Genetic Test Scores Predicting Intelligence Are Not the New Eugenics
"A world where people are slotted according to their inborn ability – well, that is Gattaca. That is eugenics."
This was the assessment of Dr. Catherine Bliss, a sociologist who wrote a new book on social science genetics, when asked by MIT Technology Review about polygenic scores that can predict a person's intelligence or performance in school. Like a credit score, a polygenic score is statistical tool that combines a lot of information about a person's genome into a single number. Fears about using polygenic scores for genetic discrimination are understandable, given this country's ugly history of using the science of heredity to justify atrocities like forcible sterilization. But polygenic scores are not the new eugenics. And, rushing to discuss polygenic scores in dystopian terms only contributes to widespread public misunderstanding about genetics.
Can we start genotyping toddlers to identify the budding geniuses among them? The short answer is no.
Let's begin with some background on how polygenic scores are developed. In a genome wide-association study, researchers conduct millions of statistical tests to identify small differences in people's DNA sequence that are correlated with differences in a target outcome (beyond what can attributed to chance or ancestry differences). Successful studies of this sort require enormous sample sizes, but companies like 23andMe are now contributing genetic data from their consumers to research studies, and national biorepositories like U.K. Biobank have put genetic information from hundreds of thousands of people online. When applied to studying blood lipids or myopia, this kind of study strikes people as a straightforward and uncontroversial scientific tool. But it can also be conducted for cognitive and behavioral outcomes, like how many years of school a person has completed. When researchers have finished a genome-wide association study, they are left with a dataset with millions of rows (one for each genetic variant analyzed) and one column with the correlations between each variant and the outcome being studied.
The trick to polygenic scoring is to use these results and apply them to people who weren't participants in the original study. Measure the genes of a new person, weight each one of her millions of genetic variants by its correlation with educational attainment from a genome-wide association study, and then simply add everything up into a single number. Voila! -- you've created a polygenic score for educational attainment. On its face, the idea of "scoring" a person's genotype does immediately suggest Gattaca-type applications. Can we now start screening embryos for their "inborn ability," as Bliss called it? Can we start genotyping toddlers to identify the budding geniuses among them?
The short answer is no. Here are four reasons why dystopian projections about polygenic scores are out of touch with the current science:
The phrase "DNA tests for IQ" makes for an attention-grabbing headline, but it's scientifically meaningless.
First, a polygenic score currently predicts the life outcomes of an individual child with a great deal of uncertainty. The amount of uncertainty around polygenic predictions will decrease in the future, as genetic discovery samples get bigger and genetic studies include more of the variation in the genome, including rare variants that are particular to a few families. But for now, knowing a child's polygenic score predicts his ultimate educational attainment about as well as knowing his family's income, and slightly worse than knowing how far his mother went in school. These pieces of information are also readily available about children before they are born, but no one is writing breathless think-pieces about the dystopian outcomes that will result from knowing whether a pregnant woman graduated from college.
Second, using polygenic scoring for embryo selection requires parents to create embryos using reproductive technology, rather than conceiving them by having sex. The prediction that many women will endure medically-unnecessary IVF, in order to select the embryo with the highest polygenic score, glosses over the invasiveness, indignity, pain, and heartbreak that these hormonal and surgical procedures can entail.
Third, and counterintuitively, a polygenic score might be using DNA to measure aspects of the child's environment. Remember, a child inherits her DNA from her parents, who typically also shape the environment she grows up in. And, children's environments respond to their unique personalities and temperaments. One Icelandic study found that parents' polygenic scores predicted their children's educational attainment, even if the score was constructed using only the half of the parental genome that the child didn't inherit. For example, imagine mom has genetic variant X that makes her more likely to smoke during her pregnancy. Prenatal exposure to nicotine, in turn, affects the child's neurodevelopment, leading to behavior problems in school. The school responds to his behavioral problems with suspension, causing him to miss out on instructional content. A genome-wide association study will collapse this long and winding causal path into a simple correlation -- "genetic variant X is correlated with academic achievement." But, a child's polygenic score, which includes variant X, will partly reflect his likelihood of being exposed to adverse prenatal and school environments.
Finally, the phrase "DNA tests for IQ" makes for an attention-grabbing headline, but it's scientifically meaningless. As I've written previously, it makes sense to talk about a bacterial test for strep throat, because strep throat is a medical condition defined as having streptococcal bacteria growing in the back of your throat. If your strep test is positive, you have strep throat, no matter how serious your symptoms are. But a polygenic score is not a test "for" IQ, because intelligence is not defined at the level of someone's DNA. It doesn't matter how high your polygenic score is, if you can't reason abstractly or learn from experience. Equating your intelligence, a cognitive capacity that is tested behaviorally, with your polygenic score, a number that is a weighted sum of genetic variants discovered to be statistically associated with educational attainment in a hypothesis-free data mining exercise, is misleading about what intelligence is and is not.
The task for many scientists like me, who are interested in understanding why some children do better in school than other children, is to disentangle correlations from causation.
So, if we're not going to build a Gattaca-style genetic hierarchy, what are polygenic scores good for? They are not useless. In fact, they give scientists a valuable new tool for studying how to improve children's lives. The task for many scientists like me, who are interested in understanding why some children do better in school than other children, is to disentangle correlations from causation. The best way to do that is to run an experiment where children are randomized to environments, but often a true experiment is unethical or impractical. You can't randomize children to be born to a teenage mother or to go to school with inexperienced teachers. By statistically controlling for some of the relevant genetic differences between people using a polygenic score, scientists are better able to identify potential environmental causes of differences in children's life outcomes. As we have seen with other methods from genetics, like twin studies, understanding genes illuminates the environment.
Research that examines genetics in relation to social inequality, such as differences in higher education outcomes, will obviously remind people of the horrors of the eugenics movement. Wariness regarding how genetic science will be applied is certainly warranted. But, polygenic scores are not pure measures of "inborn ability," and genome-wide association studies of human intelligence and educational attainment are not inevitably ushering in a new eugenics age.
A startup aims to make medicines in space
Story by Big Think
On June 12, a SpaceX Falcon 9 rocket deployed 72 small satellites for customers — including the world’s first space factory.
The challenge: In 2019, pharma giant Merck revealed that an experiment on the International Space Station had shown how to make its blockbuster cancer drug Keytruda more stable. That meant it could now be administered via a shot rather than through an IV infusion.
The key to the discovery was the fact that particles behave differently when freed from the force of gravity — seeing how its drug crystalized in microgravity helped Merck figure out how to tweak its manufacturing process on Earth to produce the more stable version.
Microgravity research could potentially lead to many more discoveries like this one, or even the development of brand-new drugs, but ISS astronauts only have so much time for commercial experiments.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth.”-- Will Bruey.
The only options for accessing microgravity (or free fall) outside of orbit, meanwhile, are parabolic airplane flights and drop towers, and those are only useful for experiments that require less than a minute in microgravity — Merck’s ISS experiment took 18 days.
The idea: In 2021, California startup Varda Space Industries announced its intention to build the world’s first space factory, to manufacture not only pharmaceuticals but other products that could benefit from being made in microgravity, such as semiconductors and fiber optic cables.
This factory would consist of a commercial satellite platform attached to two Varda-made modules. One module would contain equipment capable of autonomously manufacturing a product. The other would be a reentry capsule to bring the finished goods back to Earth.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth,” said CEO Will Bruey, who’d previously developed and flown spacecraft for SpaceX.
“We have a team stacked with aerospace talent in the prime of their careers, focused on getting working hardware to orbit as quickly as possible,” he continued.
“[Pharmaceuticals] are the most valuable chemicals per unit mass. And they also have a large market on Earth.” -- Will Bruey, CEO of Varda Space.
What’s new? At the time, Varda said it planned to launch its first space factory in 2023, and, in what feels like a first for a space startup, it has actually hit that ambitious launch schedule.
“We have ACQUISITION OF SIGNAL,” the startup tweeted soon after the Falcon 9 launch on June 12. “The world’s first space factory’s solar panels have found the sun and it’s beginning to de-tumble.”
During the satellite’s first week in space, Varda will focus on testing its systems to make sure everything works as hoped. The second week will be dedicated to heating and cooling the old HIV-AIDS drug ritonavir repeatedly to study how its particles crystalize in microgravity.
After about a month in space, Varda will attempt to bring its first space factory back to Earth, sending it through the atmosphere at hypersonic speeds and then using a parachute system to safely land at the Department of Defense’s Utah Test and Training Range.
Looking ahead: Ultimately, Varda’s space factories could end up serving dual purposes as manufacturing facilities and hypersonic testbeds — the Air Force has already awarded the startup a contract to use its next reentry capsule to test hardware for hypersonic missiles.
But as for manufacturing other types of goods, Varda plans to stick with drugs for now.
“[Pharmaceuticals] are the most valuable chemicals per unit mass,” Bruey told CNN. “And they also have a large market on Earth.”
“You’re not going to see Varda do anything other than pharmaceuticals for the next minimum of six, seven years,” added Delian Asparouhov, Varda’s co-founder and president.
Genes that protect health with Dr. Nir Barzilai
In today’s podcast episode, I talk with Nir Barzilai, a geroscientist, which means he studies the biology of aging. Barzilai directs the Institute for Aging Research at the Albert Einstein College of Medicine.
My first question for Dr. Barzilai was: why do we age? And is there anything to be done about it? His answers were encouraging. We can’t live forever, but we have some control over the process, as he argues in his book, Age Later.
Dr. Barzilai told me that centenarians differ from the rest of us because they have unique gene mutations that help them stay healthy longer. For most of us, the words “gene mutations” spell trouble - we associate these words with cancer or neurodegenerative diseases, but apparently not all mutations are bad.
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Centenarians may have essentially won the genetic lottery, but that doesn’t mean the rest of us are predestined to have a specific lifespan and health span, or the amount of time spent living productively and enjoyably. “Aging is a mother of all diseases,” Dr. Barzilai told me. And as a disease, it can be targeted by therapeutics. Dr. Barzilai’s team is already running clinical trials on such therapeutics — and the results are promising.
More about Dr. Barzilai: He is scientific director of AFAR, American Federation for Aging Research. As part of his work, Dr. Barzilai studies families of centenarians and their genetics to learn how the rest of us can learn and benefit from their super-aging. He also organizing a clinical trial to test a specific drug that may slow aging.
Show Links
Age Later: Health Span, Life Span, and the New Science of Longevity https://www.amazon.com/Age-Later-Healthiest-Sharpest-Centenarians/dp/1250230853
American Federation for Aging Research https://www.afar.org
https://www.afar.org/nir-barzilai
https://www.einsteinmed.edu/faculty/484/nir-barzilai/
Metformin as a Tool to Target Aging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943638/
Benefits of Metformin in Attenuating the Hallmarks of Aging https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347426/
The Longevity Genes Project https://www.einsteinmed.edu/centers/aging/longevity-genes-project/
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.