Scientists Discuss Epigenetics & Generational Trauma

[Music] This is Star Talk. Neil degrass Tyson, your personal astrophysicist. And today, it's a special edition. You know what that means? We've got Gary O'Reilly. Gary, hey, Neil, how you doing, man? Former soccer pro, allegedly. Chuck, yeah, man. What's all right, man? Good. You know, I'm loving these special editions because what they all have in common is something about the human condition. Yeah. What it is to be human, or what it is to no longer be human because a machine is going to replace our mind, body, and soul. All of that is in special edition. Yeah. So today's topic, epigenetics. And you, Gary, set the stage here. Uh, okay. Plenty of great ideas start with a question. And podcasts, for that matter, right? And that question would be, what, what if? So, using "what if," the stresses and traumas experienced by your grandparents could affect your genetic makeup generations later? I don't want that to be the case. All right, hold that thought. I already know that's the case, right? You have my grandparents, they wouldn't let me forget that their stresses and traumas actually are affecting. That's a, that's a verbal doubling down. But even, even though those stresses and traumas will have taken place long before you were conceived, yeah. We're back on an epigenetic trail. But this time, our destination is transgenerational, not intergenerational. So it's transgenerational epigenetic inheritance. Yes, it's for real. It's a thing. And we may have found the sharpest blade at the cutting edge of epigenetic research. So, having said all of that, please, Neil, introduce our guest. Are you saying we have a sharp blade sitting among us, in a metaphoric way? Let you know right now that the orderly have said that that's not allowed. Dr. Bianca Jones Marlin, welcome to Star Talk. Thank you for having me. Yeah. So you, you just right up the street here at Columbia University? Yes. Oh my gosh. Stu at the Zuckerman Institute. What goes on at the Zuckerman Institute? We study the mind, the brain, and the behavior of humans, of model organisms, and how the world works. Can I add, what's a model organism? Model organisms, there's like the ones that we really like, that work really well for our genetic questions, like mice, flies, non-human primates, like, like Rhesus macaques and monkeys. But we also have non-non-model organisms, like naked mole rat, for example, which are precious. You can't beat that. Exactly. What, what's the difference between a naked mole rat and a New York City rat? A lot. Um, one's brilliant. New York City one will steal your wallet. Exactly. You're clo— No, no, you'll never see a naked mole rat with a piece of pizza in his mouth going down some stairs. They like e pizza, mole rat. So what makes the mole rat a different category of animal to study relative to the list you just gave? Yes, it's because we're looking at model organisms because we have a question that can pretty much generalize amongst organisms. When you have a non-model organism, like my good friend, um, Dr. uh, uh, Ishmael Abdul Sabor, who studies his naked mole rats at Columbia, he's looking at pain. And a cool thing about them, they don't feel pain. They don't feel pain. They also don't get cancer, and they live kind of forever. So they're outside of the paradigm of what you're ex— investigating. I did not know that. They're also precious. But it allows us to, you know, ask different questions that we can ask in mice that die within two years. Your background is in neuroscience, as it specifically applies in these challenges. So first, let's just set the stage. Yes. We need to know what epigenetics is. And I know what an epicenter is. It is, you know, the part of the Earth above directly above where the sc— the earthquake took place. Epidermis. Okay. Epidermis is the skin above all your body and organs. So what is epigenetics? Is it something sitting above your genes? Perfect. On the nose. No, I don't want to be the one who explains it. You did it so well. Did I? I don't want a woman to explain you what you just said to me. Awesome. I want you to women explain me. No, no. What did I— Surely there's missing content there. Go. Yes. And so our genetic code, this is our DNA. This stays the same. And the cool part, it's the same in every cell. Our genetic code is the same in every cell. But we have eye cells, we have liver cells. We don't have eye cells growing in our liver, hopefully, and vice versa. And this is because we have epigenetic markers. Same as the epicenter and the epidermis. Epi means above. So epigenetics means above the genome. These are big proteins, big markers that sit on the genome and they say, nope, don't read this part of the genome, or come read this part of the genome. And they change the way that DNA is wrapped around histones or sit on a, in a space. So it turns them on and off. Is that a way to— we think about it that way? You can. Yes, I think you can. So the expression of the gene, better word, expression, is dependent upon the epigenetic determination. How much is expressed and when it is expressed is depends on the epigenetic, epigenetic environment. So here we have transgenerational epigenetic inheritance. How does that get inherited? Oh my goodness. I mean, if we all knew how, how it got inherited like that quickly, I think you'd be addressing me in my Nobel Prize. Uh, but we're not there yet. But there are questions around. Problem here. When you get your Nobel Prize, you're coming back here on the show. Exactly. All right, Girl Scout honor. Okay. Um, so there's many questions that are left, um, unanswered when it comes to how transgenerational epigenetic inheritance works. I think we're at the space now in neuroscience where we are observing that intergenerational inheritance of an experience is pretty much canon. Now we can say, with my studies as well as others, that an experience in a parent will change the way the offspring develop. And I'll be pretty specific with this. Experience in a parent, experience in a parent, even before the child is conceived. Exactly. Before the child is conceived. So not a pregnant pregnant model organism. Because we heard that that can be influenced. You could, you can envision a way if you have a pregnant person that's pregnant with a female, the eggs of their granddaughter could be inside of them. So you pretty much can be talking to three generations in one space. Okay. Well, catch me up on bio 101. So I knew that a girl born has all the eggs she'll ever drop. Yes. But how does the egg that she drops have eggs? Which means she has the genetics of her granddaughter, who will then make up the body and the eggs of the granddaughter inside of those eggs that's inside of the mom. So it's basically like a Russian doll? I got two Russian dolls here. Okay. Pass me my Russian doll. Okay. Oh, she's got a space, space, space station. Whose office do you think you're in? You're in the Hayden Planetarium. Neil degrass Tyson's office. Because it was a Russian doll. I turned around and expect to see like, I don't know, this is the International Space Station. And inside there is soy. So how they get it works. Okay. So each of these is is sort of a genetic expression within the previous one. So is the, the one inside, she want me to keep going? Okay. Went inside of there. So let's say, let's say Mom space station had like a stressful experience. Yes. And then baby, what's, what's on baby? This is so baby. So yes. Yeah. Baby soy is probably going to be stressed. But baby soy was there in the, in the, right now we're talking about grandbaby. Who's grandbaby? Okay. I don't know what this thing is. Sci-fi to me. So, so this is now grandchild. It sits well with I. This is way too transgenerational. We're not about great-grandchildren. I don't know anything about this yet. All right. So then the last one here, we're now four generations in. Yeah. And guess what that is? Oh, butnick, butnick, butnick. And it's Russian all the way through. Oh, look at that one. You're telling me that some parts, some elements of all of our behavior is not our fault? Ooh. I'm saying that in some model organisms, there's an experience that can happen to a, in a parent that leads to epigenetic changes that leads to changes in development of offspring. Now, we've demonstrated this in worms. My lab specifically looks at mice. When it comes to humans, the best study surrounding the most studied, uh, uh, topic surrounding intergenerational and transgenerational inheritance comes from after World War II, the Dutch hunger winter. So this is a period of time where the Netherlands were cut off from food, and it led to a man-made famine. So this is also, I think, something pretty particular. We're not anything about really 1944 to 1945. Yes. Late in the war. Then the generations were suffering from serious medical conditions of diabetes, diabetes, hypertension, even schizophrenia. Not just for the children. And we're speaking about young children who were young children who were starved, but were not pregnant. We're not procreating. We starved. They went on to have children who went on to have children, which is our generation now. Like the generation of these, these people are alive now. Uh, and what we observed is that, what other studies have observed, this is not what my lab particularly does, is that there's an increase in hypertension, diabetes, schizophrenia. And I also think it's very particular to, you think the Dutch were black? I was just gonna go there. Oh, sorry. I didn't mean go. Go. This is a man-made famine. This is not something that that's tracking with like, uh, the environment in a way that all, all things are aligned. This is a man-made famine. So you can envision a space where you have a man-made famine, a man-made, uh, decrease in food, increase only in salted food because that's all you have access, access to for salt preservation food, if you have it at all, plus a lot of stress. I would assume. If we're talking about the black population prior to, you know, the 1900s, and then introduce food deserts and access to low quality food, we can envision epigenetic space. What a food desert is. Yeah. So a food desert is, um, common, a common terminology that we use for a space in which there's not fresh food available in like an X block radius, like a walking radius. That's a food desert. Okay. You can get McDonald's before you can get broccoli. Chuck has defined food desert. So you've got this Dutch winter famine in '44, '45 as a real-time observation, a data set. Yeah. And I think it is possibly the only one that's been able, sadly, created so far. It is the best study. And this, because this is because the Netherlands took very clean note of who served in the military. So they started to see these, these data come about. Now, we know that there is a Chinese famine, um, that took place. We, of course, can look at the Black American and Native American population and tie food deprivation with stress and look at, and health outcomes. But this one is well-studied in a short period of time. If we take that and use that as a starting point, yes, you'll research at your Marlin lab. What a coincidence. You work in a lab called the Marlin lab. Voila. I chose well. What I heard the boss there is great. She's fast. What a coincidence. Exactly. Yeah. How, what are, what are you, so your research covers a number of things, but what about this epigenetic inheritance? What is your research about? Um, what is it finding? And how are you finding it and going about getting the results? Yes. We spoke about the Dutch hunger winter and and Black America. And our work is really motivated on how do we make tomorrow better than it is today? What does it mean to be a human in this space and in this place? Have experiences that are both positive but also negative? How that affects the way the brain develops, the body develops, how that affects offspring interactions with offspring, and how does that affect therefore communities, which affect the world? That really is the heart of, um, what we do in the Marlin lab. And if you didn't get it, the Marlin lab is it's my, my lab. That one. Co— Um, yes. And so I take my passion for figuring out how we can make tomorrow better than it is today, and my love for science, biology, and neuroscience to bring this together. So although our mission is to, uh, aid the world in this way, we use model organisms such as mice and techniques such as studying epigenetic inheritance to get to this answer. So how do you, I mean, okay, if we're back to trauma, what are you sadly doing to mice to inflict trauma? And how do you then balance that out to see how these changes take place? Well, first, we paint the mice black. That's the first thing. We, you know, the sad part is, oh gosh, they're called C-57 Black Six. Those are the name of the mice. It's just like in the name. Every time you write it down, we're like, black mouse. Yeah. Oh, what a shame. But we treat them very well, right? Because we really want to see. We will not allow them to get a mortgage in certain areas. We do redline them. Time for our first commercial break. We'll be back after we reset. You cut up parts of the maze. Oh, God. A maze with no exit, right? Just stuff. Just messing with you. Yes, because we want to see like, how, what is the bare minimum that you could do to create an epigenetic change? We really try to do the bare minimum. And, uh, we also respect the fact that every mouse that is part of this experiment and experience is a mouse that we're asking them to dedicate their life to this experience. So we do take that very seriously. Did she say she's asking them? We do. We do. Look, they have names. After Encore Black Six, they have a name. We give them a name. So, okay, yeah. There's Tyrone. You're going to get me in trouble here. Okay. I am forbidden from saying anything right now. Yeah, yeah. You better. Malik is my favorite. Leticia. So guys, okay, I'm, I'm pulling it back. Go, go, go ahead. Y'all got to get me in trouble. All right. Um, so they pretty much have a pretty regular mouse life, right? They hang out in a cage, they get food, sometimes they get to have sex. They live their best life. This is what they do. So there's not much, many dynamic things happening in their life when, when they're here in the lab. What we do is we place them into a new chamber. So they haven't seen this chamber before. We then introduce an odor, a smell. This is a smell, kind of smells like almond. It's called acetophenone. And we present acetophenone for 10 seconds, and then it co-terminates with a light foot shock. We give them a light foot shock on their foot, and they jump back. But in a mouse who pretty much has had the best life of eating, drinking, and hanging out, this is a terrible thing. Yes. Yes. It's like, right? It's a big deal. It's like, this is when they find out, oh my God, I'm black. This is the, you find out you're black. Until life was one day, I smell almond. I smell some almond, and I got a sh, sh, right? So they're like, what is happening? This happens, uh, five times in a row, right? And then we put them back in the cage over the span of 10 minutes. Okay. Oh, wow. We put them back in the cage, and we take them out the next day. We put them in the chamber. You could already tell they from the chamber itself. Expensive. Yes. They freeze. It's called freezing. Mice do two things. They'll either freeze or run away. Those are their two responses to stress. So they freeze when they get in. We have not given them the odor. They already know the room is already stressing them out. So then they get kind of chilled with the room, like, okay, nothing's happening. And then we turn on the odor, and they freeze again. Of course, even before you shock them, right? And they're counting down for the foot shock. And so they freeze, freeze, freeze when they smell it, and then they jump because they get the foot shock. We do this for 10, 10 minutes a day for three days. There's many ways, many things you can use, many things neuroscientists use to, um, create this pairing, like odor, or we can use sound. We use odor for sensory correspondence. Sensory correspondence. Yes. And I even said the vision, like going into the chamber will also make them scared. But we use odor for a very specific reason. And I can either tell you now, or you can ask me, and I can tell you. What do you want me to do? No, let's do it. Do you mean guessing? Okay. We use odor because odor is just a really cool sense. The lab studies smell, taste, and sound. These three, in focusing on odor. When you breathe in, you respire, you're smelling my lovely Aqua de Parma perfume, right? And you'll that you'll remember this moment forever because of this. This is how we interact with the world. When you breathe in, there's some neurons that interact both with the world and with the brain. These neurons are called olfactory sensory neurons. They're first order neurons that like explore the world and also can send a message back to the brain. And, um, I was lucky enough to train under Richard Axel for my postdoc. He won the Nobel Prize for understanding. He, along with his postdoc Linda Buck, won the Nobel Prize in '04 for ironing out what it means to have a mammalian sensory system like this, like the nose. What we see in the nose is that every neuron in the nose expresses only one olfactory receptor. So it could pretty much only respond to a chemical that binds only to that receptor. So there's a level of specificity. And, and speaking epigenetic inheritance and transgenerational epigenetic inheritance, what does it mean for us to be stressed because of our ancestors? This is what we're missing in the field. And this is why I'm so proud that my lab has been able to bring this to the field. The level of specificity, because we're not talking about your feelings getting hurt. We're talking about an odor that only binds and activates this one receptor in this nose, right? And what we've been able to replicate, because another lab did this first, and it came up with a lot of controversy, and then demonstrate to a high extent, is that those neurons that were smelled, that almond, you take that mouse out, not the mom's, only the dad's. You breed them, and you look at the next generation, and those generations are born with a different olfactory sensory. Get the hell out of here. So how do you, how do you in— It's, you can look up the nose and say, oh, you've got more, or you've got the same. So how are you testing? How are you finding your results to prove? Yes. We have a really cool new technique. Amazing. Thank you. Yes, yes. I mean, that is really, I mean, let me back up just for a minute. Yeah. You describe the experiment as though it was written on a tablet somewhere, but you had to sit down with either yourself or with colleagues and figure out what would make a good test for the hypothesis. Hands down, that took a lot of time. I just want to give credit to it. It's easy to say, put him in, give all. No, you have to think that through. I mean, that's just tremendous. Okay. And you want it to be simple enough so that there's not another, a lot of complicating other factors. The causes and effects, right? Right. On the nose. That's so great. And it's not an easy part of the brain to get to. Uh, we created techniques and we use techniques now, um, in the lab. We do brain clearing. So we can clear the entire tissue. Okay. That's, yeah. See, I'm, you listen, just use light sheet imaging and so cool. Brain clearing, straight up. They clone Tyrone stuff. And I'm not sure. Transgenerationally? Yes. Like a little transgenerational. So, so, so how, and now how exactly, and where exactly? That's going to be the name of my first book. Like, transgenerational Tyrone. Intergenerational inheritance of trauma. So what's the brain clearing, though? That's how, how do you, how do you get to that space? I totally skipped a part because we're seeing that the offspring have a brain that looks like the parent. But I didn't tell you what the parent brain looks like. We take the animal out of this chamber after three days of odor shock pairing. We actually let them relax. Day 10, they actually get to, you know, have a little fun. They breed because we're going to look at those kids later. And 21 days later, we ask them to sacrifice their life. And then we look at their, their brain, right? And if you look at the animals that just got an odor and no shock, or just got a shock and no odor, or got odor and shock, but it's not co-terminating at the same time, their brains all look the same. The paired animals, we call the animals that got the odor co-terminating with shock, they have more neurons that respond to that odor. So I want to give a second to like, give the beauty of biology that that sits there before we even get to the next generation. The brain does. The brain takes energy to make new things, to change. It's an electric, an electric device. So it makes sense. So what period of time does it take for this generation of more receptors to actually happen? We are seeing in the order of 21 days, about a month. Cool part about the main olfactory epithelium. There's stem cells in this area. What part? That's the part where the, where the, the smell. Exactly. The neurons that can smell the world and then send information. The main olfactory epithelium. Epithelium. Another Epi. Look at that. Epi. Good. Okay. And so this tissue, it has a stem cell population. There are very few, few areas of the brain that have stem cells. One is the hippocampus, an area known for placement and memory. Uh, one is the olfactory bulb. This is where these neurons send the information to that go to other parts of the brain. And, um, the main olfactory epithelium. So there's neurons that are that are there. They're not neurons. I take that back. There's cells that are there, and they're like, uh, what am I going to be when I grow up? And they usually hang out and they're like, okay, I'm going to be a peppermint cell because that's what my epigenetic modifications will like allow me to be. And then we give them this experience, this odor shock pairing. And what we've been on G, gone on to demonstrate, what my lab has demonstrated, is that these neurons are going to be peppermint. Say, as important as peppermint is, almond's more important. I'm not going to do that. I got to, I got to, I got to make a my receptor choice. Got to make a detour because because that's more important for me because now I have this experience. I just want to just that that becomes a stimuli basically. Insane. Just so we just. You're brilliant. Just thanks. Just on the same, on the same mouse page. How long does it take a newborn mouse to be old enough to have a next generation? It takes about six weeks. So a mouse is born, six weeks later, it can get pregnant. Yes. And how long is the gestation period? 21 days. That's why you said 21 days before. Because it just happens to be a, um, a coincidence that also 21 days is a good time in the nose. And the typical life expectancy of a mouse is a few years. Two years in the lab. Two, two years. A year and a half. Yeah. Two years. Okay. In the wild, a lot, a lot shorter. Yeah. Because they're tasty snacks for owls and foxes and things. So I guess what I'm getting at is mice, which are interestingly genetically similar to us because we're mammals and vertebrates and this sort of thing. I get that. But what would take us decades to manifest as an organism happens in weeks. Yes. In your lab. So that if you need to go through multiple experiments, it's way more efficient. People also study flies and worms, and they can do this seven generations in two weeks. So we're, we're dead smack in the middle. It takes, it takes a while to get to the transgenerational. That's why flies and worms show up in these kinds of conversations. You would not do it on Galapagos tortoises because that would just be too long. Zero percent chance they'll outlive your. So you conduct this experiment with an adult. Yes. How many generations will this be present? This, this change? We are observing it right now from parent to offspring, from sperm of male to offspring. Our preliminary data suggests that this is not carried on to the next generation if you do nothing to the parent. And this makes evolutionary sense. If your parent has gone through a trauma, and you have not come across this stressor or trauma in your lifespan, why would you give your offspring anxiety? Like, why is it that you would pass that on to the next generation if it's not relevant? Biology is smart. It's smarter than us. And so we sometimes speak about this in a lens of like fear. We don't want this. But really, it's, I view it as a biology wanting us to survive. Because if you have more neurons in the next generation, you probably can sense this odor, right? So it becomes a defense mechanism in, in a manner of speak. Adaptive, in a way. Right. Right. And I wouldn't call, you know, anxiety or stressors in this area adaptive. But I do think logically, the hope is that it becomes something that the animal, um, will allow the organism to survive. It, it gives a defense mechanism that wouldn't otherwise be there. And it needed it for the almonds. Even though why would you need to defend against almonds? You, in your lab, gave them the electric shock because that's what the world looks like, right? The world is dynamic. It's always changing. We're not, we're go— There may be times where something that originally is neutral becomes something that has to be aversive, and your brain has to learn that. It's the beauty of being able to learn that, having your genome learn that, and having that be passed on. So if your generations are in the same environment that caused all the trauma and stress for the original parent, and it stays like that, understandable. You've got the mechanisms that you should be able to survive. But what if that environment changes, and you don't long lead it? Surely you've got a slightly maladapted series of offspring. It's the question of maladaptation. I cannot create a space in my mind that would describe biology being maladaptive. Because what if that odor did come back? Like, like the odor could never come back, and then, yes, you probably have a few more neurons, you maybe smell a little bit less peppermint. But what if that odor does come back? Because not smelling peppermint won't kill you, but not smelling almond could. Yes. See, that just, and that's evolution, right? In a nutshell, right there, happening much quicker than we normally describe it. It's not epigenetic. But it's in, in the skeptic's community, we describe how, why is it we are so good at seeing patterns even when there's no pattern there? And it's been plausibly traced back to, if you think you see a lion in the bushes and you run away, even though there wasn't a lion in the bushes, you live another day. If you, if you don't think there's one there, and there is, then that's the end of your gene pool. Game over. Right. So, so there's a benefit to the caution, to be on the cautionary side of all this. Let's, let's throw it into the moment. We have a war in Ukraine. We have a war raging in Gaza, both with huge tolls on, on the next generation. The stress and trauma must be unimaginable for the likes of me, anyone else I can imagine. Are we likely to see future generations experiencing all sorts of issues like we did with the winter famine? It's a scary thought. Really sad. Heart. The new black people of the world. Yeah. Right. Look, this is generations on generations, right? And I do think, and I, I would love to add my hope as a neuroscientist, is that biology is adaptive and wants us to survive. And so although there is going to be an element of inheriting the man-made trauma, right? This is not ethological trauma, this is man-made trauma. That we are notice that place hasn't become stut. It's kind of hard to de-gender that. It's human-made, political, man-made trauma. Deal with it. Right. But I, I do, I would want to finish the fact that we can still learn. And so my hope is that in understanding what's happening with these mechanisms that the Marlin lab is studying, we can also understand a little bit more about what it means to readapt when things are not in a state of trauma. And that's what we hope to bring forward. So it's not all hope is lost. Is there a difference in heritability between the male who experiences the trauma and the female? The female is carrying eggs, but the male produces sperm. Can we sit on that for a second? This is the part that makes me excited about science. The mammalian olfactory epithelium turns over on the order of 21 days, maybe 40 days. So like, there's a neuron, it's born, live your best life, you're dead in 40 days, and a new one comes in. In humans and mammals. Humans. Why does it die away? Uh, so for example, maybe if anyone's had COVID over the last few years, you'll come to know you can't smell. But then after a while, you begin to smell, right? Because, or you smell things that you're not smelling, like gas. Okay. So that was my experience. I, I kept saying, who left the stove on? I'm running around the house like, someone left the stove. And they are all looking at me like, what is your problem? We have an electric oven. Good, good one. But now you can smell fine. If you ever, maybe when you played soccer, you probably headbutted a ball. Yes. And for a period of time, you probably couldn't smell well, or your taste was kind of funny. This is, oh, but no, I can see what you're saying. I can see that that there's a direct cause and effect because those neurons send their dendrites, the part of the, the neuron that takes an information out into this like this area. Remind us of the parts of the, the nerve cell. Yes. So we have the cell body that's represented here by my well, well-manicured hand. And then we have the dendrites here. The dendrites to sit out in the ether of our nasal cavity. And so as we breathe in, as we respire, we get these molecules. They bind to the dendrites. The dendrites are those looking like tentacles coming off the body. Exactly. And then they'll send this message to the cell body that says, okay, there's enough of these molecules that are bound. Let's make this neuron fire electrically because neurons are both chemical and electrical. Um, and so I'll fire electrically and it sends that electric signal down the axon, right? And then it, uh, ends in what's called the main olfactory bulb. So this is when it starts sending information to the brain, to places like the amygdala, which represent emotion, places like the piriform cortex. This stimulus gets shared with parts of the brain that can take action on it. Yes. Is that a fair way to characterize it? Yes, exactly. And this is important because it turns over every 21 days. Uh, 21 to 40 days. So do sperm, right? Our data has demonstrated that when you mate an animal 40 days after the odor shock pairing, we still see this change in the next generation. So that's got to be the female. Females are never shocked. We would never do that in the Marlin lab. Wait, wait, wait. How does it go beyond? Exactly. It's something happening that gets down to the sperm, right? It's being stored. And even new sperm. Yes. In the gonad, epididymis. Oh, well, the epididymis. It's your epididymis. I know. Don't go technical on me. Epi. That's the, that's the, what the thing that creates sperm. The epididymis. Epididymis is an area of the inside the testes, um, in which immature sperm, so like their sweet baby sperm, they go into the epididymis and they get what's called an epididymal payload. This is not the work that we have pioneered. This is work that others have pioneered that demonstrate if you have like, for example, low food, so in metabolics has been demonstrated, there's a payload of information that comes from the liver or that's in the liver and also found in the epididymis. And what happens is these sperm go through the epididymis, they mature, they get grown, and they also get this payload. The epididymis says, you were starved. And they bring that down to the next generation. Yes. So, I years ago, and I'm, you, maybe you'll know this, and I can't, I'm so sorry, but I read a study trying to look it up. I was trying to look it up, but I was trying to look at the study itself, and it dealt with sperm production and cocaine use in men. Do you know the study I'm talking about? Believe I do. It was done at Penn. Yes. Yeah, yeah, yeah. And it was fascinating because the men were passing the information on in their sperm that, uh, equated back to the cocaine use. Wow. And it was just fascinating too. But this is exactly what we're talking about. So what you're saying there is outside of stress, trauma, certain environmental circumstances can have an effect on, on the way the, the epigenetics are R to. We do know that that stress and trauma, do cocaine use, lifestyle, yes. There must be all sorts of other things. I'm guessing environmental pollutions and all sorts. So do you have a list? I mean, can you make a ranked list of, avoid this because it'll mess up your gonads? I mean, we don't want to say mess up. Will respond to that list. It may not be mess up. It will change. Change is not always bad. That's true. Right. Are you willing to take that experiment on to see if it goes good or bad? All right. So, all right, right. So what has risen to the top of people's research efforts are studying the bad effects. Yes. So give me an example of something that could be a good effect in the epigenetic transgenerational. Could I give you something that would be an example of a good effect? I think a good effect is biology saying, if it ain't broke, don't fix it. Right? Like it may not be that we. Effect is the neutral effect. Yeah. The neutral effect is right. Yeah. Spent a lot of time on a yacht. And your children come out going, what? Oh, dear. Mom, I'm so terribly, terribly hungry. Oh, yeah. The starvation threshold is different when you're on a yacht. No, for example, just as an example. Yes. It's long been known that suicide rates are higher among people who are less traumatized. Right? So suicide rate for Black Americans was way lower than than for white Americans, especially wealthy white Americans. And, and, and Black females is the lowest. Of course, they have it the hardest. Those numbers creeping up a little recently, which is a sign of more equality, I guess. But suicide. Wow. I guess we finally made it. What a metric. We did it, guys. Was angry as a white man. Okay, cool. So I don't know if this question is relevant or even interesting, but as they say, your biggest problem is your biggest problem. So if you're on the yacht and there's a delay, I see where you're going with caviar and you have a big party you're trying to put on, you could be very stressed by that. Don't judge my trauma. Like, don't judge my trauma. My is my trauma. To the therapy session. Your trauma is your trauma. From a psychologist's lens. Yes. Yes. The biggest deal in this mouse life is that it got its foot shocked. We all stubbed our toe at some point within this last week. We're not really going to remember it. It happens often. But in the dynamic of this mouse, yes, that's. Oh, better than us. I'm, I'm coordinated. Okay, sorry. I'm not going to apologize. Yes. Yes. I can see the, the biggest problem being the biggest problem. I think when we think about looking at humans, we have to take culture into consideration. And that's what we separate when we study mice. Why we have a model organism like mouse is because we can control everything else. Right. Right. There are definitely cultures in which the morbidity associated with suicide, suicidality is higher. My mother from Guyana, South America, one at some point, it had the highest suicidality rate and no longer does. I think it's number three now in the world. In the world. Wow. Yes. Right. And we saw that there was a trend with the three major populations, which are Indo, Indo-Guyanese, Afro-Guyanese, and, uh, Chinese Guyanese, or like Asian Guyanese, as well as a native population. And it was higher in the Indo. But there are also different cultural aspects of being Indo. So I think it's harder. It's harder to parse. So you got to get the basic science in there first before you get sociological. Hands down. I think it's wise. Yeah. Interesting. It's wise and respectful. Other, it's a big tangled mess, and you don't know what your causes and fix. What happens if the, the shocks were generational and continued? Yes. So right now, what we're observing is an intergenerational change. But what if the environment doesn't change, even in the next generation, or the generation after that? This is when we can start to envision a space where what we're looking at is an actual evolutionary change, not just an epigenetic change. Interesting. Because if what, and we have not demonstrated this, nor have other labs, but it could be the space in which for seven generations, you get the odor foot shock. Right? And then you have the eighth, you'll, you'll expect to see the change in brain. What if you do nothing to the eighth, and then look at the 10th? Is this when it finally has stopped becoming intergenerational and finally overrode? So in that 12th generation, what we see is the same expression that we did in the eighth and the seventh. But we created that eighth and seventh now happening. But that smells Lamarckian. Here, people say Lamarckian as if it's like bad. Okay. Well, okay. Let me, let me do right. Got to do right by Lamar. Baptist Lamar. Lamarck came a half a century before Darwin. He also wants to give credit where credit's due. Darwin's work is built upon what Lamarck, um, studied. If I could put that in a nutshell, pretty much what Lamarckian inheritance would describe is a giraffe walking in its giraffe space, and it sees green leaves on top of a tree, and it's like, okay, I really want these green leaves. I'm going to hope and wish and stretch and try to get those leaves. Try to get the leaves. And as you try, your neck gets longer, and then you have a longer neck, and the next generation is even longer. So it's characteristic from things that happen based on your circumstances or surrounded. Exactly. All right. Whereas Darwin says, you were born with a long neck. You eat all the top of the leaves. All your cousins die with short necks, and now you get to breed more and have, you were selected to remain because your neck was suited for eating trees. Everybody else died. Doesn't mean that it's one or the other. It does not have to be nature versus nurture in this space. It could be an endow— So is this adapt and survive, or is that just too broad a stroke? I think this is what it comes back to. How many generations does the smell continue on? What we can say is that former, the studies that went on after Lamarckian inheritance, um, became a concept where scientists would go in and they would say, okay, well, let's see if Lamarck is is real. We're going to go take this mouse, we're going to cut off its tail, and let's see if the next generation is born with with no tail. In fact, let's do it for three generations. We do not do this in the lab. Let me clarify. Right. But for three generations, you cut off the mouse tail. And poodles. So don't apologize for not doing. Exactly. And poodles are still born with tails. Yes. With long tails. They cut them short to to make it a little bushy-tailed. But right. So they said, okay, Lamarck is wrong. But what they didn't study is, are the mice now afraid of the scientist who comes in with the lab coat and scissors? Right? So what are we really focusing our question and answer on? Because that would be a psychological trauma, just a physical change. Let's turn this around because we've talked about traumas. We're going to cut the tails off young animals. Right. How cute. How wonderful. What if you get exposed an animal to something pleasant, and continued that pleasant exposure? Do you find that that becomes a more balanced, a happier creature? I know it is. This is not going to happen anywhere, right? But is it possible to have other things transferred, not just trauma? If I were to have a conversation with biology, I think what biology would say back to me is like, let's survive so we can thrive. All right. If sugar's good, if flowers smell good, we're good. Wait, do you have conversations with biology all the time? All the time. And it speaks back to me. Okay. Okay. In the way neurons fire. Like, science is so beautiful. All right. Right. But what we think is happening when it comes to a stressor, yeah, is that there's something called coincidence detection. And we talk about this as electrophysiologists who record from neurons in the brain. When one neuron fires and another neuron hears that fire and also fires, is coincidence detection. We have an animal who's smelling the environment, so those neurons are firing, and it gets a shock. That's another pathway that's now firing. The same time those olfactory sensory neurons are firing. If we have something pleasant, we could have the smell of a flower, maybe some dopamine be released, and like that could be paired. But it may not be. Dopamine makes you feel good. Dopamine is a neurotransmitter. Makes you feel good. But would that be enough of a threshold to say, now let's take all the energy necessary to make sure animals smell flowers more? Oh, it's already roped into what the pleasant circuitry looks like. But I think the best way to answer that question, yeah, would be, let's override it with something really good. Let's give him some good cocaine. Right? Because it's so good that it's bad. How does that change the next generation? Oh, that's the way I would approach that experiment. Is that true with most things? They're so good, they're bad? Well, yeah, I mean, sugar is certainly what, like, you know, we, there's sugar receptors in our stomach, on our tongue, and our brain. But why? Because it's essential for survival, right? It's got high calorie density. Exactly. But at one point, hijacked by, by candy bar companies. But it was, but the scarcity is what allowed it to be, oh, it's so good. And hey, I got to get this because you're not going to get it. But now that it's abundant, now it's a bad thing because you can get it all the time. It's subject to abuse. Those same receptors have, have been hijacked by modern civilization. Right? So you would agree, or possibly even lament, that these features of our adaptability in modern times, if you don't need that adaptation yet, you still have manifestations of it. A clever advertiser or a clever marketing person can hijack those sensory urges. Of course. Of course. Absolutely. And whose responsibility is that to fix that? So we've discussed Chuck's need for sugar. Quite needs to survive. Senses, sight, smell, taste. They're all senses. So it's all survival. This whole thing of epigenetic inheritance is, I mean, to thrive, a simple umbrella to my mind is survival. Yes. And so therefore, it's as necessary as oxygen. Oh, hands down. Hands down. Amazing. Sweet oxygen to aerobic. Yeah. Yes. They anaerobic life that does doesn't want oxygen. Just to be, just to be. We're being specious. We're just only talking about the important ones. Speciesist. Correct. No isms. So let's, let's see if we can.

Land. This plane. This fascinating plane. Let me be cynical here. So what now? You understand the phenomenon. What are you going to do about it? An entire generation of people survived the depression, famine, uh, racism, slavery. Can you do anything about it other than just come behind us all and say, "Well, here's why you're that way"? And then go back to your lab. Meanwhile, Chuck has hypertension. He's got, he's got race issues, prostate, prate, all kinds. Okay, if you can't do anything about it, what good is this? And if you can do something about it, then are you playing God?

I, that's a twofold answer. One is for the love and need of understanding science. The other one is for the love and need of understanding people. If there was a space in which someone who had gone through trauma ancestrally and then are born here in modern day and are suffering from all these elements, even though they eat healthy, they exercise, they still have hypertension, they still feel this anxiety, I believe to have a neuroscientist say to you, "You can take that burden off of you. It's not your fault. This is just the way that you've inherited experiences of your ancestors." That validation within itself will probably create a shift for better. So, so that, that, that, uh, thing there, it's not your fault. It's not your fault. I mean, I just heard you talk about sugar. So maybe that one is, "It's not your fault. It's not your fault. It's not your fault." Mantra. "It's not your fault." Except the sugar. That part that runs deep.

That's great. And I think the other is, if we have to understand what's happening in a, in a maladaptive situation, quote unquote, in a bad situation, we have to understand the basics of biology. We can't fix something unless we know how it broke. In, in the hit series *The Expanse*, there's talk of adapting a life form that can just simply live in the vacuum of space because that's a new frontier where a lot of people are hanging out in all the time. So I'm just wondering, do you generally, in science, if you understand something, ultimately you can manipulate it and control it?

Yes. Uh, is there a plan for that going forward where you can go in and nip, tuck, tweak, pinch, and all these symptoms go away, thereby removing the epigenetic forces operating? If we understand it, can we go in? Can we nip and tuck? In the same way, if we understand, understand the need for sugar, should we pound it into our food and candy and give it to our children? I think it has to do with responsibility as scientists to say, "We now have the ability to do a little nipping and a little tucking." But do we understand how this is going to change generations to come? If we take out the ability for you to change this adaptation, you could do them a future generation to not want sugar, and then they won't even have or not smell the smell and not have anxiety. But then constantly get... That's a really good answer. I can't even rebut that. The unintended consequences. Why do you give me such a good name? I got nothing to ask you now. You answer my question so good. Why the good doctor is here? I know, I know. To give the good answer. Good doctor. Like, so, I, I'd love everything you've described. Is there any controversy in your, among your colleagues about what you're doing? Or they do? Are there competitive ideas? Where does your work fit in the landscape of other science?

Smack in the center of the controversy. And a lot of it has to do with what we're taught in textbooks and what we decide is canon, decide is truth. And then we see that maybe Lamarck wasn't all wrong. And that really draws people's brains. So our job as neuroscientists is to say, "Put your textbook aside. This is the data. Let's look at what our studies have demonstrated and take it from there on a clean slate." Uh, but we, we, there are other labs. Publish what you do. It's, it's then reproducible. So why should anything be so controversial? As what is poking mice? I think you're on a very, a very important note of this. Unless you just special black mice, nobody else gets... Don't stop. Don't, poor Tyrone. Your name is Tyrone. Are any of your mice named Tyrone?

I can't answer the question now because, you know, one is, and I can't say it now. So of course, um, but I will say that my lab was the first to replicate the study, okay, of the original par change in the parent. Fantastic. This study was start. Yes, Brian Dez and Carl Russ. They, I got a lot of fire for it because they got a lot of, they got a lot of fire for it. So I entered into the flames thinking, like, first things first, can we replicate this cleanly using our brain clearing and using our cool microscopes? We've been able to replicate that brain clearing. We then built upon it by showing this is the mechanism. I think that unfortunately, we have to sometimes wiggle our brains out of the old mindset and just look at the data and see what that looks like. And I think that's why shows like this are so important because you're motivating people to think slightly differently and have that little bit of different of a spin and that direction. The, the way the cutting edge of neuroscience works. I mean, when you look at addiction, just addiction alone, the work that has been done to prove that addiction is not a matter of willpower, it's not a matter of desire, it's not, it's actually a brain malady. I mean, if you had told somebody that 30 years ago, they'd have laughed at you. They, they said you're a quack. And now it's just accepted. You know? So, yeah, keep going. This is great. That dovetails with the free will question, right? How much are we actually in control of our body, mind, and soul? Right? And how much of it is a chemical response? And how much of it is man-made? Right?

Well, that's, you've introduced an entirely new aspect to the bring the data. Yeah. I only talk about the data. Show. Now we have to ask because we've, like neuroscience and Star Talk special edition. So, so we're compelled to ask, how much genetic control do you have over your husband?

I rely heavily on epigenetics. My relationship with my husband and my children. Okay. Um, completely obedient households in prayer. Yeah. That's so funny. It's so funny. Thank you for sharing your expertise. And you're just up the street in Columbia? Yes, I am. We got to come back. Yeah. Just a couple miles north of here. We're at the American Museum of Natural History. And you got your own lab. And there's more research going on in different areas in the Marlin Lab. So we may well be revisiting soon. Okay. All right. Dr. Professor, thank you for joining us. All right. For having me. Chuck, always good to have you, man. Always a pleasure. All right. This has been Star Talk special edition. Here, Neil deGrasse Tyson, as always, bidding you to keep looking up.

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