Erin Kinnally
Description: Erin Kinnally is a biological psychologist at UC Davis and a core scientist at the California National Primate Research Center, where she leads the Biobehavioral Assessment program. Her work combines primate behavior and biology to understand how early life experiences shape long-term health and resilience. In this episode, we discuss how behavioral patterns in infant monkeys can predict their future well-being, how social training can reshape life outcomes, and what this research tells us about our own species. Erin also shares insights into the role of fathers in shaping offspring biology, the epigenetic impact of early adversity, and the promise of translating these findings into human health policy and aging interventions.
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Show Notes:
[0:51] Lessons from Monkeys
[2:35] Discovery of a Passion
[3:29] The Importance of Primate Research
[4:42] Limitations of Primate Models
[8:09] Biobehavioral Health Overview
[9:10] Promoting Health in Monkeys
[10:42] Biobehavioral Assessment Program
[13:23] Transitioning to Aging Research
[15:30] Technology and Behavioral Assessment
[18:19] Early Life Stress Effects
[20:36] Understanding Early Life Stress
[22:52] Maternal Influence on Stress
[25:18] Investigating Maternal and Paternal Impact
[27:12] Stress Responses in Monkeys
[28:10] Evolutionary Perspectives on Stress
[34:10] Teaching Monkeys Resilience
[35:55] Epigenetics and Stress
[39:21] The Epigenetic Clock
[41:04] Downstream Effects of Early Life Stress
[44:15] Resilience and Change
[46:26] Paternal Influence on Inheritance
[51:36] Future Research Directions
[54:26] Advice for Students
[56:08] Conclusion and Reflections
Unedited AI Generated Transcript:
Brent:
[0:47] Awesome well welcome professor Erin Kinnally thank you for coming on today.
Erin:
[0:52] I'm so happy to be here.
Keller:
[0:53] We'd love to start off by hearing what's the most interesting thing a monkey has taught you?
Erin:
[0:58] Yes, there are a lot of things. I think the most interesting thing that monkeys and really all of science has shown me is, you know, I started out in my career being really interested in genetics and biology, how biology shapes us. And I think what I've learned through my career and my life is that, you know, there really aren't many things that can't be changed you know even how our genes work it can be changed you know um it it might take some work uh but everything uh can be redone or undone.
Brent:
[1:40] And how has your perspective on human nature changed after working with the monkeys for so long?
Erin:
[1:46] This is such a good question. I think probably a lot of people who work with animals would say that it totally shapes how you see your social landscape. Like, when I see things in the world and it reminds me of monkeys and what the monkeys are doing. I was joking with you, you know, that when my son, you know, seeing my son grow up, he's nine now, I'll say like, oh, yeah, like seeing him with his friends or whatever, like, yep, yep, that's just like the monkeys, like it, it resonates. And I think, you know, studying animals and being an animal, you know, it really opens up your worldview. You know, you feel more connected to everything, but also you realize,
Erin:
[2:32] you know, we're not so unique. You know, we came from somewhere.
Keller:
[2:36] And how did you discover this passion for science? How did that lead you to studying primates?
Erin:
[2:41] Yeah. My parents always said they just could not believe that this is what I ended up doing for my job. This is the opposite of whatever they expected. I was always so curious. And like I said, I remember being really young and wondering about some of the questions that I still answer about nature and nurture because I have this big family and I love them so much. And I was just so curious about them. Hammond. And so, oh, this happens all the time. What was exactly?
Keller:
[3:18] How did you go to start like being passionate about science and studying practice?
Erin:
[3:22] And so, you know, when I, I was a total humanities person, I thought I was going to be a lawyer.
Erin:
[3:29] And I started out as a history major. And I was really interested in like the Middle Ages and the renaissance and then i took my first brain and behavior class and it just like hit me you know and i was able to do a senior thesis where i went i went to hamilton college which is a small college and so i had really close contact with professor weldon my my mentor and i got to do my own project and it just i don't know how to explain it just you just lock in and i knew that's what i wanted to do.
Brent:
[3:56] Was that project with primates.
Erin:
[3:58] No it was with rats okay yeah i named them.
Brent:
[4:01] That's fine Can we still name the monkeys here, too?
Erin:
[4:04] Of course.
Brent:
[4:05] Yeah. So why is the non-human primate model so critical for science?
Erin:
[4:11] Yeah. I have so many answers to this. Yeah. What I will say is that in order to move human and animal health forward, I am, and I don't want to speak for anybody else, but I am personally committed to, you know, asking the really important questions for human and animal health so that we
Erin:
[4:37] can push medical discovery forward and make life better for all of us. There's this concept at uc davis of one health you know we study health in humans and animals to make all human and animal health better um and primate research is is a small but important part of that.
Keller:
[4:58] Now what are some of the key limitations to primate research we talked to steve ostage yesterday he has you know strong critiques about mice and research.
Erin:
[5:05] Yeah what.
Keller:
[5:06] Are some of those for primates kind of where do they where does that extend.
Erin:
[5:08] Yeah so i mean i think and we we all have to do this we have to really carefully justify our model always so we want to ask the right the we want to ask the right model the questions so if if you're asking an inappropriate model then the information isn't as helpful so i mean for primates i think the advantages are obvious you know, they're so closely related to humans. They share, you know, developmental staging and neuroanatomy and even disease progression and comparable diseases to us. So that makes them so valuable for so, so many things. Limitations, I mean, if you were going to ask, you know, you want to conserve resources and conserve animal lives as much as possible. So you only want to ask the questions that must be asked in a primate model. So, you know, you're not going to dive into something, you know, at the top, right? You're going to do the basic research and other models first and then move to test them in primate. Um, but some of the limitations are, you know, it, it takes a primate center to house them. You know, people, there are small primate colonies, but they're hard, they're hard to run. So it takes a lot of resources. Um, but the great thing about that is it takes a lot of expertise. It brings amazing people together. People who work here are incredible.
Brent:
[6:37] Yeah. And then just give a brief overview of like the whole national primate research center model and like where Davis fits in.
Erin:
[6:44] Yeah. I'm definitely not the expert in that, but we have seven national primate research centers. If you test me, I could probably tell you where all of them are. The idea is that the National Institutes of Health fund these primate centers to be this primate resource for the entire country. And so people can come here and do research. They can collaborate with us to do research. They can buy animals for their own research. And so, yeah.
Keller:
[7:22] Is there a lot of cross-collaboration between the other national laboratories, or are they kind of independently focused on different areas?
Erin:
[7:29] That's a great question. Again, I'm not the expert on this, but I believe there's tons of collaboration between the National Primate Centers. We could all always be better, of course. There's a lot of push to create more working groups and more consortia. I know John Morrison, our former director, is involved with a lot of those working groups. But anyway, there's definitely a lot of collaboration with external investigators. And I know all of my colleagues take that really seriously. we want people to have access to primate models, even if they don't happen to be in a place where
Erin:
[8:08] there's a primate research center.
Brent:
[8:09] Yeah. And I'll kind of transition a bit to more of your work within the primate center. What is biobehavioral health as a whole?
Erin:
[8:18] Yeah. So I think of biobehavioral health as this like holistic way of thinking about a very diverse set of metrics having to do with our biology, our physiology, our genetics, our epigenetics, our immune function, our brain function. I'm probably missing some functions in there. Is it social? Huh?
Brent:
[8:42] Social?
Erin:
[8:43] Social, yeah, for sure. And our behavioral health, and how those things link together. And that's not perfect. It's not like one causes the other. They interact. So it's sort of like this holistic view. In practice, though, of course, we think about different aspects of biobehavioral health when we're trying to apply it to understand something about making people's lives better.
Keller:
[9:10] And how does the primate center here promote kind of the best biobehavioral health for their monkeys? Because I'm sure there are a lot of limitations working within a confined area to make these metrics possible.
Erin:
[9:21] Yeah. There's so, so many answers to that. So we have units devoted to units of expert people who are devoted to behavioral health, to medical health, to the housing and care of the animals. And I mean, you've met, I mean, the people who work here are the best at what they do. They're so unbelievably motivated. They go above and beyond every single day. I can't tell you the number of times where, you know, I have to come in at midnight because, actually, I shouldn't say that because I am not the front line for that. Uh, but you know, just last year, you know, I had to come in for a freezer breakdown and we have to like move a bunch of samples. And, uh, one of my team, Ashley Cruz, she's there. She's there before me. Uh, I'm totally gonna forget his name right now. I'm so sorry. Is it Ryan? He was there like right after her, like, cause he was the night person. He just comes in, they're moving samples. I mean, can you believe that? Like middle of the night?
Brent:
[10:19] Yeah i think a big thing that i learned when onboarding here is just how much longer the monkeys live here and like you're really easy like you we track all the different elements of like their health and i kind of think the bio behavioral health is a better way of saying it because there's like
Brent:
[10:36] all the different elements that you can ensure that they are actually taking like really good care of.
Erin:
[10:42] Yeah yeah i mean in and our side of things uh i don't want to anticipate But, you know, I run the biobehavioral assessment program here. I didn't start it, but I'm the director now. But there's even another behavioral health unit that is amazing that is led by Ori Pomerantz. And Ashley Cameron is another member of his team. He's been here for a really long time, as long as I have. And the the knowledge that they have about the behavioral health of the animals and when something's going on with a group where attention needs to be paid it's astonishing what they do.
Keller:
[11:21] Yeah and then diving into that more like could you explain what that assessment is and what are some of the key metrics.
Erin:
[11:26] Well for um for the biobabrior or his team i wouldn't want to speak to that because i'm definitely not the the expert there um but you know when we're out there and and our outdoor enclosures these big outdoor enclosures where our monkeys live uh you can't go out there to watch monkeys without seeing one of the pbhs team and they're watching the monkeys and they'll do things like um again i don't even want to speak to it because it's it's i'm not the expert but um they have eyes on the monkeys every single day to figure out you know if there's problems between animals and when is the problem, you know, bad. And there's a system for, you know, if there seems to be like trouble brewing to address it.
Brent:
[12:12] And then for your assessment, the BBA, the Biobehavioral Assessment, what is that program?
Erin:
[12:19] Sure. So I am the director of a program that has been running since 2001. John Capitanio and Laura Del Rosso started that program. Since we have run over 6,000 animals through this program. And the way it works is every summer until about five years ago, we only studied infants. So they would bring infant monkeys in from wherever they live in the primate center, and they would administer a whole bunch of tests geared to understand biobehavioral health with a focus on tests that are like analogous to what we do in humans in an unbelievably standardized way. And so they would evaluate things like emotion regulation and their activity budgets and aspects of their cognition, how well they can detect something that's novel in their environment, how impulsive they are, how much they interact with a novel object, their physiology, their inflammation, a whole bunch of different metrics.
Erin:
[13:24] And, you know, the idea was that we want to understand the causes and consequences of that organization. And since then, it's been 25 years now, I mean, 100 papers have been published with this data. It's a resource. So we collaborate with people and share it with them so that they can add it to their research. So people will choose their subjects based on BBA data.
Erin:
[13:52] And so... Was.
Brent:
[13:57] The idea because like initially it was just infants and now you said the last five years it's transitioned to like aging monkeys.
Erin:
[14:04] As well yeah was.
Brent:
[14:05] That the idea when it was started that eventually we will then take this into the aging population to get really good like longitudinal data.
Erin:
[14:12] Interesting question they they had i don't i don't know that that was originally the vision you know growth growth is a funny thing i'm sure they always thought that that would be a great idea and they definitely did do longitudinal studies where they'd follow up on animals like when they were teenagers or whatever um but we just happened to be really lucky it was a really amazing time um we have a very large the largest i think population of aging macaques here at our colony and um john morrison had gotten funding for that and so we said hey we should develop an assessment for the aging monkeys. And it was one of the most creative, fun things I've ever done. It's been really successful.
Brent:
[14:57] Because the idea of that is to be a continuation of the infant BBA?
Erin:
[15:01] Yeah, great question. So it can be both. The animals who are coming up to be geriatric now, they were the first babies that went through the assessment in 2001. So that's really fun. And then, of course, we study animals who didn't go through infant BBA because, you know, we didn't get every single monkey necessarily back in the day. And that's fine because we can still make that aging data available to anybody
Erin:
[15:27] who wants it or study those animals ourselves with hypothesis different work.
Keller:
[15:31] Which we do. Yeah. And since 2001, there's obviously been a lot of changes in technology. Has the way that assessments been done changed? And are there ways to maybe like looking forward, you guys are planning to integrate them while still keeping it standardized?
Erin:
[15:46] Great question. It's like you're in my head right now. Because we are redesigning the infant program right now, and we're asking ourselves these questions. We want to make—the impetus is to make the assessment easier on the humans. When I say people are dedicated, I mean, this is a 25-hour assessment. It happens in the summer because that's when the babies turn the right age. They're seasonal breeders. So, you know, May or June, that's when we start doing assessments. Hottest time of year. Like it's it's tough and so and you know back in the day i think that the most they ever did was like 350 animals in a summer can you believe that so much work so we want to integrate technology to make it easier on the people so um we are yes we are planning on integrating more technology and some technology had been implemented like they they were ahead of their time in a lot of ways the things they did. They had like an ActiWatch, which is like a little Fitbit that they had inside of the objects. And so in over a 24-hour period, we could see how much the monkey was interacting, And now we're going to implement things like we're in the past. We would have a video and we have the animals watch it and we'd see like where are they looking to get a feel for how well they how basically their cognitive function. Now we're going to give them an eye tracker. So that makes it that that's going to save somebody 300 video coding hours, painful video coding hours. So things like that.
Brent:
[17:10] Yeah, because I think what's so crazy is like kind of I'm for the listener. I'm in Aaron's lab. So I have a little bit better understanding of like how it works, but like the scheduling of just every day coming in to run the test and that's just getting the data, let alone all the backend processing to make it readable and then to be able to analyze and ask the data questions. And I feel like that's what's so crazy to wrap your head around. Because if you had to give a super rough estimate of how much you've been able to, what amount of the data have you been able to really interrogate?
Erin:
[17:48] Well, with the baby data, that's obviously been around longer. Like I said, 100 papers, more than 50 grants have gone in with this data. It's been interrogated pretty well. And there is still a lifetime's worth of questions to ask in this data. For the aging data, we're doing it now. You know, we have only just begun with the aging data. There's so much there. But we have some cool preliminary findings. I'm giving a talk after this.
Erin:
[18:19] And um so we're interested in studying like families with longevity and how they how whether they're slower agers and so we're looking at that um things like um how how is how they were as babies their biobehave health as babies how does that predict how they're aging things like that there's still so much to do yeah that's.
Keller:
[18:43] Something we want to talk more about too on the BPA data, what are some of the things you've seen on early life stress and the impacts that has on overall health as they age? Yeah.
Erin:
[18:53] So, I can go as deep as you want, but here's what I will say. I will say my sort of elevator talk way of talking about early stress, because I've spent a lot of time on early stress, is that some stressors are more potent than others. Basically the closer something is to you the harder it is on you but resilience is built in so whenever we see that there is an effect of early life stress on baby humans baby monkeys baby rats there's always this population that seems to be robust despite this exposure, And so, you know, a lot of people are really interested in studying this flip side, this resilience, as well as this early life stress effect. But I think, if anything, in the last 25 years, we've become so aware of the impact of early trauma and early stress on kids, such that it's reaching, you know, the highest levels of public health and government. They know now that it's a risk. It's something we have to pay attention to.
Erin:
[20:02] You know, people talk about ACEs, which is the Adverse Childhood Experiences Survey. And it's exciting. Like I see, you know, it's on commercials, like people saying, oh, hey, is your, you know, Kaiser will have, oh, is your ACEs score high? Don't worry, like we can help. Um, that's extraordinary to me because, you know, colleagues for the last 25 years have been painstakingly doing this work showing that early stress is a risk factor for poor health. It's not a sentence, not a sentence. Resilience is always possible.
Erin:
[20:34] Um, and change is always possible. But, um, we also can address when it is making a negative impact, which is...
Brent:
[20:46] What are some of the key like definitions of early life stress that you've worked with?
Erin:
[20:53] Yeah. So whenever you talk about stress, like it's like you think you know what it is and then it just starts blowing your mind. Right. And so, you know, I teach too. And so, you know, there's always a lecture on stress during the semester. And so I would say some of the key things that I usually talk about when it comes to stress are, you know, one definition, the best definition of stress is anything that is like a deviation from homeostasis. And the problem is, by that definition, getting out of bed is stressful. Everything's stressful, right? So what you're asking is probably like, is there good stress? Is there bad stress? Like, is there worse stress? Right? And so, like I said, I think, you know, what I've learned is that the closer you are to something, the more of an impact that it has on you. And so, a lot of animal work in the last 60 now years has focused on the relationship with the mother in animals that have mother only rearing.
Erin:
[21:56] In models like in Karen Bales' lab where they study biparental species. Dads are just as important. And in humans, that's the case. But I talk about moms all the time, much to my own mom's chagrin because it's only moms for monkeys and rats. They're the only ones doing the caregiving. So when we see a disruption of the mother-infant relationship, and that can look like a lot of things. That can look like a mother might be a little more aggressive. If a first-time mother is really stressed, doesn't know what's going on, it's a little bit harder to find the rhythm.
Erin:
[22:33] Or you could have moms who are just not very responsive, that can be a stressor. So there are lots of different qualities of that relationship that can be impactful. And if we spread it out to other species, we fully expect that dads, those same qualities in dads and offspring would have similar effects.
Keller:
[22:53] And with the the mothers and monkeys is is it a mother figure or is it a biological mother that has the same impacts whether they're you know on aggression or presence or whatever the trackers yeah.
Erin:
[23:04] They're moms so in our outdoor fields uh enclosures here when i was a grad student i had the best life like in the mornings i'd be out like it was like being on safari i'd be out like watching my monkeys and watching my moms and babies and then the afternoon i'd be in the lab like working on DNA. It was the best. So yeah, we go out and we not all that's not all models. There are so many different models disrupting that early attachment relationship. Ours is naturalistic. We just go and see what what mom's natural mothering is like and then the impact on, We also looked at things like social stress, like conflict in the cage, for example. We look at like peer-to-peer aggression, which happens, you know, there's like rough and tumble play between adolescents and even babies. And we see that those have some effect on infants, but it's not as impactful as those primary care relationships.
Brent:
[24:02] Yeah. And then within the primary care model is, because I know here, sometimes you'll match infants with their non-biological mother. Oh, like fostering. Fostering.
Erin:
[24:15] Yeah. Yeah.
Brent:
[24:16] How does that, does that, will they be able to take as good of care, for lack of better words, of the infant?
Erin:
[24:23] Yeah. You know, I want to be super careful about making human analogies, but, you know, some of our fosters are like mom initiated, which that's sort of a can of worms to open, and it's rare. But it's, it's, um, rhesus monkey moms are very willing to take a foster infant. Yeah. Um, and, and probably humans thinking about that, it's, it's, it would, it's probably the same emotional experience that we've had.
Brent:
[24:59] Yeah. And I've seen like in one of the papers we looked at, you saw immunological like response, like kind of consistent whether or not like with quality of like maternal care, like with biological mothers and foster mothers.
Erin:
[25:15] Yeah.
Brent:
[25:16] Could you explain like what was happening there, what you were looking at with that?
Erin:
[25:18] So this is a really common thing to look at when I was coming up, because there was always this, and still we have to address this question, but there was always this question of if we see an impact of an experience on a baby, especially with a parent like a mom, is it because of genetics or environment? So the argument goes, if you see a really protective mother has a positive impact on the infant, and by positive we mean the infant has a better stress response. Is it that a protective mother has the good stress response, has the genes for this kind of stress response? It's associated with being more protective, having the resources to be more protective, and then the infant inherits those genes for the whole phenotype. And so it sounds, well, I don't know how it sounds, but it sounds like a lot to happen, but especially, you know.
Erin:
[26:19] 15, 20 years ago that we were very interested in the genetics of behaviors. So it was a very real possibility. So a lot of those seminal studies that looked at the impact, like in rats, of early maternal care and the effects, they did a lot to manipulate who raised them versus who gave birth to them in a way to disentangle the genes and environment. And so we did the same thing. We looked at babies that were raised by their biological mothers and had a certain type of care and then babies that were raised by foster mothers and had this certain type of care. And the idea is that if the baby is not genetically related to the mother and the care impacts their biobehavioral health, then it's likely not mediated by genetics.
Brent:
[26:58] But by environment. And that's what you found? Yeah.
Keller:
[27:02] And when you say good stress response, I guess, what, like, what characterizes that?
Erin:
[27:06] Oh, man. So, I have so many answers to that. So, I think, um, when we talk about stress, oftentimes that's where the conversation goes, right? Like, I jumped out of a plane because I wanted to, and, you know, my adrenaline was going, but it was awesome. I loved it. I have never done that and never will do that.
Brent:
[27:25] By the way.
Erin:
[27:26] My brother did that. Luckily, he did not tell us until afterwards. Um, but some people might consider that good stress. Um, something that is sort of chronic, unpredictable, the things that, you know, get us down in our daily lives. We all have it. You know, we think of that as being bad stress. So, so, you know, we, we, we have to think about stress on lots of different levels of analysis. So really it depends, depends. So if you're, When I mentioned good and bad stress, I was more just getting to the point that not all stress is equal. What is good and bad? I mean, it can depend on the person.
Erin:
[28:10] There's an evolutionary argument to be made. Like, if something makes...
Erin:
[28:17] Yeah. I always have to be so careful when I say this because, you know, I try to look at things in a holistic, full way to understand them. It doesn't mean that if a person has an extreme stress response or human, that you wouldn't feel like if they want to make a change that we want to help them do that. But, you know, in some cases, you might ask, like, why would early stress change somebody's stress response? Like, if it's going to make them more anxious, like, that sounds like a bad thing, right? Why would that happen? If we were in class i'd say why would that happen um but it could happen because that's actually an evolutionary mechanism to like make us be able to adapt to more stressful environments so the plasticity that we we experience in response to stress in that context could could you know be advantageous but again you always have to come back to we're not a we're not in a test tube we're in life. And so we're not saying that when people experience stress, that that's a good thing. It's just that, you know, looking at it in a holistic way, you can think about stress in lots of different ways. But the end, the main point is that if stress is too much for someone and everybody's different, any, you know, not all people that experience a trauma respond to it the same way. But whatever it is, whatever changes somebody wants to make, you know, we want to have resources and policies to be able to help them do that.
Brent:
[29:44] Then when looking at the individual individual's response to similar stressors especially with something like maybe a little bit more easily definable like like cortisol levels yeah like if they have the same experience at like a i don't think this is probably the right example but like with the wildfire smoke yeah all the monkeys kind of in this enclosure experience the same like exposure to this like Toxic Air, Are you seeing any definable characteristics that make some people or some monkeys more resilient or better stress responders to a similar baseline level of stress?
Erin:
[30:25] That's a really interesting question. So do you mean like do we see any resilience conferring factors?
Brent:
[30:35] Yeah. What would be like is there a genetic is there somewhere in the genome that you'd be like that's a resilient monkey?
Erin:
[30:44] Oh, no. Not by looking at the genome. At least not in my work.
Brent:
[30:50] Or just those types of things. Here are the key things. This is what makes a resilient animal.
Erin:
[30:58] Yeah, not yet. And I think, you know, one of the things that we've always done in my lab and the biobehavioral assessment team has always thought this way, you know, thinking about it all about biobehavioral health and biobehavioral organization as a system. Right and it's a system that's full of like redundancies and um and mechanisms but things that can be overridden anyway the idea is that i my own take is that any number of things could confer resilience or any combination of things could confer resilience or risk um and so, you know we seek out we seek to find what those things are and we might be able to say which ones might be more weighted which ones might be more impactful um but even still i think they're always going to be more than one more than one certainly uh and if i had a guess because i think that's what you really want to know like is what is the thing that like can make somebody more resilient, i don't know exactly but you know.
Erin:
[32:19] Um, I've always had this idea that it's something like growth mindset. It's like, and, and everybody should be aware, like, these are my own biases and my own history and my own whatever. So this is like personal now, not, not necessarily scientific, but this is my feeling that something, this something like growth mindset this idea that you know you can always change you can always make things better and like you just kind of have to keep going and um and everybody's different like people are different and circumstances are different and you know not everybody has that that opportunity but um things at any level of analysis that are related to that idea of like growth mindset um i i suspect that that that could be a key yeah to resilience.
Brent:
[33:18] I've seen some neuroscience like results showing like there's little literal brain regions that have grown with that type of mindset or overcoming adversity like when you take it on willingly.
Erin:
[33:29] But but you know one thing that i just think always has to be said is that this is saying this is not the same as saying you can think your diagnosable disorder away right so it's such a balance it's like this this is not the same and i'm saying you know there's this could be one thing there are likely others and it's not going to work for everybody we need to find the way for everybody um but and and definitely making the point again to underline it it definitely is not the same as saying um hey just have growth mindset and you won't have anxiety anymore that's sounds great But that's,
Erin:
[34:08] you know, probably is more involved than that.
Brent:
[34:11] Has anyone attempted to teach monkeys resilience or growth mindset in that regard?
Erin:
[34:17] Oh, what an interesting question.
Erin:
[34:25] So something immediately popped into my mind, and it's probably, there might be a better answer to this question. But the thing that always comes to me when people ask me this question is a study that Steve Shapiro did a long time ago. I think it was like in the early 2000s. And he trained monkeys to become more social. Like he gave them treats. And treats, I hope I'm not saying the wrong thing, but I wish I could Google it right now. But this paper, I was kind of obsessed with it for a while. Because that's one of those things that I just never, yeah, it's a long time ago, but I just never thought that kind of thing was possible. I thought it was so amazing. Like, you know, just basically, and again, I'm sorry if I'm doing this a disservice, but like giving treats every time, you know, monkeys who didn't want to be close got a little closer, a little closer, a little closer to each other. And it seemed to be effective. And, you know, since social connectedness, we think, is one of the keys to health and healthy aging. Again, it's not the same as saying, oh, just, you know, go out and spend time with your friends. It's going to cure everything. But... It struck me as that could be a really extraordinary intervention to promote resilience in monkeys if we could try it. So I don't know that that was the intention, but it seems like it is possible.
Brent:
[35:54] Yeah, I'm sure.
Keller:
[35:56] Then tying back to some of the stressors, how do those impact epigenetic changes? I guess to start that, could you explain how do epigenetic changes happen? What is DNA methylation?
Erin:
[36:07] Sure. Um, so epigenetics, um, are, epigenetic marks are considered to be, um, uh, a set of chemical modifications that happen to our DNA. So our DNA sits there and, you know, it's, it's reasonably unchangeable and stable. It can be changed with radiation and other things, but, um, mutation, But epigenetics kind of sit on top and modulate how the DNA works. And there are different types of epigenetic marks, but how they operate affects how much of a gene can be expressed. And the seminal study that brought me to study epigenetics was the work by Michael Meany and Francis Champagne and Ian Weaver, who they discovered that baby rats that experience poor quality maternal care, which they already had shown, have a higher cortisol response to stress. They seem to be more behaviorally anxious. It turns out they have lower expression of this gene that's involved with stress response and that seems to be regulated by changes in epigenetics on the DNA, for example.
Erin:
[37:29] And so this was kind of, this blew everybody's mind at the time. It was kind of a paradigm shift in the field because it showed that your experiences, if they don't change our DNA, at least not routinely, but they can change how your DNA works. And so this impacted a lot of us and really changed how people think about nature and nurture, I think. And so their finding was DNA methylation. DNA methylation, more methylated DNA led to less expression of the genes. So more stressed rats had high levels of methylation. So we have done a series of studies looking at DNA methylation in the monkeys in response to a number of factors, things like early maternal care, early nursery rearing, which is a really common early life stressor, experimental early life stressor. We didn't implement it for the monkeys. This was something that was done to prevent transmission of a certain kind of disease between mothers and infants. Back in the day, we don't do it anymore. And so we were able to take samples from those monkeys opportunistically and look at their different DNA methylation patterns. We're looking at it now in terms of wildfire exposure, things like epigenetic clocks for the aging monkeys.
Keller:
[38:57] And I'm forgetting something, but. Could you explain the epigenetic clock a little bit?
Erin:
[39:01] Oh, yeah. So DNA methylation, we used to think, well, I don't want to say this. So DNA methylation, before Michael Meaney's finding that it was changed by early experience, we didn't think DNA methylation changed very much. And by we, of course, I mean other people, not me, because I didn't even know about DNA methylation.
Erin:
[39:22] But, you know, cancer epigenetics was the big thing before this. And so the idea was that epigenetics don't really change that much, except in cancer cells. And so they would study it. So there is, again, this interesting balance with epigenetics of something's there when we're born. and it kind of might stay, but then it's kind of changeable. So Steve Horvath discovered in multiple species now, including humans and rhesus monkeys, that if we do a survey of a bunch of DNA methylation patterns in the genome in multiple tissues, but most easily from blood, Um, the methylation pattern in, I forget, I think it's like around 200 different sites in the genome is like 99% correlated with chronological.
Erin:
[40:15] And so they call these the epigenetic clocks. And there's been an explosion of work in this area. Because we're so interested in aging and healthy aging and living longer now, you probably could actually even send your blood in and find out what your epigenetic clock is. And the idea is that, you know, we know some people seem to age really slowly. Some age more quickly, especially we think after early life stress. And so your epigenetic clock might give you a piece of that puzzle. If you are are aging more slowly you might have the epigenetic clock of a person that's younger than than your chronological age yeah i haven't done it before you ask i have.
Keller:
[40:56] Not done it.
Erin:
[40:56] I don't know if i would yeah that's an insight.
Brent:
[41:00] Maybe better not to have.
Erin:
[41:01] But so.
Brent:
[41:05] Let's say there's an early life stress we can you test the monkeys at a young age you see it you see the methylation what are some of the downstream effects like how long do these impacts persist and then after that are they heritable.
Erin:
[41:20] Yeah really really good question so again this is part of the story that i started at the beginning you know like in general this is part of what has informed my thinking about you know how does it all go and the idea that things are always changeable so So, you know, on one hand, the original story has always been, you know, it's tough to inherit. Let me start from the beginning of your question. So you said, what are the downstream effects? So, you know, on one hand, let's say we look at one gene, which that's one of the things that I published. I looked at the serotonin transporter gene. It's interesting because it's the target of Prozac. And so everybody was really interested in this gene back in the day. So we found that, you know, early quality, poor quality maternal care increased methylation of this gene, which would reduce the expression of the gene. And that was associated with some health outcomes later.
Brent:
[42:22] Would it reduce expression of the gene, meaning like there's less light serotonin transfer? So then you could then therefore like potentially have less serotonin uptake?
Erin:
[42:32] And, and we think that that might, it could, I mean, we're talking several steps removed because we're looking at it in blood, not the brain. But we think that it could, you know, really reflect or be part of a down regulation of the whole serotonin system. So just less overall serotonin function in general. But, but, you know, I don't want to overstate those cases because, you know, yes, we found that. Um i i'm embarrassed i forget the sample size it would would be around like 100 monkeys maybe, um but i think you know the kind of things i'd like to do now are okay so like back to your resilience question like if we saw that a monkey had some like really awesome experiences like later in life like would we expect to see changes there the answer would be yes i would absolutely And I suspect that these things can change for the positive by things that we know are good for our health, exercise and health-promoting behaviors and having good quality social relationships.
Erin:
[43:41] So in terms of the downstream effects, again, it might push you a little bit in one direction, but it's not like a sentence. And the reason I say that is because even in that study where we found an effect, which is amazing, I don't want to undermine that, like, you know, early life stress predicts methylation, that methylation predicts gene expression as an infant, and then later it predicts poor health. Like, wow. But like, it's a small effect. You know, it might predict 5% of your risk for
Erin:
[44:13] that health outcome. You know what I mean? So it's not a sentence. It means it might, it might be one of the things in that complex system that pushes you in one direction, but it can be overcome by other factors if, if they're around.
Keller:
[44:25] Yeah yeah and looking at like changes in behaviors saying like you know it's not not a sentence you can make changes later that can kind of change that trajectory have there been experiments here to like create a sufficiently significant positive experience and like modeling that change in the monkeys afterwards oh.
Erin:
[44:45] Yeah that's a really good question um yeah i mean um, So many. And again, like talking about other people's work actually is really intimidating in front of a microphone. I'm like, oh, God, I don't want to say I don't want to do a disservice. Um, but I mean, like Brenda McCowan does this amazing work here where, uh, you know, they'll do these manipulations to see how the, how they can sort of change an individual's experience at the group level, um, to, you know, so things like, you know, how they do social network, uh, research to see how, um, um an individual's position in the group um it's not just about rank it's about like how how many friends they have like how connected they are to others and they can have a big and really positive impact so they do work to try to figure out okay so how can we give a monkey that that power that centrality um which is like a banana it's like.
Brent:
[45:52] How cool is that.
Erin:
[45:56] It's so cool yeah so uh yeah um other like that's that's the one that first comes to.
Brent:
[46:03] Mind yeah yeah.
Erin:
[46:04] Yeah and i wanted to go back to your question about the so we talked about the lifetime of epigenetics this question about the epigenetic inheritance is such a good one because right we know now about transgenerational trauma my own work has shown that in the monkeys that if a monkey experiences early stress, it can be passed through the paternal line. And so what is that?
Brent:
[46:25] Through the paternal line?
Erin:
[46:27] Paternal line.
Brent:
[46:28] Okay.
Erin:
[46:28] Right? Exactly. Exactly. You look surprised.
Brent:
[46:31] You should.
Erin:
[46:32] Because a monkey is, their dad might not play, definitely doesn't play as big of a role as the mom. So how does that happen? Well, we think it could be something biological. We've tried to eliminate other possibilities along the way. We're not done with that. But even still, and I haven't even published this yet. So some other studies have shown that some epigenetic marks can be inherited. But in the small, small sample that I, where I looked at dads who were stressed and their sperm DNA epigenetics, their DNA methylation, and then I looked at offspring who had died of natural causes and then I was able to get their brains and then look at the epigenetics. I saw a lot of impact of stress on the dad's sperm DNA methylation. Actually, not a lot. Maybe like 20 places in the genome were differentially methylated based on early stress. Really, that's not bad, given how many. It's like billions and billions of sites. In the baby's brains, there were about 10 times that, that were impacted by having a father that was stressed. I'm like, okay, this math does not add up. What is happening here? And only one of those overlapped, one of those genes.
Brent:
[47:43] Interesting.
Erin:
[47:44] Speaking to, like, epigenetic inheritance. So the answer is actually much cooler, I think. Again, I have not published this. I probably shouldn't even be saying it. But it looks like probably what's happening is that just like any cellular environment, what's there is just the beginning. So, yeah, there might be some DNA methylation in the sperm that's there, but then that might set off a different developmental trajectory that impacts totally other genes in the developing infant. And I just loved this finding because it tracks exactly with what I started with today, which is anything can be changed. Like even in the inheritance process.
Keller:
[48:26] Things can be changed. And with that said, did you look at all on the mothers, like whether the stress on the moms had an impact on whether it was tenfold or twentyfold on the babies?
Erin:
[48:36] Yeah. So with the BBA program, this is one of the amazing things about this. So I had done some work in my postdoc in New York and I had looked at the effects of an early stressor called variable foraging demand. It's a really cool, like ethologically relevant stressor where moms and babies had to work harder to search for their food or either it would be easier or it would be harder or it would be a mix of both and they never knew what. Well, the variability one was hardest for them and it would impact their behavior and physiology for years to come. So I looked at whether or not the offspring of mothers and fathers who had experienced that stressor were different. and you.
Erin:
[49:18] So, you know, this is what science is like. So I had this population of moms. Only moms had raised the babies. Babies had never met their dads. This was a long time ago. So I was only focused on the moms. And I wrote this whole paper where I was like, okay, this is so cool. Like if the mom experienced this variable foraging demand stress, the babies show a behavioral profile that looks like they experienced that stressor. So there's this transgenerational effect between mom and baby. I was like, oh, my God, this is so cool. And right before I'm going to submit it, I was like, you know, I probably should look at the dads just to make sure. I mean, they didn't know the dad, so it's not going to be a big deal. Turns out, in all but like one or two cases, if the mom had experienced the stressor, so would the dad. So I was like, ah, probably isn't important. I think I put it in the paper. I hope I did.
Erin:
[50:09] And I'm 99.9% sure I did. So then I still collaborated with John Capitanio on the BBA program. And I was like, well, now with this population, I can really take this out for a ride. We can look at the effects of nursery rearing, which is another type of early stressor, for generations back along the maternal and paternal line. And we have both set, like, we have all configurations because we have so many animals, 5,000 animals. And it turned out it wasn't the moms. It was the dads. When you put everybody into the model and you have dads only had stress and moms no stress, we saw it was the dads. So the dad stress was perpetuated across, we've looked at three generations so far. So great grandfather, grandfather and fathers. So, and, you know, we looked at a lot of alternatives. You shouldn't go to the, you know, epigenetic inheritance right out the gate. We looked at, you know, different social structure, like maybe there were more animals that had this early stressor at the same time, or maybe, but as you know, you look at like the grandparent effect, that becomes harder to explain. You know, kids were never in the same group as their paternal great-grandfather. And we looked at all the things that could matter, like, about the group, and it didn't seem to mediate that effect. So, it's still something I have to get back to, to examine that.
Brent:
[51:34] Yeah. That's super interesting.
Erin:
[51:36] Yeah.
Brent:
[51:36] Well, as we kind of wrap up here, what do you think some of your biggest next questions are?
Erin:
[51:43] Mm-hmm. Yeah. You know, so, you know, we have a bunch of directions right now that we're thinking about going. And I think it's always been important to me, but it's more important than ever now, probably because, you know, my son and, you know, the world is changing, like, to really, like, do science that really, really helps people, like, now, you know. And so I'm interested in things like, since we have this 25-year archive, you know, climate change, you know, how are changing temperatures affecting biobehavioral health? How is it affecting biobehavioral aging?
Erin:
[52:33] Because, you know, we have to prepare, you know, if it does have an impact, we need to know so we can improve people's health care as we as we go on. We have projects where we I mentioned the longevity project.
Erin:
[52:50] We but, you know, I have to say, like, the things that I'm thinking about the most now probably aren't. I was telling you this the other day, you know, they probably aren't necessarily research directions. I've been thinking a lot about aging. It's become a big part of what we do. And I've been thinking about, you know, we're studying monkeys that are predisposed to live a long time. And how do we get that? How do we get, you know, how are we going to live to 100 years and be healthy and happy while we're doing it? And there's this longevity center at Stanford that they're devoted to all, you know, so many different aspects of longevity. But really interestingly, they're focusing in on the pragmatics of it. Like, how do we design society for an aging population? And how do we make life more meaningful as we are aging? If we really are hoping, like these people who are doing these amazing things, like getting blood tests and, you know.
Erin:
[53:46] Doing cold plunges all the time and, you know, wearing their Fitbit and make sure their heart rate is where it's showing, getting good sleep, you know, that's going to work. I believe that's going to work. And our life expectancy is going to keep going up. So the next question is, how do we live that long meaningfully? I was joking with Brett last week. I was like, you read those Interview with the Vampire books? They live 200, 300 years. they're bored like we we we should be thinking about how we stay connected and how we age well and live a better life and the beauty of that is that uh whether we live a long time or not that's.
Keller:
[54:27] And then do you have any advice to students, whether that be on how to live a better life or just broadly, if they're interested in this field, things that they should be aware of looking into?
Erin:
[54:35] Oh, God, nobody should ask me about how to live a better life. I think so. But, you know, I often say the same thing when people ask me for advice about because at this stage, right, I remember it so, so well, like you're you're worried about the future, like you're worried about what's next. The path is not clear. Um and Karen always says this you know uh Karen Bales she's our director she always says you know the path is only clear like when you look back like and I think that's so important to know it's like I told you a little bit about my trajectory I did all this weird stuff like because it interested me I was curious and I'm like I'm gonna do this I'm gonna do that did every single thing map on to where I thought I was going uh it did not but it took me in the right direction because it was what I wanted to do. So I think that, I don't know if that's the best advice, obviously, but, you know, I think if you can tolerate the stress of, I think I know where I want to go with this, but I'm also going to make room for the things that just like grab me and I'm going to do them even though I don't see how it fits yet. They're all going to fit. They're all going to fit in the end because it's going to be your path and like and you can trust that for sure that's what's going to happen so actually i shouldn't have said that last part because what do i know but um you know that's what i always what i always say.
Brent:
[56:03] Yeah no perfect i know we definitely agree yeah.
Erin:
[56:06] Okay good well.
Brent:
[56:08] Thank you so much for coming on today.
Erin:
[56:10] This was really fun.
Brent:
[56:11] A lot of fun thank you.