The Shiny–and Potentially Dangerous—New Tool for Predicting Human Behavior

Studies of twins have played an important role in determining that genetic differences play a role in the development of differences in behavior.
[Editor's Note: This essay is in response to our current Big Question, which we posed to experts with different perspectives: "How should DNA tests for intelligence be used, if at all, by parents and educators?"]
Imagine a world in which pregnant women could go to the doctor and obtain a simple inexpensive genetic test of their unborn child that would allow them to predict how tall he or she would eventually be. The test might also tell them the child's risk for high blood pressure or heart disease.
Can we use DNA not to understand, but to predict who is going to be intelligent or extraverted or mentally ill?
Even more remarkable -- and more dangerous -- the test might predict how intelligent the child would be, or how far he or she could be expected to go in school. Or heading further out, it might predict whether he or she will be an alcoholic or a teetotaler, or straight or gay, or… you get the idea. Is this really possible? If it is, would it be a good idea? Answering these questions requires some background in a scientific field called behavior genetics.
Differences in human behavior -- intelligence, personality, mental illness, pretty much everything -- are related to genetic differences among people. Scientists have known this for 150 years, ever since Darwin's half-cousin Francis Galton first applied Shakespeare's phrase, "Nature and Nurture" to the scientific investigation of human differences. We knew about the heritability of behavior before Mendel's laws of genetics had been re-discovered at the end of the last century, and long before the structure of DNA was discovered in the 1950s. How could discoveries about genetics be made before a science of genetics even existed?
The answer is that scientists developed clever research designs that allowed them to make inferences about genetics in the absence of biological knowledge about DNA. The best-known is the twin study: identical twins are essentially clones, sharing 100 percent of their DNA, while fraternal twins are essentially siblings, sharing half. To the extent that identical twins are more similar for some trait than fraternal twins, one can infer that heredity is playing a role. Adoption studies are even more straightforward. Is the personality of an adopted child more like the biological parents she has never seen, or the adoptive parents who raised her?
Twin and adoption studies played an important role in establishing beyond any reasonable doubt that genetic differences play a role in the development of differences in behavior, but they told us very little about how the genetics of behavior actually worked. When the human genome was finally sequenced in the early 2000s, and it became easier and cheaper to obtain actual DNA from large samples of people, scientists anticipated that we would soon find the genes for intelligence, mental illness, and all the other behaviors that were known to be "heritable" in a general way.
But to everyone's amazement, the genes weren't there. It turned out that there are thousands of genes related to any given behavior, so many that they can't be counted, and each one of them has such a tiny effect that it can't be tied to meaningful biological processes. The whole scientific enterprise of understanding the genetics of behavior seemed ready to collapse, until it was rescued -- sort of -- by a new method called polygenic scores, PGS for short. Polygenic scores abandon the old task of finding the genes for complex human behavior, replacing it with black-box prediction: can we use DNA not to understand, but to predict who is going to be intelligent or extraverted or mentally ill?
Prediction from observing parents works better, and is far easier and cheaper, than anything we can do with DNA.
PGS are the shiny new toy of human genetics. From a technological standpoint they are truly amazing, and they are useful for some scientific applications that don't involve making decisions about individual people. We can obtain DNA from thousands of people, estimate the tiny relationships between individual bits of DNA and any outcome we want — height or weight or cardiac disease or IQ — and then add all those tiny effects together into a single bell-shaped score that can predict the outcome of interest. In theory, we could do this from the moment of conception.
Polygenic scores for height already work pretty well. Physicians are debating whether the PGS for heart disease are robust enough to be used in the clinic. For some behavioral traits-- the most data exist for educational attainment -- they work well enough to be scientifically interesting, if not practically useful. For traits like personality or sexual orientation, the prediction is statistically significant but nowhere close to practically meaningful. No one knows how much better any of these predictions are likely to get.
Without a doubt, PGS are an amazing feat of genomic technology, but the task they accomplish is something scientists have been able to do for a long time, and in fact it is something that our grandparents could have done pretty well. PGS are basically a new way to predict a trait in an individual by using the same trait in the individual's parents — a way of observing that the acorn doesn't fall far from the tree.
The children of tall people tend to be tall. Children of excellent athletes are athletic; children of smart people are smart; children of people with heart disease are at risk, themselves. Not every time, of course, but that is how imperfect prediction works: children of tall parents vary in their height like anyone else, but on average they are taller than the rest of us. Prediction from observing parents works better, and is far easier and cheaper, than anything we can do with DNA.
But wait a minute. Prediction from parents isn't strictly genetic. Smart parents not only pass on their genes to their kids, but they also raise them. Smart families are privileged in thousands of ways — they make more money and can send their kids to better schools. The same is true for PGS.
The ability of a genetic score to predict educational attainment depends not only on examining the relationship between certain genes and how far people go in school, but also on every personal and social characteristic that helps or hinders education: wealth, status, discrimination, you name it. The bottom line is that for any kind of prediction of human behavior, separation of genetic from environmental prediction is very difficult; ultimately it isn't possible.
Still, experts are already discussing how to use PGS to make predictions for children, and even for embryos.
This is a reminder that we really have no idea why either parents or PGS predict as well or as poorly as they do. It is easy to imagine that a PGS for educational attainment works because it is summarizing genes that code for efficient neurological development, bigger brains, and swifter problem solving, but we really don't know that. PGS could work because they are associated with being rich, or being motivated, or having light skin. It's the same for predicting from parents. We just don't know.
Still, experts are already discussing how to use PGS to make predictions for children, and even for embryos.
For example, maybe couples could fertilize multiple embryos in vitro, test their DNA, and select the one with the "best" PGS on some trait. This would be a bad idea for a lot of reasons. Such scores aren't effective enough to be very useful to parents, and to the extent they are effective, it is very difficult to know what other traits might be selected for when parents try to prioritize intelligence or attractiveness. People will no doubt try it anyway, and as a matter of reproductive freedom I can't think of any way to stop them. Fortunately, the practice probably won't have any great impact one way or another.
That brings us to the ethics of PGS, particularly in the schools. Imagine that when a child enrolls in a public school, an IQ test is given to her biological parents. Children with low-IQ parents are statistically more likely to have low IQs themselves, so they could be assigned to less demanding classrooms or vocational programs. Hopefully we agree that this would be unethical, but let's think through why.
First of all, it would be unethical because we don't know why the parents have low IQs, or why their IQs predict their children's. The parents could be from a marginalized ethnic group, recognizable by their skin color and passed on genetically to their children, so discriminating based on a parent's IQ would just be a proxy for discriminating based on skin color. Such a system would be no more than a social scientific gloss on an old-fashioned program for perpetuating economic and cognitive privilege via the educational system.
People deserve to be judged on the basis of their own behavior, not a genetic test.
Assigning children to classrooms based on genetic testing would be no different, although it would have the slight ethical advantage of being less effective. The PGS for educational attainment could reflect brain-efficiency, but it could also depend on skin color, or economic advantage, or personality, or literally anything that is related in any way to economic success. Privileging kids with higher genetic scores would be no different than privileging children with smart parents. If schools really believe that a psychological trait like IQ is important for school placement, the sensible thing is to administer the children an actual IQ test – not a genetic test.
IQ testing has its own issues, of course, but at least it involves making decisions about individuals based on their own observable characteristics, rather than on characteristics of their parents or their genome. If decisions must be made, if resources must be apportioned, people deserve to be judged on the basis of their own behavior, the content of their character. Since it can't be denied that people differ in all sorts of relevant ways, this is what it means for all people to be created equal.
[Editor's Note: Read another perspective in the series here.]
A startup aims to make medicines in space
A company is looking to improve medicines by making them in the nearly weightless environment of 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.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
Genes that protect health with Dr. Nir Barzilai
Centenarians essentially won the genetic lottery, says Nir Barzilai of Albert Einstein College of Medicine. He is studying their genes to see how the rest of us can benefit from understanding how they work.
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.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
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.