Dr. David Linden: Life, Death & the Neuroscience of Your Unique Experience
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Welcome to the huberman lab podcast, where we discuss science and science space tools for everyday life. I'm Andrew huberman and i'm a professor neurobiology and opened ology at stanford school of medicine today. My guest is doctor David lindon.

Doctor David london is a professor of neuroscience at johns hopkins school of medicine. His laboratory has studied neuroplasticity. That is how connections in the brain change in response to experience. Much of that work focused on a structure called the sera belm, which is also sometimes referred to as the mini brain, because IT looks like a mini brain in the bottom and back of the human brain and is responsible for an enormous number of basic functions that we use in everyday life, including our motor behavior, that is, our ability to walk and talk, but also dance, play instruments, and is responsible for an enormous number of basic functions that we use in everyday life, including our sense of baLance, our ability to learn new motor behaviors, as well as our sense of timing.

Today, we will discuss the cereal pen, what IT does, but doctor David lindon will also teach us about the important sense of touch, as well as what makes us different as individuals. The reason today's discussion in compasses so many important topics is that doctor David lim's laboratory has focused on many of those topics, and he is also the author of five excEllent popular books about neuroscience that focus on, for instance, our sense of pleasure and where IT originates from and what controls IT in the brain, as well as our sense of touch. And today we start off our discussion by talking about the recent discovery of a set of neurons that have been known about for a long period of time, but that only recently have been characterized, that are involved in essential touch, in particular.

And it's a fascinating conversation, I assure you. In addition to that, doctor David lindon informs us about what makes us individuals, how each and every one of us perceives the same things differently. And it's an absolutely fascinating conversation, which tells you, for instance, why some of you think a smell is futured indeed smells like a vomit, whether others perhaps are not bothered by that smell, and why others still are attracted to that smell, or something that you look at or something that you hear.

We also talk about nature versus nurture and how we come to be who we are, not just through our genes and epi genetics, but also through our early childhood ence and adult experience. And then in the latter third of our conversation, we shift to talking about this so called mind body connection and the science underlying how our thoughts inform our bodily health, or lack there of, as well as how the organs of our body controlled the chemicals, hormones and fought within our brain. Then we shift to discussing doctor David lindon himself and the fact that in twenty twenty, he was diagnosed with the form of heart cancer that LED his physicians to tell him that he had six to twelve months to live.

Now, obviously, because he was in our studio to record this conversation, he has outlived that prognosis, but he lives day today with the knowledge that his death may very well come soon. Although IT isn't clear exactly when that they will come. Of course, he tells us how the initial pro gnosis of his cancer, as well as outliving that prag nosis, has informed his day to day life, as well as his thinking and his relationships.

And that leads to a very direct and Frankly, emotional conversation that includes advice on how all of us get the most out of our daily living and out of our overall life. It's an extremely powerful conversation that I believe everyone, regardless of age or health status, can benefit from. And it's one that makes clear that not only a doctor, David ledin, a spectacular scientist, but also a spectacular educator, a spectacular popular writer, a spectacular family man, including husband and father and friend to many people and his colleagues, but he is also a courageous and spectacular, large, generous human being.

Before you begin, i'd like to emphasize that this podcast is separate from my teaching and researchers at stanford. IT is, however, part of my desired effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, i'd like to thank the sponsors of today's podcast.

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Today's episode is also brought to us by waking up, waking up as a meditation APP that includes hundreds of meditation programs, mindfulness trainings, yoga eja, recessions and nsd r non sleep depressed protocols. I started using the waking up up a few years ago because even though i've been doing regular meditation since my teens and I started doing yoga eja about a decade ago, my dad mentioned to me that he had found an APP, turned out to be the waking up APP, which could teach you meditations of different durations. And that had a lot of different types of meditations to place, to bring your body into different states, and that he liked IT very much.

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And indeed, I love the fact that I can explore different types of meditation to bring about different levels of understanding about consciousness, but also to place my brain body into lots of different kinds of states, depending on which meditation I do. I also love that the waking up up has lots of different types of yoga eja sessions. Those you don't know, yoga edra is a process of lying very still, but keeping an active mind is very different than most meditations.

And there is excEllent scientific data to show that yogananda and something similar to IT called non sleeps, deep breath or nsd r, can greatly restore levels of cognitive and physical energy, even which is a short ten minute session. If you'd like to try the waking up up, you can go to waking up dot com slash huberman and access a free thirty day trial. Again, that's waking up dot com slash huberman to access a free thirty day trial. And now for my discussion with doctor David london, professor lindon. welcome.

Thanks so much for having .

me been looking for to our conversation. And we have a lot to talk about. We do lots of different aspects of science, lots of different aspects of personal journey. And what you're confronting now as IT relates to your health and your future, I want to start off with a question that I learned from the one in only the great cardio, who was the first guest on this podcast, my colleague at stanford. And for those of you that don't recognize carles name, he is a absolute phenomenon, A A active clinical psychiatrist, so is an M D, and he also is a bioengineer who's developed a lot of the modern tools for pRobing the brain and um any time I ve met with coral, the first thing he says is, what are you most excited about lately?

That's a good question.

IT is. So i'm going to steal that approach and say what you most excited about lately?

Well, very, very lately. The most interesting thing that I rerun in neuroscience is the answer to A A, A scientific problem that I think is really dear to a lot of people's hearts.

And that is, what are the nerve endings in the genitals that are responsible for sexual sensation? And you know, if you think about IT, right, people can feel sexy from being touched on lots of different parts of the body, but there is something special about the genitals, doesn't matter male or female or intersex or a gay stator buyer, whatever are, you know, the genitals are are a hot spot. And why? And you you think, as biologists, we know this by now, this would be something we could just answer.

But but it's been a mystery for a long time. And if if you go back to to eighteen sixty, there was a german neuron anomalous name, cross. And he cut thin sections of tissue from the penis and the client, and he looked at them under the microscope, and he saw a particular kind of nerve ending there that has since been called the crow's corpuscle.

And there were lots of them in these two places. And so he thought, well, maybe this is the soil lar basis of sexual sensation. Maybe these are the particular nerve dings that are responsible uh for this um but there were some things that that were in favor of that and some not.

So these new inventors are also in some other places that people can find more or less sexy like they're in the nipples and they're in the lips and they're in the anus or places that get popular um in that domain, but they're also in places like the cornea or the lining of the joints. So distribution doesn't quite make sense. And so I was never known.

And so if you wanted to really test, as a scientist, whether these new vendors are responsible, you want to record the electrical signals while the generals are being touched. You d want to inactivate these cells and see if you could interfere with with, uh, sexual sensation. And this in a preprint from David ginty's group at harvard, is just what they have been able to do in my they found a way to label and record from and activate and inactivate artificially.

Uh, the crowds core puzzles. And so you see a nerve ding in the skin. IT could be convey all kinds of information.

IT could be tuned for hot, or for cold, or for inch, or for pain, or for in, or for inflation tion, or for mechanical sensation, stretching a vibration data and share enough when they recorded this cross core puzzles they really did are, uh, mechanical sensors, as you would expect, uh, if they were involved in sexual sensation. So that was good. And then, uh, the other thing then they did is they try to artificially turn them on.

And so the way they did that, as they use genetic tricks to express one of curl disavows. Uh uh molecules that activates neurons when they when blue light is shown on them and they found that if they express um uh this artist of protein in the crown cells in a in a male mouse and then shine blue light, the mouths gets interaction all right. So far so good.

What happens if you turn them off? Well, if you turn them off in a male mouse, it's just as interested in females when they're in heat. But IT won't mount and thrust and ejaculate as much. And if you turn them off in a female mouse during the time of her cycle where he would Normally be sexually receptive, uh, you find that he is much less interested.

She's much less slightly that amount SHE is much less likely to let him finish so this is the remarkable results that uh, finally, after all these years since eight hundred and sixty now we know what the nerve dings are that convey sexual sensation. And like all good science, then you know there are a lot of questions that are really interesting to our everyday lives. Like, you know, people like different things in bed and have different propensity for orgasm or or like like to be touched in different ways as well.

Is part of the reason because of individual variation in their cross core puzzle structure um we know that sexual sensation diminish with aging is that in part because crowds core postle density is lost from the skin of the generals and that's a reasonable idea because we know, for example, that find touch sensors in the fingertips uh so called merkel and minona endings also named after german and us like so many things are uh are also lost with age. That's a reasonable ideas. So so this finding from ginty lab has opened up a whole world of science.

And i've been my my own lab doesn't work on touch. But i've been a fan boy of touch for for many, many years, mostly because where I work at john hopkins medical school, there have been many terrific touch researchers. It's been a world center for IT, and I hear about IT over a lunch, and I got all fired up. So years ago I wrote a book about, and I still follow the field. And this is the most interesting .

thing at that field recently, as I was guilty, was your neighboring hopkins before he .

moved to harvard. That's he was one of the ones going to, uh, a Steven shaw, Michael Karena. shhh. G don. There been a number of world leaders in in a regular basis of touch sensation out hopkins.

Do you recall if in the preprint that you are describing, there was an experiment where they activated these crowds core postles in females?

It's funny. You should mention that I sent that exact email to David ginty and they said they are in the process of doing that right now, and they don't quite know yet. And so I asked, I said, so for example, is erection of the clitter even a thing in mice? He said, well, we're really not sure.

So we're activating the crowd core puzzles and female mice, and we're just going to stare at IT and looking and see if anything happens there. Does the you know does the the body change shape? Is there a color change? They don't even quite know what IT is. They're looking for cues that much on the leading edge of things.

but it's a good question. Or perhaps the female mice would be more willing to made outside of the usual time frame of receptivity if, uh, these crowds core possible are are stimulated.

that's possible. My suggestion, my guess, would be not because I think that the hormonal regulation of receptivity is like a sledge hammer and very hard to overcome, but they might be more willing to continue meeting or make for longer during there uh, further time.

And I just want to remind people because we had a guest recently, uh doctor rena molik um who's a erotic gist reproductive and sexual health expert a md and uh he made clear that the the glitters and the penis come from the same embro ic origin. They are allega tissues in different individuals I do have one more question about this sexual touch thing. These are peripheral nerves, right? So these are not of the brain in spinal core. They are in what we call the periphery. And my understanding is that peripheral neurons regenerate and can remodel themselves extensively in ways that neurons within the brain and spinal cord tend to remodel less, especially as one gets older out of the so critical period um is IT possible that these cross corp skills and their patterns of innovation within the genitals change according to the stimulation that um people experience um in other words is sexual sensation experience .

dependent that is a great question and so we don't know, because monitoring this in people is not technically possible, right? IT requires, could ever to show, so you can only do at once in animals. IT IT IT will be. And IT IT could be for a couple of different reasons, and others IT could be.

I think what you're imagining is that there's actual structural plasticity if you look at these cross core puzzles or that you would actually see them changing their shape of their size or their or their density as a result of experience. But uh, what can also happen is a phenomenal like desensitization uh that is to say when the stimulation for a long time then are the receptors translate can become less sensitive to touch and IT. It's well known, particularly in mails that uh that chronic mastering can produce desensitization of sexual sensation and the piano and that could be as a result of a physical change, a method gc change and across core puzzles. Uh but it's more likely to be a change in their function that you wouldn't be able to simply see by looking, uh, at an outline of their structure the microscope.

Such an interesting topic. Thanks for opening things up with. With that, now i'll have to check out this preprint. I'm also a huge fan of David gin, this work and and colleagues, there are many people involved in that domain of work. Of course, i'd like to talk about your recent book and the sort of underlying basis of what LED you to write IT and what intrigued about this idea of human individuality the book unique is one that will provide a link to in the shower or captions and it's a very interesting idea that we are all different um especially coming from a neuroscientist to we were trained at least similarly IT to learn that sure the bombs ripped s of the brain in the fine wiring of the brain is different and we are all unique and different that we have different shapes and more logy. But focusing on human individuality is not something that modern neo science, where classic neuroscience has really done much of it's really focused on how people do x or people do why this way um tell us about unique and tells about human individuality yeah well.

I mean, you're absolutely right. So when I look at the experiments in my own lab, how do we do them? What we work on mice? do? We work on mice with genetic variation? No, we work on highly in read mice that are designed to be a genetically similar to each other as possible. And then we raise them basically in prison, in little, little cells, which may not be a good idea. And we try to give them as similar experience as possible.

They are given toys in food and water. But I agreed IT IT resembles a prison of source.

They aren't free to rome that they have nothing like the experience of a wild mouse. Let me put in that way there. Uh uh and and yes, there are, as you said correctly, there are plenty of experiments where there is enrichment.

S H. For my son, I love IT. So for example, in our lab, when we put running wheels in the cages are mice and let them run overnight, they're active at night.

Um your average mouse will run two kilometers in a night for a little tiny mouse. And some of the mice are so intense there will run twenty kilometers. Imagine a mouse doing twenty k but but that will happen.

They really, really like that. They don't like being in prison. They don't want to exercise. Uh, they're really bored. So yes, to get back to your general point, uh, so much of science is designed to try to find general principles of a function of the brain of physiology, of genetics uh and to ignore individual variation.

But individual variation is so important to our human experience and actually is so important to to the process of evolution and natural selection, how how species uh make their way in the world, that that it's it's something that that requires a lot of attention. And to me, what's really fascinating is that when you look at the variation in the way sense organs function, it's almost a miracle that we can agree on a common reality at all, even within the human species. And this is true of of more of of of some senses, more than others.

Obviously, in your world, in the retna, we have various kinds of of loss of color vision, uh, that are well known. And some other more complicated phenomenon are having to do with impairments in the perception motion uh or form. But a the place where this really happens is in the all factory system.

So we have approximately four hundred functional receptions for different ordering molecule smells uh in our nose. And if you uh sequence the genome of many people, you find that the um that the the DNA that encodes for these altering recept tors is unusually variable from individual to individual matter. Fact, if you take two different people on average, they will have functional differences in thirty percent of their older receptors.

And if you do as let's leave vaste and her colleagues did at rockpile, our university, and give older tests where they give people different things to smell, and then they dilute them and find the threshold which that can detect them. You find enormous changes from people to people, both in term, in general terms, some people are just Better smelters than others, but in terms of individual others as well. There are some others that some people can't detect and other people smell one way.

For example, there is a um there is a secrete hormone called under steady and resting on there are some people who can smell at all. For some people, uh IT smells like rather pleasant, like cut grass and for some people IT smells fl like your or sweat. And IT just depends on genetic variation in one particular altering recept sorry tript uh another .

a phenomenal researcher who studies all faction, among other things. Katherine do lock um I once heard say that some people have a gene that for them makes the smell of microwave popcorn um they experiences that smell as vomit. And other people who lack this gene like the smell of micro popcorn, at least for them it's not aversive. So I can really be a binary response.

Well, I can not. Actually, that's a very particular funny case. So the relevant chemical there is Peter acted and also I ovc acid.

And so uh, there are uh, researchers. I think racial hurts. Uh, is one of them who have given a mixture of these two chemicals people and they say, this is permission, cheers. They go, oh yeah, that's permission on cheese.

And if they give IT to other people and say this is vomit, they go, oh yeah, that's vomit and if they tell people they give them one file and say, this is a permission and SHE ego, yeah, they give another one, they say, well, yeah and then they say, well, actually we feel is the same vile. They said, you must have made a mistake. They're convinced that they couldn't have been the same thing.

So this points out not only is their genetic variation that uh is responsible for our individuals perceive older, but we are incredibly suggestible in terms of orders and we we are very dependent upon them in terms of cultural context uh and and this can be and this can be learned and and this is central to our humanity in the sense that that we humans are what i'd like to call the anti pandas as uh pandas live in one spot um in in southern china and they eat one thing bamboo and that's yet humans are the opposite. Humans can live in any ecological niche in the world from the tropics to the polls. And humans eat a wide, wide, wide variety of foods.

And as a result, IT means that we have to have a very plastic or factor system that have to be very few things that we find innately averse. There are only a handful of oders, rotting meat oders. Uh, molecules with the evocative name like canaveral and putera are things that even babies, when they're newborn, find divisive.

But other things happen that they need to be learned for example um pretty much every adult finds poop orders uh unpleasant but babies happily play with their own pop. They have to learn that disgusting. It's not cause babies have a different nose.

It's because they have to learn cultural not in ate IT is not in eight um there are only a few in eight older a versions and a few innate taste a versions that were were born with and the other things are elaborated and culturally and we can think about this in terms of how we we we talk about order. So for example, we might say vanilla smells sweet. Well, that's weird.

That's like there is a two different senses. How can something smell sweet? It's like saying that sounds red.

right? So it's a statement about right.

And but but how did you come to pass? And do people say that vanilla smell sweet everywhere in the world? Well, the answer is no.

So in places in the world where vanilla is used with sugar in in sweet foods like desserts, then people say that vanilla smell suit, or mint similarly, uh, smell sweet if IT is typically used together with sugar. But if you go to a place like, uh, uh, like vietnam, where mint is mostly used in savory dishes, people won't say that mt. Smells sweet. So there's a pair .

association there that, at least at our level of conscious understanding, feeds back onto what we call all factor smell perception. But really, it's IT must be a pair association at some point in development IT.

Is that absolutely as a pair association and it's something that goes on continue through your life, right? I mean, lots of people, for example, I have stories of foods that they wouldn't eat as a child, but they came to like as an adult. Um a good example of that is coffee.

Uh a lot people have to overcome bitter aversion to uh to become coffee efficient OS. Uh so uh you know this feeds into the more the more general theme that there is no pure perception. Perception is inference. It's not like there is a purely objective world that can somehow make its way through the senses.

And we can perceive that as the truth, all of our perception through all of our senses, both the outward pointing senses of the world like smell and taste and sight and hearing uh and the inward pointing senses like baLance and is my stomach for, uh, and things like that. All of them are based on experience and expectation and the situation of the moment. I'd like to take .

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If you'd like to try athletic Greens, you can go to athletic Greens dot com slash huberman and theyll give you five free travel packs that make IT really easy to mix up athletic Greens while you're on the road, in the car, on the plane, at a and they'll give you a year supply of vitamin d three k two again, that's a letter Greenstock comes slash huberman to get the five free travel packs in the year supply of vitamin d three k two are there any examples of uniqueness of visual perception that come to mind? I recently did a social media post um that involved IT was essentially three rings a blowing um a red ring and a blue ring in the center of perhaps IT was the other way around excuse me, IT red, blue, red and um I asked which ring is in front of our they all at in the same plane now of course it's a two dimensional image and interesting ly IT split out into about thirds. Some people see the blowing in front quite a bit.

Others see a red ring out in front. Others see them all in the same plane. In this we think has to do with um differences in two things between individuals. One is the distribution of the con photoreceptors um which we know is essentially random between individuals, maybe even between the two eyes and then um and that gives rise to this phenomenon of chromatic Operation um which is the displacement of the visual image according to the wavelength, the light. And we won't get into the physics of IT now i'll soon do a post that hopeful ly distils IT no matter that simple enough to people understand but clearly some people see certain colors in front of others um and the person right next to them could see the opposite color in front and others say, what are you talking about? All the colors are exactly the same plain of of vision um so that's the one that I know um i'm guessing you know some others and perhaps some more robust ones.

Well, I think you know perhaps this is maybe not what you had in mind, but one way in which experience modifies the visual world has to do with how much light your exposed to in the first five years or so of your life.

And so kids that don't get outside are much more likely to be my opie and I actually is near cited yes uh uh when they grow up, uh then kids who got outside and we now no that at least part of the story is that light seems to stimulate the um expression of a class of molecules called trophic. Factors that you're well acquitted with that actually changed the shape of the eyeball. So it's not really the structure of the retina or the lens of the cornea.

The actual degree of illegal ation of the eyeball changes, changing the way the the retina sets relative to the limbs and that seems to be light dependent early in life and which gives rise to a uh to A A higher instance. To my opie and to me this is really well, first of all, it's it's news you can use. You should get .

your kids outside.

super minus a point.

There will be putting me in the grave, David, and be telling people to, or maybe will be on my tombstone, say, get gets online in your eyes, especially on, especially on cloudy days, because there is still sunlight, even if you can see the physical object of the sun on cloudy days.

Well, you know, I think this whole idea of having treats that are dependent upon early life experience is fascinating because there are a number of situations where you would guess that something is genetic, but IT isn't. It's actually dependent on early life experience. And there's there's an amazing story about this having to do with the early days of world, world two.

So in the early days, world war two, the japanese army just swept through asia. They defeated the british malaysia and singapore, the over from thailand and burma. They were knocking on the gates of india. And everything was going great, except the japanese army had a problem. There were an enormous number of their soldiers who became incapacitated with each stroke.

They got their court temperature IT got too hot and uh when the army doctors, uh example, they found this was much more likely to happen in soldiers, uh, who came from the northern part of the japan. O where is you? Where is snows in the winter? I was opposed to the southern part of japan mo, which is semi tropical environment.

And the classical explanation, the biologists like us would guess, would say, oh, all right, well, this happened genetically over many years. Uh, you have a family that's been in the issue for many generations and you've selected for gene variants allowed to tolerate the heat Better. And we know actually what this is.

So if you're more heat tolerant, it's because you have more of a particular class of sweat glan called the a crime sweat land, this sort of salt water sweat gland, not the liberty stinky armed sweat gLance called the applicant ones. The aircon, once you have a higher fraction of them that are innovated, meaning that the signals from your brain that say your chores too hot can then make you sweat. So the total density of sweat lands between northern and southern soldiers in japan wasn't different.

But the southern soldiers tend to have a higher degree of innovation. R. S, say, say, okay, well, this happened genetically over many generations. But if you look at those rare cases where you have soldiers from a long establish northern family and their parents move south, and then they they grew up in the southern location, they had high sweat and innovation. They were well he tolerant. Conversely, if you have a well established southern k issue family and they moved to ocado and then have their child, that child developed the northern sweat gland innovation pattern.

So we need. Nerve innovation of those sweat lands, as you mentioned before, just as many sweat glands, just less nerve innovation. Therefore, those sweat lands could not be activated. They couldn't dump at as well.

Their heat tolerance was lower, actually, right? And what's what's what's wonderful is that this gives an advantage that you can get through evolution, and that you can happen right away in one generation, right? Evolutionary change to slow, right? And you can adapt as a species and as a family over, over many, many, many generations.

But when you have a phenomenon that is set by a early life experience, well, then you can benefit from that early life experience within your own life. It's not that you are great, great, great, great, great grandchildren will ultimately benefit. You benefit. Another wonderful example of this, a comes from field mice, voles.

And we were talking earlier about how we both worked with the scientist irv zuker uh at berkeley who is specialist in in in involved and uh what people found is that if you take uh wild cut a field, nice and uh you have uh uh pregnant mothers and you have in the lab, but you manipulate the lights so that uh you have artificial spring and other word's daylings is getting longer day after day during the pregnant say then what happens is when their pups were are born they will have a low density of fur anticipating summer temperatures are if you, however, 啊， put them in artificial fall where daily length is getting shorter 啊， they will be born now what high density of for anticipating winter temperatures? And of course, you can do this no matter what the season actually is in the world by manipulating these lights in the lab. And so like the sweating japanese soldiers, this is a great example of early life plasticity. And just the sort of trade that if you ask someone they would probably guess is hittable, but actually is not. Thanks for mentioning .

your visual ker. Who was uh, you also mentioned with a adviser to us both who an incredible work in circling biology, seasonal hythloday hormones and behavior I have such a reference for over the experiment you mentioned made me smile wide because it's but one of gosh, maybe hundreds of incredible study. So people are interested in seasonal rhymes and cracking, rythm and biology of the most interesting kind.

Definitely check out irvings. Others work at burkey. We'll provide a link to to his partment there. Since we've been taking a tour of individual variation in a factory perception, visual perception and now heat tolerance, I have to ask, are you aware of any examples off the top of your head um in the auditory domain that particularly in trial?

Yeah well, I would say one really interesting example how to do with perfect pitch. So perfect pitch as a trait that is to say, uh, you have the ability uh to to hear a note played and say, oh, that's a sea sharp, right this is a pretty real trade. So even if you look among highly trained musicians, if you went to p body conservative or at my university johns hopkins and test to people there, you would find a higher incidence of perfect pitch.

Then you would, in the general population, but still maybe one in ten trained musicians have perfect pitch. And parenthetically having perfect pitch doesn't necessarily make you a Better musician, uh, but is an interesting phenomenon. So the question is, well, is perfect pitch heritable? And the answer is, when you look at twin studies where which is what we used to estimate their ability, the answer is it's kind of low. There is a heritable component, but IT accounts for, uh, my recollection is on on the order of thirty forty percent of the variability in perfect pitch. However, if people receive your training starting at a Young age, the chance that they will develop perfect pitch can improve drastically in your book .

unique ah do you cover aspects of human individuality that extend beyond the percept in domain um into the cognitive domain?

Well, Young, absolutely. And no I think I think is good to set the stage here if we're going to be talking about here itabhi and human individuality.

And so if I can go out on a little bit of a rif, uh uh for the benefit of your of your listeners and you so if you look at human traits, whether their behavioral traits like shines or very straight ward morph hologic traits like height, uh, what you tend to find is that there are very few traits that are entirely heritable, where all their variability can be predicted based on the gene variants you get from your mother and father. And there are a few trades that are absolutely unheard able, but the most fall in between. So let me give an example.

Everyone in the world has either wet or dry your wax and IT turns out that this is determined by variation in a single gene. The name of the gene is boring. Its A B C C eleven. Uh, it's, uh, I am transporter and uh, there is, uh, variation in this gene gives rise either wet or dry ear wax IT.

Doesn't matter how your parents raise do you? Doesn't matter what foods you are growing up, doesn't matter what what a, uh diseases is your mother held when you're on the whom is one hundred percent charitable. What does this mean that A B C C eleven, we should call IT the air wax type gene? Well, no, because it's not there just for that like this.

This gene is expressed themselves ls, and all parts of the body are doing all kinds of things. Your wax is just something that we notice. Genes don't code for traits, they code for proteins.

And so we have to be careful about how we refer to them in that way. Um for example, the wet air wax g uh variant of the A B C C eleven gene also confers a slightly higher risk for breast cancer. Ah so clearly it's not just for air wax is for a bunch of things most of which we don't yet know about. But in the case of air wax, this trade is one hundred percent hittable.

At the other end of the scale, speech accent is zero percent terrible IT is entirely dependent upon the speech that you experience uh, in your childhood and interestingly, it's the speech of your peers more than the speech of your family which is why the children of immigrants sounds like the place where they wound up, not like their parents uh and there is no evidence for any degree of heard ability. And not just to be clear, i'm talking about speech accent, like whether you have a high or low voice, nasal or more less reason. These are physical things having to do with the vocal track.

And they are in part here able. Okay, so we've got one thing is a hundred percent hittable, and one thing is zero percent heritable. But where are the most things? For most things fall in the middle.

A, uh, one of the most heritable traits that we know about in humans is height. And in the united states, height is about eighty five percent heritable, eighty five percent of the variation. The trade of height can be explained, uh, by what you hear from your mother and your father.

Well, what's the rest? Well, it's nutrition. It's the diseases you fought off. It's also random variation, which will talk about a lot later. Um now you might say, okay, well, that's an estimate for people in the U S.

Is this to all over the world will know if you go to a place where people routinely don't get enough nutrition and are routinely fighting off infectious diseases like this has been studied in rural bOlivia, for example, a rural india. Now, height is no longer eighty five percent terrible. It's only fifty percent terrible.

why? Because people in these situations where they don't get enough, nuristan, where they're finding of these diseases, can live up to their genetic potential for height. If you want to make things Better for the people of the world, then everyone needs to have basic things like the ability to learn and enough nutrition and and decent medical care and schools in order to fulfill their genetic potential for positive traits.

And a height i've used as an example, because IT is very uncontroversial, but we could apply the very same analysis to intelligence, general intelligence. Now there are people argue about, do things like I Q tests really measure anything real? And there's been a lot of fighting in the scientific literature about this. But I think intelligence tests aren't perfect and they are sometimes culture bound, but they are actually quite predictive of of of of later success and uh much more so than say, S A T tests or G R E tests or m cats or other standardize tests assembly .

those correlated in some .

way they do by do, but the I Q tester Better.

Actually there is something about the classic I Q test.

I am talking about the modern variance of the classic I Q test that are ministered by train psychologists uh and aren't just to pay perform and so they're not perfect and no test will be perfect but they're pretty good. And so then if you ask the question of what is the hedblom for I Q test score, uh well the answer tends to be different depending upon the population.

If you look uh again in in countries like the U S R and western europe that are fairly affluent where where people uh tend to have good access to to nutrition and medical care and schooling and kids get to play and they're and they're not traumatized by war, then uh then I Q tests core is hittable in the ball part of sixty seventy percent. But if you look at people who don't have those benefited, who are poor, and this can be in the united states as well. If you look at uh, communities that that a face discrimination and have consistently poor, poor health care and schools, then I Q is less terrible.

why? For the very same reason that IT is in height, because people can live up to their genetic potential when they don't have. The basic thing is that .

everybody so presumably if two identical twins and I realized they are in identical, but you're familiar twins, you have twin children um if two identical twins are raised separately, the correlation in their I Q is can only is IT that only sixty? I've think you said about sixty six percent of their I Q can be predicted on the basis of their genetic makeup alone. I mean, IT makes perfect sense to me as to why if one of those twins went to schools that were demanding of know a lot of different topic matter and the other one went to schools where the the instruction level was really deficient, that one would perform far less well on an I Q test. Unless, of course, the I Q test isn't tapping into school based knowledge, is tapping into some other thermometer of of so called intelligence or IQ.

Well, you know, the thing is that good schools corporate with many other things, right? So the students that go to good schools aren't just benefiting from good schools. They tend to also have good medical care and safer, less trauma, tizer and neighborhoods.

And there are more likely to have books, parents with works in the home and uh uh and and a whole number of things that are all beneficial. So when you try to do epidemiology on this, you have to be aware that things are very deeply interconnected IT. But but you bring up a good point.

So IT turns out that the way we get these estimates of her itabhi, there's two ways. One way is to compare so called identical or monotheistic twins with so called for internal or diogo tic twins. So the identical twins will share nearly a hundred percent of their gene variants, and on average for internal twins share fifty percent of their a of their gene vaLance.

And generally speaking, when people do these studies in order to avoid confounds of sex, they will compare same sex fernal twins, so boys to boys and girls to girls, uh, uh, and uh, when you put these incidents into a formula, all Fisher's equation, then you can come up with an estimate of the heritability of the trade. But there is an assumption present in that, and it's called the equal environment assumption. You're saying, well, two kids raised in the same family have the same environment.

Well, that's not always true, right? That can be violated by a number of uh of different situation. So IT turns out that a more powerful but much more difficult way to estimate her the ability is by looking at twins read apart, either identical twins or fernal twins apart.

And there was a landmark study called the minnesota study of twins reader apart, which is abbreviated mista that is really the gold standard for assessing the herbs of many different human traits, both behavioral traits, uh, but also disease incidents. But of course it's a small end because you know the population of identical twins, we are a part that you can get into the lab. Isn't isn't that large? They had something I don't remember the exact numbers, but they had something like eighty sum uh uh identical and fifty sum return als uh in there in their sample.

But by doing this they were able to come up with a lot of interesting estimates. And so for example, most uh personality traits, uh what the psychologist uh use the acronym ocean to mean openness, conscious ously empathy, a gril baldness and noodles ism. I think I got that .

right .

build right um yeah that these traits on average tend to be about fifty percent hittable. And so okay say right well fifty percent of those personality traits heritable. The rest is gotta be like how you are raised.

It's gotten be in your family. And so everyone was shocked when they actually did the analysis um and found that family has almost nothing to do with that. And and everyone, what are you? Are you kidding?

It's it's got to and I think the important thing to realize is these trades I just listed you we call these personality traits, but they are not the same total of the way you are in the world. Parents can insulate many things in their children. They can demonstrate trades.

So people are much more likely to go into an occupation if their parents did. They can equate moral ideas and religious ideas. But in terms of these ocean personality traits, they have astonishingly little to do with that.

So then this brings up the question, well, if fifty percent of the variation on these personality traits is not from your genetics and it's not from your family, where does IT come from? And the answer seems to be, is that IT comes from the random nature of the deal amount of the body and the nervous system. And this is, this is a point that I think many people don't understand.

This is something that biologists know. But we've done a very poor job of communicating to the general public, the genome, all your DNA, all three billion bases of DNA, all ninety thousand or so genes in human, don't make a blueprint for making your body and brain. There is not a thematic diagram that connects everything to everything, particularly in the nervous system where we have these hundreds of millions of connections.

Rather it's a rather veg recipe. So the the genome doesn't say, oh okay, you glue mate using neuron and the brain ation called the foma you know growth for two hundred microns towards to the top and then and then and then cross the midline and then grow towards the year for, you know, another distance. No, IT says something like, hey, you bunch a glutamate neurons in the film is over here in this area, about half of you cross the midline.

And so what does this mean in terms of individual variation? That means, well, for for some individual, forty percent of their axels will cross the midline of the brain. And for another individual, sixty percent will even in identical twins.

And as you correctly set a moment ago, an identical twins aren't really identical either in their bodies or their temperate. So if you take a new born, identical twins and you give them a CT can just to measure the shape of their organs, they're not the same. You might have one twin whose clean is thirty percent larger than than the other twins, or whose liver is thirty percent smaller than the other twins, even though they have the exact same D.

N. A. And they were ly on right next. Each other in the woom and presumable have the same or very similar theater environment. And the reason is the round of, or as we say to caster nature of neural development, a great way to study this is with nine banded armadillos. I know didn't weird here.

but I love the army deal because i've been told, tell me I don't want to a interrupted too long. But far I know the only animal in north amErica that curious leprosy.

uh, that is that is true.

And and there's a lot of twining going on in armored illos.

right? Well, what there is is actually quoting so armado los or the nine banded armada in particular. And there are different armadas.

I'm not really an armada specialist. I don't know if this holds for all of them, but the nine bounded armadillo is born as identical quadruplets. Awesome, awesome.

So you can take these identical quadruple. That newly born armando la, I don't think you call them pups. I don't know what a baby .

arma della was called. And sure, there is some particular word for IT. Someone tell you on youtube what is the name of a baby? I baby are the mom's are jill.

The dads are bob. s. Are used to be obsessed with this kind of naming, know a business of fairs, or what is like a ganga, raccoons or whatever. So if you can tell us what the name is for the baby armadas, as well as what he call a group of armadas, you win the pride associated with being right.

right, right. One of my favorite is an austens of peos amazing.

or a murder .

of close.

I think I I think that's correct.

But so if you have four newborn, uh identical nine banded armed delos than this is a great model system that biologists can use to study uh uh uh stolk tic differences and development. And sure enough, their brains are wired slightly differently. Their bodies are slightly different.

If you test them behaviorally even very, very early in life, they have propensities summer. Bolder will explore more. Summer will tend to hide in the corner more.

And we know this from the lab. If you get a box of mice that are in read from the breeder and you pluck them out, they're not behaviorally identical. Some might try to bite your hand, some will run away.

Some will stand stock still. Where does this behavioral variation come from? In my other nearly genetically identical, well, IT comes from a bunch of things. They don't always have exactly equal experience. But mostly IT comes from the photo, random, sarcastic nature of development.

And is the zudar, random character nature of development one of the major, major, excuse me, driving forces for evolution? Because, you know, we hearing about mutations, and we always think where people tend to think rather that mutations are bad. But of course, mutations provide the variation that can also subserve adaptive traits. I mean, if you are fan of the x men, as I am huge fan of the x man, the entire series, every single one, including the wavering movies, you quickly come to learn that genetic mutation is at the heart of variation, which is at the heart of individuality.

which is what we're talking about, right? And so genetic variation is at the heart and intuition. But there is also, there are also these other things right that we've talked about. There is the effects of early life experience and there is the stock cast of nature and development.

Because if you, through the renderings of development, happen to have like a particularly great liver, you're not gona pass that on to your children, right? That isn't in your germ line. You won't pass that trades along.

Just put a brief answer here on germ line. We had dead ra shoppe on the podcast studies epigenetic transmission and um and inheritance of of of its not long market in we have to point them out, but um inherited anc of a sort of acquired traits that does happen in the german, the genes that are present in the the sperm and in the eggs. All the other um cells of your body have genes of course but um the best way but this is a simply going to the gym and getting fit does not make your children more fit because the german line, as far as we know is not modified in a direct way, is in the words the DNA with inspiring and eggs are not modified according to your behaviors in most but not all cases.

That's right. And and as you um as you correctly said about oddzon work and and other people's work, there is what's called trans generational epi genetic inheritance which means that you can have traits that our past not from one generation to the next but even two generations to the grandchildren, that don't require modification of DNA. But to date, that has been shown very convincingly in in a warms indian plants.

Uh the evidence in mammals is is really not there yet in in my opinion and most of the claims for that, and it's a very popular thing to say, I ei genetically inherit my grandmothers or great grandmother's rama. The evidence at present is is poor. Actually, a lot of IT comes from epidemiology, most of which came from famine in the other colleges region of northern sweden and the very good medical records.

And they say, oh, well, if your grandfather went through the famine, then you are more likely to have this trade. If your male, if your grandmother went through done. If you, if you're male of this train, your female of that trade. And I mean, there are two problems. One is there is not a biological mechanism, but the other problem is that the way these things were discovered is by something called harking or hypothesizing.

After the of results are no uh, they did very many statistical comparisons to try to find something to significant and you know from you're work in the lab that when you do many comparisons, you are going to get some things that looks significant just occasionally round way through through through luck and you have to apply a statistical correction called a bond feroni correction when you make many, particularly post hoc comparisons after the experiment, uh, comparisons to set the bar much higher for accepting that data. And most of those studies, they didn't apply that correction. And I remain unconvinced of trans generational epigenome heritage in mammals.

Now let's be clear, just because IT hasn't been shown convincingly now doesn't mean that IT won't be. There are some good people working very hard on this and they may well uh, describe a mechanism and show this convincing in the years to come. But right now, uh, you may well inherit your grandmas or great grandmother trauma, but you are probably doing IT socially, not through Marks on your DNA that changes how your genes are expressed or not expressed.

yeah. So I subscribe the idea that there is absolutely certainly transgender tional inherited ves of parenting and upbringing. right? I am your grandparents.

Raise your parents to raise you. Not always people can be adopted. In fact, I have adopted members of my family, but I understand what you're saying correctly. The evidence that, for instance, some stress related gene was modified during a trauma in my grandparents are great grandparents. And the idea that was passed to me through my parents that the evidence there is, is far weaker.

right? When you think about IT, well, like how did that happen? That had to get into your your grandparents burr edge cell and then produce that effect in the brain of your parents. And then I had to get into their experiment or excel and then contribute to producing that in you.

But but fragmentation of DNA and permits or an ex is is is a common thing, especially as people age D N A of sperm eggs fragment um and it's possible that some of those mutations still low for a viable embrus. So it's in theory the german line could be changed by um environmental events.

Well right uh but now I think your starting to talk about things that are heritable, right? You're not talking about Marks on DNA. You're talking about the structure of the DNA right itself, and that is its own separate issue.

Now I think I I want to be really careful about this because what is now, I think, fairly well established is that you can transfer things epigenetics over a single generation uh, if as a result of experiences that the mother has during pregNancy. So uh, for example, we know that during the thousand nine hundred eighteen pandemic flu, uh, many women were pregnant and got the flu. And if you look at their children, you find interesting statistical.

anomalies. And those children, for example, of the males, wound up going into the army for world war two. And of course, the army does a complete physical and the records are very good.

You can go into that database and you find that, uh, the male children uh that were uh in usual during the winter of one thousand nine hundred eighteen during the pandemic flu are on average a millimetre to shorter. Say i'm no to that's nothing. But in a huge statistic sample of millions of people, that's enormously significant.

More interesting is that the incident of schizophrenia went up about four fall from about one percent to about four percent. And even though autism wasn't a term in nineteen eighteen yet ah, I don't think came along later what we now retroactive C C, timely would call autism also wound up by about for food. So there's something about mom being stressed and Carrying the feast at a particular stage that seems to impact brain development and away that then makes that child more likely to be schizophrenic or artistic when they grow up.

Do we know that it's stress and mirror collection of this? I believe this was um the late paul's n bergs work as well. Maybe have that name in cracked, but in any event that IT is um if pregnant mom gets the flu in the first crime master, you see this higher incident of schizophrenia in an autistic offspring um and but do we know that it's stressed, precise because it's stressful to have the flu. But the flu a bunch of other things could be fever, could be um some break down in the immune barrier. I just want to open up the the number of variables that this could be or do we know that it's something in the python mic petitti so called stress access that is of a general hythloday c tory general access um I gives IT elevated court is all um or could IT literally be an immune neural interaction of some other sort?

It's probably the last thing you mentioned in immune neural interaction. And the reason I say that is that uh Gloria at M I T uh uh a together with her collaborators, has made a mouse model of this phenomenon. So SHE takes pregnant female mice and SHE injection with something that that is SHE doesn't actually infect them with virus SHE puts a chemical that is on the code of viruses that myself ics viral infection.

And uh then what happens is that in a way that interestingly is an interaction with with the bacteria content of her of her gut produces a surge of a immune signal molecule. The interaction seventeen, interlude seventeen can pass through the pleasant a into the fees. And if it's present, just as you said at a particular point in development, doesn't work anywhere during pregNancy, but during something that is sort of the mouse equivalent of the first prime master.

If that occurs, IT causes disorder. Development of the layers of the cortex. Instead of IT.

Looking like layers of a cake, you see balls and plumps of cells and parenthetically in some, but not all, postmortem tissue from autistic people. You can also see those balls and clumps of cells. Those balls and .

clumps of cells start to reflect alterations in cell migration.

They are yeah some I don't know if it's entirely knowing how much of the celt vision or migration, but certainly migration is a part of that and it's very likely with that critical moments uh to disrupt this ordering of the brain and produce these increases in schizophrenia a or or uh autism vulnerability uh are coming at a point where neurons are migrating uh, during development and uh so what choice group did as they do? We did all the things you would want to do as a biologist.

So they give things to block the function of of this interlude. Single and IT blocked the phenomenon. They artificially injected the signaling molecule into fetal brain when the mom hadn't been stressed. And they could they could reproduce IT.

So i'm not saying that there aren't effects of stress hormones from the hypothalamic paulita access that are important that you mentioned, but in this mouse model system work, uh IT seems that you can produce IT through this immune signaling pathway. And and so then the question is, well, like R V S, my autistic. Well, how do you know if a mouse is autistic? And and the answer is it's actually a little vague, right?

There are behaviors that neuroscientists say are analogous of human autism. And one of them is, if you give a mouse of marble in its home cage, you will bury over and over again compulsively, or bury many marbles. And people say that that is somehow analogous to some of the compulsive behaviors, is an organ. It's a bit of a stretch, right, and a chAllenge to interpret mouse behavior in in human terms but um it's a reasonable for step.

Incredible and I hope more will continue to be done as its surrounds. The first trimester influences a hypothesis because it's been around a while and um and obviously there's a spectrum uh of what we call autism mass burgers and nowadays people refer to this sometimes it's neurotypical al. There's some high functioning people with autism. There's some low functioning people autism and for that matter, there's some high functioning and low functioning people who don't have autism.

Um but this is something that I think a demands our attention and and IT that hopefully will be resolved at some point because also influenced but one immune um insult um and reasonably pregnant women are being bomb barred with all sorts of viruses and bacteria and fungal infections and fighting them off or not fighting them off. And who knows what the variation in uh nurmi interactions exist in there. They give rise to you know good variation and let's go IT um you know debilitating variation.

Well that's that's actually right. And so for one example is that a we don't know what the effects are on the children who were in euro while their mothers were fighting off coded, right? We won't know for a for a while where are .

the and cold and .

there might I mean, there might be nothing but or there might be something serious, uh, learning there like there was for pandemic flu uh, and we will be very interesting and and important to find out.

agreed. I'd love to talk with you about mind body. But before we do that, I would be totally remiss if I didn't ask for your broad top count, our understanding of the mini brain, the cereBellar, the so called mini brain.

And here's why i've been a practicing neuroscientists for close to three decades. I know where the cerebel is. I've dissected a bunch of them. I I can tell you where a few things are in there. And I certainly have read about what the cerebel m does. But whenever I do a public search on cerebel, I see an every expanding set of things that the cerebel was implicated in, not just baLance, as most people here, but also timing, also cognition. I hear about timing, in particular motor behavior, but then I also hear it's involved in learning and not just motor learning, and certainly involved in motor or learning.

Perhaps that little mini brain is, are doing fifty or thousand different things, but how should we think about the sera belm? What is IT doing? And what are some of its core Operations that inform both what is doing and perhaps what other areas of the brain are doing as well? Because I can point to the retina or the auditory cortex or the salamis. And yes, there's some mysterious nuclei in the brain. But to me, the sea bem is one of the most cyp tic and um complicated structures understand and I know you spend some time in there, so what's the cereBellar do well.

uh cereBellar researchers like to joke that the cerebellum is a counter wait to keep your head from falling .

forward for t well, with all the texting note is people need bigger service.

probably over many generations. Then that will happen along with the expansion of the thumbs. Ah so but of course, several is going to text with their mind. And about another ten years in plant you won't need your thugs .

at all yeah or maybe just five or my friend at chain is a neurosurgeon and works on the auditory system. I ve been on this podcast before. I was saying that you in theory, and actually in practice, you could just record the neural output to the muscles of the speech system essentially and you could just amplify that and you could text without actually speaking um in fact, when we read, he told me we are actually receiving the signals as if we were going to speak the words were reading but they don't quite arrive at the place where you could get uh full blown poston optic potentials. You are not actually moving the vocal machinery um so that means the motor signals are getting sent out there and so you're speaking what you are reading but .

you just don't know IT that's right an allegation to what happens during the room phase of sleep right?

When you have commands, your brain is issuing commands to your muscles to to do things uh like behave in your dreams to run away or go here, go there uh but those signals actually are blocked in the brain stem, prevented from from region your muscles because the uh nerves that don't go through your brain stamp, like the ones that control your I move months, aren't subject to that blocked. That's why you can produce the rapid aid movements in in R. M.

sleep. But yeah, this is a general theme in the brain. A lot of times you have the output but then you shut IT down and there are rim sleep behavior disorders where people flash and move in their sleep uh during during rim. And uh it's because this outflow that's Normally blocked, this isn't blocked.

Have you ever had the reverse happen? I have where you wake up and you're still in so called remember oni, you're still paralyzed and there's that split second that feels like eternity where you are wide awake and you cannot move and i'll tell you .

it's terrifying yeah sleep paralysis is and actually know it's been known uh, forever you can actually find ancient greek depictions of people lying with a demon on their chest paralyzing them and that is actually from sleep paralysis later who guards uh did a drawing uh of exactly that uh so yes, there's a well known phenomenon but to get back to the cereBellar as we started um so.

The cereBellar is, as you said, definitely involved in motor coordination. So people who have damage to the cereBellar air paralyzed, but they tend to be clumsy, uh, they tend to not coordinate their movements. They have a disturbed gate. If they're reaching for an object, they often over shoot its and have to make success of approximately motions to get back uh to their targets. So that's well understood.

But if you look through evolution, the cereBellar is connected to this brain region called the film as, and is connected from there to many regions, including the frontal cortex, where phenomena like uh like planning and uh decision making and uh moral sense and many aspects of personality seem to be encoded. So then the question becomes, well, that's very far away from being clumsy. What are these connections doing? And as time has gone on, i've been in this business from over forty years now on an old guy.

And so initially we said, oh yeah, cereBellar movement control, motor coordination, that's what it's for as time goes on, as you correctly said, the cerebellum has been implicated and more and more functions, many of which are far removed from the military system. And if we're looking for a theme about what the cereBellar does is that IT is there to predict the immediate future. It's trying to determine what's gonna happen in the next second or two to best guide behavior.

And as you can imagine, this kind of general computation could be applied very well. You can see why it's important for you know motor's systems and doing sports and know if you're trying to hit a baseball, looking what the picture is doing and trying to anticipate what the pitches. But IT also comes up in a social realm.

If we are trying to read someone and predict what they are going to do, is this person, friend, foe, which is one of the first things that we tried to access when meeting someone. Are they compete, which is the second thing we tried to assess uh, when meeting something, a lot of this depends upon predictive circuitry and uh IT depends in part on cereBellar. And IT seems to be at least partially impaired in people who sustained cereBellar damage.

So IT seems as if interestingly, the sera belm started out for prediction related for motor control. And through evolution, its basic computation has been applied to other non motor behaviors. Now i'm speaking in general, and a lot of the details of this remain to be worked out and understood, but I would say that is, in a nutshell, the modern conception of the cereBellar.

Thank you. Finally, somebody explains to me at the top control, but highly informed way what the ceremony on does. I couldn't be .

more grateful, my pleasure .

in all aspects of biology in life, the term nature versus nurture is relevant, but never so much as when thinking about the nervous system. And I know this first hand, because i've studied neural development, both the nature side called hardwired stuff, that genes just set up. Neurons war up to that neuron.

It's set the cerebrum s in the back. The eyes are in the front, the hard wired stuff, uh, and then the soft wired stuff, the nurture stuff, is the stuff that can be modified by experience. What your thoughts on nature versus nurture? And should there even be a versus in there?

Yeah, I don't think there should. And I have a lot of problems with nature versus nurture as uh as an expression IT was popular zed by Francis golden uh in the sixth century uh uh colleague of of Darwins. And I think it's wrong in or misleading in a lot of way.

So of course the nature in nature versus nurture is meant, in this case, to me in here itabhi. right? What you inherit in the gene variations from your mother and father, and nurture means like how your parents or your community raised you. The problem I have with nurture is that IT is to narrow a term that really IT should be replaced with the word experience and experience in the broadest possible sense, not just social experience, but um the ford's your mother ate when he was Carrying you in utero.

Um the diseases you fought off or your mother fought off while he was Carrying you, uh in euro, the bacteria population of your guts uh so experiences, meaning anything that in inches on you, starting from the earliest stages of fetal development, uh, continuing to the last day of your life. I think I should be very expensive, much, much more than social experience in the family or the or the community. And as you mention, I have a problem with a versus because there's this idea that these things are are essentially in opposition.

Well, is he that way because of of of his gene variants, or is that way because of what what happened to him? And I think the thing to realize is that, uh, experience and heritage interact in all kinds of interesting ways, some of which are oppositional and some of which are reinforcing. A classic one from genetics has to do with a genetic disease called fano key dina or PKU uh which is uh an inability to uh to mutabilities uh the dietary an mino asset final Allene and uh so uh in order to half this you have to in here at broken copies of this gene from both your mother and your father so it's a so called recessive trait.

And here's where the experience comes in. IT only matters if you eat foods rich and final Allene if you don't IT doesn't matter that you inherit these things, right? So that's the way which genes, an experience, interact an idea of in ways in which they they interact positively.

Um think about athletic ability, right so a lot of athletic ability is has a heritable component. If you are born fast for an example uh then you're more likely to do sports and practice them and get Better exports as a result of your experience. So here genes and experience are feeding back on each other in a positive feedback loop.

So there really isn't uh a vera versus at all. And then of course, the last thing is that this isn't the entirety. So we talked earlier about the suda random nature of development, the caster development.

And so if I would take the phrase nature versus nurture and reconfigure IT, I would change IT to read her ability, interacting with experience, filtered through the random nature of development. Now that doesn't fall off the tongue as elegant as nature versus nurture. You know, nature versus nurture is like if the loves the gloves don't fit, you must quit. You know what's got that snappy nordrum beat? But I think it's it's a more accurate.

So here, dabble, interacting with experience, filter through the rammed ness of development. Yeah so we can shorten that up and um and we'll just call IT um the london hypothesis ah you know I don't .

think I can take credit for that belongs to other people.

sure. But but there's a long history and science of things being shortened up in a coined and that's a as important not we're not trying to rab attribution here um uh and the good new is perhaps you can call IT the london hypotheses sis but I can and what i've found is as with the galpin equation, which is now author as a hydration, it's a formula a formula that a gives broad but um research informed parameters res as to how much water one should drink in order to maintain proper hydration for physiologist starter in to galpin who's A H physiology and an an expert in all aspects of exercise size there's a glp in equation. There's a sobering principle so i'm naming these things left and right um we are appropriate and um so i'm naming these things are sparingly and where appropriate um so from here on out her itabhi interacting with experience filter through the renderings of development as the london hypothesis and i'll be damned if anyone's gonna remove IT out faster that i'm going to propagate IT.

Well I think all the the geneticists will be nash ing that are teeth about this being named after someone who isn't .

actually a geneticist quite alright and their dentist will thank me let's talk about mind body. Okay, I am fascinated IT by this um for a couple of reasons, and I promise to keep this brief. But when I was growing up, I was very interested in animals and biology.

And my father's a scientist and I got very interested in neuroscientists. Ly um as people craps, no. And so much of neuroscience as I was coming up through the midlands, two thousands, two thousands ten to tony stretch was focused on the brain piece, very little on the body. There was nothing about gut brain access in the early discussions and course work um in parallel all of that have been interested in mental health, physical health and let's just call IT performance and got interested in meditation respawn base practices, things like yoga, eda things that by way of experience I understood immediately had a profound influence on the nervous system states of mind and body. Nowadays there's an entire institute of the national institutes of health for complete entree health and medicine, essentially expLoring things like organiser, aspiration practices, even supplements and things of that sort and there's this understanding that oh my goodness.

that nervous system .

extends into the body, and the body sends a neural signals back into the brain. And so this whole notion of mind body has fortunately migrated away from kind of california counter culture, excEllent n institute only, you know, happy new age magic carpet stuff. By the way, that's not what I believe that, but that's often how I was looked at in the past.

And now people at every level, science and medicine, at every major university and in every scientific terminal, are starting to publish papers about the interactions between bodily organs like the breathing apparatus I, the dire frame lungs, the heart heart rate variability we hear about and delivered, the gut rain access in particular. And so mind body, the idea that our thoughts could influence our body and that our bodily state could influence our thoughts is fortunately not just understood, but IT seems to be both accepted and appreciated. So what are your thoughts on mind body? What does that mean to you? And what do you think is the potential of the mind body interaction? That seems to me we've just barely scratch ched the surface.

Yeah well, i'm glad you ask because I think it's it's a really fascinating uh, situation and uh where things are changing very, very quickly. And I think to me the most important thing for people to understand is that when you have a hypothesis, let's say you have a hypothesis that uh meditation can uh a tenured cchr onic pain, right?

Well, there is a temptation to think that this Operates outside the realm of science and biology that is in some very, very roman clouds that this happens. And and and I been for for good reason. There are a lot of people who will describe IT in exactly that way with or as or they they clap scientific terms like a resonance and energy, but they don't actually use them in scientific way. So you know, there is a lot of very fuzzy language that surrounds this. But IT shouldn't obscure the fact that when you have a hypothesis that say some mental state like meditation or or or guided breathing, uh uh affects some process in the body, that you should be trying to understand this in terms of a biological hypothesis, not in terms of some, some, some in distinct realm that that is.

that is different, like manifestation.

Yeah, I know. I really learned this initially from my father. My father was a schistus st.

In fact, kind of a talking cure, old fashioned psychoanalysts. How to practice in a los Angeles and we would have dinner together her wednesday night. And, uh, he would always tell me about his patients.

He was very careful to keep confidential. He won't great confidentially. But you know, I would say, oh, yes, how's your nurses is, oh, we had this dream. So this was, this was, this was Normal conversation when I was fourteen and fifteen years old with my dad.

And one day I said, dad, it's really cleared to me that through this talking cure, a large fraction of your patients feel Better and they conquer their depression or or or their thoughts or things that are blocking them. How do you think IT works? And he says, what we don't really know the mechanics, but ultimately, when IT works, it's not working in some area, fairy realm that is working by changing the biology of the brain.

And when he said that, he was like a lightning bolt went off in my head and I thought, well, I don't have the kind of personality to be talking your psychiatrist. I'm not nearly nice enough, but I could understand the underlying biology. Maybe i'll do that.

And so as you've correctly pointed out, when you say the phrase mind body, you're talking about two directions. You're talking about mental functions affecting the body, and then you are also talking about how phenomena in the body affect affect the mind. And we're understanding so, so much more about how that happens.

And I think the general thing for your your listeners to appreciate is that we have some culprits here, right? And generally speaking, there are there are two glasses of culprits. So if you want to get signals about body to the mind, there's two ways to do that.

One of them is through neurons that reach out into the body and sense things. And this is referred to as intra exception, right? So i've opposed to extra reception in your outward pointing senses. These are the senses that monitoring your own body.

And while we can consciously be aware of a lot of that information, a lot of IT is happening subconsciously, like your breathing is happening automatically most of the time without you thinking about IT. And that depends upon sensors about your blood chemistry and the state of your lungs on a number of other things that are regulating that process. And it's all happening in the brain, usually below the level of your conscious attention.

In addition to the neural signals, there is also a whole realm of harmonic or defuse ble immune signals. And what these are is that these are chemicals that are released into the bloodstream and that move throughout the body and that can uh uh activate neurons in the brain or in other parts of the nervous system to produce changes in uh in mental, in mental function. And I think the real thing that is exciting, a lot of people right now has to do with immune signal molecules.

So there is a class of molecules called side kinds. Insider kinds are basically the signaling hormones of the immune system and they they can flow through the bloodstream and flu infected fluid, uh, and reach many parts of the body. Uh, we've known for a number of years that these specialized recept tors for the pyrocles are found throughout the brain.

And yet we know very, very, very little about about what they do. And that's gonna an astonishingly fruitful area of scientists research. But but to give one one example, there are a lot of things these days suggesting, uh, uh, uh, link between inflation tion in the body, whether IT be a god, or in other places, to depression.

Well, how might that work? Well, IT could work either through inflation tion, send signal on sending electrical signals to the brain, or, and it's not either or IT could be both. IT could be immune signal sideline molecules produced at the site of inflation tion that then travel through the blood streaming m fads system to then reach the brain, bind receptors and have effects.

And so, you know, one of the mystery is about depression is that a is not that tractable to pharma logical therapy. So if you look at people who suffer with depression, about a third of people see significant benefit from modern S S R I and related antidepressants rugs. Uh, about a third see very tiny benefit.

About a third cy, no benefit at all. And part of for the reason is because maybe our term depressions is too big a bucket. The problem actually many different biological disorders and only a subset of those are are helped by accessories.

And we will need different for the other ones that certainly part of IT um but part of IT might actually have to do with inflation tion. So if you think that inflation tion is a risk factor, depression, what you could do something very simple, right? You could you could gobble and i'd be proven right.

There's a whole bunch of anti in flam ory drugs that are very well understood and so well, what if you just say, all right, you know, uh, let's have a study where we have a bunch of depressed people and we have them all eat and in flam ory drugs for a few weeks and we see if this relief their depression. And the answer seems to be no. IT doesn't well.

And that's that's a little bit hard to understand because they're definitely links between inflation, tion and depression. So for example, one of the early treatments for uh for haiti to see that since been superseded by more modern drugs was a pro inflammatory sytem molecule. And when you gave IT to people to treat their habitat to see almost everyone became depressed on a drug so I oh well, this really seems like like like a link.

Likewise, there are certain uh, neurological diseases like multiple school roses IT. Turns out the incident of depression as a commodity in multiple grosses is enormous. And you might think, well, there is a trivial reason for that.

If you're paralized from M. S your bumped out about life, and that's the reason. But if you look at people who have spinal cord injuries from accidents, they actually have a major depression, a nor out rate from people who are are uninjured.

So that doesn't seem to be as serious. Ly, your bubbled out from being paralyzed, although of course it's reasonable to be bumped out about being, but that's not yet. So what happens in M, S, well, there is a bunches of side of on, including one called interlude six I six, that's alleviated massively.

If you, if you take a spinal tap and you look at three old spinal, and so that could be positive for depression. So are all these al reasons to think that inflation tion is involved? But yeah, the idea is still a little message.

So now what if instead of looking at the general population of depressed people, you look at the subset of people that don't respond to S S R I and the presence, are they helped by empta n flam, meta ies? And there there is a bit of hint that maybe they are. It's not definitive out. There are a couple of studies is right on the edge, but I think this is a really good example of how we are gonna see progress very soon in the body to mind, part of mind body medicine that is going to be of enormous uh, benefit to people.

So interesting. Could I get your thoughts on one candidate hypothesis that i've been thinking about a covered depression on a few episodes and um i've had a Robin cardboard Harris um from U C S F and doctor Matthew Johnson from your very own john hawkins university both of whom work run laboratory studying psychiatric for the treatment of depression um the clinical trials on so Simon um and to be clear so Simon still illegal, been decriminalized a few places.

But we are not talking about recreational use. We're talking about several therapy sessions and then two without sulfide and then two two point five gram approximately dosages of so sivan given separately, again with therapies present and then follow up therapy session seam to lead to relief of depression in approximately somewhere between sixty five and eighty percent of people, in some cases total remission, in some cases um some relief without remission. okay.

So we can can set that result on the shelf. It's been repeated a number of different times. Compare that to the results of S, S, which seems to help a third of people, a third minimal and a third not at all.

And of course, there's the side effect profiles of the asset arise and associated drugs, not just the association ze but reprising and the other antidepressants that are taking in prescription drug. And then there's this uh inflation tion peace. So could we hypothesize that relief from depression has something to do with neuroplasticity rewiring of neural circuits and that Sullivan we know can encourage nora plasticity and that perhaps S S S can encourage nal plasticity in some people, not all.

And that inflation tion is a barrier to neuroplasticity. Um to me, this is the only thing that can reconcile that the current status of the of the results. And then there's kadeem based therapies.

And so we have to also set that on the shelf, but let's set that aside on the shelf for now to keep IT simple. Um IT seems to me that based on the time course over which s arise work, the fact that the incase serotonin very quickly, but the reality from depression comes much later. The fact neuromodulators like serotonin are intimately involved in neuroplasticity.

They can, in some case of gate neuroplasticity that are all centers back to changing neural circuits. And so what really trying to do, whether not it's transform al magnetics existing lation or now we can throw a deine in there or suicide in our that treating depression is about rearing the brain. It's not about chemical a or b per sale.

Although serotonin seems to me what i'd love to see is, are more studies about the interaction between neuroplasticity and inflation tion and are we seeing that kind of work out there? And um because these results sort of city as desperate, somewhat conflicting, but IT seems like inflamed tion is is anti neal plasticity. And broadly speaking, here, I realized that there are many interludes there, many know, some of which are in flamingo, of which and I inflaming. But is that is that a meaningful hypotheses stem? Um do you think there's any hope whatsoever to actually cure depression if we all start to I unify the results in these different camps?

Yeah I think it's a completely reasonable hypothesis and I would be brought her and I would say honestly, the relief of any neuropsychiatric condition ultimately is from neal plasticity and some former another. And I think it's worthwhile to step back a bit and talk about what neuroplasticity means. Uh, today, there has been a focus on signals on the context between neons as the site of new plastics and that's warranted synaptic as our plastic.

They changes a result of experience, as a result of horn, changes as a result of exercise, as result of lots of things. But synapses are not the be all and end all of neural function. So for example, neurons worked by sending electrical signals uh uh along their lengths and and between neurons and into converting those with chemical signals and the processes of generating those electrical signals.

The iron channels that are involved, that are embedded memories that are involved in that are also plastic. They can also change as a result of experience. That's what we call intrinsic bless the city as opposed to synaptic plasticity.

In addition, there are literal morphological changes. So when we talk about the wiring of the brain, sometimes we're talking about literal wiring like sa wasn't connected to sell b and now IT is and that changes. And then sometimes, well, actually L A was connected to cell b, but cell b wasn't responsive enough.

And others to change in, sell b. So i'll sell a, can fire, sell b and that could build a result of a changing at synapses, make IT more receptive to know, transmit released from sale, or IT could be something in transit and cela that makes IT fire its electrical sync Spike more easily. I think that one of the key cell types that's going to be important for your hypotheses um linking inflation tion to snapp c plastic is going to be a cell called the micro gal cell.

And micro glial cells are non real cells in the brain, their motile, they can crawl around, they have long processes and they can gobble things up. They can literally sort of chew away. And I just bits of the extra sailor scaffolding that surrounds neurons and synapses and thereby renders the plastic they can uh, destroy synapses.

And there is a lot of indication that certain disease states may involve over exuberant micro glia pruning synapses to a degree that they shouldn't. And we know that microgrid are chock full of psychic receptors and so are responses to inflammatory signals. When we're talking about inflation tion and we're talking about drugs, it's worthwhile to mention that there are a lot of behavioral things that also can influence the signals.

So we know, and I know you've discussed on your program the incredibly celebrate effects of physical exercise on mental function. So exercise is about as good and anted depression as S S R eyes are. And the side effects are only good. Side effects is opposed to the bad side effects of S S R eyes. And again, this isn't working through some area ferron.

The reason that exercise works to relieve depression and the reason that exercise works to maintain your cognitive function as you age, is because of biological pathways that we are now uncovering, some of which will involve microbial cells and neurons and other types of cells in the brains, some of which will involve not the neurons in the brain at all, but the brain's vasculature. So we know that exercise is very celebrate for keeping blood flowing to the brain. And when you're Young, you have a super abundance of blood flowing to your brain. What doesn't matter if it's reduced transiently, you're fine, but as you get older, uh, your blood vessels become more included and less elastic and your closer to the to the to the trouble spot uh and if you exercise regularly, you can dilate and make your blood vessels, including those in your brain, more elastic and that is almost certainly protective against both depression and cocagne tive decline uh as we age why I am a fan of exercise but .

unfortunately that I enjoy running in some forms of resistance training um so I always assumed that the good side effects were just the positive mood effects um until the recent literature that as you mentioned, improved VS culture blood flow and reduced inflammation. If not during the exercise. When inflation tion actually increases um decreases inflation tion um i'm delighted to hear you say they were microgrid and um my postal advisor the late bed barrace would be especially delighted.

People can look up then alpert a link to his a biography and the showed captions because he really champion um to the point of of I don't know of champions even a sufficient word I mean when I was beating the DRAM saying we have to pay attention to gilia. We have to pay attention in a glia. For the longest time, glia were relegated to these other journals, even have their own journals. And in the last what is at ten years there's been A A kind of explosion of research expLoring the role of microbes and leo cell types and it's it's really fantastic to see that uh this actually the most abundant cell type in the brain is the vigilio cell um are getting the attention they deserve.

It's absolutely true. Uh and uh you know we scientists like to think that we're very rational creatures and we're not subject to fails, but we totally are right. When I started out in this field um in the early eighties, everything was about oppoi peptides and then there was a period where gaseous neurotransmitters ors like miti c oxide were all the rate. Just know right now clear on the spotlight for a good reason. I'm not trying to say that that IT isn't worthwhile, but there is this phenomenon of things being fattish ed and people jumping on bandwagon.

And that happens both in terms of the subject we study but also in terms of the techniques, views and right now the technique that is most fetish involves um single cell expression profiling that is creating a list of what genes are turned on and how strong they are turned on in single cells and seeing how that changes in different cell types and with experience. And it's a very it's a very valuable technique. But one could argue that IT is perhaps a bit over used on that fifteen years from now, people will go back and say, got those folks in twenty twenty three were really overdoing IT with the single cell profiling.

And if anyone thinking about getting into the field of neuroscience or another area of biological or other research, I can just tell you that if you're starting your phh or your postdoc, take a look at whatever fat is happening now and just know that in five years, IT will be something different in IT takes you about five years to finish your PHD, your post dog.

So pick something different than what's faddish now and you'll you'll land right on the money that there's always a lot to do. You don't have to do what everyone else is doing. And indeed, the deletion test becomes release here.

The deletion test, as IT was described be by my colleague, j. chona. Sky at stanford, is if you look around and you see one or more groups doing what you want to do very well, just pick something else, your life's going to be a lot more pleasant.

Absolutely, I agree with with ej on that entirely.

Let's get back to mind body. Um there are a bunch of different domains of mind body as you um so apply pointed out as by directional mind informs the body, body informs the mind um but we could probably break this down into uh repeat tion. So breathing um conscious patterns of breathing, emphasizing inhales or emphasizing exhales sick hype events or eating etta could also be thought patterns little bit harder.

Break those down but many not all but many forms of meditation involve having a very still body not all there's walking meditation. It's at her but still body focused mind kind of a not a state that we are in a lot of times unless we direct that state um there are still other mind body patterns of communication through very still body deep relaxation, things like organization on sleep, deep breast, there's no set there's touch based body mine communication. If we're onna talk about mind body also we should refer to his body mind um how do we dive in and think about this? Because this is involving clearly a thousand different neural pathways, is not just the vagus nerve, has typically people just kind of hang their head on mind body must be vegas nerve. And of course, that involves the vegas, but the vegas is an extensive set of pathways. So um how do you like to frame up my body and what's most intriguingly to you about mind body communication, both in terms of the biology and its practical applications?

Well, I think just as we talked about how there are two potential pathways convey signals from the body to the mind, there are also two potential pathways, at least two potential pathways to convey signals from the brain to the body. And they are the the the neural signals that are conveyed by neurons that actually get there. And they are, uh, hormones and neurotransmitters and sidelines that are released in the brain.

I should mention that that hormones are actually produced by neurons, including for example, some of the hormones that you think about uh as being produced us as sex hormones like extra jone is produced by neurons in your brain, for example. Um so let me give an example that I think is a bit out there, but I think is really, really fascinating. And this comes from uh from the cancer world.

And so a milano is a is is a bad cancer。 IT kills a lot of people that can spread, is a highly metastatic. And we know that melanomas often become innovated, that is to say, they become contacted by neurons and wrapped and receive signals from them.

And we also know that if a melanoma a becomes innovated, then the prognosis for that patient is worse. It's more likely to grow. It's more likely to spread.

Well, how does that happen? Well, recently, uh, there have been some reports that, uh, show that neurons that interface the melanoma a don't act directly onto the tumor cells, rather what they do. They secrete a signaling molecule that has a reception on immune cells that are patroling the edges of the melanoma tumor and nimbly away adults. And they, when that signal molecules released in the near on, yet a shuts down or reduces that immune patrolling function, and then as a consequence, the tumor can grow and spread and butt off .

more ready. So this signal that comes from neurons is sending the ambuLances home sort of speak.

yeah, exactly. And the signal is something called called on and gene related peptide, or C G R P. 嗯。

i'm familiar with C G R P from the domain of touching its involvement in, I think like each perception.

perception and each perception, right? yeah. And so all right. So if. Neurons can um can affect the progression of cancer through their activity, and these neurons in the perfect are ultimately connected to the brain through a couple of different hops. Um then is IT reasonable to hypothesize that mental processes could affect cancer progression. So let's say we have a hypothesis and it's owd hypothesis.

And I want to just emphasize that there is not evidence for this, but let's make the hypothesis that says that through meditation practice, you can slow the progression of certain tumors that tend to get intercepted right? Well, right now, this is just kind of a wild idea. But I think the important thing, as i've said before, that this is a wild idea with the biological substrate. It's not like you meditate and magic happens and force fields open in the Angel sing and then your tumor shrinks.

This is, we are saying that activity and certain areas of the brain is increased by this meditator practice, and that this send signals to this neuron and this neuron that actually go to the tumor and makes something happen through this biochemical pathway that we have defined, right? And to me, this is speculative, but is also extraordinary ily exciting, right? IT opens a kind of investigation of mind body signalling that has received very little attention after now.

incredible. And I say incredible, because while you're giving an example of C G R P in nerve innovation in metastatic tumors.

I .

absolutely love the idea that a phenomenon involving some practice that could be put under the umbrella of mind, body, your body, mind um becomes something entirely different when we're trying to hang that on the hook of a biological process, like something fundamentally changes there, right?

You know, it's amazing to me, for instance, that early on, psychiatry ics and breath work, conscious breath work were lumped together, cost people their jobs at major universities. I won't name the universities because we're you work at one, I work at another and there's a third one. I'm harvard.

I guess I just name them um but nowadays their laboratories that every single one of those institutions studying deliberate respiration on health as well as psychotic licks and meditation for that matter, with the goal of understanding what side of kinds, what neurotransmitters it's such a change through defined pathways including vegas but frantic nerves and uh frontal cortex and all of the stuff that is considered you know classic rigorous neuroscience. So I do think we've entered a new era. Um so it's not costing people jobs anymore.

It's actually giving people their jobs and it's federally funded, which itself is also fantastic in my opinion. So we are in a new era. What what do you think um needs to be done to .

really nailed down .

the idea that how we think influences our biology, even though it's a total because everyone knows that clinic stress for instances can be detrimental, short term stress can actually be beneficial, but um and stress is a mental process that essentially deployed chemicals in the body that then create other issues in the body that then create shifts in mental progress. You know so it's so obvious when it's spelled out but it's just remarkable to me how this has just been lumped the category of like wool science um and I can't quite figure out what needs to be done in order to convince people that their nervous system includes stuff outside the skull in spinal cord and of course, of course, of course I would work this way well.

right? And I I think this is the job of biomedical researchers right now to reclaim a lot of this from from the realm of nonsense and the problem there has been a lot of nonsense and you there's there's sort of a fiscal role reaction. You when someone says, oh yeah, well, you can do breath work and ita realize your shockers and that is, you know what will uh uh, reduce your anxiety of your garden information and i'm tempted to go, oh.

shut up but what if the shockers are collections of nerve innovation of a bodily spring?

Know you make sense, right? IT could. But if there's got to be some some biology, in some cases these analogies are rooted in something real, and in some cases they're just made up bullshit, right? And I think the chAllenge is to have really rigorous scientific tests of these things to take IT and to be willing to say, alright, there have been a lot of claims, for example, made about how mental processes can influence the body.

And only a subset of those are going to be true. And of that subset, IT is our job to understand how they work, both to rationalize them, but also to optimize them and and make them Better. I mean, there is no question that level processes affect the body.

I mean, we know, for example, that if we just keep you away and don't let you sleep long enough, you'll die. And what will you die from? You'll die from sepsis because the the barrier between your gut contents uh, and and your parent eum will, will, will we'll break down right? Well so how does that happen, right? We're just starting to understand like there's a really dramatic example, but there are gonna many more subtle example.

So you've mentioned breath work a couple of times and I think this is really interesting. Um my colleagues who are interested in aspiration tell me that you can record in many different places in the brain, many different places in the new cortex and other regions and find a signature of the breathing rythm sort of as a background, uh Turner's activity you can find in the cerebel um you can find IT in the frontal cortex, you can find IT in, uh the haben ua, which is implicated many things, including depression. You can find a lots of places. So the idea that conscious modulation of your breathing could have manifold affects on neural function, I think is reasonable given that kind of observation .

here here to talk about you a bit more um you've been so gracious and covering this wide array of topics and with uh such eloquent um I must say have been delighting in all of IT. You are in a unique position these days because uh if I understand correctly, you've been diagnosed with a faddle illness. Um I suppose we've all been diagnosed with a fatal illness of sorts because we're all onna die sooner later yes, if you're willing, could you tell us the story of how that diagnosis came to be, what your initial reaction was and where things stand now? And then perhaps we can explore some of the molecule c pleasant surprises that have emerged since that identity diagnosis.

Well, sure, I be happy to. Uh, so in the a the summer of twenty twenty, in the dark days of coded, when things we're looking really bad, I developed profound shortness of breath I couldn't get up a flight of stairs without a, uh, without halving and puffing and I thought, oh well, i've got cover but I took covered for us and there was they were all negative and I thought, oh, I must have coded i've got the symptoms of code.

I have respiratory issues and feeling weak. It's gotta code and after a while, when this didn't go away, my wife said, like, you gotto go into the doctor, this is craze. You've got to find out what's going on and I did and they they hooked me up to an electric cardiogram and they said, oh, uh, you've got a real fibula tion, meaning that your heart is doing two beats every time.

You should do once. So I have a very high heart rate. And when the heart beats that fast, IT can't work very effectively, there's enough time to recharge before the next beat comes. Now IT turns out that there is a very straight forward therapy for this. Uh, atrial fabulation comes from uh, electrical signalling in the heart sort of swing about in a circle and and reactivating part of the heart muscle faster than IT should and so if you thread through a catheter in your in in in your grain up uh up through blood vessels, you can put in a little needle and use that to quarter ize into a bate a tiny little strip of cells in the heart that will produce a barrier that will prevent that A A bearance return of electrical ectivity and will cure atrial fabulation. So I have that process, that ablation surgery and enough IT IT cured my atrial violation.

I was feeling terrific and they said, oh, as a follow up, come back, uh, a few months later and we will do an echo cardio m to see how your heart looks and they did and I want, oh my god, there is this huge mass present against your heart. It's like the size, what code can. Here's what we think IT is.

We think it's a hat, her nia, we think your stomach is poked up through the die friend muscle, and it's next ling next to your hearts. The way we diagnose this is kind of humorous. They say, chuck, this count of diet doctor pepper, and then quickly get up on the table and we will do the ecosystem.

Gram, and in the echocardiogram can see a signature of the popping seo, two bubbles in your soda. And if we see those in the mass, then we know it's your stomach. So I did that, I chucked that.

I got up, up. No, it's not. Your stomach is IT okay? Well, what we think this is is a charita.

And a teratoma is a developmental uh, anomaly that you Carry usually from fetal life where there is a group of different cells that gets in a place where IT shouldn't during development and then grows. You've probably heard about people who sometimes get like A A tooth that go hair and their abandon. Sometimes we can have these around their overall and they're not malignant ant.

They don't spread. It's a fairly easy thing, but I have this enormous cock pressing on my heart, and may have, we don't know, have been the source of mitral tribulation to start with. But in order to deal with this, I have to have open heart surgery.

So I have the surgery. And IT was a big hurry deal. I was told we laugh about five hours IT turns out of last to two days um they have me on the heartland.

Lung bypass machine longer than you're supposed to because you're very likely to throw a clot and get a stroke. Fortunately, that didn't happen. I had very skilled surgeons at john hopkins.

IT was bleeding so much that they couldn't close the chest, so they had to do all the surgery and then just leave me and advertized with my chest open until the bleeding stop. And so the surgery was a bear. And then i'm waiting to get the pathology report back on the tissue they removed.

And I came back and IT was bad news. Sorry, it's not a teratoma. It's not.

But IT is a kind of cancer called snoopy, el aroma and snowy o sarcoma is a moderately rare cancer, and IT usually affects the sono via, which is the lining of the joints or some other places. It's pretty rare to have that happen in the heart. There are a few examples.

If you look in the biomedical literature. For common cancers like stic, specular cancer or breast cancer, there are a huge tables of statistics for millions of patients on what's been tried and what works and what the prognosis says. For Sophia sarcoma of the heart, there are only individual case reports.

Oh, there's a guy in kenya, he got him. This what happened there? There's a woman in minnesota, and this is what happened with her, right? There are no statistics because because it's that rare.

And and and the oncology said, well, I think you've got sixty eighteen months to live now this was uh about uh now twenty seven months ago. So i've fortunately exceeded that life's bound estimate。 And I think we ve got to be clear also that you know, be an oncologist has got to be a terrible job for many reasons.

But one of them is that you ve got to give a lifespan estimate, even if you really don't have the data to do IT in a very effort. You can't to say, I won't do right, you gotta do IT people expected. So you know, i'm not saying like all the oncologist was incomplete because i've had lived my estimate.

You know he was trying to do something based on very little information made us best guess so um so you know I got this information and I was furious. I was so angry hard cancer, who the hell gets heart cancer? That even a thing i've ever heard of, somebody with hard cancer until no heart cancer.

What the f i've got heart cancer, this is, this is crazy time, about fifty nine years old, as I got a lot to do, I can't have heart cancer. And what was. I think transformed IT for me is that at the same time that I was feeling a White, hot, angry with the universe, I was also feeling a deep sense of gratitude for what i've had.

I've had a terrific life. I'm not that Young, had a lot of IT and I had great parents, wonderful friends growing up. I'd had a good career uh it's been a fairly easy one of IT um and I think.

The ability to have a job where you follow your own curiosity every day. There's nothing like that. So few people in the world get to live that way.

I feel incredibly grateful and I feel incredibly great for my family. And I have a wonderful wife name dinner and she's just the best. How do I deserve this? I don't deserve her.

But you know honestly um so you know in neuroscience we often think, oh well there's you know you have a state, you have a set point. Are you anxious or are you are? Are you relaxed? Are you fleeing or you approaching? You know, it's it's like a single access.

Well, what IT isn't, you know, when I think most people understand that, but me, I didn't until that moment, really understand that I could feel profoundly grateful and profoundly angry in the very, in the very same moments. And you know, having cancer and getting the kind of treatments, the chemo, the radiation, it's famously deeply unpleasant. And I had all that, and I was just as unpleasant as anyone's cancer story that that that you ve heard the radiation burn BIOS opa.

Gus, I couldn't eat for weeks. That was mom who was painful to swallow. You know, bad stuff.

Lots of people have to have bought stuff like this and and what I realized you know this is it's a deeply um on empowering situation to be a medical patient. What particularly when there is something serious, you have you have a limited sense of agency. Things are being done to you.

Drugs go in you that make you feel really bad. And there is there isn't that much to do. And I realized that for me the sense of agency came from being curious, from being a total nerd about things.

And part of what you made me curious about was my own mental processes as they related to my cancer and my cancer diagnosis. Uh, so for example, i'm getting in the key mo. And, uh, I should to say as background, i'm fortunate I I don't have a tendency for depression.

I'm a pretty upbeat guy. I don't take any credit for that. I think I was just born lucky and raise lucky right? But day after day of feeling bad in your body from chemo, boy, it's hard to be positive.

IT really is. I could not overcome that. My mood got really, really low.

And I could tell myself, this is gonna over. It's not onna. Go on forever. You won't feel this way forever.

And you would think that as a rational person, I could talk myself out of that mood, but I couldn't. No, probably because that was my brain was a washing into lucan six and I couldn't overcome that. I felt really low. But at the same time I was sort of a removed being a nerd about going like, um I bet these side of kinds are messing me up right now.

I bet that's what's going on and that gave me some sense of agency in a time where otherwise I really wouldn't have a another thing that really brought home to me is this issue that we were discussing earlier about how mineable perception is and perception of time. In particular, if someone had said to me when I was healthy before I was diagnosed, you're gonna die in five years, I would want, oh, no, no, no, no, no, no one, fifteen, nine years old, I should get way more than five years. I have a lot of things to do, uh, professional things, personal things, family things.

I got things to do. No, that wouldn't right to be very upset. But you know, if you told me after my diagnosis of six, eighteen months, oh, you can.

Five years. I do five years. Yeah, it's pretty good. I can do a lot in five years. I can finish up in the lab and I can. I can do some good work.

And I can spend time with my family and travel and save your life pleasures and do all kinds of things. Five years, great. And of course it's the same.

Five years, right? The only thing is different is the, is the context. But I think the thing that really I realized the most is that I really couldn't and still can't engage with the idea of myself being gone.

So, yeah, I can do practical things. I can update my will. I can write letters for my people in my lab. So, you know, if I kick off, you know, they've got that to take to the next job.

You know, I can do all this is nuts and bots things, but in terms of genuinely engaging with my own demise, I really find that as much as I try, I really can't do that. And at first I thought, well, that's just your own lack of imagination. Then it's just because you know, you're not very good at this.

But the more I thought about that, I thought actually, no, this is a human thing. This is a fundamental human thing. And and one of the things when I look back on the forty plus years i've been doing neuroscience that's different, is that when I was first trained, the brain was really described as a reactive structure.

Something happens in the world. You know what comes to your sense organs, your eyes, your ears goes into your brain that trigger some things. You think you make decisions, and then you make an action that goes out your muscles or or and that's the loop. And that's what the brain does. And what we have known in more recent years is that actually, when the brain is waiting for something to happen, it's not just idling and spacing out.

That the brain is that every moment, subconsciously trying to predict the in the future, predicting the near future, is predicated on the idea that there will be a near future, that is to say that you won't be dead and gone, right? That we'll be a future for you. And so I think that my ability, which I think is actually a human, I mean, not my ability, my failure, which I think is actually a human failure to truly engage with my own demise, is a feature that is, IT is a side effect of the fact of the brain, is always trying to predict the future.

And so that was interesting to me, just as a way that my illness was revealing something about the brain. But IT also made me think a lot about the world's religions. Religion is everywhere in the world.

If you ask anthropologists, is there any society that doesn't have religious ideas? We'll say, no. They said, they don't always have the word religion.

And I just say, well, yeah, this place, everybody knows that. You know, the world on the back of a turtle know this. And this happened.

There are these rules. I mean, I call IT religion, but every place in the world has religion. Not everyone is religious, but IT is across cultural, universal. And most religions, not absolutely every single one, but almost every single one has stories of afterlife, of reincarnation, in which your consciousness indoors.

Well, why would that be in in many religions, the'd got a deal, right? Follow these rules in life, and then you'll be rewarded in the after life. And that's that's a very, a very general idea.

Or punished in the, afterall, punished in the afterlife. And you know, when some of religions you made with the divine in other religions are and carded as this, or that you haven't hell, right? There's variance, but but they share that you're consciousness indoors.

And so why is this so popular all over the world? Well, I would hypothesize that. IT is a side effect of the fact that the brain can help the always trying to predict the future. When we can't imagine the world without us in IT, then we are forced to conduct stories of the afterlife .

fascinating, and makes me want to ask about this feature of time perception. My undergraduate, graduate and postdoc advisers all sadly died earlier early really by a pretty Jenny standard and I was fortunate enough to be in communication with the the last two as they were going through that process.

Um both of them described um a heighten sense of gratitude, especially for things that previously they had not pay attention to so we call this noticing the little things yes, but that makes me conclude that something about the knowledge of one's impending death, however far off that might be, shift our attention, at least temporarily, leads to the sense of slowing down a bit because in order to shift our attention to court and the little things or things that we previously overlooked um there is this sense of slowing down. And we know from basic videography photography that slowing down means an increase in frame rate. You know you shooting at a stroke frame rates gives you the strong perception strobe um shooting at very high frame rates allows you to see things in very slow motion.

You're noticing subtle variations that Normally you over luck. Um I did not trying to be overly reductionist about this this process of enhanced ed stratified that's up that you describe in how IT was a long side intense anger. But have you noticed a shift in your perception of time because you were given initially this okay x number of months and then now with the you're still here fortunately um in with this open ended well IT wasn't the prediction that was given you by your oncologist but it's unclear how long you're going to be here right um which is how most of us exist.

You have the sense that it's sooner rather than later, but you don't really know. So i'm curious as to how the idea that, okay, you have twelve months more to live verses more than twelve months but not infinite. But of course, I know that i've hopefully have more than twelve months, but it's not infinite.

So you know this this idea of the the finish line, the Cliff living inside, whatever might happen afterwards, I don't know, haven't been there. Um IT changes what we noticed by way of changing our perception of time. Um I mean, this is this is a profound tuning of our perception.

What what are your thoughts on that? And and do you notice the each step of coffee? You probably don't notice each step across the kitchen floor in the morning paying attention to your lovely wife and kids and things that day. But presumably um it's dynamic. But what is your perception of time like now with the understanding that, yes, you made IT through the past the gate that was predicted, but what's lies ahead is is uncertain .

yeah so that's really interesting. And I would say definitely my perception of time is slower and IT seems like an age since I was diagnosed. Ed, but I think part of that is because it's been action packed.

And of the words since I was diagnosed, so many emotionally salient things, non trivial things have happened. So many intense discussions with my wife and my friends and the people in my lab, you know, my wife and you've taken a lot more unification, and we Normally ly too. So you're running all over the world.

And there is a certain sense of of packing IT in that I think influences is time perception. But I would say actually for me personally, the gratitude isn't about the little things. The gratitude is about the very biggest thanks.

The gratitude is gratitude for being essentially and having that blessing. The gratitude is for being able to have a life where I can follow my own ideas and creativity. And my gratitude is four, 找 gap。

The profile love that I felt from my wife and my children. No, it's up a little stuff. It's the big stuff that I think about when I think about relatives is not noticing the of tea.

It's it's the big issues. and. You know, for me, I, you know I don't. I want to delay my death as much as possible, of course.

Butter, when I think about IT, the park that makes me upset is leaving people behind. It's not for myself. I've I had a great life.

Um i've had a lot of IT. I'm sixty one. I'd like to go longer, but that's that's a pretty good run. I've going to do lots of things in the sixty one years and have wonderful, loving, interconnecting experiences. And so the negative part is about what I live behind.

Certainly, what you've left behind is enormous and has been the consequence of actions long before you're diagnosis, which I think is is a clear lesson to everyone. I can't speak for you, but don't wait for the diagnosis.

You've mention the sense of agency that you felt by being able to pay attention to and explore your experiences of but call IT what IT is in pending death and at the same time you as you mentioned, you've amplified and accelerated the number of things that you've put into the world recently writing incredible um articles about your experience of life and death. And we of course link to those so people can read them um i've read them all and there are profound and they don't just feel important. They clearly are important. So very few people have your insight into the nervous system at the mechanistic level but also at this more holistic level that um you've clearly displayed us here in in in your research and in your books writing and public speaking. Um you know I think it's a it's a risky thing to ask somebody for the advice um but I can't help myself because I think it's a it's a real opportunity if you had a advice um to give to any and all of us based on the whole experience um all of IT from go as they say, if if you're willing and feel free to pass but if you're willing, what is your eyes .

I would say the advice that is really universal is what everybody already knows and is a bit right. But i'll say that anyway and that is appreciate what you got what you got IT and you know this isn't any big secret, and everyone knows that. I would say for a subset of people, the way of the nerd is very powering.

I don't think that's the case for everyone. I think for a subset of people who are deeply curious as their nature, turning that curiosity to your own mortality in your own medical situation can be empowering and and useful. But I don't think that should be brought advice.

I think that's only for a fraction peoples by the worst thing they could do. And there there is nothing wrong with that everybodys. Everybody's a difference, right? Not everyone should adopt the way of the nerd, but for a fraction people, it's a really, really good thing to do. This is .

Normally the portion of a conversation with a guest where I list off the many, many things they've done and how grateful I am in. And all of that is absolutely true in the case of you've here today in the work you've done. But I think it's self evident how much you've i'm just accomplish, but how much knowledge you put into the world and not just scientific knowledge, but knowledge about the human experience of others and of yourself.

And so I just want to extend a giant thank you on behalf of the listeners and one viewers and myself, thank you for coming here today. Thank you for doing what you do. And um so great to still have you here and to have this conversation. And I hope IT goes longer and no matter when IT ends, you've done an enormous service to humanity.

Well, thank you. That's very kind. It's been it's been a pure pleasure to have this discussion with you.

Thanks, David. Thank you for joining me today for this discussion with after David london. If you're learning from end or enjoying this podcast, please subscribed our youtube channel. That's a terrific zero cost way to support us. In addition, please subscribed to the podcast on spotify and apple.

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your interesting science.