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

Andrew Huberman 0:00 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

Andrew Huberman 2:35 Elardo. Dr. Melissa Elardo, welcome.

Dr. Melissa Ilardo 2:38 Thank you.

Andrew Huberman 2:40 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.

Dr. Melissa Ilardo 3:19 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.

Andrew Huberman 3:45 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?

Dr. Melissa Ilardo 5:20 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.

Andrew Huberman 5:49 So there was a blue-eyed F1 as we say-

Dr. Melissa Ilardo 5:52 That's right.

Andrew Huberman 5:52 ... like the, the, the first.

Dr. Melissa Ilardo 5:53 Mm-hmm.

Andrew Huberman 5:53 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?

Dr. Melissa Ilardo 6:08 I think that's right, yeah. I think it's the most rare.

Andrew Huberman 6:10 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?

Dr. Melissa Ilardo 6:18 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.

Andrew Huberman 6:39 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-

Dr. Melissa Ilardo 6:49 Is that right? I didn't know that.

Andrew Huberman 6:49 ... regardless of where they start.

Dr. Melissa Ilardo 6:51 Interesting.

Andrew Huberman 6:51 Yeah. So, like, a blue-eyed baby will have much bluer eyes at birth-

Dr. Melissa Ilardo 6:55 Right.

Andrew Huberman 6:55 ... than it will at age 15, at age 80, for instance.

Dr. Melissa Ilardo 6:58 Mm-hmm. Yeah.

Andrew Huberman 6:58 And we believe that's due to, uh, changes in pigmentation because of, of UV exposure.

Dr. Melissa Ilardo 7:04 That's really interesting.

Andrew Huberman 7:06 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.

Andrew Huberman 10:24 Thank you for that-

Dr. Melissa Ilardo 10:24 Yeah. (laughs)

Andrew Huberman 10:24 ... 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?

Dr. Melissa Ilardo 10:43 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.

Andrew Huberman 11:29 Excuse me for interrupting.

Dr. Melissa Ilardo 11:30 No.

Andrew Huberman 11:30 But are those changes that are passed down, are they adaptive? Are they making subsequent populations more resilient or less resilient?

Dr. Melissa Ilardo 11:36 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.

Andrew Huberman 12:51 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?

Dr. Melissa Ilardo 13:52 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.

Andrew Huberman 14:35 Super interesting. So, they're given a choice of sweaty clothing from the opposite sex-

Dr. Melissa Ilardo 14:40 Mm-hmm.

Andrew Huberman 14:40 ... potential partner, I guess they're-

Dr. Melissa Ilardo 14:42 Yeah.

Andrew Huberman 14:42 I don't know if they were, you know, sent out on dates after the, uh-

Dr. Melissa Ilardo 14:45 (laughs) Yeah.

Andrew Huberman 14:45 ... experiment, but they're, and they're smelling, let's say, 10 different T-shirts that are sweaty-

Dr. Melissa Ilardo 14:49 Mm-hmm.

Andrew Huberman 14:49 ... and then they're saying, and then they rank order them?

Dr. Melissa Ilardo 14:51 Mm-hmm. Yeah.

Andrew Huberman 14:52 And the one they like the most-

Dr. Melissa Ilardo 14:53 Yes.

Andrew Huberman 14:53 ... if you go and look at the genome of the person whose sweat-

Dr. Melissa Ilardo 14:56 Mm-hmm.

Andrew Huberman 14:56 ... was on that clothing?

Dr. Melissa Ilardo 14:57 And specifically the immune system that you're talking about-

Andrew Huberman 15:00 Mm-hmm.

Dr. Melissa Ilardo 15:00 ... you know, the, um, what is it? Histocompatibility-

Andrew Huberman 15:03 The major histocompatibility complex.

Dr. Melissa Ilardo 15:05 Yeah, yeah. The, the more different they were in that-

Andrew Huberman 15:08 Mm-hmm.

Dr. Melissa Ilardo 15:08 ... um, the more attracted they were to that smell.

Andrew Huberman 15:10 It's kind of amazing, right?

Dr. Melissa Ilardo 15:11 Yeah.

Andrew Huberman 15:11 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."

Dr. Melissa Ilardo 15:17 Mm-hmm.

Andrew Huberman 15:17 Is, um, kind of a proxy for gene expression related to i- the immune system of the offspring that you haven't even had yet with this smelly T-shirt-

Dr. Melissa Ilardo 15:28 Exactly.

Andrew Huberman 15:29 ... owning person.

Dr. Melissa Ilardo 15:29 (laughs) Yeah.

Andrew Huberman 15:29 It's kind of wild. So I think it speaks to smell, and these aren't really pheromone effects, but it speaks to smell as, uh, a pretty powerful driver of mate selection.

Dr. Melissa Ilardo 15:39 Yeah, I mean, it, I think it could be. Um, it's also interesting, you know, we have, you know, when you're talking about hybrid compatibility or hybrid...

Andrew Huberman 15:46 I,

Andrew Huberman 15:47 I called it hybrid vigor based on-

Dr. Melissa Ilardo 15:48 Yeah, hybrid vigor.

Andrew Huberman 15:48 ... no, no particular knowledge of the correct term.

Dr. Melissa Ilardo 15:50 I think that-

Andrew Huberman 15:51 That was, it's the term I use because it makes sense to me. Yeah.

Dr. Melissa Ilardo 15:53 Yeah. Something like that.

Andrew Huberman 15:55 Something like that.

Dr. Melissa Ilardo 15:55 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.

Andrew Huberman 16:21 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.

Dr. Melissa Ilardo 16:34 Mm-hmm.

Andrew Huberman 16:34 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.

Dr. Melissa Ilardo 17:36 Yeah.

Andrew Huberman 17:37 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.

Dr. Melissa Ilardo 17:46 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)

Andrew Huberman 18:22 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?

Dr. Melissa Ilardo 18:56 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-

Andrew Huberman 19:24 Mm-hmm.

Dr. Melissa Ilardo 19:24 ... 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.

Andrew Huberman 19:56 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?

Dr. Melissa Ilardo 20:07 You know, I'm gonna get myself in trouble 'cause I don't remember exactly how long ago it was.

Andrew Huberman 20:11 More than 10,000 years ago?

Dr. Melissa Ilardo 20:12 More than 10,000 years ago.

Andrew Huberman 20:12 Mm-hmm.

Dr. Melissa Ilardo 20:12 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.

Andrew Huberman 20:36 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?

Dr. Melissa Ilardo 20:50 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.

Andrew Huberman 21:17 But that meant that, uh, a Homo sapien mated with this other species of primate-

Dr. Melissa Ilardo 21:21 Yes.

Andrew Huberman 21:22 ... and the offspring had this gene incorporated into it.

Dr. Melissa Ilardo 21:25 Right. Exactly, yes.

Andrew Huberman 21:26 And then that, that offspring at some point, uh, mated with another Homo sapiens and so on and so forth.

Dr. Melissa Ilardo 21:32 Correct, yes.

Andrew Huberman 21:32 Okay. Yeah, I'm not trying to paint more color on it so that people, uh, I'm not trying to be salacious here, I just, I think that sometimes, um, we forget, um, that in the primate lineage that there, there were other primates with whom Homo sapiens were capable of reproducing with.

Dr. Melissa Ilardo 21:48 That's right, yeah. And there's actually some extraordinary work from Svante Pääbo, um, who works a lot with ancient DNA, where they found an individual who was a first generation mix. I think it might've been with Neanderthal, um, I forget now at this point, but, um, it's, so it was, it was a first generation half-human, half whatever archaic hominid it was, um, which shows you, I mean, if they found this, the chances that they would find this one, you know, mixed individual, um, are so slim that it suggested this was something that was actually happening a lot, um, f- for them to happen to find it.

Andrew Huberman 22:19 So in the diagram that everyone has seen of a, of a quadruped animal, like walking on all fours and then gradually evolving into the upright form that we know as Homo sapiens, w- which is the, uh, primate right before it?

Dr. Melissa Ilardo 22:33 Oh.

Andrew Huberman 22:33 With this, the, wh- 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.

Dr. Melissa Ilardo 22:42 That's right, that's right.

Andrew Huberman 22:42 But that's a separate point. That's an editorial point. But d- 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?

Dr. Melissa Ilardo 22:55 Yeah, um, I mean, it definitely, you know, we have an ancestor, I don't remember exactly the name off the top of my head, but I have an issue with this diagram-

Andrew Huberman 23:03 Mm-hmm.

Dr. Melissa Ilardo 23:03 ... um, 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, um, and we are the pinnacle of it. You know, we've achieved this thing. And I think it also fits with this, you know, concept of survival of the fittest, um, which I think is, you know, also a little bit misleading in that, you know, it's not about the most fit, it's about the best fit. So evolution doesn't care how fit you are in the way we think of fitness, it only cares how you fit with your environment. Um, so, you know, the idea that evolution is driving any species, but especially ours, towards some optimum, um, I think is inherently flawed.

Andrew Huberman 23:42 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."

Dr. Melissa Ilardo 23:57 That's right.

Andrew Huberman 23:57 Like, you can create immense problems in all sorts of things from, you know, pancreas function to, uh, mobility to vision with-... a deleterious mutation-

Dr. Melissa Ilardo 24:09 Mm-hmm.

Andrew Huberman 24:10 ... but it takes a very long time to create an advantage for a given species through the accumulation of new, uh, combinations of genes. Is that true?

Dr. Melissa Ilardo 24:19 Yeah. Yeah. I mean, it's, um, most mutations are deleterious. Most mutations cause problems. Um, and so we actually don't even see most mutations because they kill essentially the offspring before, you know, it's, even becomes a fetus. So most mutations are happening in a way, way that we're not even seeing them. Um, so to wait for something that comes up that's actually beneficial, um, can take forever, um, because, you know, you have to have exactly the right thing. The genome's huge. Um, s- so when those changes are happening, for it to not only happen in the right place but to not cause problems takes a really long time. So some of the faster examples that we know of of evolution, especially in humans, come from when there's variation that's just already there. And, you know, it's not particularly advantageous, um, like I mentioned with the Tibetans, until you move into a particular environment or until you start practicing a certain activity, like breath-hold diving. Um, and so, you know, we have, we call it standing variation, just there's all these differences between all of us humans on Earth. And so when you have variation that's beneficial in the right environment, um, then evolution can happen a lot faster.

Andrew Huberman 25:27 Got

Andrew Huberman 25:28 it. Okay. So I'm obsessed with the X-Men.

Dr. Melissa Ilardo 25:31 Yes.

Andrew Huberman 25:32 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.

Dr. Melissa Ilardo 25:46 Mm-hmm.

Andrew Huberman 25:46 Right? Uh, different individuals who have mutations that afford them specific gifts or abilities-

Dr. Melissa Ilardo 25:52 Mm-hmm.

Andrew Huberman 25:52 ... 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.

Dr. Melissa Ilardo 26:51 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)

Andrew Huberman 27:00 Mm-hmm. Okay. Noted.

Dr. Melissa Ilardo 27:00 No, um-

Andrew Huberman 27:01 Noted.

Dr. Melissa Ilardo 27:01 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.

Andrew Huberman 27:45 So those are trophies.

Dr. Melissa Ilardo 27:46 They're actually meant for, to protect them from-

Andrew Huberman 27:49 Ne-

Dr. Melissa Ilardo 27:49 ... uh, evil spirits and things like that.

Andrew Huberman 27:51 How long are their breath holds, uh, on record? I've heard you talk about this before.

Dr. Melissa Ilardo 27:55 Yes.

Andrew Huberman 27:55 It's a little debatable, but-

Dr. Melissa Ilardo 27:56 Yeah.

Andrew Huberman 27:56 ... the number I heard from you in a lecture, I went, "Whoa."

Dr. Melissa Ilardo 28:00 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.

Andrew Huberman 28:08 Wow.

Dr. Melissa Ilardo 28:08 Um, and this was by the father of a diver who I worked with in Indonesia.

Andrew Huberman 28:11 That's gotta be in, in the neighborhood of world record stuff.

Dr. Melissa Ilardo 28:15 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.

Andrew Huberman 28:50 Amazing. So even if it's not 13 minutes, let's say it's half that-

Dr. Melissa Ilardo 28:54 It's- (laughs)

Andrew Huberman 28:54 ... it's still super impressive.

Dr. Melissa Ilardo 28:55 It's very impressive. Yeah.

Andrew Huberman 28:57 And so do they grow up doing this?

Dr. Melissa Ilardo 28:58 They do. Yeah.

Andrew Huberman 28:59 Mm-hmm.

Dr. Melissa Ilardo 28:59 And they, in fact, they spend so much time traditionally on these houseboats and so little time on land that a lot of the children actually learn to swim before they learn how to walk. Um, so, uh, one of the divers, uh, when I was, 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, uh-

Andrew Huberman 29:24 Amazing.

Dr. Melissa Ilardo 29:24 ... because he's not using them like we do.

Andrew Huberman 29:26 Amazing. So h- how did you find this population, and then what sorts of questions did you start to ask?

Dr. Melissa Ilardo 29:31 Yeah. So I was actually, um, diving as part of a coral genomics project in Thailand, um, escaping Danish winter, uh, 'cause that's where I was doing my PhD, and I s- I heard about a population called the Moken, um, so that's another group of these sea nomads, and heard about, you know, their incredible underwater diving. Um, started looking into it and saw, um, a study that I think you've seen that, um, that showed that children, Moken children could actually see underwater better than, uh, European children.Um, and started thinking about, you know, I mean, free diving's really dangerous. Um, and so I was thinking that this could actually be something that's driving selection in this population, that's causing this population to evolve.

Andrew Huberman 30:09 In other words, just to put this in, um, everyday terms for people, if you don't get good at this, you die.

Dr. Melissa Ilardo 30:15 Yeah, exactly.

Andrew Huberman 30:16 If you die young enough, you don't reproduce.

Dr. Melissa Ilardo 30:19 Exactly.

Andrew Huberman 30:19 If you get good enough at this, uh, you can live long enough to reproduce and your children will presumably inherit whatever, uh, mutation or, or genetic variance, uh, afford this ability.

Dr. Melissa Ilardo 30:32 Exactly, yeah.

Andrew Huberman 30:32 Mm-hmm.

Dr. Melissa Ilardo 30:33 Yeah, and you know, I mean, we see with competitive breath hold divers, um, you know, I, I've never actually been to one of these competitions, but I've read about them, people pass out underwater all the time. Um, 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, um, might survive that.

Andrew Huberman 31:02 And in this case, the safety at diving comes from being able to stay under longer. And we can talk about that, but as long as we're on this point and because some people will be tempted to, uh, to go test their breath holding, uh, time, which please don't do it, um, just, I'm just gonna do it across the board. Just don't do it.

Dr. Melissa Ilardo 31:19 (laughs)

Andrew Huberman 31:19 L- l- learn from an expert. If you're gonna learn to free dive, learn from somebody who's truly expert under the right conditions. Uh, I'll put a link to a couple folks I know that I have no business relation to, uh, Mark Healey and some other people that teach this on land first.

Dr. Melissa Ilardo 31:30 Mm-hmm.

Andrew Huberman 31:31 Actually, you know what? I'll just tell you, you know what they told me was the first step-

Dr. Melissa Ilardo 31:34 What?

Andrew Huberman 31:34 ... in one of these, uh, free diving classes, I chose not to do it, is to ... Do not do this.

Dr. Melissa Ilardo 31:39 (laughs)

Andrew Huberman 31:40 But I was told, "Here's the first step. You're gonna hold your breath on land and force yourself to not breathe when the gasp reflex hits-"

Dr. Melissa Ilardo 31:46 Yes.

Andrew Huberman 31:47 "... until you pass out."

Dr. Melissa Ilardo 31:48 Yes.

Andrew Huberman 31:48 And I was like, "I, you know what? I'm not gonna take this course."

Dr. Melissa Ilardo 31:50 Yeah.

Andrew Huberman 31:51 Right?

Dr. Melissa Ilardo 31:51 So this is exactly what gets people in trouble because yeah, like, you know, we, we don't have a reliable sensor for when our, our oxygen is low. And so that happens to people underwater because that feeling, that f- wanting to breathe is a buildup of carbon dioxide. Um, and so yeah, people ch- teach themselves to overcome it, like they're-

Andrew Huberman 32:07 Mm-hmm.

Dr. Melissa Ilardo 32:07 ... suggesting you do there. And then, you know, you're underwater and you pass out and that's it.

Andrew Huberman 32:11 I've been told that you go from feeling that gasp reflex, you learn to ride that like a bump.

Dr. Melissa Ilardo 32:17 Mm-hmm.

Andrew Huberman 32:18 Um, the same way you might stay in a cold plunge or something a little bit longer than your impulse would have you stay in.

Dr. Melissa Ilardo 32:23 Mm-hmm.

Andrew Huberman 32:24 But in this case, you're underwater and then it passes and then you're, you're swimming freely about and you're, uh, you feel good, you're relaxed, you're doing slow exhales to let off that carbon dioxide, whatever c- carbon dioxide is left, and then (fingers snap) it's just lights out.

Dr. Melissa Ilardo 32:38 Yeah.

Andrew Huberman 32:38 That there's no, there's no flickering. Uh, it just goes to complete blackout-

Dr. Melissa Ilardo 32:43 Right.

Andrew Huberman 32:43 ... like curtains as they call it.

Dr. Melissa Ilardo 32:44 Yeah.

Andrew Huberman 32:44 And then you're dead.

Dr. Melissa Ilardo 32:45 Yeah.

Andrew Huberman 32:45 Unless somebody pulls you up to the surface.

Dr. Melissa Ilardo 32:47 Exactly. Yeah.

Andrew Huberman 32:48 Yeah. So hopefully we sufficiently scare people-

Dr. Melissa Ilardo 32:50 Yeah. Yeah. Yeah.

Andrew Huberman 32:51 ... into, into doing this.

Dr. Melissa Ilardo 32:51 (laughs)

Andrew Huberman 32:52 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.

Dr. Melissa Ilardo 33:08 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.

Andrew Huberman 33:32 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?

Dr. Melissa Ilardo 34:23 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-

Andrew Huberman 34:33 Mm-hmm.

Dr. Melissa Ilardo 34:33 ... 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?

Andrew Huberman 35:11 Just out of curiosity, um, and, uh, because I like seafood, um, what, what are they fishing for?

Dr. Melissa Ilardo 35:17 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-

Andrew Huberman 35:30 Mm-hmm.

Dr. Melissa Ilardo 35:30 ... which they dry out in the sun and then eat later.

Andrew Huberman 35:33 It's like pure protein.

Dr. Melissa Ilardo 35:34 Yeah, yeah.

Andrew Huberman 35:34 Yeah. Very interesting.

Andrew Huberman 35:36 So what did you study in the, in this group?

Dr. Melissa Ilardo 35:39 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.

Andrew Huberman 36:41 How significant is that oxygen boost?

Dr. Melissa Ilardo 36:43 It's about 10% in, in most of us, um-

Andrew Huberman 36:46 That's pretty impressive.

Dr. Melissa Ilardo 36:47 Exactly, yeah. Yeah, it's ... I mean, it's enough to, to make a difference.

Andrew Huberman 36:51 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.

Dr. Melissa Ilardo 37:02 Mm-hmm.

Andrew Huberman 37:03 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.

Dr. Melissa Ilardo 37:11 (laughs)

Andrew Huberman 37:11 It works even better if you're slightly dehydrated.

Dr. Melissa Ilardo 37:13 Interesting.

Andrew Huberman 37:13 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.

Dr. Melissa Ilardo 37:20 Mm-hmm.

Andrew Huberman 37:21 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%.

Dr. Melissa Ilardo 37:33 Okay.

Andrew Huberman 37:34 So this is what people are fighting for using these kind of, uh, baroque protocols.

Dr. Melissa Ilardo 37:38 Mm-hmm.

Andrew Huberman 37:38 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.

Dr. Melissa Ilardo 37:44 Yeah, that's right.

Andrew Huberman 37:45 Um, just when you put your face into colder than ambient temperature water?

Dr. Melissa Ilardo 37:51 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.

Andrew Huberman 37:58 For how long?

Dr. Melissa Ilardo 37:59 Um, well, d- depends on how long you can hold your breath. (laughs)

Andrew Huberman 38:02 Oh, right. Um...

Dr. Melissa Ilardo 38:03 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.

Andrew Huberman 38:20 Mm-hmm.

Dr. Melissa Ilardo 38:20 So those r- y- it refills with red blood cells and that oxygen is no ... the extra boost is no longer in circulation.

Andrew Huberman 38:27 Ah, so it's only during the breath hold.

Dr. Melissa Ilardo 38:29 That's right, only when you need it the most.

Andrew Huberman 38:31 Interesting. What an incredible adaptation of the human body.

Dr. Melissa Ilardo 38:34 Yeah.

Andrew Huberman 38:34 Wh- what are some other functions of the, of the spleen just for ... I ... this is the first time the spleen has ever been discussed on this podcast, I think.

Dr. Melissa Ilardo 38:41 Yeah. (laughs)

Andrew Huberman 38:41 Um, we don't think about spleens too often. Um...

Dr. Melissa Ilardo 38:45 Well, you can live without one, so it seems like how important could it be?

Andrew Huberman 38:48 Right.

Dr. Melissa Ilardo 38:49 But, um-

Andrew Huberman 38:49 Well...

Dr. Melissa Ilardo 38:50 For diving, yes.

Andrew Huberman 38:50 For this population, it sounds like it might be critical. You'll, you'll tell us.

Dr. Melissa Ilardo 38:53 Exactly.

Andrew Huberman 38:54 Um, yeah, what are some other things that it does?

Dr. Melissa Ilardo 38:56 It's, um, it's involved in the immune response to certain bacteria, um, and, uh, actually now I'm trying to think of what else it does, but that's, you know.

Andrew Huberman 39:03 That seems-

Dr. Melissa Ilardo 39:03 The main role is immunological. (laughs)

Andrew Huberman 39:05 Mm-hmm. One thing I ... In anticipation of this episode, I did a little reading about it and it's, it gets very heavy neural enervation.

Dr. Melissa Ilardo 39:12 Hmm.

Andrew Huberman 39:12 Which is interesting. We don't normally think about our peripheral organs besides our heart as getting a lot of neural enervation.

Dr. Melissa Ilardo 39:18 Mm-hmm.

Andrew Huberman 39:18 Of course, the gut has neural enervation, et cetera.

Dr. Melissa Ilardo 39:20 Right.

Andrew Huberman 39:20 But the spleen gets very heavy neural enervation-

Dr. Melissa Ilardo 39:23 Interesting.

Andrew Huberman 39:23 ... which makes me think that maybe there's the opportunity for more perhaps even conscious control of the spleen. Does this population, um, communicate about any sense that they, they can, like, switch this thing on or is this just all kind of, um, unconscious genius related to their, their behavior?

Dr. Melissa Ilardo 39:40 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-

Andrew Huberman 39:47 (laughs)

Dr. Melissa Ilardo 39:47 ... it wasn't something that they had ever thought about, um, or, you know, experienced any kind of sensation in the area where the spleen is found. Um, yeah, but who knows? I mean, it's, uh, encapsulated in smooth muscle, I think, the spleen-

Andrew Huberman 39:59 Mm-hmm.

Dr. Melissa Ilardo 39:59 ... and that's what controls that contraction. So yeah, maybe there could be some way to, um, you know, to consciously contract your spleen.

Andrew Huberman 40:06 Mm-hmm.

Dr. Melissa Ilardo 40:06 We also ... Our spleens contract when we exercise to a lesser extent, um, and this is why, like, horses and apparently greyhounds, um, someone wrote to me after the study came out, have massive spleens.

Andrew Huberman 40:17 Hmm.

Dr. Melissa Ilardo 40:17 Um, as do seals who do a lot of deep diving, but that makes a little more sense.

Andrew Huberman 40:21 Interesting. Horses, I don't, I don't think about horses being under water very often.

Dr. Melissa Ilardo 40:25 Right, right.

Andrew Huberman 40:25 Or greyhounds for that matter.

Dr. Melissa Ilardo 40:27 Yeah.

Andrew Huberman 40:27 I wonder if they incorporate breath holds as a way to deploy red blood cells.

Dr. Melissa Ilardo 40:34 Yeah. It could be that, yeah, something in the kind of breath holding aspect of extreme bouts of exercise-

Andrew Huberman 40:41 Mm-hmm.

Dr. Melissa Ilardo 40:41 ... is also contributing to c- uh, to that contraction.

Andrew Huberman 40:45 Like when, uh, when one becomes a bit hypoxic because you just can't keep up with whatever exertion-

Dr. Melissa Ilardo 40:51 Mm-hmm.

Andrew Huberman 40:51 ... like, you just can't breathe in enough oxygen, dump enough carbon dioxide to keep up with your physical activity-

Dr. Melissa Ilardo 40:56 Mm-hmm.

Andrew Huberman 40:56 ... is there any th- is that one of the conditions under which it sort of m- mimics a breath hold, or do you need this cold th- w- there seems to be something about the face being cold.

Dr. Melissa Ilardo 41:06 Yeah, there's, um, 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, is crucial, um, to triggering the response. But there is, I think, a component of if you're just holding your breath where that also kind of triggers it. So, um, but yeah, it's really amazing to think that as mammals this evolved sometime 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.

Andrew Huberman 41:38 Wild. Yeah, so you sort of answered my next question, which was, uh, why do we have a dive reflex? I mean, we're not a harp seal.

Dr. Melissa Ilardo 41:45 Right.

Andrew Huberman 41:46 And we're not a diving bird.... uh, why do we, why do we have this?

Dr. Melissa Ilardo 41:51 Yeah. I mean, it's a great question. I don't think we really know. Um, there's a ... Some people talk about something called the aquatic ape hypothesis, um, that says that one of our ancestors-

Andrew Huberman 41:59 No.

Dr. Melissa Ilardo 41:59 Is a-

Andrew Huberman 41:59 Sorry. (laughs) I'll stop. I'm trying not to interrupt, but-

Dr. Melissa Ilardo 42:02 Yeah.

Andrew Huberman 42:02 ... I just, uh ... Uh, someone I've heard of the stoned ape hypothesis, you know?

Dr. Melissa Ilardo 42:05 Okay. (laughs)

Andrew Huberman 42:05 All the psychonauts love the stoned ape hypothesiS-

Dr. Melissa Ilardo 42:07 Okay.

Andrew Huberman 42:07 ... which is that psychedelics what, are what led to new ideas and daytime dreams that led to our evolution and, uh ... Anyway, uh-

Dr. Melissa Ilardo 42:14 That's a new one for me. Yeah. (laughs)

Andrew Huberman 42:14 Forgive me for interrupting you. It was, it was an interruption of, of, of the stoned ape.

Dr. Melissa Ilardo 42:18 Yes.

Andrew Huberman 42:18 Um, so the d- please t-

Dr. Melissa Ilardo 42:20 Well, maybe the, the aquatic ape was right there-

Andrew Huberman 42:22 The aquatic ape.

Dr. Melissa Ilardo 42:22 ... alongside the stoned ape.

Andrew Huberman 42:23 Ah.

Dr. Melissa Ilardo 42:24 (laughs) 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.

Andrew Huberman 42:43 As many of you know, I've been taking AG1 daily for more than 13 years. However, I've now found an even better vitamin mineral probiotic drink. That new and better drink is the new and improved AG1, which just launched this month. This next gen formula from AG1 is a more advanced, clinically backed version of the product that I've been taking daily for years. It includes new bioavailable nutrients and enhanced probiotics. The next gen formula is based on exciting new research on the effects of probiotics on the gut microbiome, and it now includes several specific clinically studied probiotic strains that have been shown to support both digestive health and immune system health, as well as to improve bowel regularity and to reduce bloating. As someone who's been involved in research science for more than three decades, and in health and fitness for equally as long, I'm constantly looking for the best tools to improve my mental health, physical health and performance. I discovered and started taking AG1 way back in 2012, long before I ever had a podcast, and I've been taking it every day since. I find that it greatly improves all aspects of my health. I just feel so much better when I take it with each passing year. And by the way, I'm turning 50 this September. I continue to feel better and better, and I attribute a lot of that to AG1. AG1 uses the highest quality ingredients in the right combinations, and they're constantly improving their formulas without increasing the cost. So I'm honored to have them as a sponsor of this podcast. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. Right now, AG1 is giving away an AG1 welcome kit with five free travel packs and a free bottle of vitamin D3K2. Again, go to drinkag1.com/huberman to claim the special welcome kit with five free travel packs and a free bottle of vitamin D3K2. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes sodium, magnesium, and potassium in the correct amounts, but no sugar. Proper hydration is critical for optimal brain and body function. Even a slight degree of dehydration can diminish cognitive and physical performance. It's also important that you get adequate electrolytes. The electrolytes sodium, magnesium, and potassium are vital for functioning of all the cells in your body, especially your neurons or your nerve cells. Drinking LMNT dissolved in water makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes. To make sure that I'm getting proper amounts of hydration and electrolytes, I dissolve one packet of LMNT in about 16 to 32 ounces of water when I first wake up in the morning, and I drink that basically first thing in the morning. I'll also drink LMNT dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. LMNT has a bunch of great tasting flavors. I love the raspberry. I love the citrus flavor. Right now, LMNT has a limited edition lemonade flavor that is absolutely delicious. I hate to say that I love one more than all the others, but this lemonade flavor is right up there with my favorite other one, which is raspberry or watermelon. Again, I can't pick just one flavor. I love them all. If you'd like to try LMNT, you can go to drinklmnt.com/huberman, spelled drink L-M-N-T dot com slash Huberman, to claim a free LMNT sample pack with a purchase of any LMNT drink mix. Again, that's drinklmnt.com/huberman to claim a free sample pack.

Andrew Huberman 46:00 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-

Dr. Melissa Ilardo 46:10 Mm-hmm.

Andrew Huberman 46:10 ... 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-

Dr. Melissa Ilardo 46:22 Mm-hmm.

Andrew Huberman 46:22 ... 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?

Dr. Melissa Ilardo 46:32 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-

Andrew Huberman 46:57 What's the alternative?

Dr. Melissa Ilardo 46:58 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.

Andrew Huberman 47:10 It's fascinating. S- so what did you discover in this, uh, group of incredible divers?

Dr. Melissa Ilardo 47:16 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.

Andrew Huberman 48:13 But does-... diving increase the size of the spleen?

Dr. Melissa Ilardo 48:16 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.

Andrew Huberman 48:45 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?

Dr. Melissa Ilardo 49:15 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.

Andrew Huberman 50:26 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.

Dr. Melissa Ilardo 51:07 Yeah. Yeah, and we don't, I don't think, know how quickly the spleen reuptakes those red blood cells-

Andrew Huberman 51:12 No.

Dr. Melissa Ilardo 51:12 ... 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-

Andrew Huberman 51:22 Mm-hmm.

Dr. Melissa Ilardo 51:22 ... 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.

Andrew Huberman 51:58 Fascinating. And then the other

Andrew Huberman 52:00 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?

Dr. Melissa Ilardo 52:28 Yeah, absolutely. Yeah.

Andrew Huberman 52:29 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.

Dr. Melissa Ilardo 52:47 Oh, absolutely. Yeah.

Andrew Huberman 52:48 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?

Dr. Melissa Ilardo 52:59 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.

Andrew Huberman 53:21 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."

Dr. Melissa Ilardo 53:32 (laughs)

Andrew Huberman 53:33 Um, which is still-

Dr. Melissa Ilardo 53:34 I mean, that's still impressive.

Andrew Huberman 53:34 ... pretty impressive, right?

Dr. Melissa Ilardo 53:35 Yeah, swimming a mile is a, yeah, that's quite impressive.

Andrew Huberman 53:37 Four days a week?

Dr. Melissa Ilardo 53:38 Yeah.

Andrew Huberman 53:38 At 94?

Dr. Melissa Ilardo 53:39 Mm-hmm.

Andrew Huberman 53:40 Presumably that's not backstroke.

Dr. Melissa Ilardo 53:41 (laughs)

Andrew Huberman 53:42 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?

Dr. Melissa Ilardo 53:50 I would imagine.

Andrew Huberman 53:51 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?

Dr. Melissa Ilardo 53:58 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.

Andrew Huberman 54:13 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?

Dr. Melissa Ilardo 54:26 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.

Andrew Huberman 55:00 I don't think of humans as an underwater species, but you're changing my view of this.

Dr. Melissa Ilardo 55:03 (laughs) .

Andrew Huberman 55:03 I feel like we need to think about humans as some, some humans in the past and now spend a lot of time underwater-

Dr. Melissa Ilardo 55:11 Yeah.

Andrew Huberman 55:11 ... without a scuba tank.

Dr. Melissa Ilardo 55:12 It seems to be that way, yeah. All over the world.

Andrew Huberman 55:15 That's super interesting.

Andrew Huberman 55:17 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.

Dr. Melissa Ilardo 55:34 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.

Andrew Huberman 56:09 No wetsuits?

Dr. Melissa Ilardo 56:10 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.

Andrew Huberman 56:40 I was wondering, how deep do they dive?

Dr. Melissa Ilardo 56:42 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-

Andrew Huberman 57:07 Well, 30 feet's not nothing.

Dr. Melissa Ilardo 57:08 That's right.

Andrew Huberman 57:08 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-

Dr. Melissa Ilardo 57:19 Mm-hmm.

Andrew Huberman 57:20 I mean, 20 feet is 20 feet.

Dr. Melissa Ilardo 57:22 Right.

Andrew Huberman 57:22 30, 30 feet... And, and it's not a linear experience, right?

Dr. Melissa Ilardo 57:25 Yeah, exactly, yeah.

Andrew Huberman 57:26 With every additional foot, like, the b- you're, you're really experiencing more and more pressure, so.

Dr. Melissa Ilardo 57:30 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) .

Andrew Huberman 57:36 Oh, I'm not countering. I was just, I was just-

Dr. Melissa Ilardo 57:38 Yeah, yeah.

Andrew Huberman 57:38 I just, for sake of people out there who perhaps haven't spent time at the bottom of a pool-

Dr. Melissa Ilardo 57:42 (laughs) .

Andrew Huberman 57:43 Um, a 20-foot pool, like, thir- 30 feet is, is still really impressive.

Dr. Melissa Ilardo 57:46 It's, yeah, it's very impressive, yeah.

Andrew Huberman 57:48 And, and, and they're bringing a fetus down that low.

Dr. Melissa Ilardo 57:50 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.

Andrew Huberman 58:30 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?

Dr. Melissa Ilardo 58:52 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.

Andrew Huberman 59:12 Or the men are afraid of the cold.

Dr. Melissa Ilardo 59:13 It could be, could be that too. (laughs) .

Andrew Huberman 59:14 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.

Dr. Melissa Ilardo 59:23 Mm-hmm.

Andrew Huberman 59:23 In my experience, this is not a controlled studies, uh, women are more tolerant of the cold, at, at least in terms of being willing to embrace it the first time around.

Dr. Melissa Ilardo 59:35 Interesting.

Andrew Huberman 59:36 I have stories of, uh, I won't say which countries, but elite special forces, it wasn't the US, uh, guys, in that case it was guys, being terrified of getting into cold water-

Dr. Melissa Ilardo 59:46 (laughs) .

Andrew Huberman 59:47 ... but otherwise being willing to do very, very challenging and indeed-

Dr. Melissa Ilardo 59:49 Right.

Andrew Huberman 59:49 ... very dangerous things. Um, 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.

Dr. Melissa Ilardo 1:00:00 Mm-hmm.

Andrew Huberman 1:00:01 And then now there's a lot of debate online about cold tolerance in, in the, in the two sexes, but I, I don't, uh, the data aren't really solid there.

Dr. Melissa Ilardo 1:00:09 Right, right.

Andrew Huberman 1:00:09 Um, so-Maybe the men are just afraid of going underwater.

Dr. Melissa Ilardo 1:00:13 It could be.

Andrew Huberman 1:00:13 Yeah.

Dr. Melissa Ilardo 1:00:13 These are some tough ladies, I will tell you that. Um-

Andrew Huberman 1:00:17 Yeah.

Dr. Melissa Ilardo 1:00:17 ... even into old age. My, my colleague, um, 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 haenyeo, and the only ones she could find were over 100 years old because they basically don't retire. (laughs) They just dive until they can't, until they die, essentially. So (laughs) she had, you know, these two women who are about three feet tall, who were retired haenyeo, 'cause those are the only ones she could find.

Andrew Huberman 1:00:42 They're 100 years old?

Dr. Melissa Ilardo 1:00:43 Mm-hmm.

Andrew Huberman 1:00:44 As we have this conversation, I think it's very important to remind people that correlation isn't causation-

Dr. Melissa Ilardo 1:00:48 Sure.

Andrew Huberman 1:00:48 ... with all the obsession with longevity and living longer.

Dr. Melissa Ilardo 1:00:51 Yeah.

Andrew Huberman 1:00:51 I'm not gonna rule out the possibility that getting into cold water, in particular, dot, 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.

Dr. Melissa Ilardo 1:01:02 No, no. And, um, yeah, I mean, it would certainly be interesting to explore, but, um, I don't think there is any evidence so far, other than anecdotal.

Andrew Huberman 1:01:10 I would love to do that study.

Dr. Melissa Ilardo 1:01:10 Yeah. (laughs)

Andrew Huberman 1:01:10 The problem is that you need to do a very long study.

Dr. Melissa Ilardo 1:01:12 Right.

Andrew Huberman 1:01:13 And the other problem with longevity studies is you don't really have a good control group, at least within subject-

Dr. Melissa Ilardo 1:01:18 Right.

Andrew Huberman 1:01:18 ... 'cause you don't know when you would've died.

Dr. Melissa Ilardo 1:01:20 Right. Exactly. Yeah.

Andrew Huberman 1:01:22 Yeah. Okay, so these, uh, incredible women are diving-

Dr. Melissa Ilardo 1:01:25 Yes.

Andrew Huberman 1:01:25 ... up until their 70s, 80s?

Dr. Melissa Ilardo 1:01:27 70s, 80s, um, beyond, I guess. Um, the oldest diver that I've personally worked with was over 80. Um, but yeah, they, uh, and they, and they're, you know, I mean, they're so athletic as they do it. Um, but yeah, in terms of are they revered, um, I think now, yes. I think that wasn't always true. Um, one haenyeo told me that, in her youth, she was kind of embarrassed to be a haenyeo.

Andrew Huberman 1:01:49 Hmm.

Dr. Melissa Ilardo 1:01:49 Um, and a lot of it's because, you know, they're exposed to the sun, so they have darker skin than a lot of other women. Um, they're, they tend to be very loud because a lot of times they rupture their eardrums, um, from diving. Um, you know, if they don't pressurize correctly, you know, they can, they can have hearing damage, so they're, they're very, they're (laughs) known for being very loud. Um, and so, you know, I think there was kind of a marginalization early on, but now, um, they're recognized as a UNESCO World Heritage, um, like intangible site, essentially. Um, and there's just, I think, tremendous respect for the population now.

Andrew Huberman 1:02:22 Very cool. W- what are they gathering down there?

Dr. Melissa Ilardo 1:02:25 They are diving for all kinds of things. Um, they're diving for sea urchin, abalone. They also harvest seaweed. Um, I've seen them pull up octopus. Uh, they'll spear an octopus. Um, d- and they, and they do it in a very interesting, kind of controlled way. Like, they're really guardians of their marine environment, um, where they don't ... they make sure that they don't overfish things.

Andrew Huberman 1:02:47 Mm-hmm.

Dr. Melissa Ilardo 1:02:47 So the sea urchin season is very short because, you know, if they overharvest the sea urchin, that population won't replenish. So they have this, you know, system where they, they really take care of the marine environment.

Andrew Huberman 1:02:58 So it's all the proteins again.

Dr. Melissa Ilardo 1:02:59 Mm-hmm.

Andrew Huberman 1:03:00 It's expensive sushi.

Dr. Melissa Ilardo 1:03:01 Yeah. Oh, yeah.

Andrew Huberman 1:03:01 Uni.

Dr. Melissa Ilardo 1:03:02 Delicious, too. (laughs)

Andrew Huberman 1:03:02 I'm still developing a taste for uni. I, I'm trying, but oc-

Dr. Melissa Ilardo 1:03:05 When it's, when it's fresh out of the shell, there's nothing better. (laughs)

Andrew Huberman 1:03:08 Okay. I'm, I'm willing to try. Octopus, uh, I have too much a, an affinity for cephalopods to eat octopus-

Dr. Melissa Ilardo 1:03:14 Mm-hmm.

Andrew Huberman 1:03:14 ... but I have in the past, and it, it can be delicious. Um, and, uh, so

Andrew Huberman 1:03:20 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.

Dr. Melissa Ilardo 1:03:33 Mm-hmm.

Andrew Huberman 1:03:34 It's just kind of incredible how hard they'll work for proteins and lipids combined in delicious form.

Dr. Melissa Ilardo 1:03:40 Yeah.

Andrew Huberman 1:03:40 I mean, th- they're, we're not aquatic animals.

Dr. Melissa Ilardo 1:03:43 Right, right.

Andrew Huberman 1:03:43 And they're willing to risk th- their lives and the lives of their fetuses-

Dr. Melissa Ilardo 1:03:47 Mm-hmm.

Andrew Huberman 1:03:47 ... to, the next generation, right? There's nothing, I think, that a species tries to protect more than-

Dr. Melissa Ilardo 1:03:52 Exactly.

Andrew Huberman 1:03:52 ... than, than the next generation, one would hope, that they're willing to risk their lives on a daily basis, multiple times per day-

Dr. Melissa Ilardo 1:03:59 Mm-hmm.

Andrew Huberman 1:03:59 ... to go collect protein, basically.

Dr. Melissa Ilardo 1:04:02 Yeah. Yeah.

Andrew Huberman 1:04:03 I- i-

Dr. Melissa Ilardo 1:04:03 And in these cold temperatures as well.

Andrew Huberman 1:04:05 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?

Dr. Melissa Ilardo 1:04:23 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.

Andrew Huberman 1:05:06 Super

Andrew Huberman 1:05:07 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.

Dr. Melissa Ilardo 1:05:27 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.

Andrew Huberman 1:06:04 Yikes.

Dr. Melissa Ilardo 1:06:05 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.

Andrew Huberman 1:06:37 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.

Dr. Melissa Ilardo 1:06:54 Mm-hmm.

Andrew Huberman 1:06:54 It's the fastest way I'm aware of to consciously slow our heart rate down.

Dr. Melissa Ilardo 1:06:57 Mm-hmm.

Andrew Huberman 1:06:58 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.

Dr. Melissa Ilardo 1:07:22 Right. Yeah.

Andrew Huberman 1:07:23 It's usually a, a fraction of that.

Dr. Melissa Ilardo 1:07:25 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.

Andrew Huberman 1:08:16 That's interesting. So for non-divers, so for pregnant women on land who aren't from this population-

Dr. Melissa Ilardo 1:08:22 Mm-hmm.

Andrew Huberman 1:08:22 ... 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.

Dr. Melissa Ilardo 1:08:33 Mm-hmm. Right.

Andrew Huberman 1:08:33 So they're having these hypoxic episodes.

Dr. Melissa Ilardo 1:08:35 Exactly.

Andrew Huberman 1:08:35 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.

Dr. Melissa Ilardo 1:08:48 Hmm.

Andrew Huberman 1:08:49 This is a kind of well-known thing in certain sports communities.

Dr. Melissa Ilardo 1:08:51 Okay.

Andrew Huberman 1:08:52 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."

Dr. Melissa Ilardo 1:08:58 Mm-hmm.

Andrew Huberman 1:08:59 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.

Dr. Melissa Ilardo 1:09:05 It is, yeah.

Andrew Huberman 1:09:05 I, I think we think of it as just snoring, right?

Dr. Melissa Ilardo 1:09:07 Like diving, yeah, right.

Andrew Huberman 1:09:07 But it's super dangerous.

Dr. Melissa Ilardo 1:09:09 Yeah. Yeah, you're putting yourself into a state of hypoxemia, so your, your oxygen is very low.

Andrew Huberman 1:09:14 So for pregnant women who are concerned about hypoxia-

Dr. Melissa Ilardo 1:09:19 Mm-hmm.

Andrew Huberman 1:09:20 ... uh, what are the, what are the, um, options that they have besides becoming a diver in this, you know, joining this incredible community in, in, in Korea?

Dr. Melissa Ilardo 1:09:28 (laughs) Yeah, I mean, I think, well, you know, 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, uh, you know, hypertensive disorder pregnancy in pregnant women who have apnea for other reasons.

Andrew Huberman 1:09:48 Mm-hmm.

Dr. Melissa Ilardo 1:09:49 Um, but otherwise, I would say I think, you know, preeclampsia used to be a death sentence for mothers and fetus, you know, um, which is why it was such a dr- strong driver of evolution. Um, now I think awareness of it enables treatment, um, but that's only something that's happened in the last, you know, I don't know how many decades. Um, so that's why it was, it could have been such a powerful force in this population.

Andrew Huberman 1:10:12 Uncomfortable

Andrew Huberman 1:10:13 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.

Dr. Melissa Ilardo 1:10:43 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.

Andrew Huberman 1:10:59 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.

Dr. Melissa Ilardo 1:11:16 Mm-hmm.

Andrew Huberman 1:11:16 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.

Dr. Melissa Ilardo 1:11:29 Right.

Andrew Huberman 1:11:29 And, and the, and the pregnancy is terminated.

Dr. Melissa Ilardo 1:11:31 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.

Andrew Huberman 1:11:44 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-

Dr. Melissa Ilardo 1:12:29 Mm-hmm.

Andrew Huberman 1:12:29 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.

Dr. Melissa Ilardo 1:13:15 Mm-hmm.

Andrew Huberman 1:13:16 I'm also interested in the inverse of that, where there are peripheral markers of central advantages.

Dr. Melissa Ilardo 1:13:23 Mm-hmm.

Andrew Huberman 1:13:23 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?

Dr. Melissa Ilardo 1:13:48 Mm-hmm.

Andrew Huberman 1:13:48 Does that make sense?

Dr. Melissa Ilardo 1:13:49 Yeah, absolutely.

Andrew Huberman 1:13:50 Yeah.

Dr. Melissa Ilardo 1:13:51 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-

Andrew Huberman 1:14:05 Mm-hmm.

Dr. Melissa Ilardo 1:14:05 ... 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.

Andrew Huberman 1:14:31 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,