Do your genes determine your success in life?: Big Brains podcast

Show Notes

Experts say we’re living through a renaissance in genetics research. The Human Genome project has explained our most fundamental genetics, CRISPR gene editing can be used to shape genetic code, and companies like 23 & Me can trace your ancestry from a single saliva swab. But all this new genetic information has people asking: How much do genetics determine our outcomes in life?

We all understand that our genes determine our height, hair and eye color, but what about intelligence, educational attainment or financial success? In a new book, The Genetic Lottery: Why DNA Matters for Social Equality, behavior geneticist Kathryn Paige Harden explores these uncomfortable corners of genetics research and explains why our economic and sociopolitical systems need to take it into account.

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(Episode published November 4, 2021)

Transcript:

Paul Rand: When you think about genetics, what comes to mind, science fiction?

Tape: They extract the preserved blood from the mosquito ant. Bingo, Dino DNA.

Paul Rand: CRISPR gene editing?

Tape: If there’s something that you want to fix on a strand of DNA, with CRISPR, you could theoretically find it, cut it out, and paste in a fix, at which point, presumably, Clippy shows up and says, “Hi, it looks like you’re trying to play God and alter the basic building blocks of life. Need some help?”

Paul Rand: Or maybe at home DNA kits.

Tape: The company 23andMe promises genetic information made easy.

Paul Rand: The last decade has been called a genetic Renaissance. And as science gets better and better at identifying the power of our genes, people want to know how much do our genes determine our future.

Kathryn Paige Harden: Your DNA sequence might be fixed, but the power of your genome for your life is not fixed. It’s not inexorable.

Paul Rand: That’s Kathryn Paige Harden, a professor of psychology at the university of Texas at Austin, who focuses on behavioral genetic. And is the author of a new book, The Genetic Lottery, why DNA matters for social equality?

Kathryn Paige Harden: There’s this double consciousness around genetics mattering. It’s knowledge that seeing both as obvious by many people, but also as deeply controversial and surprising by other people. And those two narratives are existing at the same time.

Paul Rand: Nature, nurture, it’s an old debate, but Harden says it’s becoming increasingly clear that nurture plays a role in working with our genes. But those genes determine more about us than we’d all like to think.

Kathryn Paige Harden: And not just on your height or your eye color, but also people who are born with a certain set of DNA variants are more likely to go further in school. And obviously, because of the ways that education is rewarded, to make more money, to be wealthier, and to be healthier throughout their lives.

Paul Rand: Harden’s work takes us to some deeply uncomfortable places, but she says we need to confront it head on and use it to build a more equitable in just society.

Kathryn Paige Harden: What I’m asking people to do then is actually a really difficult thing, which is to say, “Okay, yes, I have that reaction. What does that tell me about the extent that I’ve internalized this idea of intelligence as worth?” And if we really thought of intelligence as morally arbitrary, as height, where does that take us in terms of our vision of justice and vision of equality?

Paul Rand: From the University of Chicago Podcast Network, this is big brains, a podcast about the pioneering research and pivotal breakthroughs that are reshaping our world. On this episode, the unexpected role that genetics could play in building social justice. I’m your host, Paul Rand. In October 1990, scientists around the globe began the human genome project. 13 years later, the results gave us an unprecedented look at what lies within us on the most fundamental level.

Tape: And with the fruition of the human genome project in 2003, what we were doing was identifying that the book of life could be read in the As, and Cs, and Ts, and Gs of genetic code.

Paul Rand: Since then, scientists have been trying to identify specific sentences in that book, figuring out which genes are associated with which traits. And recently, they’ve begun looking beyond just our physical traits to see if genes also have a hand in determining how successful we may be in our society.

Kathryn Paige Harden: Almost everything that we are interested in studying in humans is not influenced by one gene. There’s not an intelligence gene. There’s not a gay gene. There’s not a depression gene. There’s not even a tall gene. All of these things are what people often refer to as complex traits, which means that they are influenced by many, many, many, many genes, each of which have a tiny association. And that often work in ways that most of the time, the vast majority of the time, we don’t even know why they’re associated. So these are things that are polygenic.

Paul Rand: Polygenic sounds like a big word, but it just means many genes, like a mosaic scattered throughout your genetic code that together creates the traits that make you who you are. Individually, the different pieces of my mosaic and your mosaic are called SNPs.

Kathryn Paige Harden: Single nucleotide polymorphisms, polymorphism just means many versions, and single nucleotide means single DNA letter. So these are differences between people in single DNA letters. All of our genome is made up of four DNA letters, G, C, T, and A. And so, we differ in particular spots in terms of these letters. So I might have a T in one spot, whereas you have a G in that spot. And that’s a variant or a polymorphism. It’s a way that people differ genetically.

Paul Rand: In order to pinpoint how all these SNPs shape our lives, Harden and her colleagues use something called genome wide association studies or GWAs for short.

Kathryn Paige Harden: So a huge sample of people, usually who are homogenous, very similar with regards to their self-identified ethnic ancestry and with regards to their genetic ancestry, so the patterns of similarity that we can see between people that exist because they share recent genetic ancestors. So again, it’s this backdrop of genetic similarity that people have by virtue of having shared recent ancestors. We look at differences between them and their SNPs that we’ve measured and correlate them with something that has been measured about their outcome.

Paul Rand: Basically, if many mosaics look the same in certain places, and those people have similar outcomes, we can conclude that those patterns are correlated with a certain trait.

Kathryn Paige Harden: So this could be their height, which SNPs are more common for taller people versus shorter people. This could be their physical disease.

Paul Rand: But the specific traits that harden is looking for are more controversial.

Kathryn Paige Harden: And in our cases, we’re looking at the sorts of outcomes that economists, sociologists, and psychologists usually study, which are things like educational attainment, ADHD in childhood, at what age did you first have a child. By educational attainment I mean how far you go in school. Income, so what’s your household income or personal income per year. So it’s simply asking which genetic variance are correlated with whatever we’re measuring as an outcome. And then, those correlations can then be taken and applied in a new study of a new group of people. So I’ve done a large GWAS of these SNPs are correlated with having more ADHD symptoms in childhood. Now I’m going to measure the DNA of a new group of children, and I’m going to measure theirs SNPs. And I’m going to use the correlations that I’ve estimated in my GWA to add up information about their genome into a single number. And we call that number a polygenic score or polygenic index.

Paul Rand: Harden says they can use polygenic scores to predict all sorts of things. But out of all the traits that harden looks for, educational success is at the forefront because...

Kathryn Paige Harden: Education plays such an outsized role and store inequality in America right now. We can think about three ways that people’s lives turn out differently by the end of their life. And one is around physical health, like how healthy are you? Do you have diabetes? One is around mental health and psychological wellbeing. And then one is around economic outcomes. How wealthy are you? How money do you make? All three of those things are increasingly structured by participation in higher education. So more educated Americans, they don’t just make more money; they also show lower rates of psychiatric disease, more psychological wellbeing, and live longer, more physically healthy lives. So if you want to think about, what is the fault line for inequality in America? One of those is education. And I think it just makes it a really important thing to study.

Paul Rand: Okay. You’re saying those were some pretty fancy words. Show me the evidence. Well, one place geneticists look for evidence is by studying twins.

Kathryn Paige Harden: If we look at identical twins who are, very, very similar, as close to similar as we get in humans in their genome, but also are starting their life in the same social position in terms of being born to the same parents, in the same historical moment, in the same neighborhood. If we look at how much identical twins differ, that gives us some window and to how often do people’s lives turn out differently when they have the same starting point. In practice, as we’ve currently constructed our educational system in high income countries in Northern Europe, America, Australia, which is where twin research is conducted, how often do they end up different? And they do end up different in their divorce, and they do end up different in their income, but they don’t end up that different in their cognitive ability in education.

Kathryn Paige Harden: So identical twins end up about a similar for their education as they end up for their height. And that’s not all genetics. The big part of that is their social environment. But a in terms of their differences, they’re much more minimal than I think people have realized and internalized when they think about how much latitude people have around their education relative to their starting point in a life.

Paul Rand: Harden has also been working on GWASs that have identified genetic correlations with educational attainment. One study actually show that genes could capture 10% to 15% of educational success. And that may not sound like a lot at first until you realize that wealth and equality accounts for only 11%. Basically, she says your genes play as much a role in your educational success as your parents’ wealth. Harden has done another GWAS that showed individuals with a high polygenic score for externalizing, which is a tendency to violate rules and social norms, where three times more likely to be incarcerated. And if all of this is starting to make you feel a bit uneasy, well, you’re not alone.

Kathryn Paige Harden: I think that the idea of genes mattering, of them making a difference, and particularly making a difference for social and behavioral life outcomes that are valued and rewarded in society is, of course, associated with controversy in people’s minds because of the history of the eugenics movement, particularly in that earlier part of the 20th century.

Paul Rand: Many people have worries about race dynamics here. And one of the most concerning factors in this genetics research is that it’s only been focused on people with white European ancestry.

Kathryn Paige Harden: I think it’s very concerning. I think in terms of our responsibility as a scientific community, to be inclusive, and also the limitation scientifically when you’re focusing on only this really narrow slice of global genetic diversity.

Paul Rand: Because of genetic variations, the discoveries of a GWAS of all white people just aren’t transferable to others. For instance, a particular gene mutation that causes cystic fibrosis in 70% of European populations, only causes it in 30% of cases in African populations. You can’t neatly correlate a green mosaic with a purple one, with an orange one.

Kathryn Paige Harden: We just are shooting ourselves in the foot in terms of discovering genes that are associated with human variation. I mean, particular, when we’re thinking about African populations, they are more genetically diverse than the rest of the globe. Even things that we think of as very genetically simple, such as skin pigmentation. Sarah Tishkoff has done really beautiful work with her colleague showing how much we don’t know because we’ve only studied variants that exist in Northern Europeans. And there’s a whole sets of genetic diversity that are invisible to us when we’re not studying people from around the globe.

Paul Rand: It’s also worth mentioning that as far as people will benefit from learning about how their gene shaped their lives, if these studies are only done on one group and those findings can’t translate to another, only white Europeans will reap the benefits.

Kathryn Paige Harden: So I think there’s so much opportunity for scientific knowledge to be had from being more inclusive in our science.

Paul Rand: But there’s also an understandable fear that if we start looking for genetically determined differences within a particular group of people, like a GWAS, then some people might look for them between whites and blacks, for example. And inaccurate science could give fuel to white supremacists.

Kathryn Paige Harden: Because especially in the American context, as soon as you start talking about genes and education, people immediately start thinking about race. Even though the genetic research is not informative about racial differences at all. And race is not a genetic construct.

Paul Rand: I guess I’m a little confused by this.

Kathryn Paige Harden: Yeah. A lot of people are. It’s really confusing.

Paul Rand: Yeah. So I guess is the answer, especially knowing who the studies have been done on that, some of these basic traits that we’re talking about, even schooling and how well you’ll do in school is not going to differ on your race because the genetic codes are similar enough in people anywhere in the world. Or is that not what you’re saying?

Kathryn Paige Harden: Yeah. That’s not quite right. They might differ by ancestry in the sense that some ancestry groups have different patterns of genetic variations. So something varies in a spot that doesn’t vary for another group in that spot. And ancestry is correlated with race. And then, also, our genes are influencing our bodies and brains, but then society respond in those unracialized ways. So we see, for instance, that an educational attainment polygenic score, SNPs associated with going further in school, that’s developed in big GWASs of European ancestry people. If you use that same polygenic score but calculate it in a group of African American school children in the US, it’s not related to how far they go in school.

Kathryn Paige Harden: And why is that? No one really knows the answer. Is it because the genes involved with the traits that are selected for in schooling are different in African ancestry populations? Or is it that, for instance, children who are bright, and inquisitive, and white are rewarded, but maybe they’re stigmatized as oppositional as their children of color. And that actually hurts their chances of schooling. And there are these racialized biases that are responding to the same genetically influenced traits in different ways. So those are really big scientific unknowns right now that people are pointing out.

Paul Rand: So if this is so concerning, why aren’t there more studies done on non-white non-Europeans?

Kathryn Paige Harden: It’s simply because that is where the data is and that’s where the money is. So the biggest sources of data for GWAS come from biobanks, such as UK Biobank, which is predominantly white British, European genetic ancestry, customers of direct to consumer genomics companies, like 23andMe, and then data from countries that keep very detailed records, such as Iceland or Finland.

Paul Rand: But it isn’t just racial dynamics that causes people discomfort with this work. It’s that it stabs at the very heart of our system of meritocracy. And if some portion of your success is just the lucky genetic hand you were dealt, what does that say about ownership and fairness in society?

Kathryn Paige Harden: When I think about the role that luck has played in people’s lives and shaping their “economic success”, it’s even harder for me to find the arguments that people don’t deserve certain things because they didn’t succeed in school, they didn’t succeed in the labor market. I find them even more troubling and insufficient.

Paul Rand: And as we said, genes can account for 10% to 15%. And it could be even more of your educational success, just as much, if not more than your parents’ wealth. But what about that other 80%? We’ve given nature it’s due, but what about nurture?

Kathryn Paige Harden: So ages ago, when I was still a grad student, I was able to teach my last year, my PhD, a seminar for upper level UVA undergrad. So they’re mostly seniors.

Paul Rand: Upper level, meaning they have higher genes for intelligence. Is that what you’re trying to say?

Kathryn Paige Harden: The title of the class was called the Nature Nurture Debate, but their essay for their final was, explain why your instructor hates the phrase, the nature nurture debate.

Paul Rand: Okay. So not nature versus nurture.

Kathryn Paige Harden: That’s really a false distinction because we know that for every individual person, genes and environments are always working in combination with one another over development. If you went to a restaurant and someone at the end of your meal was like, “Which was more important to you? Having a chair to sit in or having salt in your food?” That would be a nonsensical question. You obviously need both of those things in order to enjoy your meal. And it’s the same thing about development. We’re always talking about an interaction and a transaction when we’re talking about development of people.

Kathryn Paige Harden: So I’m most interested in saying nature versus nurture. And more interested in how can understanding nature in terms of these new tools we’ve gotten. We can measure the human genome. I mean, these are amazing technologies. How can they help us understand nurture to what extent is nurture an important process of nature having in its effect? So people have genetic differences but they provoke different things from their social environments. And in fact, I think one of the biggest possibilities for science in the coming decades, what I’m really excited about, thinking about is how we can use genetics to identify opportunities for environmental change.

Paul Rand: The dangers and possibilities of those environmental changes, after the break. Perhaps you’ve seen the 1997 sci-fi film Gattaca. It tells the story of a dystopian society in which people have been divided into a genetic caste system.

Speaker 5: We now have discrimination down to a science. For all my brave talk, I knew it was just that. No matter how much I trained or how much I studied, the best test score in the world wasn’t going to matter unless I had the blood test to go with it.

Paul Rand: Well, we don’t seem to be anywhere near a point in which we can predict a person’s future based on their genes. But of course, people are fearful that that’s where the work of scientist, like Harden, is going. And if it does, what’s to stop that from happening? And there’s privacy concerns too. Suppose we’re able to identify a polygenic score for the increased likelihood of you becoming an alcoholic, can you imagine if that information was sent to your possible future employer or significant other?

Kathryn Paige Harden: I do think, think that there is a space here for we already regulate what information can be used in certain context, employment context, or credit context, or insurance context, to what where do we need to say polygenic score information or genetic information needs to be regulated in similar ways. I also want to point out that people are very attuned to the ways in which talking about genetics could be used in harmful ways.

Paul Rand: It’s interesting, I was on a drive yesterday listening to an interview with Kara Swisher and the founder of 23andMe. And all of the components and worry is about privacy and genetic markers. And she was arguing if you could understand your DNA and you could actually help make sure that your child was not going to get breast cancer, wouldn’t you do it? Now, if I now take that same argument to this and say, “Well, if I actually could produce, because now I understand the links between DNA to intelligence and I could make my child more intelligence, why wouldn’t I do it?” And is that different back to this?

Kathryn Paige Harden: Well, it’s really different in one way, which is it’s really different scientifically. So when we’re talking about BRCA, we’re talking about-

Paul Rand: What’s BRCA?

Kathryn Paige Harden: The breast cancer mutation.

Paul Rand: Okay.

Kathryn Paige Harden: We’re talking about a single gene with a large effect that we’re not seeing this massive polygenicity that’s in many, many genes affecting something. What you get with polygenicity is also the same genes are associated with lots of different traits. So in our work, we’ve looked at genetic variants associated with going further in school that are not associated with intelligence test score performance, what economists often call non-cognitive skills. And what we see there is that some of the same genetic variants are associated with going further in school, but also having a higher risk for schizophrenia. So whenever we’re moving away from single genes of large effects, to many genes with small effects, but multiple effects with [inaudible 00:21:14] effects, these multivariate space.

Paul Rand: Back to there is no intelligence gene.

Kathryn Paige Harden: There is no intelligence gene. So we are talking about would a parent increase the child’s probability of having a higher IQ test score if the expected gain from that selection, when you’re selecting within embryos created by a family, is very marginal and comes with off target selection effects where you’re also marginally increasing their risk of schizophrenia, bipolar disorder, and autism.

Paul Rand: But that doesn’t mean that Harden wants to completely disentangle genetics from social policy and politics. In fact, she wants to tangle them up even more.

Kathryn Paige Harden: So I didn’t think it would be enough to just say this is what the genetics are saying. Just a logical appeal. I think given the history of how this work has been used and construed and talked about, I thought it was important to also have an ethical appeal in there, to say this is how I think this work fits in with the concerns that many people do have about equality and inequality.

Paul Rand: Harden believes that we can learn from genetics research to make more equitable societies by taking genetic differences into account when designing the politics and the systems that define our world. As she says in her book, there’s a famous quip from economist Art Goldberger, your genetics cause your poor eyesight, but your eyeglasses still work just fine.

Kathryn Paige Harden: It felt like I couldn’t describe the science and just walk away from the conversation. If I was going to describe the science, it also felt incumbent on me to do to the best so that I could describe, “Well, how do I see this fitting into the larger egalitarian project?” And that’s, obviously, a riskier thing to do as a scientist. I mean, it puts my own self into the book in a way that many academic press science, non-fiction books wouldn’t do. But I think is a way of broadening the conversation about what is this for?

Paul Rand: All right. Give me an example. Let get practical with this. What policies and laws specifically, do you say this insight tells us that we have to do this differently. If you were saying, "Listen, we are at the Harris School for Public Policy, what’s the public policy school at UT Austin?

Kathryn Paige Harden: LBJ.

Paul Rand: LBJ, of course. And now you’re saying, “I want you to consider this as you’re informing your policy decisions. And I want LBJ to start teaching this because it’s really important.” What are they teaching or thinking of differently on a very practical basis that you think is important? What insight has to be there that shapes policy at law?

Kathryn Paige Harden: Yeah. So I would say right now, what I would want them to do is evaluate the research on which the policy is based differently. It’s funny. I’m giving you a very unsexy example because I think when people think about genetics, they immediately want to go to, "Okay, well, how are policy makers going to measure something about people’s genes and do something differently?" And actually, I think we’re not even there. I think we’re at a spice in which most of the things that policy makers try particularly in the realm of education and child development, most of our interventions that people say, and now we’re going to teach parents to talk more to their kids, or we’re going to try this new fangled thing in our schools, most of that makes absolutely no difference for children’s cognitive development or emotional development.

Kathryn Paige Harden: And there’s lots of reasons for that. But one reason is that the research on which those policy proposals is often based is based on correlating things about kids with their parents and then saying, “Oh, no, we’re going to change this aspect of their parents, and it’s going to make their lives better.” And all of that research has this flaw in it, which is that it ignores genetic differences between people. So if policy makers just walked away from my book being like, the science is cool, and when someone comes to me with this hot new idea that what we should do is change X about parents to improve kids lives, they just looked at it with an eye of “Did this science take into account that parents also pass on their genes to their kids?” Just as a filter, like as a credibility check, I actually think that that would be like my big push for policymaker right now, which is so unsexy compared to personalizing education.

Paul Rand: Yes. It’s very unsatisfying. So I’m going to try to push for something that, to me, might be a little more satisfying. If there’s an insight that you want to be taken and say, "Listen, when you were considering developing policy, if you understood this about genetics and how it impacted how people took their lives, you would structure these policies different." So either there are reasons that it goes beyond people’s control over what they’re capable of doing. Or if parents have this issue and it’s led by this, it’s very likely that’s going to pass on to their kids, so you have to account for this. It doesn’t matter what program it should put in place. Work that out for me a little bit more clearly.

Kathryn Paige Harden: So right now, we have these studies of this genetic lottery of within family variation. And then, over here, social scientists are doing work on policy valuation, RCTs of interventions. Let’s combine those. Let’s think about the ways that the genetics can be leveraged to figure out things about the mechanisms of the environmental shock, and the environmental shocks can be leveraged to figure out the mechanisms of these genetic influences. I’m not a policy scholar. I want policy scholars to be thinking about genetics and where they can run with it. I want it to be seen as a limited but useful methodological tool that can then be integrated in the work, frameworks of social scientists doing their work rather than always treated with these kid gloves of like, "Oh, but are we unlocking some eugenic Pandora’s box?" That would ultimately be my goal. I’m here to make genetics boring for social scientists as part of their regular workday.

Paul Rand: All right. What did I not ask you about, Paige, that you think, based on some of the things we’ve talked about, would help run round out the story? Anything?

Kathryn Paige Harden: That’s a really good question. One thing we didn’t talk about is just how personal this feels to so many people. There’s an academic conversation about it, which is how can we use this in policy evaluation, or what regulation and do we need, or how can we use this as an adjunct to instrumental variables designs? And then there’s the historical political conversation about it. What I’ve been really surprised by is the number of emails that I’ve gotten in the last three weeks, where people just want to tell me their story, about their kids, or their adoption, or their siblings, or their class of students that they teach, or how they found their biological parent as an adult. These stories of difference and connection, and always feeling weird and not really having narrative around it, and then wondering how genetics played a role in their own story. So to your listeners, if you read the book and you have a story like that, please write me because I love hearing them, and I love hearing about how people think of genetics through this lens of a personal narrative.