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In 'The Genetic Lottery,' Kathryn Paige Harden Considers A New Moral Framework For Genetics

In this Oct. 9, 2018, photo, Zhou Xiaoqin installs a fine glass pipette into a sperm injection microscope in preparation for injecting embryos with Cas9 protein and PCSK9 sgRNA at a lab in Shenzhen in southern China's Guandong province. China's government on Thursday, Nov. 29, 2018, ordered a halt to work by a medical team that claimed to have helped make the world's first gene-edited babies. (Mark Schiefelbein/AP)
In this Oct. 9, 2018, photo, Zhou Xiaoqin installs a fine glass pipette into a sperm injection microscope in preparation for injecting embryos with Cas9 protein and PCSK9 sgRNA at a lab in Shenzhen in southern China's Guandong province. China's government on Thursday, Nov. 29, 2018, ordered a halt to work by a medical team that claimed to have helped make the world's first gene-edited babies. (Mark Schiefelbein/AP)

A polygenic score. Have you heard of it? Researcher Kathryn Paige Harden says it’s a set of DNA variants added up into a single number.

“It can predict which math class you get tracked into high school, your likelihood of graduating from college,” she says. “And it predicts those things even above and beyond you’re controlling — something like family income.”

Journalist Carey Goldberg says it’s not science fiction.

“Now what’s happening is that some companies are offering polygenic risk screening for embryo selection.”

Which is why Harden says aiming for equality while insisting genes don’t matter is “building a house on sand.” She says she wants society to embrace what she calls anti-eugenics.

“By anti-eugenics, I mean — how can we observe the fact that there are genetic differences between people?” Harden says. “And then how can we use the knowledge of genetics to identify inequalities of opportunity?”

Today, On Point: A new moral framework for how we talk about genetics.

Guests

Kathryn Paige Harden, professor in the department of psychology at the University of Texas, Austin. She leads the Developmental Behavior Genetics lab and co-directs the Texas Twin Project. Author of “The Genetic Lottery.” (@kph3k)

Carey Goldberg, Boston Bureau Chief at Bloomberg. (@goldbergcarey)

Also Featured

Eriona Hysolli, head of biological sciences at Colossal.

Sekar Kathiresan, CEO and founder of Verve Therapeutics.

Dorothy Roberts, professor of law, sociology and Africana studies at the University of Pennsylvania.

Interview Highlights

How much do genetic differences matter when it comes to understanding social differences?

Kathryn Paige Harden: “The question of how much it matters always depends on what exactly you’re looking at. In my work, I focus a lot on how children do in school and the basic cognitive abilities and personality traits that shape how they move through the educational system. And what we find pretty consistently across a number of different methods is that genetic differences between children are as important as environmental differences between them. So it’s not ever just genes or just environment. Always both of these things are contributing to the differences we see in how children are faring in school, or their likelihood of struggling with sort of mental or behavioral health problems such as depression or delinquency.”

What is a polygenic score?

Kathryn Paige Harden: “A polygenic score comes from this new ability to measure the genomes of people directly. As you said in your intro, our genetic technology has improved by leaps and bounds. So now, in my lab, for instance, we have children spit into a tube. And for less than $60 per person, we can measure hundreds of thousands or even millions of DNA differences between them. We’re mostly focusing on differences between them in sort of single DNA letters, which are called snips.

“So what we’re doing in these large-scale studies, which are called genome-wide association studies, is we’re correlating those measured DNA differences between people. And differences in social and behavioral outcomes. So this is something that is really familiar to people, I think, in the medical world. Looking for genetics that are related, for instance, to obesity or hypertension or diabetes. What we’re doing is we’re relating these DNA differences to social and behavioral traits.

“So things like risk of ADHD, or how far children go in school. What we can do with that information after we complete a genome-wide association study is take the correlations between all the DNA variants that we’ve estimated and then apply that information to a new sample of people. And basically use it to add up information about their entire genome into a single number. And that number is called a polygenic index or polygenic risk score.

“What’s interesting about polygenic indices is that on the one hand, they’re really messy. They’re aggregating a ton of information across the whole genome. But at the same time, they are often as strongly correlated with the sort of outcomes that psychologists study as variables that we’re kind of used to looking at in the social sciences. So the classic example is that polygenic index is strongly correlated with your likelihood of graduating from college, as family income is associated with your likelihood of graduating from college.”

What are one or two of the studies that you think point to the importance of thinking about genetics when it comes to social outcomes?

Kathryn Paige Harden: “There’s two studies that really pop out in my mind as being very compelling examples of why we need to have a conversation about this and our moral framework for genetic research. The first is one I briefly referenced already, it was a 2018 study in Nature Genetics. They were studying 1.1 million people and they found that a polygenic index from their genome-wide association study of educational attainment was as strongly related to the likelihood of graduating from college as family income.

“So if you’re looking at students in the bottom 25% of the polygenic index, they were four times less likely to graduate from college than students in the highest 25% of the polygenic index. More recently, my colleagues and I, we just published a paper in Nature Neuroscience where we’re looking at this not with education, but with problems related to addictive behavior and behavior problems. So ADHD, problematic alcohol use, illicit drug use. And we see similar patterns in that. For instance, a polygenic index can predict your likelihood of developing an opioid addiction problem, of ever being fired from work, of contact with the criminal justice system.

“These are life outcomes that we care about. That we have policy conversations about, that we want to close inequalities about. And we have this information that we’re getting just from the genome that isn’t predicting perfectly. This isn’t a fortune teller, but it is capturing some of the differences. And so I think when we’re thinking about we can connect genetics to something like education or opiate addiction, we really have to think about how this information is going to be conceptualized and used moving forward.”

How predictive is is the value here?

Kathryn Paige Harden: “Let me give you a concrete example. Because I think it’s easier to talk about when we’re talking about a specific outcome. So I think people already recognize that there’s genetic influences on your likelihood of developing an alcohol abuse problem and that genes are relevant for your likelihood of becoming addicted to a substance. And part of that genetic influence is operating through how does your body metabolize alcohol or how does your brain respond to the rewarding effects of alcohol? But we also know from genetic research that part of the genetic influences operating through personality traits that get you into certain types of environments.

“Do I like going to parties? Do I like hanging out with friends as a teenager who are going to be introducing me to substances? And it turns out that we can’t — and I don’t think we should — be manipulating, for instance, teenager’s genes. But we can put their families in family therapy where we teach their parents to monitor their curfew and their friend groups better. And when we do that, this is one of my favorite studies. We see that that polygenic risk score that predicts your likelihood of developing an alcohol use problem stops being predictive of alcohol use among teenagers whose families have been in this family therapy.”

On a new moral framework for genetic testing

Kathryn Paige Harden: “Maybe the best way to think about it is to again come back to this question of what world would you want to live in? What society would you want to live in if you had no idea what the outcome of the genetic lottery was going to be for you or your kids. And I think if we take that perspective into thinking about how we design education policy, how we design health care policy. As a mother, if I’m looking at what makes a good school, I’m not looking for a school that’s going to treat all of my kids the same. I’m looking for a school that’s going to equalize their ability to profit from that school, to learn, to accommodate their uniqueness.

“Ultimately, I think that lies very close to the heart of what makes a social structure or policy good. So I want people, when they think about genetic difference, to think about if genes really do matter. And I think they do. What kind of world do we want to live in, given that every time we conceive a child, we have so little control over what’s going to happen there. How do we accommodate that role of chance and luck for everyone to participate as equals.”

How do you prevent genetic absolutists from co-opting your moral framework?

Kathryn Paige Harden: “There’s no way that we can prevent bad actors. But in order to say what we want to do, we need to have an articulation of what is the goal, what are we moving towards? And even if that goal … is idealistic, it gives us a framework to evaluate, Is this policy closer to an antigenic framework, or is this policy something that’s going to entrench the inequalities of birth that are already so pernicious in our society? I think we need to know where we’re going in order to know whether we’re making progress getting there.”

Book Excerpt

Excerpted from THE GENETIC LOTTERY: Why DNA Matters for Social Equality by Kathryn Paige Harden. Copyright © 2021 by Kathryn Paige Harden. Reprinted by permission of Princeton University Press.

From The Reading List

Bloomberg: “Picking Embryos With Best Health Odds Sparks New DNA Debate” — “Rafal Smigrodzki won’t make a big deal of it, but someday, when his toddler daughter Aurea is old enough to understand, he plans to explain that she likely made medical history at the moment of her birth.”

This article was originally published on WBUR.org.

Copyright 2021 NPR. To see more, visit https://www.npr.org.