01 Cognitive Performance, Autism, Creativity; Genetic Determinism & Mindset 01:36:30 Genetics & Ethics, CRISPR, Embryo Genetic Screening 01:44:36 Admixture, Genetics; Are Humans a Single Species? 01:49:39 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Melissa Allardo, 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 Huberman 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 mammalian dive reflex, a physiological reaction to breath holding in cold water that, as Dr. Elardo 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 mammalian 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 external traits signal important variations in organ function, hormone levels, and even brain physiology. Toward the end of our conversation, we discussed 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. Olardo does incredible real-world 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 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 zero cost 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. Melissa Elardo. Dr. Melissa Elardo, 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 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 gonna 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.

I think we're still learning with epigenetics and all of these new fields just how much we can actually change things. There are of course things that are kind of written in our genes, but I think we're learning that there's a lot more that we can change. Most of us at some point in high school learn Mendelian genetics. Mendel, the monk and his peas in his garden. Most people probably don't remember the details of that, but we also learn about eye color. It's commonplace 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 light-eyed parent and one dark-eyed parent, then you start to enter the probability game. And then at some point, your parents dictate a lot of your appearance, your phenotype 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 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 gonna change your eye color by behaving differently. But what are some examples where we can change our gene expression quickly, relatively quickly, by doing something differently? Yeah, just going back to eye color, because this is just one of my favorite genetics facts.

So everyone with blue eyes descends from the same person. 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 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. That's right. The first.

Let's stay on eye color for a moment because I, before we get into how genes can be modified by behavior, I've been told that the green eye phenotype is one of the more rare eye colors, is that true? I think that's right, yeah. I think it's the most rare. Okay, so can we assume that there was an original F1 brown-eyed 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. And so then, yeah, having these other eye colors arise

in the population 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. 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 Regardless of where they start interesting. So like a blue-eyed baby will have much bluer eyes at birth And it will at age 15 at age 80 instance. Yeah, we believe that's due to Changes in pigmentation because of UV exposure. That's really interesting that's due to changes in pigmentation because of UV exposure. That's really interesting. I'd like to take a quick break and thank our sponsor, JOOVE.

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including Mexico and the UAE. Again, that's 8sleep.com slash Huberman to save up to $350. Thank you for that. Because I think that most everyone is interested in eyes and eye color. What are the 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 that are governed by some change in behavior.

Yeah. So I mean, our genes are constantly changing how they're expressing based on what environmental stimulus is coming in. So we have these changes that happen on the order of 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 there can be epigenetic changes. So these are changes, little modifications to the genome that happen by things actually, molecules actually attaching to the genome and changing how genes express that can be passed down. So this is really interesting from the perspective of things like trauma. We know that refugee populations actually have some of these changes that they've inherited from their parents even if they weren't victims of the event that caused them to be refugees.

Excuse me for interrupting, but are those changes that are passed down, are they adaptive? Are they making subsequent populations more resilient or less resilient? Yeah, that's a very good question. In the case of trauma in 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 that affected Dutch people several hundred years ago, I think. And that was actually also kind of recorded 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 think about in a contemporary situation

where food is abundant, maybe that is no longer beneficial, even though at one point it was. And so then we have this other kind of order of change, which is actual changes in the genes themselves that either arise from mutations in these single-based pairs or at many different sites or things like variation that's already present in the population at a certain amount that then increases in frequency throughout the population. And this is where a lot of my work has focused.

And these are changes that until recently we thought would take 5,000 years, 10,000 years at least. And now we're starting to understand that maybe that can happen in as know, 5,000 years, 10,000 years at least. And now we're starting to understand that maybe that can happen in as short as 1,000 years, 2,000 years. This might be slightly out of line with what we're talking about right now, but I'm really fascinated by this concept of hybrid vigor. I was taught, I don't know if the data still hold up, that if you give mice a choice of other mice to mate with, to produce offspring with, that they will select a mouse whose major histocompatibility

complex which is a reflection of diversity of immune genes, so to speak. They'll pick 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? They'll pick 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 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 a choice produce offspring with people that are more different from them as opposed to similar To them they did a very similar study in humans and humans also are drawn to other humans that have these differences So it's interesting especially with the immune system. there was a study where I think they had people smell sweaty t-shirts of members of the opposite sex if they were heterosexual to see how attracted they felt to the person just based on the smell of their sweaty t-shirt. And people were more drawn to people

who had very different immune systems than their own. So I think this is something, we see it in mice and it's easy to say, oh, you know, it's their 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 they're given a choice of sweaty clothing

from the opposite sex potential partner. I guess they're, I don't know if they were, you know, sent out on dates after 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, what is it, the histocombatibility?

Major histocombatibility complex. about you know that major has to come out of the complex yeah the more different they were in that 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 kind of a proxy for gene expression related to the immune system of the offspring that you haven't even had yet with this smelly t-shirt-owning person. Exactly. 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 a pretty powerful driver of mate selection. Yeah. I mean, I think it could be. It's also interesting, you know, we have, you know, when you're talking about hybrid compatibility or hybrid... I called it hybrid vigor based on no particular knowledge of the correct term. I think that's...

It's the term I use because it makes sense to me. Yeah. Something like that. Something like that. You know, we're having with globalization people 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 And that's creating some 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 that are now showing up together. I Find this super interesting For a couple of reasons. First of all, 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 but that's a different podcast. But that yes, people are intermarrying and or producing children with people that – whose backgrounds, genetic backgrounds are very different than their own.

And if we take the opposite extreme, it makes perfect sense as to why this hybrid vigor thing would exist 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 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. And then of course there's the moral and ethical and all that aspect, but Mother Nature actually punishes individuals that do this through mutation. Yeah, when you have two individuals who are closely related,

that dramatically increases the chance that they're both carrying a variant that has a negative impact on the offspring. So when you have people kind of mixing more outside their families, then it's very likely that even if you're carrying this deleterious variation, it's gonna be kind of watered down by outside genetic material. But yeah, as soon as you have people too closely related to each other, those things are ending up together and creating disease. Yeah, so it's definitely nature has a system built in

that says don't do that. Yeah, I find it amazing that these things are operating below the level of conscious decision-making to influence preference like this smell or that smell, right? And we've established, you've told us that the smells that reflect the most distant immune system are the most attractive smells, which is really wild. So is it fair to say that humans are continuing to evolve 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 think we're done. We've reached this ultimate point of evolution. We've finished evolving. But as long as there are things that are affecting our ability to reproduce, we're going to continue to evolve. And especially once you have this introduction

of new genetic variation, I mean, some of the greatest adaptations in the history of humans have come from the introduction of new genetic material. So the Tibetan high-altitude adaptation is actually believed to have arisen from the crossing of humans with another early hominid group called Denisovans. So we essentially stole the advantageous genes from this other group. And so maybe you'll start to see that happening, as you have a more globalized population where, you know, different groups of humans are creating these interesting phenotypes 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 this gene that affords better abilities at altitude or ability to survive at altitude enter the human population? You know, I'm gonna get myself in trouble because I don't remember exactly how long ago it was. More than 10,000 years ago. More than 10,000 years ago, but it only became advantageous when the ancestral population 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. And so they, you know, passed that along 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, was able to reproduce with a species that was not homo sapiens, and that's how the gene entered the homo sapien population. That's exactly right.

So yeah, we see that happening with Neanderthals as well, but also this other population of, they call it archaic hominids, Denisovans. So these were a population that were found in areas of Asia and their genes were introgressed, we say, so essentially inserted into the human genome. So individuals from that region tend to have a higher ancestry coming from that hominid 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 offspring at some point mated with another homo sapiens and so on and so forth. Correct. Okay. Yeah, I'm not trying to paint more color on it so that people are not trying to be salacious here.

I think that sometimes we forget that in the primate lineage that 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 Svante Pabo, 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 Neanderthal, I forget now, at this point. But it was a first generation half human, half whatever archaeocompetent it was, which shows you, I mean, if they found this, the chances that they would find this one mixed individual are so slim that it suggests that this was something

that was actually happening a lot for them to happen to find it. So in the diagram that everyone has seen of a quadrupede animal, like walking on all fours, and then gradually evolving into the upright form that we know as homo sapiens. Which is the primate right before it? 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. 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 because it's, you know, it's the classic depiction of evolution, right? But it really suggests, kind of like I was saying before, this trajectory. And we are the pinnacle of it. We've achieved this thing. And I think it also fits with this concept of survival of the fittest, which I think is also a little bit misleading in that 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 So, you know the idea that evolution is driving any species, but especially ours Towards some optimum 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 offspring to evolve a given trait, but it takes very few to devolve a trait.

That's right. But you can create immense problems in all sorts of things from,creas function to mobility to vision with a deleterious mutation. But it takes a very long time to create an advantage for a given species through the accumulation of new combinations of genes. Is that true? Yeah, yeah. I mean, it's most mutations are deleterious. Most mutations cause problems. And so we actually don't even see most mutations because they kill essentially the offspring

before it even becomes a fetus. So most mutations are happening in a way that we're not even seeing them. So to wait for something that comes up that's actually beneficial can take forever because you have to have exactly the right thing. The genome's huge. 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 evolution, especially in humans, come from when there's variation that's just already there. And it's not particularly advantageous, like I mentioned with Tibetans, until you move into a particular environment, or until you start practicing a certain activity,

like breath-hold diving. And so 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 that's beneficial in the right environment, then evolution can happen a lot faster. Got it.

OK. 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 like the perfect form of entertainment for me, right?

Different individuals who have mutations that afford them specific gifts or abilities, but it creates some, 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 real life 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 these underwater free divers that you've studied? This is a collection of studies I realized but maybe the first study because I find this to be one of the more incredible examples of behavior shaping what we think of our fixed properties of the human body. Please just tell us about it. It's such a wonderful story. Yeah, absolutely.

And I also love the X-Men. Although if you ever want to ruin a perfectly good sci-fi movie, watch it with an evolutionary biologist or … Noted. Noted. Yeah. So there are these incredible people – well, really all around the world, but I started my work in Indonesia called the Bajo.

They are a group of what's called sea nomads. So sea nomads are these people who spend their whole lives essentially at sea, traditionally. They live on houseboats and everything they need they get from the sea. And they do this through fishing, of course, and other things like that, but also through an incredible amount of breath-hole diving. So they're extremely good at this. They can hold their breath for many minutes at a time. They dive to incredible depths.

A lot of them wear these jewelry made of black 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 to protect them from 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 and I always emphasize that I was told I did not see this I did not record it I was told 13 minutes 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 So a lot of the breath hold records that we think of are people floating in a pool. They're not moving. They're not expending any energy. They're not using up that oxygen as quickly. And these sea nomads 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 surface, the bottom of the ocean with their spear guns and 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 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. So when I was out there, one of my colleagues noticed that one of the diver'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 how did you find this population and what sorts of questions did you start to ask? Yeah, so I was actually diving as part of a coral genomics project in Thailand, escaping Danish winter because that's where I was doing my PhD. And I heard about a population called the Mokin.

So that's another group of these sea nomads. And heard about their population called the Mokan. So that's another group of these sea nomads. And I heard about their incredible underwater diving. Started looking into it and saw a study that I think you've seen that showed that Mokan children could actually see underwater better than European children. And started thinking about, I mean, free diving is really dangerous. 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 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, you can live long enough to reproduce and your children will presumably inherit whatever mutation or genetic variants afford this ability. Exactly, yeah. Yeah, and you

know, I mean we see with competitive breath hole divers, you know, I've never actually been to one of these competitions but I've read about them, people pass out underwater all the time and they're, you know, pulled to the surface and revived But if you're a sea nomad diving in the middle of the ocean with no one nearby Nobody's gonna 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 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 go test their breath holding time, which please don't do it. Just, I'm just going to do it across the board. Just don't do it. 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 of folks I know that I have no business relation to, Mark

Healy 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 in one of these freediving 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, you know what? I'm not going to take this course. Yeah. So this is exactly what gets people in trouble. Because yeah, we don't have a reliable sensor for when our oxygen is low. And so that happens to people underwater. Because that feeling, that wanting to breathe

is a buildup of carbon dioxide. 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 Feeling that gasp reflex you learn to ride that like a bump Mm-hmm 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 swimming freely about and 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 just lights out.

That there's no flickering, it just goes to complete blackout, like curtains as they call it, and then you're dead, unless somebody pulls you up to the surface. Exactly. Yeah. So hopefully we sufficiently scared people 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 dioxide.

They presumably learn through experience that if you do the right things, you live and reproduce family eats you do the wrong things you die, right? Yeah, there's so much 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 You know 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 one of the most revered or expert divers, I'm very curious as to how this weaves back to an earlier part of our conversation.

Is prowess at diving based on how long someone can stay under and is prowess at diving because it correlates with the ability to secure resources? Is that somehow correlated with 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, like you can imagine differences in hormone levels to begin with, eating more during puberty and growing stronger or whatever it is, 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, more children to be direct? You know, it would be interesting to count that. I think now, you know, things are changing for the Bajau, at least the community that I worked with, where a lot of people are moving away from traditional diving and into other kinds of fishing practices. And so I think at this point, you know,

this prowess, this respect for 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. But yeah, it would be really interesting. I know actually the one diver came from a very big family, and that was something that the Bajo actually asked me about was why did the Bajo have so many children? And so it would be interesting to see if, yeah, diving success correlates with reproductive success because you can imagine that it would.

I mean, they're diving for things that they're eating. So why wouldn't that increase your success on that? Just out of curiosity, and because I like seafood, what are they fishing for? They dive for, it depends on where they are. They're spearing a lot of fish. Everything is delicious. They dive for shellfish.

They also harvest seaweed sometimes. And 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. Very interesting. So what did you study 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, which got us looking at the dive reflex, or the mammalian dive reflex. So this is, if anyone, and again, I hesitate 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. And what that means is that your heart rate slows down, your blood vessels and your extremities constrict because 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.

And then your spleen contracts. And so the spleen certainly wasn't the first organ that I thought about when thinking about diving, but the spleen is a reservoir. I mean, the spleen certainly wasn't the first organ that I thought about when thinking about diving. But the spleen is a reservoir. I mean, the 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 most of us. That's pretty impressive. Exactly. Yeah. Yeah.

I mean, it's enough to make a difference. Yeah. By comparison, you know, there are 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 hyperthermic, right? 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. Do you get an overproduction of red blood cells in the subsequent days? And this is used for a performance enhancing effect in elite athletes, mainly. You have to, again, avoid dehydration, death, etc. But this is done and there are – someone will correct me, but the shift in available oxygen is in the low percentages, like 1 or 2%. So this is what people are fighting for using these kind of Baroque protocols. You're talking about a 10% increase in available oxygen through a contraction of the spleen.

I didn't even know the spleen could contract. Yeah that's right. Just when you put your face into colder than ambient temperature water? Yeah usually in like lab protocols we do it about 10 degrees Celsius or 50 degrees Fahrenheit so quite a bit colder. For how long? Well depends on how long you can hold your breath. Oh right. Yeah so that you know the extent to which like how long you can hold your breath. Oh, right. Yeah, so the extent to which, like how long the contraction actually takes, I think we have room to learn more about that. But one thing that's slightly different from what you're talking about is that after you

stop holding your breath, your spleen takes that oxygen back, essentially. So it refills with red blood cells, and that oxygen, that extra 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 yeah We don't think about spleens too often

Well, you can live without one so it seems like how important could it be right? on this podcast, I think. We don't think about spleens too often. Well, you can live without one, so it seems like how important could it be? Right. Well, for this population, it sounds like it might be critical, you'll tell us. Exactly. Yeah, what are some other things that it does?

It's involved in the immune response to certain bacteria, and actually, I'm trying to think of what else it does, but the main role is immunological. One thing I, in anticipation of this episode, I did trying to think of what else it does. But the main role is immunological. One thing I, in anticipation of this episode, I did a little reading about it. And it gets very heavy neural innervation, which is interesting. We don't normally think about our peripheral organs

besides our heart is getting a lot of neural innervation. Of course, the gut has neural innervation, but the spleen gets very heavy neural innervation, which makes me think that maybe there's the opportunity for more, perhaps even conscious control but the spleen gets very heavy neural innervation, which makes me think that maybe there's the opportunity for more perhaps even conscious control of the spleen. Does this population communicate about any sense that they can like switch this thing on or is this just all kind of unconscious genius related to 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 or experienced any kind of sensation in the area where the spleen is found. Yeah, but who knows? I mean, it's encapsulated in smooth muscle, I think, the spleen, and that's what controls that contraction.

So yeah, maybe there could be some way to consciously contract your spleen. We also, our spleens contract when we exercise to a lesser extent. And this is why like horses and apparently greyhounds, someone wrote to me after the study came out, have massive spleens, as do seals who do a lot of deep diving,

but that makes a little more sense. Interesting, horses, I don't think about horses being underwater very often. Right, right. Or greyhounds for that matter. Yeah. I wonder if they incorporate breath holds as a way to deploy red blood cells. Yeah, it could be that.

Yeah, it's something in the kind of breath holding aspect of extreme bouts of exercise is also contributing to that contraction. Like 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 that one of the conditions under which it sort of mimics a breath hold or do you need this cold, there seems to be something about the face being cold. Yeah, there's, it's stimulation of the vagal 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 crucial 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. But yeah it's really amazing 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 mammalian dive reflex in mice. Wild.

Yeah. So you sort of answered my next question, which was 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 have this? Yeah. I mean, it's a great question. I don't think we really know. There's a, some people talk about something called the aquatic ape hypothesis that says that one of our ancestors is a- I'm trying not to interrupt, but I just, someone I've heard of the stonedoned ape hypothesis Okay, all the psychonauts love the stoned ape hypothesis Which is that psychedelics what are what led to new ideas and daytime dreams that led to our evolution and anyway Forgive me for interrupting. It was an interruption of the stoned ape. Yes

So that the aquatic ape was right there alongside the stoned 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, proto mammal that was doing some kind of diving. And because of that, this response is present to varying degrees in all modern mammals.

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I'm jumping around here, but I feel like these are the questions that are hopefully springing to people's minds here and there. I've seen these videos of babies being born into a swimming pool and that you get on their belly it looks like the nirvana cover and you know 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 sac and they're underwater so to speak.

Do we come into this world knowing how to dive and be underwater because of our experience during pregnancy? I mean, it seems like it. I mean, I've seen, you know, if you take babies and not recommend anyone do this, but like blow in their face, you know, they instinctively hold their breath and can be put underwater. And actually, Bajo people told me, and I don't know if this is something they actually do, but that the test of a Bajo is as a baby,

they pass the baby under the canoe. And if the baby comes out the other side, then it's a Bajo because it has held its breath like it will for the rest of its life. What's the alternative? Yeah. That's why I said, I don't know if they actually do this. But it was just something that they told me.

But yeah, I think there is some innate response where we know even as babies to hold our breath. It's fascinating. So what did you discover in this group of incredible divers? So we discovered that they have larger spleens. So you know, I mentioned the spleens role in diving. It's increasing your, sometimes people call it a biological scuba tank, it's increasing the amount of oxygen available to you. So our hypothesis was that they would have larger spleens

because a larger spleen presumably means longer diving, safer diving. 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 Bajo children are in the water

from the moment they're born, almost. And then children in this other village didn't know how to swim. And so we found that compared to that village, the Bajo had significantly larger spleens. So their spleens were about 50% larger on average. And this was true for divers and non-divers. So that showed us that it was very likely to be something

genetic, rather than the fact that your 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 I've measured this, divers and non-divers have the same size spleen. However, other people have shown that, you know,

when you train, if you train people, if you recruit people to a study and train them in breath hole diving, their spleens increase in size. 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. 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. 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 overproduction of thyroid, or they want to increase their 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 correlates with higher than average thyroid hormone levels. So not, you know, like clinically hyperthyroid, but higher than average. And this. So not like clinically hyperthyroid, but higher than average. And this is actually also true for Europeans who are carrying the same genetic variant. We showed in another group of individuals

that if you have this gene variant, you have higher thyroid hormone levels and you have a larger spleen. So it's not just something that's true in the C-nomads. And so what we think is going on potentially, and this relates to the work that we did with mice as well, is that because of these higher, I hesitate to say elevated because that's a clinical term, higher

than average thyroid hormone levels, people are, the mice, the humans, whoever it is, are producing more red blood cells. And so now whether that's kind of stretching the spleen, because the spleens that we saw in the mice were larger but less dense, 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 what we saw in the C-nomads, increased the size of the spleen, increased hemoglobin, increased hematocrit, 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.

You're a runner, maybe there's a way, I'm not suggesting this as a protocol, that 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. But you said you have to be holding your breath 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 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 re-uptakes those red blood cells, but it does do that eventually. So maybe this is something that would be advantageous for short bursts 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 the work that we did in the mice where we replicated what we saw in these divers, they had larger spleens, they had higher red blood cell count, but they did not have any change in erythropoietin, which is how we normally think about changes

in red blood cell count. This is a drug that was really popular with cyclists for a while. People would self dose with erythropoietin and it would increase their red blood cell count dramatically to improve their performance. So this is like an erythropoietin independent mechanism of increasing your red blood cell count that could have an advantage in performance, I think. Fascinating. And then the other scenario is for robustness of one's immune system.

I for one don't like being sick. And if there's anything I can do to increase the function of my immune system, including sleep, exercise, sunlight, all those things, 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. Yeah, absolutely. And if sticking my face in a bowl of cold water, 50 degrees, 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 idiot that 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 that is generating the dive reflex can afford any enhancement in immune system function? I haven't seen any studies that look at that, but it would be really interesting because, yeah, I mean, like you, I also would do anything to not get sick.

And we do see in these populations a lot of older people who are continuing to dive, 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. She goes, no, wait.

She swims a mile a day four days a week, which is still pretty impressive. Swimming a mile is, yeah, that's quite impressive. Four days a week at 94? Presumably that's not backstroke. Some of it's, yeah, I think that, like, is there something to being in water that just generally is good for us? I would imagine. A shower, a bath, 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 so low impact and such a natural way to, you know way to move, to exercise that. Yeah, I think especially as we age, it would be a really wonderful way to stay fit and healthy. Has the size of spleens, or rather the genes related to what you're talking about, has that been correlated with whether or not people evolved from coastal versus more central regions of continents?

That's a really good question. We haven't looked at that, but it would be really interesting to see because, I mean, you know, the oceans are an incredible resource in terms of food availability, especially to early humans. So you would imagine that anyone living near a coast anywhere would take advantage of this resource. So it would be interesting to see if maybe coastal populations are more likely to carry the genetic variation 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. 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 humans in the past and now spend a lot of time underwater without a scuba tank. It seems to be that way, yeah, all over the world. Super interesting. So this isn't the only population you've studied. If you would, could you tell us about the recent work, the women – study on women in particular and I'm very interested in how this relates

to cardiovascular health. Yeah. So, you know, speaking of older divers, there's a group in Korea on an island called Jeju. These are all female divers. They're called the henyo, which just means sea women. And the average age of the henyo currently is around 70 years old. So that's when I think of robustness with age I think of the henyo. But this all-female diving population has likely been diving in that region for thousands of years. 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 Bajo in Indonesia. No wetsuits. No wetsuits. Well, now they wear wetsuits. 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.

So diving with no protection in extremely cold water. And as women, they're diving throughout pregnancy. So they're diving up until the day they give birth sometimes. 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? And there's just not really data, so we don't really know. Now we're starting to see, we're looking at the Henyo, we actually tracked some of their diving, and their dives tended to be much shallower, not really going any deeper than 10 meters, 30 feet, but they're also in their 70s, 80s even. We had an 81-year-old diver in our study.

And 30 feet's not nothing. We had a 20-foot deep end in the pool, recreational pool near my home growing up. And when you're down at the bottom, you feel significant pressure. You can let some air out to relieve some of that pressure, but 20 feet is 20 feet. 30 feet, and it's not a linear experience. Yeah, exactly. With every additional foot, you're really experiencing more and more pressure. So yeah, yeah.

And I shouldn't say it like that. It's just that compared to, you know, the Bajo have been documented to dive deeper than 200 feet deep. Oh, I'm not countering. I was just, I just, for sake of people out there who perhaps haven't spent time at the bottom of a pool, a 20-foot pool, 30 feet is still really impressive. It's very impressive.

And they're bringing a fetus down that low. Right. I mean, again, there's no documentation of how these women have been diving throughout their pregnancy other than we know that they were diving throughout their pregnancy. But yeah, presumably in their youth, they were diving to these depths with their unborn child inside them. So it's a really, I mean when we think about natural selection and evolution, something that's able to act on a pregnant woman has the opportunity to take out two generations if there's not genetic variation there that's protective. So it's like if we want to talk about really fast examples of evolution, it's anything that's acting on pregnancy.

And that's what we think has been happening in this population. I have so many questions, some of which are cultural, some of which are biological. I'll start with the cultural questions. Why in this culture is it the women specifically that dive? Are they revered? And are they diving for a particular resource that is, well, because it's underwater, presumably is not available elsewhere? But what are they diving for? We don't totally know. I have my own personal theory, which actually relates to the fact

that in a lot of places with cold water, so in Korea, in Patagonia, in Aboriginal Tasmania, it's all women diving. So I suspect that there's something unique about the physiology of women that makes us better at diving in cold temperatures. Where the men are afraid of the cold. It could be that too. I hear about a lot of guys that will spend dozens

of hours picking apart deliberate cold exposure when it would take them a fraction of the amount of the time to get into the water. In my experience, this is not a controlled studies, women are more tolerant of the cold at least in terms of being willing to embrace it the first time around. I have stories of, I won't say which countries, elite special forces, it wasn't the US, guys, in that case it was guys, being terrified of getting into cold water but otherwise being willing to do very, very challenging and indeed

very dangerous things. I know a woman who first cold plunged 10 minutes, she was just in there. In my experience, women are more willing to get into the cold the first time. And then now there's a lot of debate online about cold tolerance in the two sexes, but I don't – the data aren't really solid there. So maybe the men are just afraid of going underwater. It could be. These are some tough ladies, I will tell you that, even into old age.

My colleague, Ju Young Lee at Seoul National University, she's been working with them for a very long time, and she did a study where she was trying to find retired hynyeo. And the only ones she could find were over 100 years old, because they basically don't retire. They just die until they die, essentially. So she had these two women who were about three feet tall who were retired hynyeo, because those are the only ones she could find. They're 100 years old?

As we have this conversation, I think it's very important to remind people that correlation is a causation with all the obsession with longevity and living longer. I'm not going to rule out the possibility that getting into cold water, in particular diving or generating the dive reflex with cold water, doesn't have a longevity effect, but I don't think there's any direct evidence that it does. No, no. And yeah, I mean, it would certainly be interesting to explore, but I don't think there's any direct evidence that it does no no and I mean it would certainly be interesting to explore But I don't think there's any evidence so far other than anecdotal study

Yeah, the problem is that you need to do a very long study right and the other problem with longevity studies is You don't really have a good control group at least within subject because you don't know when you would have died right exactly Yeah, okay, so these Incredible women are diving up until their 70s, 80s? 70s, 80s, beyond, I guess. The oldest diver that I've personally worked with was over 80. But yeah, they're so athletic as they do it. But yeah, in terms of are they revered, I think now, yes, I think that wasn't always true. When Hanyo told me that in her youth, she was kind of embarrassed to be Hanyo. And a lot of it's because they're exposed to the

suns, they have darker skin than a lot of other women. They tend to be very loud because a lot of times they rupture their eardrums from diving. If they don't pressurize correctly, they can have hearing damage. So they're known for being very loud. And so I think there was kind of a marginalization early on, but now they're recognized as a UNESCO World Heritage intangible site, essentially. And there's just, I think, tremendous respect for the population now. Very cool.

What are they gathering down there? They are diving for all kinds of things. They're diving for sea urchin, abalone. They also harvest seaweed. I've seen them pull up octopus, they'll spear an octopus. And they do it in a very interesting kind of controlled way. Like they're really guardians of their marine environment, where they don't, they make sure that they don't overfish things.

So the sea urchin season is very short, because if they overharvest the sea urchin, that population won't replenish. So they have this system where they really take care of the marine environment. So it's all the proteins again. It's the expensive sushi. Yeah, oh yeah.

Umi, I'm still developing a taste for it. I'm trying, but. When it's fresh out of the Yeah, oh yeah. I'm still developing a taste for it. I'm trying, but... When it's fresh out of the shell, there's nothing better. I'm willing to try. Octopus, I have too much an affinity for cephalopods to eat octopus, but I have in the past, and it can be delicious. And so it's amazing to me if I step back

from these two populations, and I think more broadly as well about what people are willing to work for. Humans will work very hard to get protein. It's just kind of incredible how hard they'll work for proteins and lipids combined in delicious form. I mean, we're not aquatic animals. They're willing to risk their lives and the lives of their fetuses To the next generation right there's nothing

I think that a species tries to protect more than exactly and then the next generation one would hope That they're willing to risk their lives on a daily base multiple times per day to go collect protein basically yeah Yeah, and in these cold temperatures as well go collect protein, basically. Yeah, yeah. And in these cold temperatures as well. So do you think between on-land hunting and what you're describing that if we think about homo sapien evolution generally, that a big part of homo sapien evolution,

as it relates to selection of particular genes to drive particular traits and abilities, relates to this thing of just trying to get more protein and fat? I mean, it certainly could. Diet is an incredible driver of selection. So a very common example of natural selection is lactase persistence, so our ability

to continue to consume milk past infancy. And that happened very quickly in multiple different human populations. So it happened in Africa, and it happened in Europe. And another example is the Greenlandic Inuit. A huge part of their diet was marine mammals that have really high lipid content. And so they actually evolved to be

able to better metabolize those lipids so that it wouldn't kill them from heart disease or something like that. So yeah, diet as a driver of selection is extremely strong. So it may be that this has been shaping our species in ways that we don't even know. Super interesting. So in this group of Korean women divers, what's going on with their cardiovascular system? You know, earlier we were talking about how this might have implications for oxygen utilization

in the brain and body and potential disease treatment ramifications? Yeah, so we found two different adaptations. And I say adaptation, but there's kind of adaptation in a physiological sense, this thing that you can do by training, or adaptation in a genetic sense. And we have found one of each. So the training adaptation that we found was that, I mentioned before that when you dive,

your heart rate slows down to try to conserve oxygen. So the training adaptation that we found was that I mentioned before that when you dive, your heart rate slows down to try to conserve oxygen. So their heart rate through a lifetime of training slows down even more. So we could actually – you could visually see this when they were doing these dives. Watching their heart rate, you could just see it plummeting. We had one individual whose heart rate dropped more than 40 beats per minute in less than 15 seconds. So really dramatic.

And the reason that we think that that's a training adaptation rather than a genetic adaptation was that it was only true in the divers. So non-divers with the same genetics didn't have this phenomenon. So that was – I mean that has – it's interesting to think about how – what the potential health benefits of that could be. I mean, it's clearly something that you can train. This has also been observed in other competitive breath hole divers.

But in terms of how that could benefit your health, I mean, maybe it's good for your heart to have that kind of plasticity in terms of its response. Yeah, when I think about heart rate, I think mainly about autonomic function. And again, vagal innervation seems to be a theme there, that the vagus is responsible for slowing the heart rate down.

Anytime we exhale through, you know, respiratory sinus arrhythmia, we essentially slow our heart rate down. It's the fastest way I'm aware of to consciously slow our heart rate down. So as one dives, I guess if they're exhaling, letting out some air, dumping some carbon dioxide, which is probably a good thing if you're a free driver I don't want to encourage people to do this because it shuts off the gasp reflex that would have you you know jolt to the surface But assuming no one's gonna go out and and and try this by dumping air you're you're You're exhaling exhaling slows the heart rate, but not 40 beats per minute. Yeah, it's usually a fraction of that

Yeah slowing slows the heart rate, but not 40 beats per minute. It's usually a fraction of that. Yeah. And so then we also found this genetic adaptation that we think is driven by the fact that they're diving through pregnancy. So when pregnant women have sleep apnea, which is where you hold your breath in your sleep, so it's kind of, you can think of it as unintentional diving through pregnancy, they tend to develop these blood pressure related complications. So like preeclampsia, they're just, they call them hypertensive disorders of pregnancy. And so we think that, there's no studies that have shown this yet,

but we think that if you're diving, different kind of apnea through pregnancy, that would also increase your risk for these disorders. And so what we saw was that there was a genetic variant that was actually driving their, like a lowering of their diastolic blood pressure while they were diving. And so we think that this is protective against these hypertensive or high blood pressure effects. That's interesting. So for non-divers, so for pregnant women on land

who aren't from this population, the picture I'm getting is that they're sleeping on their back, perhaps because it's more comfortable as they get very pregnant and their airway is getting cut off at some point. So they're having these hypoxic episodes. And then there's some gasping as the carbon dioxide gets high. This is also, incidentally, what people who are overweight or, by the way, people with very big necks. This is why a lot of big-ne you're not going to be able to sleep early.

You're going to be able to sleep early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to be sleeping early. And that's why you have to be aware of the fact that you're going to die early, but make sure you're breathing right at night because sleep apnea is very dangerous. It is, yeah.

I think we think of it as just snoring, right? But it's super dangerous. Yeah. You're putting yourself into a state of hypoxemia, so your oxygen is very low. So for pregnant women who are concerned about hypoxia, what are the options that they have besides becoming a diver and joining this incredible community in Korea? Yeah, I mean, I think, well, that's

one of the things that we're hoping to find from studying these women. So if they've evolved some kind of protective mechanism that protects them in the case of apnea, maybe that's something we could develop into a therapeutic that could be used to help prevent that same hypertensive disorder of pregnancy in pregnant women who have apnea for other reasons.

But otherwise, I would say, I think preeclampsia used to be a death sentence for mothers and fetus, which is why it was such a strong driver of evolution. Now, I think awareness of it enables treatment. But that's only something that's happened in the last, you know, I don't know how many decades. So that's why it was, it could have been such a powerful force in this population. Uncomfortable topic, but I think an important one.

Earlier, you were talking about genetic selection and what determines survival of offspring. Is it the case that many miscarriages, if not most miscarriages, are because the mutations that arise would have been destructive at some point postnatally, after birth? So it's a kind of a nature's veto on the genetic program. Yeah. I mean, you know, I'm not a maternal health specialist but I do know that most mutations create non-viable embryos and so yeah, that's I think that could certainly be driving the early miscarriages especially.

So it could be pre-implantation or post-implantation, a mutation arises and somehow the genetic programs of embryology are somehow made aware that down the line this is going to lead to a stillborn fetus or something. So I mean, nature doesn't have a conscious logic in the same way that we think, but the genetic decision therefore is to stop, is essentially a stop cell proliferation and the pregnancy is terminated. Yeah, because I mean, a lot of proteins are involved in many, many systems. And so if you have a mutation that's problematic in one of those proteins that's involved in all these different systems, it's just going to start to go haywire very early on.

I'm very curious about how these genetic adaptations and how they relate to behavior impact organs versus things on the surface of the body that we can see versus both. I don't know if this is true, but long ago I heard that, and I don't want to scare anyone because it's not true in every case. I'll repeat, it's not true in every case.

But I was told by a friend of mine who's a physician that a lot of the wine spot pigmentation of the surface of the body, like a baby will come out with a very dramatic like wine spot pigmentation of part of the face or the head, sometimes not always is correlated with mutations in internal organs. And this is having run a mouse lab for a long time. You study mouse mutants, mice that overexpress or lack or are hypomorphic for a particular gene and you learn as you work with one of these populations that oftentimes the mutation that impacts a retinal development for which I need to take the retina out, look at it under a microscope and find which cells are miswired or something like that, correlates with something

on the surface of the body where you go, oh yeah, the ones with the curly tails, those are the ones that are likely to be the mutants. You still have to do the genotyping. You still got to send out DNA and, you know, or analyze DNA. Nowadays you send it out. But in the old days we genotyped our own mice. And what you find is that oftentimes there are these peripheral markers of central issues. I'm also interested in the inverse of that, where there are peripheral markers of central advantages. So in these populations that you studied, they have these larger spleens or this ability to dive deeper and longer, can overcome hypoxia through a drop in heart rate.

Is there anything about their external appearance that isn't about soft feet or exposure to the sun that tells you like this population is different? They look different in ways that we don't expect different populations to just look different. Does that make sense? Yeah, absolutely. Yeah. And I mean, to your point, like the phosphodiesterase that we found that was evolving in the Bajau,

phosphodiesterases are involved in so many different functions. And so there are chances for these mutations to affect not just the systems that we're interested in, but other systems as well. I mean, in both populations, the people look incredibly fit and athletic. And they tend to have just a very robust appearance. Now, is that because they're diving every day? And there aren't that many 70-year-old women

who are jumping off a boat every day to go to work? Or is it something related to their genetics? I don't think we know yet, but it would be really interesting to look into that more. The reason I ask this is that, as we were discussing at the beginning of today's conversation, mate selection, we think of they smell so great,

we like them for this reason, we like them for that reason, and there's the conscious choices that we're making, and then there's all the stuff working below our level of them, they smell so great, we like them for this reason, we like them for that reason. And there's the conscious choices that we're making and then there's all the stuff working below our level of consciousness like, oh, they smell great and you're actually selecting at least in part for their immune system and the potential immune system of offspring. Even if you decide you never want to have children with this person for whatever reason, this stuff is happening in parallel, consciously and unconsciously. And so when I think about, you know, the ability, the special abilities of different populations at the level of internal organs, like a spleen ability, you also have to wonder if this is

represented at the level of, you know, I don't know, like the, I mean, it could be anything, right? I mean, it could be the ones with the better spleens have really nice hands. I mean, and you don't think about it, you don't think to correlate those things. But as in the example I was discussing with the mice in a laboratory, when you get mutations that you know impact an internal organ, almost always there's something about, you know, they might have a particular fur pigmentation pattern, assuming it's a whole body mutation.

Or sometimes they'll have like one webbed toe or they'll have a pinkies that, pinkies is mice, they have a little back puff digit that faces in not out like the others. And so you learn when you work with these things to say, those are the good ones, those are the mutant ones. Or in some cases, those are the good mutant ones, right? And I think as humans, we don't tend to do this consciously. It's not how we're trained to think, thank goodness. That would complicate all the dating apps.

People would have to show their digits and Lord knows what else. But human mate selection is in part genetic selection. So what are your thoughts on this in terms of how these things correlate with human choice and behavior? I'm asking you to speculate here, obviously. I think that certainly, you know, I mean, we know that these populations have been evolving. We have theories as to what is driving that selection, but there, I mean, could be sexual

selection. It could be like you're saying, like that people carrying this genetic variation that happens to also make them a good diver in ways that we expected to find, also make them more attractive in ways that we weren't even looking for. And we weren't even thinking about pregnancy, really, when we started the study with the Henyo.

It wasn't until we got these results and we're saying, what is this difference in blood pressure? And speaking with maternal health specialists, that we really pieced it together. So I think it's the kind of thing where, yeah, you just, you don't even really know necessarily all of the pieces of the puzzle. And that's where it's a lot more questions for us to ask in the future. I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a function member after searching for the most comprehensive

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There's so many things related to your mental and physical health that can only be detected in a blood test. The problem is blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function Simplicity and at the level of cost. It is very affordable.

As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com slash Huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman podcast listeners. Again, that's functionhealth.com slash Huberman to get early access to Function. As long as we're talking about diving underwater as a vision scientist, that's where my initial

training was. I have to ask about vision underwater. Do these two populations use goggles? So now they do. Okay. But I mean, you can imagine goggles haven't been around that long. So at some point in the past, they didn't. And the study that first got me interested in this

was a study done in Mokin children, where I think it was literally a researcher who was on vacation in Thailand noticed these little kids diving for things and having this ability to see underwater and set up an experiment and had European children and Mokin children diving to look at things underwater. And the Mokan children had better eyesight underwater than the European children.

Now that same researcher, after publishing this paper, went back to Europe and trained European children to do the same thing, essentially, to perform at the same level as these Mokan children. And so, you know, there was this kind of dismissal, like, oh, well, you can train Europeans to see underwater just as well. So it must not be evolved.

It must not be genetic. It has to just be training. But I think that's a logical fallacy that has stopped a lot of, or has prevented a lot of research from being done in these populations. Because just because you can train someone to be at the same level as someone else doesn't mean that that person didn't have an advantage And so I think that's a yeah

I mean there definitely there's a difference in their vision and what causes that I think we still don't know so interesting, I'm just gonna take one minute and explain to people the underwater thing because I Find it fascinating that the surface of the eye is rounded, obviously. People get that. And that's what allows you to refract, to bend the light to a single point so that things look nice and crisp. And when you're underwater, the water essentially fills in the roundness around it.

The air does, of course, above water as well. But because of the similarity and basically the density of the water and the surface of the eye even though they're different, you get less of a bending of the light to a point. So the reason I'm saying this, the reason I'm giving this very crude lesson in optics is there were really two possibilities. One is that kids that dive a lot in their youth have a flatter eye, right? If you think about a goggle or any kind of underwater scene device, you're basically

putting air between the eye and the water and you're making it flat. So the idea that the eye would become more flat through diving isn't inconceivable. I suppose it could happen. But it makes perfect sense to me as to why the European children could do this also because you train it enough, it turns out it's the ability to constrict the pupil down really small that can account for this adaptation. It's Truck Month at GMC. Tackle the open road with added confidence in a 2025 Sierra 1500 Pro Graphite at 0% financing

for up to 72 months with an available 5.3-liter8 engine 20 inch high gloss black painted aluminum wheels off-road suspension with available 2 inch factory installed lift kit plus a towing capacity of up to 13,200 pounds you'll be ready for anything this truck month. Truck month is on now ask your GMC dealer for details. Ask your GMC dealer for details. So I wouldn't have thought that diving underwater and learning to pick up small objects underwater would make the eye more flat, kind of like wearing a goggle underwater. But the point you make is an extremely important one because if you take a population that is already afforded some sort of potential genetic advantage and you train them even further, that's when you get X-Men-like behavior. afforded some sort of potential genetic advantage and you train them even further Exactly, that's when you get x-men like behavior. Mm-hmm. This is really all about the x-men Yeah, right and women as you clearly pointed out. Yeah, and I think that brings us to this question of Like human super performance. Mm-hmm. I think about the fact that almost always when I see a marathon winner nowadays

the fact that almost always when I see a marathon winner nowadays and I think about is it Elio Kipchogi, sorry my my my normally I don't bring them into the the frame consciously here but for the audience here but I my producer and business partner at the Human Lab podcast is a triathlete what is the guy's name? Elio Kipchogi. Elio Kipchoge set the marathon record with it with mile times on the order of? 435. 26.3, 26.2 miles at you know somewhere in the four and a half minute mile pace continuously. Incredible. So he represents among the pinnacle of that sport.

Almost always when we see these incredible endurance runners, they seem to descend from specific regions of the world. Can we talk about why that's so? Are they inheriting some sort of red blood cell trait? Is it the light-bonedness combined with that? What leads to incredible human performance? I know you're a runner, your husband's a runner, so how much hope is there for the rest of us

and why is it that folks like Iliud are so unbelievably spectacular? You know, I would love to look at that scientifically. He's absolutely incredible. I mean, breaking the two-hour marathon record is also just unbelievable. But I think there have been, I'm not as familiar with this literature,

but there have been studies looking at the proportion of bone lengths in certain parts of Africa especially. It's also interesting to note that a lot of these really talented runners come from Ethiopia, where there are highland areas where humans have actually adapted to altitude. So in addition to some of these biomechanical advantages, they may actually also have physiological advantages

that enable them to run faster. But yeah, I think this is an excellent example of there's clearly something biological making people from this part of the world really excellent runners. And just because you can train a European runner to compete at nearly the same level, that doesn't mean that there's not something special about people like Kipchoge.

And so this comes up a lot with the Bajo as well because people say, oh, well, they don't hold the free diving depth record. It's like, well, yeah, but they're not training to hold that record. They're training, they're diving just to collect food for their families. They're not training. So what would happen if we did train them? I think it's – yeah, it's a great point. If we take this out of the realm of physical performance and we take it into cognitive

or mathematical performance, I feel like there are some fun thought experiments we could do. Before we started, you were talking about your time at Princeton as an undergraduate seeing John Nash, you know, famed for sadly having schizophrenia, diagnosed schizophrenia, the topic of the movie Beautiful Mind with Russell Crowe. But at the same time, having incredible abilities based on presumably things that either correlate with or just by chance run in parallel with the schizophrenia. Who knows what's driving what, or if they're in parallel.

We have examples, again, I'm pulling from movies like Rain Man where there's a person has autism of a type that makes social interactions very challenging. But in that example, which is I think representative of at least some people with autism, extreme mathematical calculation abilities, especially in the physical space, being able to see things and count them very rapidly. Last example I'll give is there's this math competition held in India where the kids can update the numbers

by moving their hands with a sensor on it, and they're adding the numbers very fast. And you just see this kid basically spooling numbers, spooling the numbers, spooling the numbers. At the end, they get one opportunity to answer the addition of this immensely long string of numbers correctly, and this kid nails it. And you go, whoa, like he's adding things very fast, presumably through some training.

But is it possible, is it within the realm of reality, based on what we know about human genetics that there could be genes that select for, say, rapid updating of visual scenes combined with short-term memory or whatever duration of memory is required that would afford certain people certain advantages in this based on inheritance that's then combined with training. Much in the same way that the ability of the spleen to expand if you dive a lot and you happen to be born in one of these communities that we've been talking about. Is that possible? Yeah.

I mean, I think certainly, you know, I mean, there's an interesting correlation between people in STEM fields and having family members with autism. And so I was actually at a lecture in Princeton where the professor asked the incoming class of students how many of you have a family member with autism and then of those, and he displayed the statistics, how many of you are joining the engineering department. And it was much higher amongst engineers.

And he explained that this can have to do with the fact that people on the spectrum tend to have an ability to hyper-focus and that actually makes you have an ability to hyper focus and that actually makes you, the ability to really kind of narrow yourself to this one thing can make you a really good engineer. And so in that way it's a huge advantage because it's allowing you to succeed in that field depending obviously where you are on that spectrum and how that affects you in other ways.

And so if that in some way is giving you an advantage, why wouldn't it be selected for? Of course, there are other ways that it could be a disadvantage. Oliver Sacks, I think, wrote about how people with Tourette's may have faster processing speeds. And so again, maybe this is a place where that is advantageous, despite the other disadvantages that might come along with having that syndrome. Huge Oliver Sacks fan here.

He's amazing. I'm sort of becoming a historian of him, an informal historian, and he also loved to spend much of his time underwater. Oh, did he? I didn't know that. Yeah, he was an avid diver and snorkeler and scuba diver and I think in part, he said, because it's so quiet down there. Incidentally he had propozsagnosia.

He couldn't recognize faces. I think I have that, right? I've known a few other people with that. And propozsagnosia, the inability to recognize faces also seems to correlate with this, for lack of a better way to put it, kind of nerdy, quirky phenotype. A former advisor of mine had this. Although in part I thought he told us that because then it gave him an out anytime

he couldn't remember somebody's name. The disorder. Yeah, it's a great thing to put forward if you can't remember people's names. No disrespect to the actually clinically diagnosed people with propozygnosia. Gets you out of a lot of having to remember things. Yeah, I find this fascinating because in this day and age

of pathologizing everything, it's interesting to take, as you just did, and I really appreciate taking a step back and saying, yes, there are instances where people on the spectrum have, you know, they need assisted living their entire lives, but there are also people who are living, you know, incredibly productive lives, even making incredibly enormous, meaningful, and uniquely meaningful contributions to society who we would say are probably on the spectrum. And so the question then becomes to what extent is it genetic? To what extent are genes driving a proclivity for numbers or a proclivity for engineering?

And on the opposite side, like, are great creatives, are they carrying a different set of genes or are they just the ones that can't pay attention to anything so they start throwing things together? You know, that was a joke against the creators. It's interesting because it becomes a really difficult thing to test because how do you measure creativity in a way that you could then link to genetic information? So a lot of these kinds of understandings of genes come from things called genome-wide association studies, where essentially they perform a correlation at every site in the

genome to see which of these sites correlate statistically with whatever phenotype it is. So whether that's kidney disease or creativity. But you have to have a really good way of quantifying that trait. So creativity is nearly impossible to quantify. Something like mathematical ability, there's so many potential environmental nurture factors that could contribute to how that manifests in an individual that it also becomes quite difficult to quantify,

and therefore difficult to find any genetic factor that's contributing. It's so interesting how we classify intelligence. You know, in some years back there was a lot of debate about IQ versus emotional intelligence, but there's this wonderful documentary. By the way, there's several movies by this title, but the one I'm thinking of is the documentary Spellbound, which is about the spelling bee competition and it was the case for a long time that how well and how quickly kids could remember to spell certain

words was thought of as some important correlate of intelligence which is kind of crazy in now in the day an age of autocorrect and things like that but one could argue that being able to spell is an interesting one but that the different kids that they detail one from a farming community, one from a community where the parents were really hard driving about academics, it tiles the entire representation of every kind of background you can imagine. Different types of parents, blue collar parents, highly educated parents, boys, girls, one that set that's clearly on the spectrum and you see it in the family.

You can see that and everything in between. And what you come to realize is that training effects are very real. Like if you take a kid in particular and you give them an activity and they repeat that activity, no surprise here. They get very good at that. But it also narrows the number of things that they can also be good at. This is what I think we forget about neuroplasticity is that the choice to get very good at one thing is also the choice to not get good at a bunch of other things.

So when you step back and I'm not going to ask you for parenting advice but when you step back and you think about what you know about human genetics, is there a kind of a assuming one doesn't have to hunt for their food the way these populations you've been studying do, is there a kind of an optimal way to think about kind of genetic bias and what we perhaps should focus on or are you an equal opportunity to get after whatever interests you the most kind of person? I mean, you know, there's like companies where you can test yourself to find out what kind of athlete you should be.

And I think that kind of gets into something called genetic determinism, which is this idea that your genes determine everything about you, which we know isn't true. We know that it's a combination of, you know, genetic factors, environmental factors, all of these different things. But I think it's interesting how much the idea that we're genetically predisposed to something or we're genetically better at something can actually influence how we are at that thing. So we talked a little bit before about there was a study where they told people, they said

we're going to take your DNA, we're going to genotype you, we're going to find out whether if you train you're going to get faster or whether it's not going to genotype you, we're going to find out whether if you train, you're going to get faster or whether it's not going to affect you at all. And so they did that, and they put people into these groups, and then they tested them after a few months. And the people who they told were going to do better did better.

And this was something they can measure at the biological level. They could measure specific molecules that had changed in that population of people compared to the other group of people. Now the trick was that there was no difference genetically between these groups. It was just what they were told. So it's really interesting to think about, you know, if you tell a child what they should or shouldn't do based on, you know, their genes, I think that's a really dangerous thing. Or potentially you could motivate them through that. So interesting. I mean, I think that's a really dangerous thing. Or potentially, you could motivate them through that.

So interesting. I mean, I think mindset effects are so important, under discussed. I'm so glad this is coming up. Ali Crum was a guest on this podcast. And she shared with us some incredible data on it. You tell people that stress is good for them. You stress them out, their health improves. You tell that stress is good for them, you stress them out, their health

improves. You tell people stress is bad for them, you stress them out, their health gets worse. And on and on. There are just so many examples of these. Most of the time, people aren't taking a genetic test to determine whether or not they're likely to be good or bad at something. They're looking at their family photos or they're looking at their parents or their grandparents.

This is the old version of genetic information. And I'm guessing here too, one should be very cautious. If your parents weren't athletes, does that mean that you don't have the genes to be a great athlete? Clearly the answer is no. Likewise for intellectual pursuits. We really have very little evidence that intelligence is heritable. So I think that's a big one, especially

if you feel like you're not coming from a very intelligent family, that doesn't mean anything, really, based on what we know currently. What about rhythm and dancing ability? Oh, man. I don't know. But I'll tell you, I did not inherit any rhythm from my dad. I didn't inherit any rhythm from my dad or my mom.

Although my dad is a bit more musical by virtue of being more mathematical. But that is not the same thing as dancing ability. I don't know if we have any truly bad dancers in our family, but we have at least one with exceptional rhythm and ability. She happens to be adopted. So there you go. There you go. Yeah.

That's a different version of genetic variation. And an important one in the sense that it's a cross fostering experiment. Exactly. To put it in animal laboratory terms. If you don't mind, I'd like to talk about the ethics of genetics and genetic engineering. A few years back, a guy in China running a laboratory used CRISPR to modify the genome of babies. I believe he mutated the HIV receptor. I believe it wasn't to prevent them from contracting HIV under any

circumstances but rather the relationship between the HIV receptor and some things related to human memory. That was the speculation. There was very little known about this because this was happening in China in a kind of a closed format. It wasn't published in a peer-reviewed journal but he showed up at a human genetics meeting and he announced to the world that he had genetically modified babies through the use of genetic engineering Now on the backdrop of this up until now

We've basically been talking about genetic selection through partner selection through all sorts of things so that there are kind of indirect ways to Genetically select I think people forget that but here we're talking about deliberate gene insertion or removal in embryos creating genetically modified humans. After he did that, there was a sort of pause, as I recall. I was paying very close attention to this, as to whether or not the international community of genetic ethicists and scientists would say, wow, this is potentially a feat of human engineering that could prevent disease, etc., etc. Or they were going to chastise him and it turned out they chastised him. And as it were, we were told that he was actually put into prison.

Now whether or not that prison included a laboratory, we don't know, right? We have no idea. And there were a few other countries that chimed in and a laboratory, we don't know, right? We have no idea. And there were a few other countries that chimed in and said, oh yeah, you know, programs like this have actually been underway elsewhere for a long time. And then it just went silent. Right now, the idea of the use of CRISPR to improve babies or to protect them against potential diseases is not commonplace or if it is it's not discussed. What are your thoughts on the use of CRISPR

to protect children from certain diseases? Let's just put in that domain and then of course we could talk about the misuse of this but you know you could think of parents who are maybe carrying a mutation they don't want their kids to have Huntington's, for instance. And you could potentially fix that gene. So I'm just going to cast all of that out there to give that kind of backdrop and get your thoughts. And there's clearly no right or wrong answer here.

But this is very likely to be a big topic in the upcoming decade. Yeah, I mean, it's a really great question, and I think one without a very good answer at this point. I think one of the things holding back this discussion up till now is that CRISPR is still a little bit of a blunt tool. You know, we're not, we haven't, like the way that we're applying it isn't as precise as we'd like it to be

to do the kind of gene editing that you would need to protect babies in the way that you're describing. And there are things like off-target effects, they say. So you're trying to edit one very specific part of the genome, but it ends up editing places that you didn't intend it to edit. So that's kind of one of the issues, I think, technologically that... I think if I remember right when that happened, people were a little bit like, that technology

isn't ready to be used in that way yet. But of course, that's something that is changing really rapidly. We're getting so much better at this. We're able to do it successfully in lab animals. And so, yeah, ethically, I mean, it's just, I think it's also interesting to think about enhancement versus correction. Like at what point, where's the line between those two? So if we're correcting some kind of genetic defect, first of all, some defects,

other people might not even see them as defects, they might just see that as variation amongst humans. So where's the line between defect, normal, enhanced? And so it's, yeah, it's, I don't know who would make those decisions once the technology is even available to apply that in unborn children. I mean, of course, it would be a dream to prevent disease using these technologies, but it's a slippery slope maybe. Yeah, there's a lot of debate right now online

about some of these companies that allow for a deep sequencing of embryos. I mean, in particular in cases of IVF, there's a company I believe is called Orchid up in the Bay Area that's kind of foremost in this where typically for IVF or even for natural pregnancy, there'll be an analysis of like is there trisomy like you know extra chromosomes which we know can lead to Down syndrome etc.

But these companies for a price offer deep deep sequencing of genes that correlate with right they're not causal in many cases. Sometimes yes, but oftentimes correlate with you know potential spectrum phenotypes or you know things of that sort. Cancer susceptibility, BRCA mutation, right? I know several people unfortunately that died from cancer and they carried BRCA mutations. So there's a, this is real stuff. I think that the challenge for a lot of people is that as it stands now, it's very costly. So it sets up a scenario where wealthy people can afford to analyze embryos more vigorously than people who don't have the means to do it.

But if we look back 10, 20, 30 years, the means to do it. But if we look back 10, 20, 30 years, you know, getting your whole genome sequenced in the early 90s, when Venter and those guys first nailed that ability, something like that. I'm thinking 90s sometimes, okay, maybe I'm a little early or a little late on that one, but it was extremely expensive. But now it's like, what, 100 bucks? Or even free in some cases. Yeah, depending on the coverage.

Yeah, you can sequence a genome for pretty cheap these days. Yeah, so most technologies tend to advance that way. So it gets back to also this issue of how much information do you want. And so I guess given your training and understanding of human genetics, there's obviously no one size fits all answer. But when it comes to understanding how much control to exert over the genome, where do

you land on this? I'm not trying to put you in the hot seat here. I think people are going to hear more about these technologies and just want to understand how to frame them. Yeah. Well, first of all, for context, I only have dogs, so I don't have to think about this in terms of human babies. But yeah, I think, say you get your baby's genome sequenced and that baby is going to be blind. Is that a problem? A lot of blind people would say no. So, you know, it's, I think it's such a personal question.

No, I think that's a great answer. I think it's a really hard question to answer for any of us. But I appreciate you being able to look at it and consider it dog genetics is fascinating. There, the selection seems to be for phenotype, but also behavioral type, which is fascinating. Yeah, my fur babies were 100% selected to be cute. That was the basis?

It was the eye contact? For that, yeah, I mean, actually, literally, one of my dogs is a type of dog that was bred to be a companion. So the only thing that they selected for was cuteness and companionship. This is the Bolognese? Yes, that's right, yeah.

There is a dog named after the spaghetti sauce, or vice versa. Yeah, named after Bologna in Italy. Right, that's right, yeah. There is a dog named after the spaghetti sauce or vice versa. Yeah, named after Bologna in Italy. Oh, right, no, I was joking. Tell us, what is the breed of dog? Bolognese. And it's a mix between? It's in the family of like the Maltese Bichon Cotone family,

so these little fluffy white dogs that are in Renaissance paintings, sitting in the laps of royalty. It strikes me that whether or not we're talking about Mendel's peas in the garden, whether or not we're talking about dogs, whether or not we're talking about corn varieties, or we're talking about humans, that for some reason we like to underestimate the power that genes and natural selection have. And behavioral selection, I guess, is the more appropriate term, right?

I'm very curious about this concept of ad mixing. If you could explain what ad mixing is. And what I'm getting at here is probably the biggest question for me, which is, are we all really one species? I mean, I like the idea that we are all one, collective consciousness and unity and peace on earth. Awesome. But really in a serious sense, is homo sapiens one species?

I mean, there's a lot of genetic variation. And so if you could explain ad mixing, and if you're willing to go out on a limb and address whether or not there might be multiple species of Primates walking around that we say that's a person but they might be that much different than us When does fast grocery delivery through Instacart matter most when your famous grainy mustard potato salad isn't so famous without the grainy mustard When the barbecues lit but there's nothing to grill when the in-laws decide that actually they will stay for dinner. Instacart has all your groceries covered this summer, so download the app and get delivery in as fast as 60 minutes.

Plus, enjoy zero dollar delivery fees on your first three orders. Service fees exclusions and terms apply. Instacart, groceries that over-deliver. Yeah, so starting with admixture. Admixture is just when different ancestry populations mix. So it's kind of this relative term, because if we're all descended from one ancestral population, then maybe we all have one ancestry.

But I always like to put it in the context of myself. So my dad is 100% Italian. My mom's a mix of Northern European. I am an admixt individual, you know, if you think about it that way. And the reason that this is important in genetic studies is that if I claimed to be Italian and were included in a genetic study of Italians, the genetic variation that I have coming in from my mom's side would confuse that analysis.

So admixture creates a ton of problems when we try to do genetic analyses. And so that's generally why we try to quantify it in genetics. But yeah, you know, when we're talking about, it depends on kind of what scale, because I'm 100% European, so in that way I'm not admixt if we're talking on the scale of continents. So it becomes kind of a blurry concept of admixture, depending on what level we're looking at. But as to your question of whether we are all one species, I would say I've actually

– this is not the first time we've been asked this, especially given these, you know, we call them superhuman populations, these people who have these extraordinary abilities, extraordinary physiology that makes them really good at what they do. I think the thing to keep in mind is that some of that variation can come from just a single base pair of difference. I mean, a lot of times it's multiple genetic changes that create the differences between individuals.

But like when you think about eye color, that's just one genetic variation or genetic variant in some cases, like the case of blue eyes, you know, so you could be exactly the same as someone else, except for this one change out of 3.5 billion, you know, so does that, like at what point do we need enough genetic diversity to call a group of humans a different species? And I don't think that's something that we see anywhere

on the planet that I know of. Well, this has been incredibly illuminating. I've learned so much and I know everyone listening has as well. I don't think we've ever had a discussion about these topics on this podcast in a solo episode or guest episode. You're truly the first person to come on here and talk about human genetics. And these incredible populations that you study are not only interesting in their own right

but they really shed light on the interplay between culture, selection, behavior, genetics and basically what's possible in terms of human potential. They also have important relevance to human disease as you mentioned with the hypoxia work. It also shines light on something that I don't think we can get enough of which is the incredible things that humans are capable of in these very different populations that grew up and continue to exist in ways that are so different than us. I think it can't help but turn the mirror on ourselves and ask ourselves like what are we doing in our daily lives behaviorally?

How might that be impacting our genes and to start to speculate about that in constructive ways. So I just really want to thank you for coming here today and sharing your knowledge for the incredible work that you're doing. To be honest, I'm envious if I were ever going to do a sabbatical. I don't think I'll ever have time to take the sabbatical that I've been accruing. But if I ever did, I'd love to study one of these incredible populations and try the free dive thing.

It's really wonderful work and it's having a huge impact. It's in the news often, as we'll put links to and recently as well. I'm not going to ask you what you're on to now and what's coming next because we'll save that for a future installment. But I just want to really extend my gratitude and on behalf of myself and all the listeners, thank you so much for the work you do and for educating us. Thank you so much for having me and you're welcome in the field anytime. Awesome. I'll take you up on that. Thank you for joining me for today's discussion with Dr. Melissa Lardo. To learn more about her work, please see the links in the show note captions. If you're learning from and or enjoying this podcast,

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