Epigenetics & The Full Story of Inheritance with Bianca Jones Marlin

23:47You would not do it on Galapagos tortoises because that would just take too long. Zero percent chance. They'll outlive your land. That's funny. So you conduct this experiment with an adult. Yes. How many generations will this be present, 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?

24:32Why is it that you would pass it 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 fear. We don't want this. But really, I view it as biology wanting us to survive. Because if you have more neurons in the next generation, you probably can sense this odor more quickly. It becomes a defense mechanism in a manner of speaking. Adaptive in a way. And I wouldn't call anxiety or stressors in this area adaptive. But I do think biologically, the hope is that it becomes something that the animal will allow the organism to survive.

25:06It 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. 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.

25:43But 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 the odor could never come back and then yes, you probably have a few more neurons and maybe you 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? And that's evolution right in a nutshell right there.

26:20It's happening much quicker than normally. We describe that, it's not epigenetic, but it's in the skeptics community, we describe how wide it is 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 don't think there's one there, and there is, then that's the end of your gene pool. Game over! So there's a benefit to the caution, to be on the cautionary side of all of this. Let's throw it into the moment.

27:04We have a war in Ukraine, we have a war raging in Gaza. Both with huge tolls on the next generation. The stress and trauma must be unimaginable for the likes of me and anyone else I'd 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. It's a really sad and heartbreaking scary thought. It would be the new black people of the world. Yeah. Look, this is generations on generations, right? And I do think, and 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?

27:51This is not like ethological trauma. This is man-made trauma that we are... Notice that phrase hasn't become degendered. Man-made trauma. I said what I said. I was going to say. I didn't stutter. It's kind of hard to degender that one. It's a human-made trauma. Political, man-made trauma. Deal with it. 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 Marlon 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. That's what we hope to bring forward.

28:28So it's not all hope is lost.

28:49is there a difference in heritability between the male who experiences the trauma and the female The female's carrying eggs. Hands down. But the male produces sperm. Yeah. Can we sit on that for a second? This is the part that makes me excited about science. The male factor of epithelium turns over on the order of 21 days, maybe 40 days. So 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. Why does it die away? So, for example, maybe if anyone's had COVID over the last few years, you'll come to know you can't smell. Couldn't smell.

29:23But then after a while, you begin to smell, right? Because there's a turnover. You smell things that you're not smelling, like gas. Okay, I'm sorry you had that. That was my experience. I kept saying, who left the stove on? I'm running around the house like, someone left the stove on. And they're all looking at me like, what is your problem? Terrifying. We have an electric oven. Good one. But now you can smell fine. Yeah, I'm fine. Maybe when you played soccer, you probably head-butted a ball. Yes. And for a period of time, you probably couldn't smell well, or your taste was kind of funny. but no I can see what you're saying there's a direct cause and effect because those neurons send their dendrites so the part of the neuron that takes an information out into this area remind us of the parts of the nerve cell yeah so we have the cell body that's represented here by my well manicured hand and then we have the dendrites here the dendrites 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 a tentacles coming off the cell body.

30:25Exactly. Go ahead. 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. And so it'll fire electrically and it sends that electric signal down the axon. Right. And then it ends in what's called the manilfactory bulb. So this is when it starts sending information to the brain, to places like the amygdala, which represent emotion, places like the puriform cortex. So this stimulus gets shared with parts of the brain that can take action on it.

30:53Yes. Is that a fair way to characterize it? Yes, exactly. And this is important because it turns over every 21 days, 21 to 40 days. So do sperm. 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 Marlon lab. Wait, wait, wait. Then 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 creates the sperm. Yes. In the gonads. In the gonads. The epididymis?

31:33Is it epididymis? Oh, voila. Epididymis. Yes. And the epididymis. That's a word. Epididymis. It shouldn't be. Epididymis. Epididymis. It's epi again. It's your epididymis. Don't go technical on me. Epididymis. Epididymis. That's the epididymis. That's the what? The thing that creates sperm. The epididymis is an area inside the testes in which immature sperm, so like their sweet baby sperm, they go into the epididymis, and they get what's called an epididymisomal payload. This is not the work that we have pioneered. This is work that others have pioneered that demonstrate, if you have, for example, low food, and metabolics has been demonstrated, there is a payload of information that comes from the liver, or that's in the liver and also found in the epididymis.

32:17And what happens is these sperm go through the epididymis, they mature, they get grown, and they also get this payload, the epididymisome, that says you were starved. And they bring that down to the next generation. Yes. So I, years ago, and maybe you'll know this, and I can't, I'm so sorry, but I read a study. You were trying to look it up? I was trying to look it up, but I was trying to look up the study itself. And it dealt with sperm production, and cocaine use in men. Do you know the study I'm talking about? I believe I do. It was done at Penn? Yes. Yeah. Yes. And it was fascinating because the men were passing the information on in their sperm that equated back to the cocaine use.

33:07Wow. And it was just fascinating too, but this is exactly what we're talking about. So what you're saying there is outside of a stress trauma, certain environmental circumstances can have an effect on the way the epigenetics are all too. We do know that stress and trauma do exacerbate this. Cocaine uses lifestyle. There must be all sorts of other things. I'm guessing environmental pollutions. Do you have a list? Can you make a rank list of avoid this because it'll mess up your gonads? We don't want to say mess up. People will respond to that list. It may not be mess up. It will change. Change is not always bad.

33:46That's true. Are you willing to take that experiment on to see if it goes good or bad? All right. So what has risen to the top of people's research efforts are studying the bad effects. 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. It may not be that we need to... So the good effect is the neutral effect. Yeah, the neutral effect is... Right, yeah. Now, studies are going on. You spend a lot of time on a yacht and your children come out going, Oh, damn.

34:24Mom, I'm so terribly, terribly hungry. The starvation threshold is different than when you're on a yacht. But for example, just as an example, it's long been known that suicide rates or higher among people who are less traumatized. So suicide rate for black Americans is way lower than for white Americans, especially wealthy white Americans. And black females is the lowest. Yeah, of course, those numbers. They have the hardest. Those numbers have been 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.

35:14I was angry as a white male. 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 in the 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. Don't judge my trauma. My trauma is my trauma. To the therapy session, your trauma is your trauma. From a psychologist 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.

35:47We're not really going to remember. It happens often. But in the dynamic of this mouse, yes. Oh, it's better than us. I'm coordinated, okay? Sorry, I'm not going to apologize. Yes, I can see the biggest problem being the biggest problem. I think when we think about looking at humans, you 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. There are definitely cultures in which morbidity associated with suicidality is higher. My mother's from Guyana, South America. At some point, it had the highest suicidality rate.

36:24It no longer does. I think it's number three now. In the world? In the world. Wow. Yes. And we saw that there was a trend with the three major populations, which are Indo-Guyanese, Afro-Guyanese, and Chinese-Guyanese, or Asian-Guyanese, as well as the native population. and it was higher in the Indo-Gyanese. But there are also different cultural aspects of being Indo-Gyanese. So I think it's harder to parse that. So you got to get the basic science in there first before you get sociological. It's hands down. I think it's wise. Interesting. Of course. It's wise and respectful. Otherwise, it's a big tangled mess and you don't know what your causes and effects are.

36:54And no one fix anything. What happens if the shocks were generational and continued? Yes. So right now what we are 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 evolution change, a change in evolution and 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 expect to see the change in brain.

37:28What 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 8th and the 7th, but we created that 8th and 7th. And now it's just happening. But wait, wait. But that smells Lamarckian here. People say Lamarckian as if it's like that. Okay. Well, okay. Let me do right by Lamarck. First of all, who was Lamarck? You got to do right by Lamarck, okay? Who is Lamarck? Jean-Paptiste Lamarck. Jean-Paptiste Lamarck came half a century before Darwin's.

38:04you also want to give credit where credit's due. Darwin's work is built upon what Lamarck 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. Try to get those leaves. And just try to get the leaves. And as you try, your neck gets longer. And then you have a longer neck, voila. And the next generation is even longer. So it's an acquired characteristic from things that happen.

38:34On your circumstances or surroundings. Exactly. Okay, all right. Whereas Lamarck, I mean, 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 a long neck. And that would be you were selected to remain because your neck was suited for eating trees. And everybody else died. And it doesn't mean that it's one or the other. It does not have to be nature versus nurture in the space. It could be an end or. So is this adapt and survive, or is that just too broad a stroke? I think this is what comes back to how many generations does the smell continue on?

39:05What we can say is that former studies that went on after Lamarckian inheritance became a concept where scientists would go in and they would say, okay, well, let's see. If Lamarck 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 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. We do it with poodles. Don't apologize for not doing it to mice. Okay, exactly. And poodles are still born with tails. Yes. With long tails.

39:34They cut them short to make a little bushy tuft. Okay. 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? So what are we really focusing our question and answer on? Because that would be a psychological trauma, not 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?

40:10Kumbaya. I know, this is not going to happen anyway, 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 is good, if flour smells good, we're good. But do you have conversations with biology? All the time. all the time. And it speaks back to me. Nice. Okay, okay. In the way neurons fire. Science is so beautiful. All right. But what we think is happening when it comes to a stressor is that there's something called coincidence detection.

40:44And we talk about this as electrophysiologists who record from neurons in the brain when one neuron fires and another neuron hears that firing and also fires, it's 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 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 it's already roped into what the pleasant circuitry looks like but I think the best way to answer that question would be let's override it with something really good Let's give them some good cocaine.

41:33Right? Because it's so good that it's bad. How does that change the next generation? That's the way I would approach that experiment. Isn't that true with most things? They're so good, they're bad? Well, yeah. I mean, sugar is certainly one. Like, you know, there are sugar receptors in our stomach, on our tongue, in our brain. But why? Because it's essential for survival. It's got high calorie density. Exactly. But at one point - Then it gets hijacked by candy bar company. 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.

42:08But now that it's abundant, now it's a bad thing because you can get it all the time. Right. So it's subject to abuse. Those same receptors 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. Yeah. Absolutely. And whose responsibility is that to fix that? Yeah. So we've discussed Chuck's need for sugar. because he quite needs to survive.

42:52Senses, sight, smell, taste, they're all sensory. So it's all survival. This whole thing of epigenetic inheritance is... Survive 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. Nice. Sweet. Oxygen to aerobic. Breathe. Yeah, to aerobic. Yes. They're anaerobic. life that doesn't want oxygen just to be just to be we're being specious we're just only talking about the important ones correct no isms so let's let's see if we can land this plane this fascinating plane let me be cynic here so what now you understand the phenomenon what are you going to do about it an entire generation of people survive the depression famine uh racism slavery can you do anything about it other than just come behind us all is that, well, here's why you're that way, and then go back to your lab.

43:51Meanwhile, Chuck has hypertension. He's got issues. Anxiety, anguish. He's got race issues. Prostate. 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 think that's a twofold answer. One is for the love and need of understanding science, and 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.

44:30They 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 that 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 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 maladaptive situation, quote unquote, in a bad situation, we have to understand the basics of biology.

45:09We can't fix something unless we know how it broke. 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 all the time. So I'm just wondering, generally in science, if you understand something, ultimately you can manipulate it and control it. Yes. Is there a plan for that going forward? where you can go in and nip, tuck, tweak, pinch, and all of these symptoms go away, thereby removing the epigenetic forces operating. If we understand it, can we go in and can be nip, tuck?

45:48In the same way, if we 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 the responsibility of 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 doom a future generation to not want sugar and then they won't even have the unintended... Or not smell the smell and not have anxiety but then constantly get slapped up. That's a really good answer.

46:14I can't even rebut that. The unintended consequences. Why are you giving me such a good... Damn, I got nothing to ask you now. You answer my question so good. That's why the good doctor is here. I know, I know. To give the good answers. So I love everything you've described. is there any controversy among your colleagues about what you're doing? Are there competitive ideas? Where does your work fit in the landscape of the neuroscientists? It is dead smack in the center of the controversy. And a lot of it has to do, A, with what we're taught in textbooks and what we decide is canon, decide is truth.

46:50And then we see that maybe Lamarck wasn't all wrong and that really jars 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. But presumably there are other labs. There are other labs, yes. If you publish what you do, it's then reproducible. So why should anything be so controversial as what is poking mice? I think on a very important note of this reproducibility. Unless you just have special black mice that nobody else gets. Don't stop. Don't stop. Poor Tyrone.

47:25Why do you name him Tyrone? Are any of your mice named Tyrone? I can't answer the question now because you know who one is. and I can't say it now, so of course. But I will say that my lab was the first to replicate this study of the original change in the parent. This study was done... That's a start. Yes, Brian Diaz and Kerry Russell. They got a lot of fire for it because... They got a lot of fire. 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.

47:55We 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 different of a spin. And that can take things in a different direction. 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.

48:23It's not a matter of desire. It's actually a brain malady. I mean, if you had told somebody that 30 years ago, they'd have laughed at you. They'd have said you're a quack. And now it's just accepted. So, yeah, keep going. This is great. That dovetails with the free will question. 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 where you've introduced an entirely new aspect of the conversation. I only bring the data. Yeah, I only talk about the data show. Now, we have to ask because we like neuroscience and StarTalk Special Edition.

49:03So 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. Completely obedient household. Epigenetics and prayer. That's so funny. That's so funny. Thank you for sharing your expertise. And you just upped the street in Columbia. Yes, I am. We've got to come back. Yeah, just a couple miles north of here. We're at the American Museum of Natural History. And you've 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. All right.

49:40Dr. Professor, thank you for joining us. Thank you for having me. Chuck, always good to have you, man. Always a pleasure. All right. This has been StarTalk Special Edition. Neil deGrasse Tyson, as always, bidding you keep working up.

49:56Thank you.