Ep 147: The Genetics of Vice (with Kathryn Paige Harden)

What role do genes play in complex human behaviors? If behavior is largely shaped by a combination of experience and luck, how should we rethink blame, punishment, and forgiveness?

In this episode, we talk with Kathryn Paige Harden, a Professor of Psychology at the University of Texas at Austin, where she leads the Developmental Behavior Genetics lab and teaches Introduction to Psychology. Paige is also the author of the recent book Original Sin: On The Genetics of Vice, The Problem of Blame, and The Future of Forgiveness. We talk with Paige about her book, which explores long-standing questions about what role genes play in moral and ethical human behavior. She says that whereas genetic variation does cause differences in behavior, such effects are rarely simple and direct.

If you like this episode, check out our other episode with Paige about her first book The Genetic Lottery: Why DNA Matters for Social Equality. 

Cover art by Brianna Longo

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  • Marty Martin  0:06  

    Hey, Cam, have you read James Tabery's book called Tyranny of the Gene?


    Cameron Ghalambor  0:11  

    No, but didn't you text me about this the other day? 


    Marty Martin  0:13  

    I did, good memory. I've only just started it, but so far, I'm really enjoying it. James, if you're listening, don't be surprised if we invite you to the podcast soon to discuss it.


    Cameron Ghalambor  0:22  

    Whoa, it's that good, huh? So tell me a little bit about what it's about.


    Marty Martin  0:26  

    Well, again, I'm just three chapters in, but its focus is personalized medicine, which in this book largely means the use of genomic information about an individual patient to improve outcomes for all sorts of disease, from cancer to Alzheimer's.


    Cameron Ghalambor  0:38  

    Yeah, that sounds right up our alley for Big Biology, but there have been many books about that topic. What is it about this particular book that excites you?


    Marty Martin  0:47  

     Well, it won't surprise you when I say it's Tabery's challenge to genetic determinism, the idea that pervades the concept of personalized medicine. His basic conviction is that for decades, if not longer, we've had a very good sense of what causes many diseases, or at least how we can intervene and make them better, and it's only sometimes genes. Most of his points so far follow from Ben Franklin's witticism: "An ounce of prevention is worth a pound of cure". I don't want to get too much into the book now, as I haven't finished it, and also because listeners might not tune in if we talk to him next year.


    Cameron Ghalambor  1:17  

    Okay, but I don't follow exactly what the problem is.


    Marty Martin  1:21  

    Essentially, Tabery's claiming that personalized medicine is very unlikely to be a panacea to human health as it's now being represented. One of the big problems he's covered so far is that personalized drugs can be afforded by only a very few people, and until health care policy changes, only a select few are apt to benefit from personalized treatment,


    Cameron Ghalambor  1:41  

    Okay, but I think that's fairly obvious, and that's more a problem with our health care system than with personalized medicine per se. I mean, tell me more about the connection with your earlier point about genetic determinism.


    Marty Martin  1:54  

    Well think about it this way. In a general sense, one would probably expect a true personalized medicine to apply to all facets of a person's health— things they do in aspects of their lifestyle, after but also before they get sick. In other words, a truly personalized medicine would include the diet, exercise, sleep and other aspects of a person's experience that impinge on their health, maybe in the context of information about their genomes. In practice, though much of personalized medicine is about designing drugs that work well, contingent on specific genetic variants. People that have particular SNPs for cytochrome p450, for instance, they sometimes metabolize drugs too fast for the drugs to have a positive effect. The claim is that personalized medicine could resolve that.


    Cameron Ghalambor  2:36  

    Okay, well, I mean, aside from the cost problem, that sounds like a good thing. I mean, we know there's tremendous genetic variation in the human population, so it's really unlikely everyone will respond to the same drug in the same way.


    Marty Martin  2:49  

    It is a good thing if it works. But as a big fan of phenotypic plasticity and G by E, you know that fitness, evolutionarily and in terms of health, is as much related to the environment a person experiences as the genetic variants that person has. Tabery says that many of the people pushing personalized medicine are not addressing those issues well enough. So not only will personalized drugs be off limits to most patients because of their costs, personalized drugs might not even work if a patient's behavior and experiences alter the way their genomes interact with the drug.


    Cameron Ghalambor  3:20  

    But you must be bringing this up because of our guest today.


    Marty Martin  3:23  

    Correct you are, sir. Today, we welcome back to Big biology. Kathryn Paige Harden, Professor in the Department of Psychology at the University of Texas, where she leads the developmental behavior genetics lab and co-directs the Texas twin project.


    Cameron Ghalambor  3:36  

    Our first chat with Paige was back on episode 79 when we discussed her book, The Genetic Lottery. I wasn't part of that interview, but that was one of the most thought provoking episodes I heard. Definitely check it out if you find this episode compelling.


    Marty Martin  3:50  

    In this new book, Original Sin, Paige tackles a very fraught but very important topic: how do genes affect human behavior related to vice, and how should we think about blame and forgiveness.


    Cameron Ghalambor  4:01  

    Paige's book covers some of the same ground as the last book, but this one is written in a much more casual and personal style, and it confronts difficult topics related to long-standing questions about a variety of different behaviors that have moral, ethical and even religious dimensions. If a family member or a non-scientist friend of yours has an interest in this research area, I really encourage you to pick up this book for them. It's very readable and relatable, but it also pulls no punches, and Paige bravely uses a lot of personal examples about her own religious upbringing, being a parent and wanting to live in an equitable society, in order to make her points.


    Marty Martin  4:38  

    We'll let Paige explain more in just a minute, but I wholly agree with Cam. This book is a fantastic treatment of the importance and trickiness of thinking about human genetic variation, and I really encourage you to read it for what I feel is a really deeply researched but very fair and transparent treatment of the topic. It's also very impressive and inspiring to see a scientist write in such a familiar and open way so as to communicate and revenge. Message. I don't think I could ever be that brave, but it's great that she is. 


    Cameron Ghalambor  5:04  

    Ah, yes, and now I get why you set up Paige's book with the one by Tabery. It's because Paige does a really good job of discussing how we should think about genes as causal forces for human behavior. Unlike the oversimplified perspective implicit in personalized medicine that Marty was talking about, Paige makes clear that genes are just one of a constellation of contributing factors to behavioral variation. She makes it very clear there are limitations to what can be inferred from genes alone, and how they need to be considered as parts of an entangled web of environmental, experiential and even epigenetic forces.


    Marty Martin  5:41  

    But before we get to that chat with Paige, don't forget to go to our Substack page big biology dot substack dot com and subscribe, where you'll get full access to this show and our whole back catalog of episodes.


    Cameron Ghalambor  5:53  

    We offer several subscription tiers on substack, including group subscriptions that teachers, managers or PIs can share with their staff and students. For just the cost of a cup of coffee per day, you can help keep us producing episodes by supporting our team of producers and interns. Importantly, when you subscribe, you also get access to our blog by Clayton Glasgow and Marty's recent musings about this thing he calls Cognitive Plasticity.


    Marty Martin  6:20  

    But if you can't afford a subscription, just let us know, and we can drop the paywall for you for free. Most of our listeners are students, and although it's been a while for both of us in that role, we can commiserate at how tough financially it is to be a student right now.


    Cameron Ghalambor  6:33  

    And lastly, if you can't afford a subscription, do us a free favor to share your interest in Big Biology with a friend. Tell the world about Paige's new book or your favorite episode on your favorite social media mechanism. We're on all of them, from Instagram to blue sky, so any posting will help. Now on to the show. 


    Marty Martin  6:52  

    I'm Marty Martin 


    Cameron Ghalambor  6:53  

    And I'm Cameron Ghalambor


    Marty Martin  6:54  

    And this is Big Biology.


    Marty Martin  7:14  

    So Kathryn Paige Harden and welcome back to Big Biology!


    Paige Harden  7:17  

    Thanks for having me back.


    Marty Martin  7:18  

    Yeah, you're one of our very few repeat guests we really enjoyed the first time, so welcome to that select group. The last time we talked to you was a little while ago about your first book, or your older book, The Genetic Lottery, and that was before Cam's time. Art Woods was still co-hosting. And it's clear from this book that you've been really busy since, but given the topic and the content, it also seems that you're really ready to discuss fraught topics. But before we get to that, I want to talk about your process, and in particular, why books at all? So you're a really successful professor at University of Texas. Why devote time to books and not more papers and especially grant proposals? Because I know that's what my university wants me spending all of my time on. Why do you put your attention to books?


    Paige Harden  8:02  

    Yeah, that's such a good question. And the short answer is, I'm not quite sure. Pub week is an ironic time to ask an author that you really have this crucible of, why did I do this? What have I gotten myself into? I didn't set out to write books, so my first book, I initially intended it for it to be a review paper, kind of a psych review type, or annual, annual reviews of psychology type, theoretical paper. I had a small grant from the Templeton Foundation, and the project was called the: Implications of genetics for distributive and retributive justice". Distributive justice being what do people deserve in terms of financial rewards, for instance, and retributive justice being around punishment. And it was a grant with a philosopher, and we were going to write a few papers. And so that first paper, it just kept growing and growing and growing, and there were so many things that I wanted to explain. And also it was at a time kind of peak Twitter, where I found myself for the first time in a lot of conversations with people outside of my discipline, and that made me realize that there were things that I had always taken for granted that weren't obvious to another perspective. So the scope of the project grew. And then someone from Princeton University Press approached me, they followed me on Twitter, and they said: "Have you ever thought about writing a book?" And I was like, No, I you know, I'm not in a book discipline that hadn't occurred to me, and I was newly tenured, so it probably wasn't the best timing wise either. You know, I think often people wait until they're more established and full professors. But I wanted to do I was interested in the project, and I kind of thought, what's the point of tenure if it doesn't give you freedom to work on the work that you find most interesting at that time. So that turned into the first book. 


    Paige Harden  10:05  

    And you know, if you write, that can give you more opportunities to write. And so I began to, at first I thought, "well, I'm not, I'm never doing this again." I mean, sort of like after you have your first child, you're like, 


    Marty Martin  10:20  

    No more. 


    Paige Harden  10:21  

    No more. One is enough. One and done is perfect. But then, once you have given yourself permission to think at that scale, the scale of I'm going to spend this many years working on something, I'm going to have the space to explore this many dimensions of a topic. And also, it turns out that I just really like having kind of a container for my attention. There's something about writing a book where you watch movies and you listen to songs and you read books that you don't think are going to be related, but you kind of have a filter set up for how does this relate to my theme? And it turns out that I really like that, I think, as a person who is somewhat ADHD-like, having this overarching project that structures my intention for a long period of time, I just really enjoy spending my time that way, and so that it blossoms into a second one. My husband has made me promise I won't attempt to write a third one for five years. So we'll see whether I keep that promise. 


    Cameron Ghalambor  11:25  

    Okay, well, so maybe to follow up on Marty's question. Then, you know, he was like, why books? And then I guess my question is, like, why this particular book? And I have to say, as I was reading, you know, the chapters of the book have these, like single word titles, like desert, animal, choice. And I wasn't really quite sure what to expect, but I have to say the chapter title that I think I would have suggested was "brave", 


    Paige Harden  11:56  

    Oh thank you.


    Cameron Ghalambor  11:56  

    Because writing about genetics and biology and how those should be viewed by society, and how it interacts with our views of religion, morality, free will, punishment. That's a really scary place to go. I think most people might think about those things in their heads, most biologists, I'm sure, that we all kind of think about that, especially if we were interested in genetics and behavior. But you know, we don't actually want to go there publicly, and especially in a book like this. So what motivated you to want to go into a space that I'm sure you must have known touches on so many sensitive topics, and it's so like personal for a lot of people.


    Paige Harden  12:45  

    So in some ways, I've always been interested in these topics. I write about this in the book that my first job in science was a research assistant for a behavioral neuroscience lab that did mouse models of opiate addiction, tolerance and withdrawal. So my introduction to science was we can take a phenomenon that has legal implications, is moralized. People have attitudes about opiate addiction. We can model it in animals, and we can manipulate it, potentially, using something in the brain to change behavior. And, you know, I write in the book how this was really revelatory for me, not just as a young person, but also as someone who had been raised in a fundamentalist evangelical Christian church for the first, you know, through my whole childhood this very enveloping religious environment. So that interest in how does our biology, including our inherited biology, affect our behavior, including behaviors that are moralized or legally punished? I began my scientific career being interested in those questions. And many of us are, I mean, there's a there's NIDA, right? There's a National Institutional on Drug Abuse. This is not a niche topic. How does the body and the brain affect drug addiction? 


    Paige Harden  14:10  

    I think what's unusual is writing about it, writing about it in a register that's intended to be understood and read not just by our fellow scientists or fellow disciplinary scientists, and also being, you know, in some ways, biting off more than I can chew. I mean, I say very, very clearly in the intro, these get at really abiding questions about what it means to be human, and I'm not going to answer that in the space of one book. I'm not going to solve the human condition for you. To some extent, there's something really selfish about it, which is that I don't think that I can really know what I think until I spend time writing seriously about it. I mean, I tell my graduate students this all the time, which is, writing is where your half-baked ideas go to die. You think you have it straight in your head, and then as soon as you attempt to put it on the page, especially in an extended form, all the contradictions and all the holes and all the things that don't add up, and all the things that you thought you knew disappear. So in some ways, writing about it is a gift to myself. I'm giving myself the freedom to spend time arriving at not a settled answer, but by allowing myself to write about it over an extended period of time, I think I know what I think a little bit more clearly. 


    Paige Harden  15:27  

    And I think the other thing is, you know, it's very salient to people generally that there's dangers to picking a big and controversial topic and the loudest backlash is the most obvious to another audience. But I think what people don't see is the relationship that I had with readers after my first book. And there were so many people who wrote me and said: "Thank you for writing this. I've always been different from my parents. I've always been different from my siblings. I'm adopted. I have adopted kids. I chose not to have kids because this thing runs in my family."  And you realize that these are not just academic topics. These are topics that really touch on people's lives. And I think the opportunity to shape how ordinary people think, even if they disagree with me, even if it's like you've given me something to push off of, and now I can crystallize what I think in opposition to how you've described it. Is a real privilege and that privilege is for me worth the sharp, kind of sharper backlash that you might get from people who don't think you should be writing about this at all.


    Marty Martin  16:58  

    So your first book was genetic the genetic lottery. And you know, the title of the new one is original sin. Did, did was, I mean, I think there's obviously a thread between them. But what was the experience in the first one that motivated this one? How are they connected?


    Paige Harden  19:39  

    They're connected by the theme of luck, or the theme of the luck of inheriting certain genes, the luck of coming home from the hospital to a certain set of parents and a certain family environment. And how do we make sense of the role of luck in human lives? And how then should we treat each other if we appreciate the role of luck. The Genetic Lottery, which is, you know, written in a more kind of I would think it's an it's written in a more standard social science register. I think it's a more academic book, it's a more technical book, it's with an Academic Press, and not a popular press, but it considers this, you know, theme of, we can see that there are genes that children happen to inherit that, on average, tend to make them more successful at school, and then we have made educational success so load bearing on our ideas of merit and fairness and reward in an American society, should we, can we, how do we re-examine the latter in light of the former? And then the new book is we happen to inherit genes that might predispose us towards antisocial behavior or aggression or addiction, which are punished, which are moralized, which are considered blameworthy. So there's the praiseworthy and the blameworthy. You can sort of think of this as kind of the the dark doppelganger of the first book, in some ways. 


    Paige Harden  20:06  

    So in my first book, I talked about how much I was influenced by the political philosophy of John Rawls, who was a, you know, late 20th century political philosopher, he wrote, Justice is Fairness really kind of towering figure in the articulation of what you know, what liberalism is, and has this really compelling metaphor of the veil of ignorance. So how would you set up society if you had to come up with the rules and the procedures for setting the rules behind this veil of ignorance, which is, you wouldn't know what the outcome would be in the social and then what he called the natural lottery, which is, if you didn't know what your genotype was going to be, and you didn't know who your parents were going to be, and you didn't know your social position, what would you think would be a fair society? So John Rawls is interesting as a character because he was also a very devout Christian until the end of college, and then he fought in World War Two, and the the experience of the war radically changed his religious beliefs and but his senior thesis in college was on original sin, which I didn't I didn't realize until I was well into writing my book. But I do think that there is an intellectual similarity there of potentially leaving behind a Christian doctrine of election, but still being very preoccupied with, what do we inherit? What is the luck that has shaped our lives, and what does that mean for what we deserve, which is both a scientific question and a political philosophy question, but also a, you know, a question that the Christian church has grappled with for millennia. 


    Cameron Ghalambor  24:59  

    So let's maybe transition to, sort of the the core scientific ideas that also form the foundation for both books, and getting to the to the meat of it, you know, is, how do we study and interpret the genetic basis of complex traits, particularly in humans, and so for traits that have a Mendelian pattern of inheritance, you know, there isn't a lot of controversy in terms of the way the genetic variation shapes the phenotype. But when we start talking about highly polygenic traits that are controlled by hundreds, thousands of loci distributed across the genome, most of which are having individually pretty small effects, although we have a statistical bias for picking out the ones of large effect, the genotype to phenotype map is a much more complicated problem. And we also know that polygenic traits tend to be very plastic and sensitive to environmental context and so the sort of common statistical approach we use right now is to look for genetic variants that are within the genome and their statistical association with certain phenotypes, so GWAS.  And I think maybe a lot of our listeners are already familiar with what GWAS is, but you know, GWAS also, I mean in general, and I don't know the behavior genetics, but I'm guessing, like most traits, you know, we still are only explaining, usually, a pretty small amount of the phenotypic variation with most of our GWAS studies. So as somebody who studies human behavior, arguably the most complex phenotype of all, how do you think about the statistical correlation between variance and behavior versus the causal relationship between genes, where we know some aspect of the function and behavior, but we can't always do the sorts of transformations and experiments that we do with, say plants or Drosophila to do knockouts or things like that, where we can establish that degree of causality. How do you approach that?


    Paige Harden  27:20  

    Yeah, so I think you've the most controversial word that we've said so far is not sin or agency, it's causal. I think there's probably no concept that for for which scientists carry very strong implicit theories of what, what is a cause and what constitutes evidence of causality, and that there's very strong differences, I think, between the social sciences and the natural sciences in terms of disciplinary training about what's sufficient to call something a cause and even what a cause is. And this was a chapter in my first book that generated a lot of controversy and continuing conversation throughout. So one philosophy of causation is that a cause is a difference maker, so that if, if x, then y, if not x, if the cause had been different than the probability of the outcome would have been different. And this is, I think, the standard econometric definition of a cause. So if I go to my economist colleagues and they say, you know, a change in minimum wage laws in New Jersey was a cause of labor force difference, you know, participation changing. They're not saying that know why or how that works, they're just saying that it made a difference to the outcome. 


    Paige Harden  28:50  

    So if we're applying that change or cause as difference maker frame to complex trait genetics, then some of the strongest evidence for causal relationships that we have are within-family studies in which children are randomized to genotypes pending or controlling for the parental genotype. And this has been a standard approach in medical genetics, you know, the transmission disequilibrium test, or some sort of within-family design for a long time. And so  I'm operating under that kind of econometric philosophy of science, of causation, of genes are difference makers, and we can call them causes, and it's good evidence that they're difference makers when we see that the genotype is predictive of the phenotype, even controlling for the parental genotype, because conditional on the parental genotype, the child's genotype is as if randomly assigned. 


    Paige Harden  29:57  

    What I find really interesting about the domain of what I'll call externalizing behaviors, and we can come back to what that is. So the topic of my second book, so this constellation of doing things that are disinhibited antagonistic, doing things that are punished, and doing them anyways, is that the within-family genetics have worked out much more nicely than the within family genetics for something like education. So for education or intelligence, what you generally see is that you can do a GWAS, identify genetic variants associated with going further in school. Those genetic variants are correlated with years of education in independent samples. But then, if you control for family background by comparing siblings or controlling for the parental genotype, those associations tend to go down. They don't disappear, but they tend to be attenuated, in some cases considerably, and it's a sign that our genetic studies are not successfully disentangling the genetics that are influencing success in education from correlated environments that are stratified between families. We've now done this. We did an initial large scale GWAS of externalizing in 2021 we have a new pre-print out, which I think I'm not technically supposed to talk to the media about, because it's still under peer review.


    Cameron Ghalambor  31:26  

    That must mean it's in review at a high profile journal.


    Paige Harden  31:31  

    But I can talk about the things that over you know, I can talk about there's some results in that which confirm and overlap with our previous results, and I can obviously talk about our previous results, and then several other groups have now run with those results, and what we find is that the genes we're finding with large scale GWASes of substance-use disorders and of antisocial behavior-related phenotypes, again, we can go back into how we're defining those if you want. Those effects, tend to be much less attenuated, much stronger relative to the kind of confounded between-family or population associations compared to other complex traits like education.


    Cameron Ghalambor  32:13  

    So in other words, the environment that you grow up in has less influence on the expression of those traits.


    Paige Harden  32:20  

    I don't think it's that the environment that you grow up has less influence, but I think the environment that you grow up in, the environments that are relevant for the development of addiction and anti social behavior, are less dynastically stratified between families in ways that are correlated with genotypes and thus confound genetic studies. So certainly, environments matter. Family environments matter a ton for the development of these phenotypes. And in fact, for children at genetic risk, the family environment might matter more, but those family environments tend not to be dynastically maintained in a way that's correlated with genetic structure in the same way, as you see, for something like education.


    Marty Martin  33:07  

    Okay, there's a lot going on here. Yeah, I want to


    Paige Harden  33:10  

    We went from like, very sweeping to like, real technical, really fast.


    Cameron Ghalambor  33:14  

    Yeah no that's ok.


    Marty Martin  33:14  

    Technical is great. That's, that's what we go for. I'm just, there's so many questions that I have, and you've sparked things that I wasn't even thinking about. So lets see if I can put these together. Cam's question was, how do we think about these causal relationships? And I agree with you, that's really, really fraught, without getting you back into old weeds, one of the things that I think recurrently comes up is the context in which these things are done. When we when we do the GWAS, you know you need to interpret them within the sort of populations from which the genetic data are derived. So when you start to talk about genetic effects outside those populations, things can get kind of messy. So can you, can you sort of help us to understand that to what extent maybe it says anything about the sort of other scenarios that you're talking about, you know, in the more recent research, and I guess in the sense that maybe interactions among genes, but the complexity of traits, the complexity of the environments, is there some way to come to generality for these genetic variants, or is it always going to be these contingencies? Because if it's the latter, I don't envy you your job. I mean, Cam and I do this kind of research too, but we don't work on human behavior. So to ever get to the end of the chain where we can say definitively genes do this as cause for behavior, it seems like everything's an exception. 


    Paige Harden  34:39  

    Yeah. So to just zoom out a second, and I think your question is something that comes up a lot, from biologists who have a lot more experimental control over their organisms, and they're studying phenotypes that are just obviously less contextually dependent than a child torturing the family cat, right? Like that is a behavior that is highly social and highly culturally dependent. And how does that compare to, you know, a phenotype that you have in a very constrained model organism? I think one thing I want to know going into it is that is the case for all causes of human behavior, not just genetic ones. So if I stopped doing genetics tomorrow, if I was still but I was still a clinical psychologist, and I was interested in what makes people depressed, what makes children constantly be getting into fights and not seem to be able to stop themselves or feel guilty about it, I would still have the same problem of some might say, challenge of the causes of those things are necessarily going to be so multi-factorial and so interactive and so contextually dependent. So a lot of this, I think, is not really a problem with social science genomics. It's the difficulty of studying humans, studying free-range humans, generally, we're always going to be in this, in this problem. 


    Paige Harden  36:07  

    And then the other element that you're picking up on is, is what people have sometimes called the portability problem, which is, you're you're identifying genes by comparing people who are necessarily designed, that sample is necessarily designed to be homogenous with regards to genomic background. So for instance, most of our genetic studies are people from the the Northern European population registers, people who identify as white British from UK Biobank, people who look like white Britishers, who are 23andme customers. And the criticism or the concern is always, well, you've discovered this for this slice of humanity, but that slice of humanity differs not just in genomic background, but in environmental risk from everyone else on the planet. So is what you're studying kind of like niche to white people in this way that isn't, isn't, isn't going to be broadly generalizable. And my first answer to that is, maybe, you know, it may be that the things that we discover when we're looking at a really narrow slice of humanity don't generalize broadly across the population, and that's an empirical question that we're only just now beginning. I cannot talk about the result, but if you look at the pre print that we just posted, we do look at the genetic correlation between genes associated with externalizing and European-like and African-like samples. And so there isn't there that's not a that's not an impossible question to answer as to whether or not we're getting a similar genetic architectures across people. 


    Marty Martin  37:52  

    Just an expensive question to answer. 


    Paige Harden  37:54  

    It's an expensive question to answer, but it's not an, in principle, impossible question exactly answer. And then I think the other thing is, we actually, to some extent, are already doing this over a much bigger leap, because we model anti social behavior and aggression and addiction and non-human animal species all the time, right? We're looking at what genes change when you breed beta fish to be more aggressive. And I have a colleague who studies social dominance in mice, which is very correlated with aggression, right? Like dominance hierarchies are like who bites who and it's which genes change expression when you pop a little alpha mouse out, and people start competing for that hierarchy. And those are being funded by the National Institutes of Health, because we do presume that there's something universal about the mammalian brain. There's some mechanisms that transcend species barriers. And so if we can think that we can learn something about antisocial behavior or addiction by modeling it in rats, then I think that we can learn something perhaps more generalizable about the biology of these things, even if we're studying a kind of narrow slice of human behavior. 


    Paige Harden  39:06  

    And then the last thing I would note about this is, you know, a lot of people make the mistake and they think that I'm studying crime, I'm not studying crime. Crime is a social judgment about what carries legal consequences. It is inherently culturally dependent. I'm studying ant-social behavior, which is, I do things that hurt other people, and I keep doing it. And if you're looking at that, not just not if you're going to jail for hurting someone else, but if you're looking at, you know, antisocial behavior in children, the prevalence of that is remarkably consistent across countries. The sex ratio is remarkably consistent across countries. The prevalence is remarkably consistent across racial and ethnic groups in the United States. So it's there are very socially patterned phenotypes. Education is one of them, and I've written about that how I'm. Defining it. Addiction is something that happens across people. antisocial behavior is something that's happening across people. So I don't think that we should be so quick to say because our samples of GWAS are are very currently biased towards people of European ancestry, that I don't think we should mistake that for thinking that we're studying a phenomenon that only occurs within a small slice of the globe's population.


    Cameron Ghalambor  40:28  

    Okay, well, so I think, I think we're, we're sort of indirectly talking a lot, aside from the pre-print that's out there, but I think a lot of this kind of maybe goes back to this 2021, paper that you co-authored in Nature Neuroscience, where you looked at 1.5 million people, I think is, this is the UK Biobank data.


    Paige Harden  40:51  

    It's a lot of UK Biobank but also a lot of psychiatric genetics consortium data in 23andme.


    Cameron Ghalambor  40:57  

    Okay, and so in that paper, if I recall, you found something like over 500 variants, genetic variants that were associated with the suite of behaviors that we've kind of been talking about here and in the new book, you know, these are the, these are the the behaviors that fall maybe under this broader category of "sin". But at their core, they seem to be behaviors that are associated with the inability for self-regulation and or on the flip side, excessive behavior like addiction, which maybe is, you know, very much related to self regulation. So can you talk a little bit about like these traits in terms of, like, how you phenotypically score them. Like, are these self reported data and and then I think more interestingly, like, you know, what are actually some of the interesting genes themselves that pop out from these studies that have more strong effects than than others.


    Paige Harden  42:02  

    Yeah. So the the phrase that we use in most of our scientific work is externalizing, which is something that psychologists and psychiatrists immediately recognize. What that is, and other people are like, "What are you talking about?" So externalizing is a phrase that goes back to the 1960s and 70s the work of Thomas Achenbach, who was a child psychiatrist, who was one of the first people who really objected to psychoanalytic classifications for psychiatric disease, and thought "we could get at this more empirically by observing what symptoms tend to go with, what symptoms and what constellations of symptoms tend to go with with other ones". So it was the earliest application of what we would now think of as a factor analytic approach to understanding children's psychiatric problems. And what he was doing is he was looking at people's hospital records and saying: "Okay, well, this child was referred to psychiatric hospital. This is before de-institutionalization, so people were in psychiatric hospital. This child's in psychiatric hospital because they compulsively start fires and are chronically skipping school, right? And then this other child is chronically skipping school and is addicted to alcohol at the age of 14, and he basically clustered children's psychiatric problems into two broad categories, which he called internalizing and externalizing. And internalizing was internal suffering. You were depressed, you were anxious, you were fearful. You thought of it still within a psychoanalytic framework, a sort of internal conflict within the self. And externalizing was children who seem to have problems with external rules and social expectations. And so this phrase "externalizing", sort of carried through child psychology research, and it basically captured this idea that there's different buckets of diagnosis. So this child might be diagnosed with ADHD, and this other child might be diagnosed with conduct disorder, and as an adult, they might be diagnosed with a substance use disorder, but if you look across the lifespan, these are highly comorbid conditions. So a child with conduct disorder, which is defined by persistently lying, stealing, hurting others or animals, is 10 to 12 times more likely to get a diagnosis of ADHD. Nearly 75% of them will meet criteria for a substance use disorder in adulthood. And then, if you look within family pedigree data, you know this is where the Northern European massive population registers have been helpful. You can see that these diagnoses, which are intended by the DSM or psychiatry, to be discrete buckets, run together in families. So if a child has a parent who has a substance use disorder, they're not just more likely to have a substance use disorder, they're also more likely to have ADHD, they're also more likely to have a conduct disorder, they're also more likely to be arrested for a violent crime that's not substance related. So that's the kind of theoretical and empirical background of thinking of externalizing as a cluster. 


    Paige Harden  45:14  

    Now within psychiatric genetics, there's been this, obviously, a huge explosion in GWAS to look at, what are genes associated with schizophrenia? What are genes associated with bipolar disorder? And the externalizing disorders, with the exception of some substance use disorders, have been really neglected within that landscape, in part because there's a, there's a little circularity problem here, in that there's, there's no drugs that you can give a child if they get a conduct disorder diagnosis. So there's, for many years, no way to get reimbursed as a psychiatrist for diagnosing them with that. So therefore it doesn't go into the medical record. So therefore there's no data to do a GWAS on it. So therefore it's considered not biological. So therefore there's no, you know, there's a circular loop there. So what we were interested in is, how can we find genes that are associated not just with one of these things, but with all of these things? And our challenge is, there aren't large medical registers where children have been given the conduct disorder diagnosis and have also been genotyped. So our solution was to try to get it kind of get in through the back door, which is based on the twin literature. What are, we might think of them as misdemeanors, what are other forms of rule breaking or disinhibited behavior, other things that people do that someone says they shouldn't do and they do it anyways? If we pool enough data on enough of those different behaviors at different points in the lifespan, and then we look specifically for genes that are that are not specific to one, but general to all of them, can we identify genes that are getting at this more cross-cutting liability and that also are associated with the more clinically significant forms of anti social behavior that at least I'm particularly interested in. So it was kind of like a sneaky strategy. 


    Paige Harden  47:11  

    So what we did is we identified seven phenotypes for which there was sufficient genetic data and also sufficient evidence from twin and adoption studies that they were genetically correlated with more serious antisocial behavior and substance use, and that was ADHD symptoms in childhood, age at losing your virginity, age at first sexual intercourse, number of sexual partners, ever smoking pot, ever smoking a cigarette, describing yourself as a risk taker, "I am someone who likes to take risks", and problematic alcohol use. And a lot of those are self defined. I mean, the are you a risk taker? Is one item in UK Biobank. Do you think of yourself as someone who likes to take risks? Yes or No. It's kind of a garbage item. But it was genotyped in 500,000 people. So you have an enormous amount of power. I also, I once gave a talk on this, and the economists in the room said: "I don't trust the reports of sexual behavior, because they're all self report". And I was like, "what is the alternative to self report here, on the number of sexual partners you've ever had?"


    Paige Harden  48:22  

    So, you know, as a psychologist, I was trained to really value measurement, and the moving into GWAS has forced me to break up with a lot of that, because the measurement properties aren't great. But what we found is we could identify genes. There's a lot of genetic signal there, and those genetic variants do predict more serious symptoms of conduct disorder, of antisocial personality disorder, of ever being incarcerated for a violent crime, of ever being arrested. And at least in children where we have good family studies, they predict conduct problems in children, even controlling for the genotype of the parents. So it doesn't appear that we're just picking up on kind of population stratification or environmental confounding. And then so there was a multi barreled question that I gave a multi barreled answer. So I'll stop there and see, and I'll let  Ya'll ask me more.


    Paige Harden  48:54  

    Well I think just the last part was like, so what percentage of the variation are you explaining with these variants?


    Paige Harden  49:27  

    Yeah, so what we're, what we're, if you're looking at like a common factor of externalizing. So basically, we've studied genes, we're looking for genes that have cross-cutting liabilities, and so then if in independent data sets, you come up with this kind of factor representing all of these risk taking behaviors. In our first study, we were accounting for about 9 to 10% of that variance, and then it's going up as the studies get more powerful. Now, 9 to 10% this is, I think, another thing where the biologists and the social scientists sometimes have very different intuitions about what kind of effect sizes are worth getting excited about, because if you are like, I want to build a comprehensive biological, mechanistic model of antisocial offending, 9% doesn't sound like that much to write home about. But if you're a social scientist that's used to under you know studying epidemiological studies of children, 9% is a massive effect size. It's bigger than the correlation with child maltreatment, it's bigger than the correlation with lead exposure, it's bigger than the correlation with parental SES, we have a study comparing it, and it's bigger than that, even when you're looking within families. And that's because, again, this is a really complicated set of behaviors. It's not influenced by one thing. We're never going to be explaining it fully with one dimension, but we are meaningfully moving the needle in terms of how much variance we can account for by looking at these measures of genes.


    Marty Martin  51:00  

    Well as ecologists that work on wild animals, we're a fan of the 9% we're used to getting those low percentages, maybe a little bit higher, but I would take 9%.One of the other pieces that Cam asked you about, Paige, is the identity of some of these genes, and one of them that was really a fashion a while ago, this Caspi study MAO-A, is that something that popped out for you guys? And where's that standard? What other ones did you find as interesting?


    Paige Harden  51:27  

    Yeah, so, so MAO-A is fascinating because it's it got a lot of attention. So MAO-A is it codes for mono amine oxidase, a enzyme that degrades mono amine so it affects how neurons are communicating with one another, and it initially became something that a lot of people were interested in in the 1990s because there was a very well known study of a Dutch pedigree where they identified that a very rare variant In MAO-A that was, you know, protein truncating, so like it didn't, you know it was, it made it not work, was associated with serious, impulsive, anti social behavior and aggression in the men in this family. So obviously, it's an X-linked gene. Men only have one X so the women who inherited this mutation were unaffected, but the men who inherited this rare mutation had really and again, this is not light. This is not I was kind of in trouble in class. This is I raped my sister, I stabbed my boss with a pitchfork. I committed arson. Many of these men were in prison. And this is a rare variant. It's, you know, it has been discovered in some families since then, but this is not explaining the, you know, violence in the general population. 


    Paige Harden  52:47  

    And then fast forward to the early 2000s Avshalom Caspi and his colleagues in the Dunedin longitudinal study looked at a common variant in MAO-A that they argued was associated with antisocial behavior, if it occurred in combination with childhood maltreatment. Now, we now know that that study's results aren't trustworthy, because it was this candidate gene paradigm, and there was just a lot of false positives, but people didn't know that, you know, at the time. The thing about MAO-A is, again, it's on the X chromosome, and everything that we've done so far is only on the autosomes. So I have no data that speaks to Moa. I have actually have my former postdoc, Camille Williams, is working on this now, is looking looking at and everything we're looking at is pooled across sexes too. So we don't have sex-specific effects. We don't have have sex amplification effects, right? So do the same variants have larger effects on men because of some sort of interaction. And we don't have X chromosome specific effects. So that's an unknown question. Well, we do have data to, is that the size of the effects of individual common variants is, like every other trait, very small. So we know we can say with confidence that the size of the effects that Caspi was documenting are unlikely, very, very, very unlikely to be the true size of any effect of a common genetic variant, because common genetic variants just don't have huge heaping effects on behavior like that. The genes that did come out were, I mean, this is, this is what has happened with all of the candidate gene literature. Is the genome GWAS has shown us how bad our hypothesizing about which genes were going to matter is.


    Marty Martin  54:36  

    It's a big genome, right?


    Paige Harden  54:38  

    Yeah, like, it's just like, "Oh, you, you, that's so cute that, like you thought that, you know, because you can't, because you giving dopamine agonists to Parkinson's patients makes them risk taking, that it's all going to be dopamine genes. Like that was such a cute hypothesis. No, like that isn't the case at all. I would say the most consistent associate has been CADM2, which is a cell adhesion molecule. And it was one of those things where, like, you just could not, you just couldn't do a GWAS, of anything remotely risk taking involved without hitting CADM2. I have in my book a description of so at some point, people were like, well, let's just do that. Let's look at CADM2 variants, and do a PheWAS  in UK Biobank, and I think 23andme of what this is related to. And it's like, you know, everything from putting salt in your food to having sex with more people to smoking to smoking pot to having conduct disorder to pulling a knife or gun on someone well, and that's I find that fascinating, that the violations of kind of more puritanical morality, like you just want your food to taste good, you put salt on it, but you know you shouldn't, because it's bad for your heart, all the way up to really serious, you know, aggression towards people, and people aren't going into it linking those together. It's just the same genes keep popping up across them. And I find that really fascinating, right? 


    Marty Martin  56:10  

    Yeah, that is interesting, huh? 


    Cameron Ghalambor  56:12  

    Okay, well, so, so we have these, these genes. We have some genes we have, you know, but we also have a lot of genetic variation and, and I think where the environment and the genetic variation kind of meet has historically been sort of framed in this, like nature versus nurture sort of debate. And one of my research interests is phenotypic plasticity, and that falls squarely within this nature nurture debate, and my views on this have changed, because I don't, I no longer sort of see the dichotomy between nature versus nurture as really very productive. But what I see, you know, in my own research and across the literature, you know, in the evolutionary biology literature, is the common presence of a of genotype by environment interaction. And what I mean by that, because I think a lot of times people get when they say there's a genotype by environment interaction, they just associate that as being plasticity. But specifically, what I mean is that, you know, I can take, I can create a bunch of family lines of fish with different genetic backgrounds, and then when I put them in the same environment, like if I expose them to a predator cue, they vary in their phenotypic response. So, the interaction is like akin to the statistical interaction, the slope of the response across the different environments is different and and why that's significant for us as a as evolutionary biologist, is that's the genetic variation for plasticity. That's what selection acts on. And also, what's interesting then, is that the phenotype is very context dependent, but if I know the genotype and I know the environment, I can, with some probability, predict what the phenotype would be. And I know this is a general problem, like with GWAS, in general, is that these kinds of genotype by environment interactions are often difficult to incorporate. And so I guess, like, how does that view of you know me playing with my fish and giving them predator cues and looking at the variation in the plastic responses. How does that fit with your view of like human genetic variation and the capacity for, for example, different individuals to not show the same phenotypic response, even when placed in the same exposed to the same kinds of environments? Does that? Does that make sense?


    Paige Harden  59:03  

    Yeah, it does. And I think I would probably say that I think of things very similarly as you have arrived that from a different,  obviously, from a different scholarly tradition, but have arrived at a very similar place. I also don't think that the nature versus nurture dichotomy is all that useful. It's kind of where science goes to die, or interesting science goes to die. 


    Cameron Ghalambor  59:27  

    Okay


    Paige Harden  59:28  

    And one thing that I'm interested in, you know, because I think when you get sucked into this question of, is it what's more important, nature versus nurture, then all of the stuff at the interface of what we call nature and what we call nurture gets lost or is unfairly apportioned to one versus the other, and also, I think it reifies this view of the self that I actually really don't agree with anymore. I mean, I think that nature versus nurture is such a sticky concept in science and in science communication, because humans are such essentialist thinkers about themselves. And so we have this idea that there's some, you know, DNA that's core to me inside my body, and then environment or nurture is everything that happens to me outside my body. But we know that that's not how development happens, that the insides of our bodies and the outsides of our bodies are much porous, much more porous. That line is much fuzzier. You know, where does my niche, how far does my genotype extend outward in terms of forming my niche, and how much does the environment penetrate inwards into my inner workings of my cells. Both of those things are true, so I very much agree about that, you know, taking those big abstractions and then like, how does that affect scientific practice? What we're doing with GWAS is very poorly suited for identifying specific genotype by environment interactions, because we are scanning data from people from such large samples, we are necessarily aggregating over a wide variety of early childhood environments and looking at, you know, what's the average effect size of this allele? And then if you take a polygenic score constructed from those results, and then you go looking for, does it interact with measured environments? You don't find very much, because you're you're prioritizing the things that are have an average signal, and any crossover interactions, you know, aren't going to be visible there. I think where it's very useful, potentially, is in tracing what I, as a behavioral geneticist, think of as gene-environment correlation, which is, how do these genotypes affect the environments that children elicit and seek out? What kind of social niches do they build? And then, how much is that process necessary? How much is that feedback loop, to some extent, necessary in order for this genotype-phenotype association that we're seeing at the end, we're, you know, seeing the net result of in our GWAS results, for it to come to fruition. So, and I think this is where, you know, some of the early twin studies were also really useful. So looking at fraternal twins, and one of them has an initially higher level of sensation-seeking temperament. How does that predict differential parental treatment? And then, how does that differential parental treatment predict subsequent differences in the child's phenotype and as a developmental ist, you know, as a mother, as a as a clinical psychologist, it's those genotype to environment to person to environment to person feedback loops that actually, I find the most interesting.


    Cameron Ghalambor  1:03:02  

    Marty, and I talk a lot about the, you know, we always like to push back on the sort of linear kinds of responses and and more of those kind of feedbacks, and how common they are in all kinds of facets of biology. 


    Paige Harden  1:03:18  

    Yeah. So I think in the specific case of externalizing behavior. I think some of our best evidence actually comes from the adoption studies, because then you see children have a biological parent, and something about the biological parents phenotype is indicative of some potential genetic risk. So the biological parents are they have a substance use disorder, they've been incarcerated for a violent crime, they have serious antisocial behavior, and then they give up the child for adoption. And the adoptive parents, you know, and in the cleanest cases, these are closed adoptions, so there's no contact now with the with bio Mom and Dad and I find the research fascinating, which is, what about the child? What? What about the child's biological parents' characteristics predict how the adoptive parents treat the child? So it's genetic risk to eliciting some environment and then what about the adoptive parents treatment predicts the best outcomes for kids who have this kind of biological loading or biological liability, as evidenced by their biological parents phenotype? And this, you see a very clear result, which is that children at elevated genetic risk for antisocial behavior tend to elicit more coldness and more harshness from adults so they're harder to bond with, and people respond to bad behavior by, you know, reaching for harsh discipline. You also see this in experimental studies where children with conduct disorder are brought in and they're just assigned a volunteer from the community, you know, a strange woman they've never interacted with to interact with. And those women treat children with conduct disorder with less warmth and more punitiveness by the end of the interaction. And terribly, tragically, ironically, it is that exact feedback loop that is the worst for those kids, because the thing that predicts the most positive outcomes for children who are disinhibited, have self-regulation problems are antagonistic, is non-punitive discipline and warmth. I mean, that's the best parenting for all children, but it's particularly important for children who have these risks. So we can see both how the genetic liability pulls for certain things from the environment, and that also how not doing that parents, who are, you know, very skilled and successful at stopping that feedback loop and actually responding in the other way, those children have the best outcomes. I'm not, I don't want to overly compare children to dogs. Children are not dogs and and I'm a dog owner, and a mom, parenting is not owning a dog. But there's a similar thing where if you have a very, very strong willed dog, it is harder for an unskilled dog owner to not respond inconsistently and punitively. And that is the worst possible thing for a strong-willed dog, and it's the same dynamic that we see with children, 


    Marty Martin  1:06:25  

    Yeah, yeah. It's funny you use the example of dog. 


    Cameron Ghalambor  1:06:28  

    I have a strong-willed dog, and we talk about it a lot, and we just sometimes end up staring at each other for like, you know, five minutes. I'm like, come on, really? 


    Paige Harden  1:06:38  

    Like I'm the alpha in this situation. What type of dog do you have? 


    Cameron Ghalambor  1:06:41  

    I have a Tibetan Terrier, which is known for, it's, it's been described as being a third dog, a third cat and a third human. They are like, I would say, like, semi domesticated, as opposed to our previous dog that just lived to please you. And you know, yeah, nothing else.


    Paige Harden  1:07:03  

    Yeah, yeah, my dog doesn't live to please me, either. And you know, and some children do, they are very they do. They are very attuned to pleasing their parents. They want to please adults. And those are what we call easy children. And not all children are easy children. Not all of them live to please their parents, and it requires so much more skill and patience and emotion regulation on the part of the parent. And then, if we're thinking about how genes, genes and environments are correlated at the parental level too, the parents who are often tasked with parenting the most temperamentally intense, punishment insensitive children are the ones who also might be addicted to substances themselves, or might be dealing with that themselves. And so there's kind of a perfect storm often when you're when the same parents are providing both the environment and the genes to the kids.


    Marty Martin  1:07:55  

    Yeah, so I, you know, Cam's right that we're really intrigued by this dialecticism. Clearly, you know, you're a fan of this, and you read Kevin Mitchell's Free Agents book, he talks about spiral causality. A lot of people are excited about these ideas, but I mean to you, the person that's going to go out and try to figure out how to put this into play. I mean, what are we going to do? It's already really difficult to get the data to just, you know, figure out that 9% of variation. I mean, now you're talking about something that's challenging to find the data, and then challenging, maybe to find whatever it is that you're going to be looking for. Because how do you look for, how you call something a loop? And when did you decide to stop calling it a loop? Because it'll loop again. Like, do you think that epigenetic variation, this is definitely a range, is that part of it? It feels like it's a step, but to me, it's like, you know, the step on a ladder that's infinitely tall, maybe.


    Paige Harden  1:08:52  

    I mean, I think epigenetic variation is definitely part of it, obviously, and we do in our lab some work specifically on DNA methylation in response to environmental intervention, but that work has been very poorly integrated, even in my lab, I mean, especially in my lab, with what we were discovering at the level of the genome. And this isn't just for antisocial behavior. This is for other complex traits too. So y'all are, you know, of the same generation I talk in my book about how I started in science the summer after my freshman year of college, so the year 2000, the same year that the Human Genome Project draft was finished. And there was this sense that if we just got one more layer of information, that it was just gonna give up its secrets, we're almost there.


    Marty Martin  1:09:50  

    We're almost there. Yeah, exactly.


    Paige Harden  1:09:52  

    And, you know, we're gonna find the ten genes that are involved in schizophrenia, and then we're gonna have a blood test for what mental disorder you have. And we're going to immediately develop a wealth of new drugs. And, of course, it didn't work out that way. And so I'm a little bit, you know, I'm I have the jadedness of middle age, when people pin their hopes on epigenetics are going to help us. I think that we are fortunate to live in a world in which it is has such depth of mystery that we will never not have something really interesting to think about and ponder and feel like it exceeds our grasp, like that's also very exciting that we're not going to run out of mysteries to think about.


    Paige Harden  1:10:36  

    Much more pragmatically, you know, the other hat that I wear, in addition to my lab and author, is that I'm the Director of Clinical Rraining for the clinical psych PhD students. And most of them are not going to be, you know, most of them will be research active, but most of them will not be rR scientists. Most of them will be clinicians, in some capacity. And two days a week, they go to the VA and they sit with men who are veterans and also addicted to opiate drugs, and they have to think about, well, how does the abstractions of what we're doing scientifically relate to how I'm actually going to help this person that's in front of me? And I think there's, you know, I think there's a couple ways where I think, pragmatically, this work could potentially be useful. I don't know if it's going to be I mean, no one knows if what they're doing is going to be useful, but could be useful. One is, can we stratify people for early intervention, like, can we prioritize, in the same way that the doctors say you have a family history of heart disease, and you have these genetic risk variants for blood pressure. And so we're going to put you on we're not going to wait, we're going to put you on statins early. You know, there are definitely 13-year-olds who are very risk taking, and it's a blip, it's a developmental blip, and there are 13-yea- olds where it's not a blip, and this is the first part of a really serious, antisocial, offending life course that they're on. Is there a way to identify those two apart even a little bit better than we can, you know, that's kind of one issue. 


    Paige Harden  1:12:15  

    And then the other. And this, I would say, is probably, you know, of all the controversial things, this might be the most controversial thing I'm gonna say. But we are living through a revolution in which there is a medication that treats a that meaningfully changes a highly polygenic phenotype that is governed by gene environment interactions, and that is ozempic and body weight, where even if the biological even if the individual genetic variants all have very tiny effect sizes, they're pointing to a mechanism that, if you can push on it really hard, can really change it. And if we're thinking about the psychiatric medication landscape, if your child's dominant problem is they're depressed or they're anxious, drugs aren't going to be a cure all, but they are part of the treatment strategy for many families, and psychiatry is something to offer if your if your child's predominant problem is that they are violent, aggressive, and don't feel bad about it, there's nothing that psychiatry can offer you. And that's not because there's no tractable biology there. It's because it hasn't even been investigated as a, even a biomedical phenomenon of interest. And so that's the thought that I, that I keep returning to, is, what if we took this phenomenon seriously, not just as kind of bad kids, but as something that, like maybe medicine has something, something to add here?


    Cameron Ghalambor  1:13:46  

    It's a little bit of a tangent, but but also somewhat related. So my my sister-in-law is a genetic counselor, actually, and so she's not a she's not a clinical psychologist, but she is on the front line of having to communicate on a daily basis, you know, with with expecting parents. And you know, in my conversations with her, it's, it's, it's easy for her to communicate about disease risk, Mendelian traits, you know, it's, it's a it's more black and white, and she's less often in a position where she has to discuss more complex traits and risk factors like their child, like a child's propensity for being violent or something. But the thing that she deals with, often on a daily basis, especially in cases where there's a genetic disease, is this overwhelming feeling of guilt by the parents. And you know when they find out that they have passed something on, and you talk about this, I think, also in the book, to some degree. And can you, can you speak a little to like your thoughts on on this idea of guilt and blame? Because I think it plays a pretty big role in in your book, especially in the second half.


    Paige Harden  1:15:19  

    Yeah, so that's a really interesting phenomenon. I feel guilty about passing on a gene to my child, because if we think about it from the perspective of our usual role of choice and control in what whether we should feel guilty or blame someone for something, it doesn't really make sense, right? Usually, we think, well, you're to blame for something because you could have done otherwise and you didn't. You had a choice over it. And so many of our conversations about blameworthiness revolve around this idea of choice or ability to do otherwise. And that that suggests a little bit of a puzzle that, like we should be curious about this phenomenon, because parents must obviously know on a rational basis. They did not choose which egg, right? They didn't choose which sperm. We can come back to conditions in which parents might choose an embryo later. And they didn't have control over inheriting it. So why would that be attached to guilt and blame like that doesn't make sense from the perspective that you're guilty for what you had the opportunity to choose to do differently. And I think it speaks to another story about blame that runs through our culture, that is maybe less rational or less commonly thought of in academic philosophy, but I think is every bit runs through American culture, and that is a really Christian idea about inherited sin and inherited blaming, blameworthiness. So my book is called original sin. And what you know, what's the doctrine of original sin? The doctrine of original sin was Augustine. He was a bishop from North Africa who was writing in this interesting period after Rome had become officially Christian, but right before the fall of Rome, so at this time in which church power and imperial power were really merging. And he proposed this idea, which was relatively novel to Christianity, which was that you were born inherently bad. You were born inherently sinful and not inherent sinfulness. Could not be expunged in this life by joining the church or becoming a Christian, which is very convenient when you're trying to make the case for why the church needs to have more power, right? Like the church needs to have more power because no one's capable of choosing good on their own. It's a very power-justifying ideology. And it also made sense as to why people suffered. Like everyone suffers, even children suffer, and they don't suffer because God allows evil to happen in the world. They suffer because they deserved it, and they deserved it as an inherent condition of being human. And what's more is that that badness is physically inherited. I mean, this is why Augustine was so anti-sex, because sex led to babies, and the sex act is what led to the propagation of this evil across humans. 


    Paige Harden  1:18:33  

    And if you were not raised in the church, and particularly if you're a scientist, you might be thinking, I obviously don't believe that. Like, I don't believe that people are that all humans are born inherently bad and worthy of eternal damnation, and that includes infants, right, like, that's a pretty dark ideology. But we live in America in a profoundly Christian inflected culture, and I think that idea of I'm doing something wrong just by being having a body and passing on that flawed body to the next generation. Would be, if would it be an idea that would immediately make sense to the Augustine era church, they would be like, Yeah, that's right. You, you had sex and you perpetuated this flaw, you know, this kind of this, this human fallibility, which is inherent on to the next generation. And I think going back to our first conversation, this is why I don't think the debate about nature versus nurture is ever going to go away, not anytime soon, because in addition to all of our rational ideas about what genes are, I think that DNA, genetics, all the science around it, is being heard and interpreted, not just in well, what have I learned in high school biology about Mendel's pea plants, but also through the lens of a set of inherited ideas, which very much associate the body, both with what's fallible and damnable about you, and also with the thing that you need to overcome, and also the part of you that's kind of essentially you. You know, there's an there's a kind of biological essentialism to Augustine, that you inherited badness, and that badness colors everything. There's no escaping it.


    Marty Martin  1:20:24  

    So can we turn this around? You said just a minute ago that probably a lot of the scientists listening would not go for original sin as a concept. But what would you say to atheist science scientists about sin? Meaning that, you know, I loved how you used the example in the book of sex as something profoundly human, profoundly about life, and you use that as a sort of way to think about responsibility and morality. So I don't think that you're meaning to say at all that sin as a word is not something that should be part of how humans understand and maybe motivate their behavior. But that little twist there about the sort of core of what sex represents to humans was really creative. Can you say a little bit about that?


    Paige Harden  1:21:10  

    Yeah, so in some ways this is kind of responding to a more Sapolsky-style determinism.


    Marty Martin  1:21:16  

    Yes, that's exactly why I was asking you


    Paige Harden  1:21:18  

    Which is, you know, Sapolsky and I, you know, we're both scientists, and we both think that the genotype and in early environments and the circumstances that attended your life have profoundly shaped what you do. I think he's more committed to a full determinist view of behavior than I am, perhaps. And then the question is, well, what does that mean for how we treat each other, right? And Sapolsky view, similar to Gregg Caruso and to Derk Pereboom, there's a couple of psychologists, philosophers in this way, which is basically that, like this, renders moral, the idea of moral responsibility and punishment and guilt obsolete. Sapolsky has this phrase where he says, it's you know, "It's as useless to be angry at a murderer as it is to be mad at the sky for raining." And it's just, you know, and it's again, if we're going back to this tension between our subjective sense of ourselves as agents who interact with each other as agents, I think of you as a mind, not just as a collection of phenomenon. And this objective you, he basically lends into the subjective view as an illusion. The objective view is what should matter and like that's, let's lean into that. And I think that that misses that there's something about how other people matter to you in the way we call moral that's really fundamental to human experience, and that advocating for it to go away, advocating for what there's a philosopher, Peter Strawson who called this the reactive attitudes, which is, how do I feel In ways that only makes sense because I view myself as an agent who's morally responsible, and I view you as an agent who's morally responsible. So I feel guilt, I feel shame, I feel pride, I feel blame, I feel resentment, I feel outrage. And I think that those reactive attitudes are as baked into the human experience, probably into the mammalian experience, honestly, of like being in a cooperative society as sexual reproductionists. 


    Paige Harden  1:22:05  

    So for me, it's what my kind of broadly Peter Strawson view of this is like it might be true that our behavior is determined. It's definitely true, undoubtedly true, that all that we do is profoundly shaped by luck, by genes and environments over which we had no control, and also we still are part of a community, and so there's no there's no getting out of mattering to each other in this way that we call moral. And so our trick there, our challenge is, how do we fashion a system of accountability that really takes it seriously as a social condition, not as a supernatural condition, so not as like there's some spirit in the body that's somehow untethered, untethered from material reality, and that's the thing that's choosing the good versus bad, and God is going to punish you for what you didn't, didn't do. That's one version of who deserves to suffer. I think that we have a problem that faces all mammals, which is we have to live together, and there is no becoming celibate as a species. There might be a few people who are celibate, but there's no there's no universal abstinence, not for all of us, and some people might be very good at setting aside their moral anger, but there's no getting out of having to live with each other and mattering to each other in this way. So what does accountability look like if you if you take both. Our need for accountability and our how we've been profoundly shaped by luck, if we take both of those seriously at the same time.


    Cameron Ghalambor  1:25:10  

    So Paige that, I mean two, two sort of thoughts on that. I mean, one is that this, that that tension between, I guess, another way of rephrasing that is this kind of tension between selfishness and cooperation, you know, that strikes me as a sort of very universal biological problem, like an organism, an individual group of cells, faces the same tension between, you know, cooperating to maintain, you know, the whole as opposed to acting selfishly like a cancer cell that you know, shows uncontrolled cell division. And then, obviously, we have so many examples of that, in terms of, you know, social animals. But within all of those sets of you know from levels of biological organization, there are also mechanisms in place that sort of keep individuals from acting too selfishly. Marty and I were talking about the example in your book about the paper wasps that that you bring up very


    Marty Martin  1:26:19  

    vivid, very, very well done.


    Cameron Ghalambor  1:26:20  

    Thank you. And so, you know, there does seem to be a universal, I hate to use that word over and over again, but some there always has to be some mechanism for enforcement. And so, you know, in terms of and that's a hugely complex problem in humans. And, you know, I was pleasantly surprised when I got to the part of your book and read about Norway, because I moved here from the US about five years ago. And, you know, a lot of the ways that people think about culturally and how they view ideas of punishment are just so fundamentally different than what it was like growing up in the US and so. So there's still rules, there's still mechanisms in place. But there's also, like, a lot of, I guess, emphasis on, like, not losing your humanity. I guess in terms like, there are limits to because it seems like if you if the enforcement mechanisms become too strong, it sort of breaks down the cooperative side of things.


    Paige Harden  1:27:39  

    Yeah, it's like an autoimmune disorder, right, where you have something that is designed to bring the body to heal, but in fact, actually ends up destroying it. 


    Cameron Ghalambor  1:27:48  

    Yeah, exactly.


    Paige Harden  1:27:50  

    Yeah I'm so glad that you brought up the paper wasps, because I, you know, it articulate something. I think often people I went  in, probably went into thinking about these issues with the idea that you need to find some pocket of human life in which we are not creaturely, in order to justify punishment or accountability or moral responsibility. And then thinking about cooperation in non-human species or other levels of organization throughout life, really changed the way that I think that that there's no part of our life that's immune from our creatureliness, but we don't need to find some exception to our creatureliness in order to hold each other accountable, because that's also what all creatures do. They all have systems of cooperation and mechanisms to enforce them, but those mechanisms are remarkably flexible. And we don't have to imagine utopia to think about doing things differently, we can look at other societies that do things differently, and I think Norway is an amazing example of this, in which Norwegians believe in free will just as much on average as Americans. What they don't believe in nearly as much as hell. They don't imagine that the fitting punishment for badness is eternal torment. And I think it's interesting that that view of the afterlife coincides with a system that is remarkably non-punitive compared to American society.


    Paige Harden  1:29:33  

    So when I bring up the Norwegian example often, you know, in my book, I talk about Anders Breivik, who is a mass murderer, I mean he killed 77 people, most of them teenagers. Also was clearly conduct disordered from childhood, like at four a social worker said this is a nasty, aggresive child, other kids aren't allowed to play with them, when their pets are around. And I think that's a great example of how even a very comprehensive social safety net does not, it certainly reduces violence, it certainly reduces antisocial behavior, but it does not solve the problem that humans can develop in very antisocial ways. That happens in even very egalitarian societies. And he was given a sentence of 21 years, which is the maximum sentence, and it might be extended if he's found to be dangerous at the end of 21 years, but to the American mind, the fact that a mass shooter of teenagers only for 21 years in prison is shocking, right? And it speaks to a level of non-retributiveness and also the conditions under which he's imprisoned. I've talked about this on other podcasts, but it is so compelling is that there's this Instagram, a meme that was going around, like a year ago, in which people were asked to say whether it was a Scandinavian prison or a London hotel room,


    Paige Harden  1:30:53  

    And people couldn't tell the difference. The only real giveaway is the security dome of cameras on top of the. So it's it is a level of affirming the dignity of a person, even when they've done something terrible, and also affirming their potential for change, and also relinquishing this entitlement to hurt someone that is core to the retributive urge that I think is really a profound example for the American mind. So I end the book there, or closer around there, there, and then also how some African communities have had to deal with the problem of child soldiers, which is similar thing of someone profoundly shaped  before they could consent, and also they've done terrible acts of violence. What both of those are very different contexts, Norway. Mozambique is the specific example I'm talking about, very different crimes. But what both of those approaches have in common is all a focus on both the dignity of the perpetrator, a willingness to keep in mind the both and, they both did horrible things, and they were shaped by factors, by on their control. And also, I think, a concern for preserving the soul of the person doing the punishing. I think it really, I think it's really corrosive to our soul to treat a fellow human horribly, even if that person did a horrible thing, and how corrosive that is to us, is an under-recognized aspect of punitive culture in America.


    Marty Martin  1:32:32  

    Look Paige this has been a fantastic conversation, I've really enjoyed it. I've won to do that. I guess I want to tie all of this together. The best part of being a biologist these days is that every day there's some amazing new discovery and methodological opportunity and new way of looking at data and the merging of fields, but it is intimidating, and it's sort of mind rattling, and I always feel like I'm behind. That leads me to believe that lots of listeners are going to be a little bit lost in parts of our conversation. Really, it's just because of the complexity. So to go all the way back to the first one of the first questions, I asked you, what was the thread between the books? And you said, luck. How do you want? I've started to do this in the classes that I teach, tell it to your grandmother. How would you explain this complexity to your grandmother? What do you want the general listener interested in human genetic variation and behavior, punishment, you know how the courts might work, attribution of guilt. In the shortest way that you could frame it, how do you want people to understand that? 


    Paige Harden  1:33:42  

    Oh, gosh, saving the most difficult question for last, 


    Marty Martin  1:33:45  

    That's what we do, that's what we do.


    Paige Harden  1:33:48  

     I think the thing that I would most want people to do is to see if they're willing to play with some ideas. I don't even do one podcast or even one book could convince you of them. And they might not be right, you know, I'm still working my way through this. But here are some ideas, yeah, right, that I want you to play with is one. There's no set of behaviors, regardless of how social or moral we think they are that are somehow not connected to our DNA to our cells to our neurons to our brains. We are fundamentally embodied people, and that goes all the way down. Two is that the question of whether behavior is caused by nature or nurture matter a lot less than you think it does. What matters ir that it is caused. Why that matters is not because it's going to help us figure out who deserves to suffer or who deserves to be praised. That's an endless black hole that is never going to be solved. What it can do is give us a dose of empathy and wonder at ourselves and our fellow creatures that can countervail the harsh retributiveness that I think many of us have grown up with. And even if free will is an illusion, we still have to live our lives looking forward. And if the question is, how then do I want to treat each other? How do I want to treat someone else, knowing what I know about all the ways science is discovering that we're shaped by factors beyond our control? I think that can be a really productive way to be forward looking.


    Marty Martin  1:35:38  

    Excellent 


    Cameron Ghalambor  1:35:39  

    In some ways. That's a really good place to wrap. But there's, well, I have like a million questions, but, but there's one question that 


    Marty Martin  1:35:49  

    But, but he's not gonna let you go. Can you tell that he's not gonna let you go?


    Paige Harden  1:35:53  

    He's like but I have more questions


    Cameron Ghalambor  1:35:54  

    I really wanted to get your opinion on before we wrapped up. So human behavior and our bound up in our genetic history evolved under various kinds of social conditions that seem to be rapidly changing, and, and I and, and as we talked about, you know, all the the complexities of the, you know, within this nature nurture, feedbacks and complexities of of your genes interacting with your environment. The one thing that I kept thinking about was, you know, this thing that is the environment is now like what we are doing, which is interacting remotely, online, not with other people in person, but often, you know, in this digital world where we're it's easy to go into your own universe, your own bubble and and, you know, the ability those, those enforcement mechanisms, the social enforcement mechanisms that we were talking about, can easily be removed, and it can let, you know, people's predispositions be acted on in maybe ways that weren't as easily accessible in the past. And so, you know, to me, that's, like, profoundly disturbing, because I think it means that, like, the extremes are more likely to be exposed and enforced. And is there research on that? Like, it's not, it's just a curiosity. I don't know anything about it.


    Paige Harden  1:37:43  

    Yeah, so, I mean, I think about this. I think about this all the time. I mean, we have more people alive now than we have ever had on earth before, and what that means is that there's more extreme outliers of everything. There's more musical geniuses, there's more, I was recently in LA and Malibu, and I just thought, I'm not supposed to be exposed to this many beautiful people all in one place, like in a previous time in human history, there would be one person in your village that maybe was approach the attractiveness of this. And now I was just walking around being like, what is happening here? 


    Paige Harden  1:38:20  

    We also have more people who are have very high genetic loadings for antisocial behavior than we've ever had before. And we know that one of the worst things you can do if you're trying to deflect an antisocial child's trajectory is to concentrate them with other antisocial children, like what we do in Texas, where we say you don't get to go to normal school now you go to alternative school, where you've taken all the most delinquent teenagers and put them in the same classroom together. Is the absolute worst possible thing you could do. And what is the internet, but that right? And so what we have an this is not just this conversation. This is the rise of individual freedom is good and it has costs. And the ability for you to find like-minded people is good and it has cost. And, you know, I live a modern life you do too, in which you live very far from where you were born. And my children are being raised without a dense, multi-generational kin network. And that has given me an amazing professional opportunity, and it means that my children are being raised in a nuclear family without this dense web of ties. So people talk about evolutionary mismatch all the time. You know the evolutionary mismatch between our food environment and our evolved weight mechanisms. I think that we live in an extreme evolutionary mismatch in terms of our opportunity to engage in antisocial behavior or opportunity to be exposed other highly antisocial people that normalize it and the the loss of a cohesive community that that enforces cooperation, not through force, but through a dense web of affection and affiliation and care. So I there's no solution to this. I will. I was recently in San Francisco, and there were all of these signs saying, stop hiring humans. And I was very depressed. And in the San Francisco Airport, I saw the San Francisco Airport has a banging airport bookstore, which I wasn't surprised. You know, it wasn't just like the top ten management books or whatever. And they had in there this collection of essays by Wendell Berry called "What are people for?" And I read it on the plane home, and it was a really good antidote to being in San Francisco. And as a mom, how do I think about what people are for and how to facilitate that flourishing in our culture is an ongoing challenge.


    Marty Martin  1:41:06  

    Well, again, Paige, this has been fantastic. We will not ask you any more questions, except that if there's anything we didn't prompt you, any question that we didn't ask to sort of bring out some part of the book that you wanted to cover, anything else you wanted to say?


    Paige Harden  1:41:18  

    No, I just want to say that if your readers pick it up. I would love if they wrote me to tell me their thoughts on things. The social media can feel both omnipresent but also alienating. There's this kind of talking into the void, capacity to it. And when people write me and they say I read it, and this is the part I really responded to, or this is the part that changed how I thought, or I totally disagree with you about this because of this life experience or the scientific knowledge I have, I really appreciate that. So I hope people buy it, I hope people read it, and I hope people write to me about it so that we can continue to be in conversation about it. 


    Marty Martin  1:41:51  

    Well, good luck with it, and we look forward to the next one, five years from now, 


    Paige Harden  1:41:58  

    Five years


    Marty Martin  1:41:59  

    Five years.


    Cameron Ghalambor  1:42:01  

    Yeah, thanks so much. 


    Paige Harden  1:42:02  

    Thank you guys.


    Cameron Ghalambor  1:42:18  

    Thanks for listening to this episode. If you like what you hear, let us know via Bluesky, Twitter, Facebook, Instagram, LinkedIn, or leave a review wherever you get your podcast, and if you don't like something, we'd love to know that too. All feedback is good feedback.


    Marty Martin  1:42:33  

    Thanks to Steve Lane, who manages the website, and Molly Magid for producing the show. 


    Cameron Ghalambor  1:42:37  

    Thanks also to Caroline Merriman and Cass Biles for help with social media. Brianna Longo, who produces our awesome cover images, and Clayton Glasgow, who blogs about topics covered in the main show. Check out his work on our substack page. 


    Marty Martin  1:42:50  

    Thanks to the College of Public Health at the University of South Florida, our Substack and Patreon subscribers and the National Science Foundation for support.


    Cameron Ghalambor  1:42:58  

    Music on the episode is from Poddington Bear and Tieren Costello.

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