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Dr. Melissa Ilardo on Huberman Lab: Why Behavior Alters DNA

Spleen size expands through behavioral pressure in one generation; Ilardo explains the dive reflex, epigenetic marks, and how these traits pass to descendants.

Andrew HubermanhostDr. Melissa Ilardoguest
May 26, 20251h 52mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:00 – 2:35

    Melissa Ilardo

    1. AH

      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 Elardo, professor of biomedical informatics at the University of Utah. Dr. Elardo 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 discuss the current state and ethical considerations of gene editing in humans, something that's apt to be an increasingly important topic in the years to come because gene editing in humans is now possible and is happening. As you'll soon learn, Dr. Elardo 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

  2. 2:35 – 7:06

    Nature vs Nurture, Gene Expression, Eye Color

    1. AH

      Elardo. Dr. Melissa Elardo, welcome.

    2. MI

      Thank you.

    3. AH

      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 it's nature, some of it's 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.

    4. MI

      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 in these things that we thought were totally predetermined in the past. Um, and so, yeah, I think, uh, we're still learning with epigenetics and all of these new fields just how much we can actually change things. Um, there are, of course, things that are kind of written in our genes, but, um, I think we're learning that there's a lot more that we can change.

    5. AH

      Most of us at some point in high school, um, learned Mendelian genetics, right? Mendel the monk and his peas in his garden. Um, most people probably don't remember the details of that, but we also learn about eye, eye color. You know, it, it's, uh, you know, commonplace for people to understand that if both your parents have dark eyes, uh, with very rare exception, it's unlikely that you're going to get light eyes, uh, 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, uh, and yet that there are aspects of our parents that are not seen in us at all and vice versa. And so I think for most people when we think about genes, we 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 or relatively quickly by doing something differently?

    6. MI

      Yeah, um, just going back to eye color 'cause this is just one of my favorite genetics, um, facts, so everyone with blue eyes descends from the same person. Um, so at one point in human history, one person had a change in their eye color, and it's just, like, amazing to imagine this person who had blue eyes for the first time, um, and then through many generations, probably because that was a very attractive and interesting feature in that individual, you know, that spread throughout human populations as we know them. So I always just find that to be fun about blue eyes.

    7. AH

      So there was a blue-eyed F1 as we say-

    8. MI

      That's right.

    9. AH

      ... like the, the, the first.

    10. MI

      Mm-hmm.

    11. AH

      Um, uh, let's stay on eye color for a moment 'cause I, uh, before we get into, uh, how genes can be modified by behavior.Um, I've been told that gr- the green eye phenotype is one of the more rare eye colors. Is that true?

    12. MI

      I think that's right, yeah. I think it's the most rare.

    13. AH

      Okay. So, and can we assume that there was an original F1 brown-eyed person that gave rise to the entire lineage of brown eyes subsequently?

    14. MI

      Yeah, I think in the history of humans as a species, I think that was our original eye color. Um, and so then, yeah, having these other eye colors, um, arise in the population, um, created these events. I think green eyes, if I'm not mistaken, there were multiple people. You know, that comes from different genes from different individuals in the history of humans. Um, but yeah, blue eyes is just this one individual.

    15. AH

      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-

    16. MI

      Is that right? I didn't know that.

    17. AH

      ... regardless of where they start.

    18. MI

      Interesting.

    19. AH

      Yeah. So, like, a blue-eyed baby will have much bluer eyes at birth-

    20. MI

      Right.

    21. AH

      ... than it will at age 15, at age 80, for instance.

    22. MI

      Mm-hmm. Yeah.

    23. AH

      And we believe that's due to, uh, changes in pigmentation because of, of UV exposure.

    24. MI

      That's really interesting.

  3. 7:06 – 10:24

    Sponsors: Joovv & Eight Sleep

    1. MI

    2. AH

      I'd like to take a quick break and thank our sponsor, Joovv. Joovv makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, it is the incredible impact that light can have on our biology. Now, in addition to sunlight, red light and near infrared light sources have been shown to have positive effects on improving numerous aspects of cellular and organ health, including faster muscle recovery, improved skin health and wound healing, improvements in acne, reduced pain and inflammation, even mitochondrial function, and improving vision itself. What sets Joovv lights apart and why they're my preferred red light therapy device is that they use clinically proven wavelengths, meaning specific wavelengths of red light and near infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv whole body panel about three to four times a week, and I use the Joovv handheld light both at home and when I travel. If you'd like to try Joovv, you can go to Joovv, spelled J-0-0-V v.com/huberman. Joovv is offering an exclusive discount to all Huberman Lab listeners with up to $400 off Joovv products. Again, that's Joovv, spelled J-0-0-V v.com/huberman to get up to $400 off. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure a great night's sleep is to make sure that the temperature of your sleeping environment is correct, and that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. Eight Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. I've been sleeping on an Eight Sleep mattress cover for over four years now, and it has completely transformed and improved the quality of my sleep. Eight Sleep has just launched their latest model, the Pod 5, and the Pod 5 has several new important features. One of these new features is called Auto Pilot. Auto Pilot is an AI engine that learns your sleep patterns to adjust the temperature of your sleeping environment across different sleep stages. It also elevates your head if you're snoring, and it makes other shifts to optimize your sleep. The base on the Pod 5 also has an integrated speaker that syncs to the Eight Sleep app and can play audio to support relaxation and recovery. The audio catalog includes several NSDR, non-sleep deep rest, scripts that I worked on with Eight Sleep to record. If you're not familiar, NSDR involves listening to an audio script that walks you through a deep body relaxation combined with some very simple breathing exercises, and that combination has been shown in peer-reviewed studies to restore your mental and physical vigor. And this is great because while we would all like to get to bed on time and get up after a perfect night's sleep, oftentimes, we get to bed a little late or later. Sometimes we have to get up early and charge into the day because we have our obligations. NSDR can help offset some of the negative effects of slight sleep deprivation, and NSDR gets you better at falling back asleep should you wake up in the middle of the night. It's an extremely powerful tool that anyone can benefit from the first time and every time. If you'd like to try Eight Sleep, go to eightsleep.com/huberman to get up to $350 off the new Pod 5. Eight Sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com/huberman to save up to $350.

  4. 10:24 – 15:47

    Epigenetics, Trauma, Mutations; Hybrid Vigor, Mate Attraction

    1. AH

      Thank you for that-

    2. MI

      Yeah. (laughs)

    3. AH

      ... because I think that, uh, most everyone, um, is interested in eyes and, and eye color. Uh, what are the, um, sort of examples that come to mind when you think of rapid changes in gene expression in any organ, could be at the surface of the body or it could be internally, uh, that are governed by some change in behavior?

    4. MI

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

    5. AH

      Excuse me for interrupting.

    6. MI

      No.

    7. AH

      But are those changes that are passed down, are they adaptive? Are they making subsequent populations more resilient or less resilient?

    8. MI

      Yeah. (laughs) That's a very good question. Um, you know, in the case of, of trauma and refugees, I'm not sure. I do know in terms of starvation, that's been something that's been studied as well. So there was a famine, um, that affected Dutch people several hundred years ago, I think. And, uh, and that was actually also kind of recorded in these, in these epigenetic changes. And so presumably, that's a change that is helping that population to better survive that famine. So in that way, it's resilient. But then, you know, you think about in a contemporary situation where, um, you know, food is abundant, maybe that is no longer beneficial, even though at one point it was.Um, and so then we have this other kind of order of change, which is, um, you know, actual changes in the genes themselves that either arise from mutations in, you know, these single base pairs, um, or at many different sites, or things like variation that's already present in the population at a certain amount that then, you know, increases in frequency throughout the population. And this is where a lot of my work has focused. Um, and these are changes that until recently we thought would take, you know, 5,000 years, 10,000 years, um, uh, at least, and now we're starting to understand that maybe that can happen in as short as 1,000 years, 2,000 years.

    9. AH

      This might be slightly, uh, out of line with what we're talking about right now, but I'm really fascinated by this concept of hybrid vigor. Uh, I was taught, I don't know if the data still hold up, that if you give mice a choice of other mice to mate with, to produce off- offspring with, that they will select a mouse whose, um, major histocompatibility complex, which is a reflection of diversity of, of, uh, immune genes, so to speak, they'll pick the, the mouse whose immune system is most different from theirs. Presumably, the just-so story, because we're making stuff up about why they do this, right? Nobody really knows. The, the just-so story is that they do this in order to produce offspring that have a much broader array of immune genes to be able to combat a much broader array of potential pathogens. Is that true in mice still, and is it true in humans as well? Do people elect to produce offspring, if given a choice, produce offspring with people that are more different from them as opposed to similar to them?

    10. MI

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

    11. AH

      Super interesting. So, they're given a choice of sweaty clothing from the opposite sex-

    12. MI

      Mm-hmm.

    13. AH

      ... potential partner, I guess they're-

    14. MI

      Yeah.

    15. AH

      I don't know if they were, you know, sent out on dates after the, uh-

    16. MI

      (laughs) Yeah.

    17. AH

      ... experiment, but they're, and they're smelling, let's say, 10 different T-shirts that are sweaty-

    18. MI

      Mm-hmm.

    19. AH

      ... and then they're saying, and then they rank order them?

    20. MI

      Mm-hmm. Yeah.

    21. AH

      And the one they like the most-

    22. MI

      Yes.

    23. AH

      ... if you go and look at the genome of the person whose sweat-

    24. MI

      Mm-hmm.

    25. AH

      ... was on that clothing?

    26. MI

      And specifically the immune system that you're talking about-

    27. AH

      Mm-hmm.

    28. MI

      ... you know, the, um, what is it? Histocompatibility-

    29. AH

      The major histocompatibility complex.

    30. MI

      Yeah, yeah. The, the more different they were in that-

  5. 15:47 – 25:28

    Globalization; Homo Sapiens, Mating & Evolution; Mutations

    1. AH

      I called it hybrid vigor based on-

    2. MI

      Yeah, hybrid vigor.

    3. AH

      ... no, no particular knowledge of the correct term.

    4. MI

      I think that-

    5. AH

      That was, it's the term I use because it makes sense to me. Yeah.

    6. MI

      Yeah. Something like that.

    7. AH

      Something like that.

    8. MI

      Um, uh, you know, we're having with globalization people, um, meeting each other, you know, across cultures, across continents for the first time. So we're getting genetic combinations that have never been possible in the history of humans, um, and that's creating some interesting both kind of resilience and then also disease because you have, you know, combinations of genetic variants that have never been in the same individual before, um, that are now showing up together.

    9. AH

      I find this super interesting, um, for a couple of reasons. First of all, uh, 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.

    10. MI

      Mm-hmm.

    11. AH

      Now that's changed, right? And I think that's reflective of a number of things. I mean, there's cause and effect directionality here that we could get into, but that's a different podcast. Uh, but that, yes, people are, um, intermarrying and/or producing children with people that, uh, whose backgrounds, genetic backgrounds are very different than their own. Um, and if we take the opposite extreme, it makes perfect sense as to why this hybrid vigor thing would exist. And, and the opposite extreme is a very uncomfortable thing, but if you think about incest, incest has been discouraged in populations for a very long time. Without anyone understanding genetics, like the m- 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.

    12. MI

      Yeah.

    13. AH

      And then, I mean, and then of course there's the moral and ethical and all, all that aspect, but, but Mother Nature actually punishes individuals that do this through mutation.

    14. MI

      Yeah. When you have two individuals, um, who are closely related, you know, that dramatically increases the chance that they're both carrying, um, you know, a variant that has a negative, uh, impact on, on the offspring. So, you know, when you have people kind of mixing more outside their families, then it's very likely that even if you're carrying this deleterious variation, um, it's gonna be kind of watered down by outside, uh, genetic material. But yeah, as soon as you have people too closely related to each other, you know, those things are ending up together, um, and creating disease. Yeah, so it's definitely nature has a system built in that says, "Don't do that." (laughs)

    15. AH

      Yeah. I, 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, you've told us that the, the smells that reflect the most distant immune system are the most attractive smells, which is really wild. Um, so is it fair to say that humans are continuing to evolve, uh, given that people are traveling further, meeting people from further away, having children with people from origin populations that presumably have never mixed before in the course of human evolution?

    16. MI

      Yeah, absolutely. I think sometimes people kind of, you know, think we're done, we've reached this, you know, ultimate, uh, point of evolution, you know, w- we've finished evolving. Um, but as long as there are things that are affecting our ability to reproduce, we're gonna continue to evolve. Um, and, you know, especially once you have this introduction of new genetic variation, um, I mean, some of the greatest adaptations in the history of humans have come from the introduction of new genetic material. So-

    17. AH

      Mm-hmm.

    18. MI

      ... like, um, the Tibetan high-altitude adaptation is actually believed to have arisen from the crossing of humans with another, um, 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 again, you know, as you have a more globalized population where, you know, different groups of humans are, are creating these interesting phenotypes, um, through the mixing of their genes that maybe will lead us to be more resilient as our planet is changing around us.

    19. AH

      How long ago did the, uh, did this gene that affords, uh, better abilities at altitude, or ability to survive at altitude enter the human population?

    20. MI

      You know, I'm gonna get myself in trouble 'cause I don't remember exactly how long ago it was.

    21. AH

      More than 10,000 years ago?

    22. MI

      More than 10,000 years ago.

    23. AH

      Mm-hmm.

    24. MI

      But it only became advantageous when the ancestral population, um, of Tibetans moved into these extremely high altitudes. So they kind of, you know, it was just sitting there waiting for a chance to be really advantageous, and then as soon as they went to these high altitudes, people carrying that genetic variation were at a huge advantage, um, and so they, you know, passed that along to their, to their children and their children's children and so on.

    25. AH

      Okay. So does that mean that at some point the species we know as Homo sapiens was able to reproduce with a species that was not Homo sapiens, they gave... and that's how the gene entered the Homo sapien population?

    26. MI

      That's exactly right. So yeah, it happened. We see that happening with, um, Neanderthals as well, um, but also these, this other population of, they call it archaic hominids, um, Denisovans. Um, so these were a population that were found, uh, in areas of Asia, um, and their genes were introgressed we say, um, so essentially, you know, inserted into the human genome. So individuals from that region tend to have a higher ancestry coming from that hominid group.

    27. AH

      But that meant that, uh, a Homo sapien mated with this other species of primate-

    28. MI

      Yes.

    29. AH

      ... and the offspring had this gene incorporated into it.

    30. MI

      Right. Exactly, yes.

  6. 25:28 – 32:52

    Sea Nomads, Bajau & Moken Groups; Free Diving, Dangers & Gasp Reflex

    1. AH

      it. Okay. So I'm obsessed with the X-Men.

    2. MI

      Yes.

    3. AH

      I love that series. I've probably watched it five different times. I mean, for a biologist who's interested in all animals, but the human animal perhaps most, you know, it's, uh, it, it's like the perfect form of entertainment for me.

    4. MI

      Mm-hmm.

    5. AH

      Right? Uh, different individuals who have mutations that afford them specific gifts or abilities-

    6. MI

      Mm-hmm.

    7. AH

      ... but it creates some, uh, let's just say some social tension between those that have and those that don't, and it's about learning these, to use these mutations for good versus evil, and it gets into all sorts of interesting human psychology. You work on the actual, uh, real-life version of what I think of X-Men and, as you'll tell us today, women as well, which is, as you just told us, there's variation in all of our genomes, and occasionally, by virtue of the needs of a particular group or individual, those mutations afford them an incredible ability to do incredible things. So if you would, could you tell us about, uh, these underwater free divers that you've studied? Uh, this is a collection of studies, I realize, but maybe the first study, uh, because I find this to be one of the more incredible examples of behavior shaping what we think of our fixed properties of the human body. And, um, please just tell us about it. It's such a wonderful story.

    8. MI

      Yeah. Absolutely. And I also love the X-Men. Although if you ever wanna ruin a perfectly good sci-fi movie, watch it with an evolutionary biologist or a- (laughs)

    9. AH

      Mm-hmm. Okay. Noted.

    10. MI

      No, um-

    11. AH

      Noted.

    12. MI

      Uh, yeah. So there are these, these incredible people, um, well, really all around the world, but I started, uh, my work in Indonesia, um, called the Bajau. Um, they are a group of what's called sea nomads. Um, so sea nomads are, they're these people who spend their whole lives essentially at sea traditionally. Um, they live on houseboats, um, and everything they need they get from the sea, and they do this through fishing, of course, and other things like that, um, but also through an incredible amount of breath-hold diving. So they're extremely good at this. They can hold their breath for many minutes at a time. They dive to incredible depths. Um, a lot of them wear these, uh, jewelry made of black coral. Black coral only starts growing at about 100 feet deep, so that tells you how deep they're diving.

    13. AH

      So those are trophies.

    14. MI

      They're actually meant for, to protect them from-

    15. AH

      Ne-

    16. MI

      ... uh, evil spirits and things like that.

    17. AH

      How long are their breath holds, uh, on record? I've heard you talk about this before.

    18. MI

      Yes.

    19. AH

      It's a little debatable, but-

    20. MI

      Yeah.

    21. AH

      ... the number I heard from you in a lecture, I went, "Whoa."

    22. MI

      Yeah. So I was told, and I always emphasize that, I was told, I did not see this, I did not record it. I was told 13 minutes.

    23. AH

      Wow.

    24. MI

      Um, and this was by the father of a diver who I worked with in Indonesia.

    25. AH

      That's gotta be in, in the neighborhood of world record stuff.

    26. MI

      It is, yeah. I'm trying to remember what the current world record is, but it's also, I mean, you have to think about if you see them diving, like it's incredibly active. Um, so a lot of the breath-hold records that we think of are people floating in a pool. They're not moving. Um, they're not expending any, you know, energy. They're not using up that oxygen as quickly. Um, and these, these 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, on the surface of, you know, the, the bottom of the ocean with their spear guns, and they, they look like hunters. It's incredible to see.

    27. AH

      Amazing. So even if it's not 13 minutes, let's say it's half that-

    28. MI

      It's- (laughs)

    29. AH

      ... it's still super impressive.

    30. MI

      It's very impressive. Yeah.

  7. 32:52 – 35:36

    Cultural Traditions, Free Diving & Families; Fishing

    1. MI

    2. AH

      Okay, so this population presumably is not thinking about carbon dioxide thresholds for the gasp 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, your family eats. You do the wrong things, you die.

    3. MI

      Right. Yeah. There's so much, um, cultural knowledge that's integrated into the practice and that's passed on from, you know, generation to generation because a lot of times they're doing this in family units. Um, you know, the, one of the divers that I worked with, his dad used to be the most famous diver in the village. Now he's the most famous diver in the village. And, and so there's a lot of that tradition and that traditional knowledge that's passed on, despite it maybe not looking like what we would read in a textbook.

    4. AH

      When you say the, um, one of the most revered or expert divers, I'm very curious as to, uh, how this weaves back to an earlier part of our conversation. Is prowess at diving based on how long someone can stay under and is prowess at diving because it correlates with the ability to secure resources? Is that, um, somehow correlated with desi- like desirable mate? Do these people tend to have more offspring than people that are not as good at diving? And of course there are confounds here. Like you can imagine differences in hormone levels to begin with, uh, eating more during, uh, puberty and growing, you know, stronger or whatever it is, um, or more, uh, or smarter (laughs) and not just smarter, but d- do you see this? Like are the people who are great divers in the village, do they tend to be the ones with more, um, uh, more children to be direct?

    5. MI

      You know, it'd be interesting to count that. I think now, um, you know, things are changing for the, for the Bajau, at least the community that I worked with where a lot of people are moving away from traditional diving-

    6. AH

      Mm-hmm.

    7. MI

      ... and into other kinds of fishing practices. Um, and so I think at this point, you know, this prowess, this respect for these, you know, these divers is more respect for the fact that they're keeping the tradition alive and they're continuing this tradition even though it's a very hard thing to do. Um, but yeah, it would be really interesting. I know actually the one, the one diver came from a very big family and that was something that the Bajau actually asked me about was why, why do the Bajau have so many children. And so it would be interesting to see if yeah, diving success correlates with reproductive success, 'cause you could imagine that it would, I mean, they're, they're diving for things that they're eating, so why wouldn't that, um, in- increase your success on that?

    8. AH

      Just out of curiosity, um, and, uh, because I like seafood, um, what, what are they fishing for?

    9. MI

      They dive for, it depends on where they are. Um, they're spearing a lot of fish. Everything is delicious. Um, they dive for shellfish. Um, they also harvest seaweed sometimes. Um, and they, they actually collect a lot of sea cucumbers-

    10. AH

      Mm-hmm.

    11. MI

      ... which they dry out in the sun and then eat later.

    12. AH

      It's like pure protein.

    13. MI

      Yeah, yeah.

    14. AH

      Yeah. Very interesting.

  8. 35:36 – 42:43

    Mammalian Dive Reflex, Oxygen, Spleen, Cold Water & Face; Exercise

    1. AH

      So what did you study in the, in this group?

    2. MI

      Yeah. So we started thinking about, okay, you know, for natural selection to act in this population, it needs some kind of physical trait to act on. Um, which got us looking at the, you know, the dive reflex or the mammalian dive reflex. So this is if anyone, um-... and again, I hesitate to, to tell people to do this, but if you hold your breath and put your face in a bowl full of cold water, your body responds as if you're diving, um, and, and what that means is that, um, your, your heart rate slows down, um, your blood vessels in your extremities constrict, uh, because, you know, your fingers will be okay with a little bit less oxygen, but your brain really needs that oxygen. So it's keeping the blood central where you need it the most, um, and then your spleen contracts. And so, the spleen certainly wasn't the first organ that I thought about when thinking about diving, um, but the spleen is a reservoir. I mean, 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.

    3. AH

      How significant is that oxygen boost?

    4. MI

      It's about 10% in, in most of us, um-

    5. AH

      That's pretty impressive.

    6. MI

      Exactly, yeah. Yeah, it's ... I mean, it's enough to, to make a difference.

    7. AH

      Mm-hmm. Yeah, by comparison, you know, th- there are, um, a lot of discussions online about, you know, if you finish your exercise resistance training or cardiovascular exercise with a brief sauna session.

    8. MI

      Mm-hmm.

    9. AH

      So s- going slightly hyperthermic, right? This ... You have to hydrate, et cetera, but it actually works even better, as long as we're talking about dangerous practices.

    10. MI

      (laughs)

    11. AH

      It works even better if you're slightly dehydrated.

    12. MI

      Interesting.

    13. AH

      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.

    14. MI

      Mm-hmm.

    15. AH

      Um, you have to, again, avoid dehydration, death, et cetera, but this is done and there a ... someone will correct me, but the, the shift in, uh, available oxygen is in the low percentages, like 1% or 2%.

    16. MI

      Okay.

    17. AH

      So this is what people are fighting for using these kind of, uh, baroque protocols.

    18. MI

      Mm-hmm.

    19. AH

      You're talking about a 10% increase in available oxygen through a contraction of the spleen. I didn't even know the s- the spleen could contract.

    20. MI

      Yeah, that's right.

    21. AH

      Um, just when you put your face into colder than ambient temperature water?

    22. MI

      Uh, yeah, usually in, um, like lab protocols, we do it at about 10 degrees Celsius or 50 degrees Fahrenheit, so quite a bit colder.

    23. AH

      For how long?

    24. MI

      Um, well, d- depends on how long you can hold your breath. (laughs)

    25. AH

      Oh, right. Um...

    26. MI

      Um, yeah, so the, but, you know, the extent to which, like, how long the contraction actually takes, I think, we have room to, to learn more about that. Um, but one thing that's, that's slightly different from what you're talking about is that after you stop holding your breath, your spleen takes that oxygen back, um, essentially.

    27. AH

      Mm-hmm.

    28. MI

      So those r- y- it refills with red blood cells and that oxygen is no ... the extra boost is no longer in circulation.

    29. AH

      Ah, so it's only during the breath hold.

    30. MI

      That's right, only when you need it the most.

  9. 42:43 – 46:00

    Sponsors: AG1 & LMNT

    1. MI

    2. AH

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  10. 46:00 – 52:00

    Free Diving, Spleen, Thyroid Hormone, Performance Enhancement

    1. AH

      I'm jumping around here, but I feel like these are the questions that are hopefully springing to people's minds here and there. Uh, I've seen these videos of b- babies being born into a swimming pool, and they can-

    2. MI

      Mm-hmm.

    3. AH

      ... and that you can ... On their belly. It looks like the Nirvana cover, and you know, they're ... They seem perfectly happy to be underwater shortly after birth, which makes intuitive sense. They were in the womb, they were floating in the amniotic sac and-

    4. MI

      Mm-hmm.

    5. AH

      ... they're underwater, so to speak. Um, do we come into this world knowing how to dive and be underwater because of our experience during pregnancy?

    6. MI

      I mean, it, it seems like it. I mean, I've seen, you know ... If you take babies and, uh, not recommending anyone do this, but, like, blow in their face, you know, and they, they go instinctively hold their breath and can be put underwater. And, uh, and actually, Bajau people told me, and I don't know if this is something they actually do, but that the test of a Bajau is, as a baby, they pass the baby under the canoe, and if the baby comes out the other side, then it's a Bajau because it has held its breath like it will for the rest of its life. Um-

    7. AH

      What's the alternative?

    8. MI

      Yeah. (laughs) um, I don't ... That's why I said I don't know if they actually do this, but, um, it was just something that they told me. Um, but yeah, I think there is some innate, uh, response where we know even as babies to, to hold our breath.

    9. AH

      It's fascinating. S- so what did you discover in this, uh, group of incredible divers?

    10. MI

      So we discovered that they have larger spleens. Um, so you know, I mentioned the spleen's role in diving. Um, it's, it's increasing your ... They ... Sometimes people call it a biological scuba tank. You know, it's increasing the amount of oxygen available to you. So, you know, our hypothesis was that they would have larger spleens because a larger spleen presumably means longer diving, safer diving. Um, and so we compared them to a nearby population living in a very similar environment, but with a history of farming. So these are people who live right next to the ocean, but aren't really interacting with it. So, you know, Bajau children are in the water from the moment they're born almost, um, and then children in this other village didn't know how to swim. Um, and so we found that compared to that village, um, the Bajau had significantly larger spleens. So their spleens were about 50% larger on average. Um, and this was true for divers and non-divers. So that showed us that it was very likely to be something genetic rather than, you know, the fact that you're diving increases the size of your spleen.

    11. AH

      But does-... diving increase the size of the spleen?

    12. MI

      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, um, you know, when you train, if you train people, if you recruit people to a study and train them in breath-hold diving, their spleens increase in size. Um, so I don't know if it's just that the populations that I've worked with have some kind of genetic factors that override that change. Um, but yeah. An open question, I would say.

    13. AH

      I know you've done some work parsing which genes are different in this population and developing some animal models for that, and that some of this converges on thyroid hormone. Um, could you tell us the relationship between thyroid hormone levels, that people are fascinated by thyroid hormone, it seems. E- everyone either thinks they have a thyroid deficiency or an overproduction of thyroid, or they wanna 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?

    14. MI

      The gene that we found that was evolving in the population, um, correlates with higher-than-average thyroid hormone levels. Um, so not, you know, like, clinically hyperthyroid, but higher than average, and this is actually also true for Europeans who are carrying the same genetic variant. Um, you know, we showed in another group of individuals that if you have this gene variant, um, you have higher thyroid hormone levels and you have a larger spleen. Um, so it's not just something that's true in the sea nomads. Um, and so what we think is going on potentially, and this relates to the work that we did with mice as well, is that, um, because of these higher, I, I hesitate to say elevated because that's a clinical term, higher-than-average thyroid hormone levels, um, people are prod- or the, you know, the mice, the humans, whoever it is, are producing more red blood cells. Um, and so now whether that's kind of stretching the spleen, um, you know, 'cause the spleens that we saw in the mice were larger but less dense, um, or, you know, if there's some other mechanism, we're not completely sure yet. But yeah, it seems like these higher-than-average thyroid hormone levels, at least when the genetic cause was, um, was what we saw in the sea nomads, increased the size of the spleen, increased hemoglobin, increased hematocrit, um, increased red blood cell count.

    15. AH

      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, you know, like, getting your face into some cold water, holding your breath could afford you a kind of a boost. So instead of the scuba tank boost underwater, you're getting the above ground boost in endurance or in strength output. But you said you have to be holding your breath at the, uh, at the same time in order to take advantage of that deployment of red blood cells, which is a little confusing to me because I imagine if this, uh, 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.

    16. MI

      Yeah. Yeah, and we don't, I don't think, know how quickly the spleen reuptakes those red blood cells-

    17. AH

      No.

    18. MI

      ... 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-

    19. AH

      Mm-hmm.

    20. MI

      ... but that's really interesting because, um, the work that we did in the mice where we replicated what we saw in these divers, um, they had larger spleens, they had higher red blood cell count, but they did not have any change in erythropoietin, which is how we normally think about, um, changes in red blood cell count. This is a drug that was really popular with cyclists for a while. Um, people would self-dose with erythropoietin and it would increase their red blood cell count dramatically to pro- improve their performance. Um, so this is, like, an erythropoietin-independent mechanism of increasing your bl- red blood cell count that could have an advantage in performance, I, I think.

    21. AH

      Fascinating. And then the other

  11. 52:00 – 55:17

    Dive Reflex, Immune System; Swimming & Health; Coastal Regions & Genetics

    1. AH

      scenario is for, uh, robustness of one's immune system. I, for one, don't like being sick and if there's anything I can do to increase the function of my immune system, including sleep, exercise, sunlight, all those things, uh, but in particular, if I feel like I'm traveling an, an additional amount or not sleeping as well, I'd be willing to do pretty much anything within the realm of reason to improve my immune system vigor, right?

    2. MI

      Yeah, absolutely. Yeah.

    3. AH

      Uh, 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, the idiot that, uh, is doing this thing without any specific clinical trial yet, but I'd love to see a clinical trial on this.

    4. MI

      Oh, absolutely. Yeah.

    5. AH

      Has anything been done to explore how that particular behavior or g- that is, uh, generating the dive reflex can afford any, uh, e- enhancement in immune system function?

    6. MI

      I haven't seen any studies that look at that, but it would be really interesting, um, because yeah, I mean, like you, I also would do anything to not get sick. And we do see in these populations, um, a lot of older people who are continuing to dive, um, and, and there is a seeming health and robustness that I wonder if it's related to the activity of diving itself.

    7. AH

      We have a family friend who's 94. My mom just told me, 94, and my mom said over the phone, "She swims four miles a day." And I'm like, "There's no way." And she goes, "No wait. She swims a mile a day, four days a week."

    8. MI

      (laughs)

    9. AH

      Um, which is still-

    10. MI

      I mean, that's still impressive.

    11. AH

      ... pretty impressive, right?

    12. MI

      Yeah, swimming a mile is a, yeah, that's quite impressive.

    13. AH

      Four days a week?

    14. MI

      Yeah.

    15. AH

      At 94?

    16. MI

      Mm-hmm.

    17. AH

      Presumably that's not backstroke.

    18. MI

      (laughs)

    19. AH

      So certainly some of it's, uh... Yeah, I think that... Like, is there something to being in water that just generally is good for us?

    20. MI

      I would imagine.

    21. AH

      I mean, I shower, I bathe, but, you know, is there something good about swimming or floating or diving just for our general human physiology that we're aware of?

    22. MI

      Yeah, I mean, it's, it's so low impact and, and such a natural way to, you know, to, to move, to exercise, that, um, I, yeah, I think especially as we age, it would be real- a really wonderful way to, to stay fit and healthy.

    23. AH

      Has the size of spleens, or rather the-... genes related to, um, what you're talking about. Um, has that been correlated with whether or not people evolved from coastal versus more, um, central regions of, of continents?

    24. MI

      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. Um, so you would imagine that anyone living near a coast anywhere would take advantage of this resource. Um, so it would be interesting to see if maybe coastal populations are more likely to carry the genetic variation, um, that enables this behavior. Although, there are actually skeletons that have been found in various parts of the world near river systems that also suggest that those people have been diving. Um, so maybe it's just being near water anywhere in the world.

    25. AH

      I don't think of humans as an underwater species, but you're changing my view of this.

    26. MI

      (laughs) .

    27. AH

      I feel like we need to think about humans as some, some humans in the past and now spend a lot of time underwater-

    28. MI

      Yeah.

    29. AH

      ... without a scuba tank.

    30. MI

      It seems to be that way, yeah. All over the world.

  12. 55:17 – 1:03:20

    Female Free Divers, Haenyeo, Cold Water, Age, Protein

    1. AH

      So, this isn't the only population you've studied. Um, if you would, could you tell us about the, the recent work, um, uh, the women, study on women partic- in particular? Uh, and I'm very interested in how this relates to cardiovascular health.

    2. MI

      Yeah. So, um, you know, speaking of older divers, um, there's a group in Korea on an island called Jeju. Um, these are all female divers. Um, they're called the Haenyeo, um, which just means sea women. And, uh, and I... The average age of the Haenyeo currently is around 70 years old. Um, so that's... When I think of robustness with age, I think of the Haenyeo. Um, but this all-female diving population has likely been diving in that region for thousands of years. Um, and what's really extraordinary about the Haenyeo, there's a few things. First of all, they're diving in extremely cold water, especially compared to the Bajau in Indonesia.

    3. AH

      No wetsuits?

    4. MI

      No wetsuit. 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, a cotton swimsuit, essentially. Um, so, you know, diving with no protection in extremely cold water and, um, and as women, they're diving throughout pregnancy, so they're diving up until the day they give birth sometimes, um, and, and then they're back in the water a few days later. So, this has really shaped this population in really interesting ways.

    5. AH

      I was wondering, how deep do they dive?

    6. MI

      This is a really good question I get asked a lot, how deep do any of these populations dive. Um, and there's just, like, not really data, so we don't really know. Um, you know, now we are starting to see, you know, we're looking at, um, the Haenyeo, we actually tracked some of their diving and their dives tended to be much shallower, you know, not really going any deeper than 10 meters, um, 30 feet. But, um, but they're also in their 70s, 80s even, you know, we had an 81-year-old diver in our study. Um-

    7. AH

      Well, 30 feet's not nothing.

    8. MI

      That's right.

    9. AH

      We had a 20 f- foot deep deep end in the pool I, you know, 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 you're-

    10. MI

      Mm-hmm.

    11. AH

      I mean, 20 feet is 20 feet.

    12. MI

      Right.

    13. AH

      30, 30 feet... And, and it's not a linear experience, right?

    14. MI

      Yeah, exactly, yeah.

    15. AH

      With every additional foot, like, the b- you're, you're really experiencing more and more pressure, so.

    16. MI

      Yeah, yeah. And I shouldn't say it like that. It's just that compared to, you know, the Bajau have been documented to dive deeper than 200 feet deep, so. (laughs) .

    17. AH

      Oh, I'm not countering. I was just, I was just-

    18. MI

      Yeah, yeah.

    19. AH

      I just, for sake of people out there who perhaps haven't spent time at the bottom of a pool-

    20. MI

      (laughs) .

    21. AH

      Um, a 20-foot pool, like, thir- 30 feet is, is still really impressive.

    22. MI

      It's, yeah, it's very impressive, yeah.

    23. AH

      And, and, and they're bringing a fetus down that low.

    24. MI

      Right. When they're... I mean, you know, and w- again, there's no documentation of how these women have been diving throughout their pregnancy other than, you know, 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. Um, so it's a, 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, um, that's protective. So, it's like if we wanna talk about really fast examples of evolution, it's anything that's acting on pregnancy, um, and that's what we think has been happening in this population.

    25. AH

      I have so many questions, some of which are cultural, some of which are biological. Uh, I'll start with the cultural questions. Uh, why in this culture is it the women specifically that dive? Um, are they revered? Um, and are they diving for a particular resource that is... Well, because it's underwater, presumably is not available elsewhere, but, like, what are they diving for?

    26. MI

      We don't totally know. I have my own personal theory, um, which actually relates to the fact that in a lot of places with cold water, so in Korea, in Patagonia, in, um, Aboriginal Tasmania, um, it's all women diving. So, I suspect that there's something unique about the physiology of women, um, that makes us better at diving in cold temperatures.

    27. AH

      Or the men are afraid of the cold.

    28. MI

      It could be, could be that too. (laughs) .

    29. AH

      I hear about a lot of guys that, that will, will spend dozens of hours picking apart deliberate cold exposure, uh, when it would take them a fraction of the amount of time to get into the water.

    30. MI

      Mm-hmm.

  13. 1:03:20 – 1:05:07

    Human Evolution & Diet, Lactase, Fat

    1. AH

      it, it's amazing to me, if I step back from these two, um, these two populations a- and I think more broadly as well, about what people are willing to work for, humans will work very hard to get protein.

    2. MI

      Mm-hmm.

    3. AH

      It's just kind of incredible how hard they'll work for proteins and lipids combined in delicious form.

    4. MI

      Yeah.

    5. AH

      I mean, th- they're, we're not aquatic animals.

    6. MI

      Right, right.

    7. AH

      And they're willing to risk th- their lives and the lives of their fetuses-

    8. MI

      Mm-hmm.

    9. AH

      ... to, the next generation, right? There's nothing, I think, that a species tries to protect more than-

    10. MI

      Exactly.

    11. AH

      ... than, than the next generation, one would hope, that they're willing to risk their lives on a daily basis, multiple times per day-

    12. MI

      Mm-hmm.

    13. AH

      ... to go collect protein, basically.

    14. MI

      Yeah. Yeah.

    15. AH

      I- i-

    16. MI

      And in these cold temperatures as well.

    17. AH

      So do you think between on land hunting and, 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?

    18. MI

      I mean, it certainly could. Diet is an incredible driver of selection. So, um, you know, a very common example of natural selection is lactase persistence, so our ability to continue to consume milk past infancy. Um, and that happened very quickly in, in multiple different human populations. So it happened in Africa, and it happened in Europe. Um, and another example is, uh, 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, you know, kill them from heart disease or something like that. Um, so yeah. Diet as a driver of selection is extremely strong. Um, so it may be that, that this has been shaping our species in ways that we don't even know.

    19. AH

      Super

  14. 1:05:07 – 1:10:13

    Korean Female Free Divers & Adaptations, Cardiovascular, Pregnancy

    1. AH

      interesting. So i- in this group of, uh, Korean women divers, um, what's going on with their cardiovascular system? Uh, 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.

    2. MI

      Yeah. So we found two different adaptations. Um, and I say adaptation, but there's kind of adaptation in a physiological sense, this thing that you can do by training, um, or adaptation in a genetic sense, and we have found one of each. So the training adaptation that we found was that, um, 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. Um, so we could actually, you could, you could visually see this. When they were doing these dives, we, watching their heart rate, you could just see it plummeting. Um, we had one individual whose heart rate dropped more than 40 beats per minute in less than 15 seconds.

    3. AH

      Yikes.

    4. MI

      So really dramatic. Um, 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, um, this phenomenon. Um, so that was, I mean, that has, you know, 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-hold divers. Um, 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.

    5. AH

      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, uh, you know, respiratory sinus arrhythmia, we essentially slow our heart rate down.

    6. MI

      Mm-hmm.

    7. AH

      It's the fastest way I'm aware of to consciously slow our heart rate down.

    8. MI

      Mm-hmm.

    9. AH

      But, uh, so as one dives, I guess if they're exhaling, like letting out some, some air, dumping some carbon dioxide, which is probably a good thing if you're a free diver. I don't wanna 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, uh, you're exhaling. Exhaling slows the heart rate, but not 40 beats per minute.

    10. MI

      Right. Yeah.

    11. AH

      It's usually a, a fraction of that.

    12. MI

      Yeah, and so then we also found this, uh, genetic adaptation that we think is driven by the fact that they're diving through pregnancy. So when pregnant women have sleep apnea, um, 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, um, they tend to develop these blood pressure-related complications. Um, so like preeclampsia as a, a... they're just, um, uh, they call them hypertensive disorders of pregnancy. Um, and so we think that, there's no studies that have been, that have shown this yet, but we think that, you know, if you're diving, same, different kind of apnea, um, 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, um, like a lowering of their diastolic blood pressure while they were diving. Um, and so we think that this is protective against these hypertensive or high blood pressure effects.

    13. AH

      That's interesting. So for non-divers, so for pregnant women on land who aren't from this population-

    14. MI

      Mm-hmm.

    15. AH

      ... um, the, the picture I'm getting is that they're sleeping on their back perhaps 'cause it's more comfortable as, as they get very pregnant and their, their airway is getting cut off at some point.

    16. MI

      Mm-hmm. Right.

    17. AH

      So they're having these hypoxic episodes.

    18. MI

      Exactly.

    19. AH

      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-necked, very lean men die in their sleep.

    20. MI

      Hmm.

    21. AH

      This is a kind of well-known thing in certain sports communities.

    22. MI

      Okay.

    23. AH

      It's a very, it's very tragic. You know, you say, "Well this person's a, you know, fit, but they're lying on their back. They, they have big necks and their airway is compressed."

    24. MI

      Mm-hmm.

    25. AH

      If you have a big neck, doesn't necessarily mean you're gonna die early, but make sure you're breathing right at night. See, because, uh, sleep apnea is very dangerous.

    26. MI

      It is, yeah.

    27. AH

      I, I think we think of it as just snoring, right?

    28. MI

      Like diving, yeah, right.

    29. AH

      But it's super dangerous.

    30. MI

      Yeah. Yeah, you're putting yourself into a state of hypoxemia, so your, your oxygen is very low.

  15. 1:10:13 – 1:17:15

    Miscarriages & Genetic Selection; Bajau, External Appearance, Mate Selection

    1. AH

      topic, but I think an important one. Uh, earlier you were talking about genetic selection and, um, what determines survival of, of offspring. Is it the case that many miscarriages, if not most miscarriages, are because the mutations that arise would have been, uh, destructive at some point, um, postnatally after birth? So it's a kind of a nature's, um, uh, nature's veto on, on the genetic program.

    2. MI

      Yeah, I mean, you know, I'm not a maternal health specialist, but I, I do know that most mutations create non-viable embryos. Um, and so, uh, yeah, that's I think, I think that could certainly be driving the early, um, miscarriages especially.

    3. AH

      So it could be pre-implantation or post-implantation, um, that a mutation arises and somehow, um, the, the genetic programs of embryology are somehow made aware that down the line this is gonna lead to a, a, uh, uh, stillborn fetus or something.

    4. MI

      Mm-hmm.

    5. AH

      So, so, uh, I mean, uh, nature doesn't have a, a conscious logic in the same way that we think, but, but the, the, the genetic decision therefore is to, uh, is to stop, is essentially a stop cell proliferation.

    6. MI

      Right.

    7. AH

      And, and the, and the pregnancy is terminated.

    8. MI

      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, in one of those proteins that's involved in all these different systems, it's just gonna start to go haywire very early on.

    9. AH

      Mm-hmm. I'm very curious about how these genetic adaptations and, and how they relate to behavior impact, um, 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 wanna 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, um, wine spot, um, uh, pigmentation, uh, of the surface of the body, like a, a baby will come out with a, with a very dramatic, like, wine spot pigmentation of part of the face or the head, sometimes, not always, is correlated with, uh, mutations in internal organs. And this is-

    10. MI

      Mm-hmm.

    11. AH

      So... And, and this is...... having run a mouse lab for a long time, you, um, study mouse mutants, uh, 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, say, retinal development, for which I need to take the retina out, look at it under a microscope and, and find which cells are miswired or something like that, um, 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 gotta send out DNA and, you know, or analyze DNA. Nowadays, you send it out, but in the old days, we genotyped, uh, our own mice. And what you find is that oftentimes, there are these peripheral markers of central issues.

    12. MI

      Mm-hmm.

    13. AH

      I'm also interested in the inverse of that, where there are peripheral markers of central advantages.

    14. MI

      Mm-hmm.

    15. AH

      Um, so in these populations that you study, they have these larger spleens or this ability to dive deeper and longer, uh, can overcome hypoxia through a drop in, in heart rate. Is there anything about their external s- 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?

    16. MI

      Mm-hmm.

    17. AH

      Does that make sense?

    18. MI

      Yeah, absolutely.

    19. AH

      Yeah.

    20. MI

      Yeah, and I mean, you know, 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's, you know, there are chances for these mutations to affect not just the systems that we're interested in-

    21. AH

      Mm-hmm.

    22. MI

      ... but other systems as well. Um, I mean, in both populations, the people look incredibly fit and athletic, um, and they're, you know, they tend to have a, just a very robust appearance. Now, is that because they're diving every day, you know, and there, there aren't that many 70-year-old women who are jumping off a boat every day to go to work? Um, or is it something related to their genetics? I don't think we know yet, um, but it would be really interesting to, to look into that more.

    23. AH

      The reason I ask this is that, as we were discussing at the beginning of today's conversation, um, mate selection, we think of the, they smell so great, we like them for this reason, we like them for that reason, and, and there's the, 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 (laughs) selecting, at least in part, for their immune system-

Episode duration: 1:52:10

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