3 Takeaways - How Your DNA Interacts With the World Around You (#246)

Episode Date: April 22, 2025

Are we shaped by our genes or by our environment? For centuries, this question has fueled one of science's most enduring debates. But the truth is more shocking—and more fascinating—than either side ever imagined. Princeton professor Dalton Conley reveals why we need to abandon the idea of "nature vs. nurture" and embrace a radically new understanding of human development.

For centuries, we've wrestled with the question of what makes us who we are. Is it our genes or our environment? Are we born with a set of traits that define us? Or is it the world around us that shapes the course of our lives? It turns out that it's not as simple as one or the other. What have we learned about nature versus nurture and what makes us who we are? Hi, everyone, I'm Lynn Toman and this is Three Takeaways. On Three Takeaways, I talk with some of the world's

best thinkers, business leaders, writers, politicians, newsmakers, and scientists. Each episode ends with three key takeaways to help us understand the world and maybe even ourselves a little better. Today, I'm excited to be joined by Dalton Connolly, a Princeton professor who studies the role of genes and the environment.

He's the author of the new book, The Social Genome. I'm excited to rethink everything we thought we knew about the nature versus nurture debate and what makes us who we are. Welcome Dalton and thanks so much for joining Three Takeaways today. Thanks for having me, Lynn. My pleasure. It's my pleasure. Can you please read aloud a great quote of yours?

Sure. When scientists started decoding the human genome, many assumed the nature-nurture debate was over and that soon we know the genetic blueprints for everything, obesity, intelligence, susceptibility to chronic disease, even individual personality traits. Pharmaceutical companies would develop drugs that could target the handful of genes responsible for, say, arthritis or heart disease or schizophrenia. The end of illness would soon be at hand, but it wasn't that simple. So Dalton, why wasn't it that simple? Is there one gene for arthritis or heart disease or schizophrenia?

No, there's no one gene for any of those chronic diseases that affects so many Americans. In fact, there's not even a handful of genes, much to the chagrin of the scientists who had first worked on the Human Genome Project in a few short years after the human genome was decoded in 2003, we learned a hard lesson, which is most things we care about, everything from height to schizophrenia to arthritis to heart disease, you name it, is highly polygenic, which means that it's not controlled by five or six genes, but it's controlled by hundreds of genes across the whole genome, thousands of locations in your chromosomes. That was a huge disappointment because that meant that you couldn't easily just gene edit or

develop a pharmaceutical to knock down or enhance a handful of genes to fix the problem. Even the genes don't tell the whole story. Can you explain gene expression, what it is and how it works? When the human genome was decoded, there was a vetting pool that how many genes are humans going to have. Lowly corn has 100,000 genes. It turned out that we had only 20,000 genes, which nobody was even close.

And what that means is that those 20,000 genes are doing a lot of work in every cell in your body, you have the exact same blueprint, but your skin cells are obviously very different than your liver cells and your brain cells. So gene expression is the switching on and off of those genes and those particular cells that make a brain cell unique or different from a skin cell. Those switches the gene expression are also affected by the environment, which is a very exciting area of research as well. So, if you have a lot of stress in your life, genes for cortisol receptors are going to be switched off, for example, because you've had too much stress

for too long. So, yes, it's a way that the environment comes under our skin and affects how our genes work. But it's not just the genes that we actually have, it's which genes are turned off or turned on. Exactly. It's usually not an on-off switch, I should say. It's more like a dimmer, but in certain cells or in certain conditions, certain times of life, you'll produce more of this genes protein or less of it. It's usually not just completely off or completely on. So interesting. We often think of our genes and our environment as separate forces, but you believe they're actually intertwined and that there's a feedback loop. How does that

work? And can you give an example? I love your example of the sprinter. Biologists have known that you can't talk about genes independently of the environment or the environment independently of genes. But what's really exciting as of late is that we now have tools because we've measured the whole human genome and we have a lot of data that we didn't have before that measures millions of people's genomes. We can construct these polygenic scores that predict outcomes like schizophrenia, educational attainment, height, body mass index, you name it, there's a polygenic index for it. That is a tool for us to see how genes and environment interact. And genes and environment interact in three ways.

And the first is, I'll give the example that you mentioned, is imagine a kid that's born with two working copies of the sprinter's gene, the fast twitch muscle gene that almost all elite athletes have. She's going to probably be picked first when they choose up sides in the schoolyard. She's probably going to win all the games upsides in the school yard. She's probably going to win all the games of tag or races in school. Maybe she's going to be spotted and picked to go into organized sports and she's going to excel there. All that exposure, all that environment of getting chosen to be on an organized sports team, getting more

investment in terms of summer camps and training, that's environment, but it's a result of her genes. It's a mechanism by which her genes are going to have the effect of making her, let's say, a division one athlete when she gets to college. A second aspect of how genes and environment are kind of indistinguishable is that the environment we encounter, your parents, of course, your siblings, your peers at school, your coworkers, they all matter to how you turn out or how you behave or your health, but they're partly made up of the genes inside their bodies. We can show that, for example, if you marry somebody with high polygenic index for depression, that affects your likelihood of becoming depressed. In fact, the effect of your spouse's genes

on depression are a third almost as big as your own genes inside your body in terms of influencing your likelihood of depression. The genes of your classmates in school affect your likelihood of smoking almost as much as your own genes do. I call that the social genomer. The environment is really genetics one degree removed to some extent. And the third way is that when there are massive environmental shifts, genes can matter more or less. So in the early 20th century, calories were scarcer,

physical labor was more routine for most of us, and obesity was pretty rare and genes didn't predict who was heavier or thinner. But fast forward to today in our like calorie abundant world and our more sedentary lifestyle and the population is heavier, the distribution of weights is wider and it turns out that genetics predict where you fall in that distribution much more than they did before. So, those are the three ways genes create the environment they want or need so to speak. The environment is in part genetics, one degree removed is the genes of the other people around you affecting you.

And third, the environmental landscape influences how much genes matter or don't matter. How does this apply to intelligence or personality traits that are often considered intrinsic. For something like intelligence, how that works is that the genes give your brain a machine learning algorithm, like an AI algorithm. It says go out and get data, train this algorithm on data and it'll refine this algorithm. And we see that happen in that the genetic influence on IQ is very low in early childhood. It's like about 20% and it rises to about

80% by age 35. So the genetics blossom through more exposure to the environment, more feedback, interaction, asking questions in school, choosing harder classes, reading more, getting more information, training your mind. All the genes give you is a, like I said, an algorithm for interacting with the world. And that second step of the interacting with the environment is really crucial for IQ to become genetic. So ironically, as you get older and more experienced in the environment, the random aspects of the environment matter less and your genes selecting your environmental inputs and interactions matter more and IQ ends up being about as heritable and that meaning as genetically

determined as height, but it's a very different pathway to get to that 80 or so percent. Your genetics alone just inside your brain or inside your skin aren't going to be determinative. They need to interact with the environment to come to fruition. So, parents might unknowingly treat their children differently based on their kids' genetic traits. Can you give some examples of how that plays out and what impact it has? So imagine two sisters that one is born with perfect pitch, the other is not. And that's a genetic, highly genetically influenced trait.

The parents are just going to invest more in the kid with perfect pitch in terms of musical training. The kid without perfect pitch is not going to want even to go to a musical summer camp or go to conservatory because it's not fun to do something you stink at. It is fun to get positive reinforcement. And that's happening within the family. It's going to happen in the wider world. That would be a rational example of gene environment interplay. Like if you have the innate talent for something, you get more investment. But it might be that there's a third sister and she has perfect pitch too, but she's not as attractive as

the first sister who has perfect pitch and, but she's not as attractive as the first sister who has perfect pitch. And she gets less attention or less investment from her parents. They even think that she doesn't quite sound as good. And that's unconscious bias based on her looks, which are genetically determined as well. Another example of how this can be kind of pernicious sometimes is a study we did looked at African-American siblings and we looked at whether or not one was born with lighter or darker skin than the other. And

we found that the sibling born with darker skin is more likely to get hypertension than the one with lighter skin, presumably because they get more stress and discrimination, they're treated differently based on their skin tone. And genetic effects can work in all sorts of ways. Skin tone is controlled by your genes, eye color is controlled by your genes, and people react to you differently based on those physical characteristics. So it doesn't have to be necessarily a sprinter getting good training because of their talent. It can be something like that as well, unfortunately. As the parent of school-aged children,

how has your own perspective on raising children changed now that you understand the interplay between genes and the environment so deeply? I have two older children that are adults now, and I raised them before I really knew the power of genes. And I thought that I had a lot more power over how they're gonna turn out than I did. I'd recognize that as a parent, you're not in control.

You're being parented by your kids' genes, at least as much as you're parenting them. But then I had a third kid 20 years later, and I was in the thrall of genetics at that point. We were doing IVF to conceive him. And I thought of, wow, we could optimize it, you know, among the embryos, we could choose the one with the highest polygenic scores for certain traits or the lowest for other traits. What about that? We turned out

not to do that. And I'm of course glad that we didn't because I'm really, I love the kid we got by chance. And I also now realize that using that kind of simple genetic prediction idea ignores the fact that we've been talking about genes and environment are braided together. And I can control the environment of my child a little bit in response to their genes. So to give an example of that, if I found out that my son had a musical talent, which would be quite a shock to me because I have zero, I would expose him to instruments and to lessons from a young age and see if they took and could start that forward feeding snowball. If he had tested to be off the charts for the PGI for opioid addiction, I would try

to make sure that if he breaks his arm or if he has a surgery, he's not prescribed opioids as a painkiller after that, or that he's aware of that as he gets older and makes his own medical decisions. If there's one thing that you'd want people to understand from your research, what would it be and how can we use this knowledge to make better choices in each of our own lives? Dr. Ben and has become more and more predictive of outcomes. They're still in their infancy, they're noisy, they predict poorly, but they're getting better every year. And they're gonna radically transform society. We have a lot of talk about the promise and perils of AI.

We've had a lot of public discussion about CRISPR gene editing as a potential revolutionary technology. But I think the polygenic index is just as revolutionary as those other two and is here already. Genetic prediction is going to soon be taken up by insurance companies. Like if you want to apply for a life insurance policy or a long term care insurance or even car insurance, they might soon ask for a swab of your cheek, a saliva sample or a blood spot and analyze your DNA to make better pricing of your premiums.

Are people okay with that? IVF clinics, some IVF clinics already offer what I had thought I wanted seven or eight years ago, the polygenic screening for embryos to select which one you want to implant. So people are going to be optimizing babies long before there's going to be genetically modified babies running around preschools. Sperm and Ova banks might use this genetic prediction algorithms to

screen donors or to offer clients different samples based on their price point and how good a genetic sample they want. That's just a few of the examples of how this area of genetic prediction is going to sweep across society. And we have had no discussion about it. I think we should keep in mind it's not a blueprint, it's an algorithm and it depends on the environment and the environmental landscape. And we need to have a nuanced discussion of how should a prediction should be, and it should not be used given that insight. So genetics and the environment, how important are they both?

Is it 60-40 genetics versus the environment? Is it 90-10? Where do you come out? There was a recent review article that looked at 50 years of twin studies, which were the bread and butter of trying to separate out genes and environment. And they came to the conclusion across thousands of outcomes that the average was 49% genetic and 51% environmental. And again, you might just look at that and say it's a tie, but I think that kind of misses the point. Actually, that's a false dichotomy, the nature versus nurture and it's nature plus nurture

that really is how things operate. So even if that 49%, a lot of that goes through how those genes extract nurture in the world. Dalton, what are the three takeaways? Number one, there's a genomic prediction revolution happening as we speak, and we should have a public debate about how we want to use genetic prediction. In schools, in insurance companies, in fertility clinics and so forth, is an important debate that's missing. Number two, we shouldn't think of genes as a blueprint. We should think of them as a

greedy AI algorithm. They need the environment to come to fruition and the effect of the genes doesn't stop at our skin. And three, we really can't separate out nature and nurture. We should just retire that 150 year old debate, nature versus nurture. How nurture matters depends on our genes and how our genes matter depends on our environment. So interesting. Thank you, Dalton. Thanks, Lyn.

If you're enjoying the podcast, and I really hope you are, please review us on Apple Podcasts or Spotify or wherever you get your podcasts. It really helps get the word out. If you're interested, you can also sign up for the Three Takeaways newsletter at ThreeTakeAways.com, where you can also listen to previous episodes. You can also follow us on LinkedIn, X, Instagram, and Facebook. I'm Lynne Toman and this is 3 Takeaways. Thanks for listening.