The Shiny–and Potentially Dangerous—New Tool for Predicting Human 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.]
Opioid prescription policies may hurt those in chronic pain
Tinu Abayomi-Paul works as a writer and activist, plus one unwanted job: Trying to fill her opioid prescription. She says that some pharmacists laugh and tell her that no one needs the amount of pain medication that she is seeking. Another pharmacist near her home in Venus, Tex., refused to fill more than seven days of a 30-day prescription.
To get a new prescription—partially filled opioid prescriptions can’t be dispensed later—Abayomi-Paul needed to return to her doctor’s office. But without her medication, she was having too much pain to travel there, much less return to the pharmacy. She rationed out the pills over several weeks, an agonizing compromise that left her unable to work, interact with her children, sleep restfully, or leave the house. “Don’t I deserve to do more than survive?” she says.
Abayomi-Paul’s pain results from a degenerative spine disorder, chronic lymphocytic leukemia, and more than a dozen other diagnoses and disabilities. She is part of a growing group of people with chronic pain who have been negatively impacted by the fallout from efforts to prevent opioid overdose deaths.
Guidelines for dispensing these pills are complicated because many opioids, like codeine, oxycodone, and morphine, are prescribed legally for pain. Yet, deaths from opioids have increased rapidly since 1999 and become a national emergency. Many of them, such as heroin, are used illegally. The CDC identified three surges in opioid use: an increase in opioid prescriptions in the ‘90s, a surge of heroin around 2010, and an influx of fentanyl and other powerful synthetic opioids in 2013.
As overdose deaths grew, so did public calls to address them, prompting the CDC to change its prescription guidelines in 2016. The new guidelines suggested limiting medication for acute pain to a seven-day supply, capping daily doses of morphine, and other restrictions. Some statistics suggest that these policies have worked; from 2016 to 2019, prescriptions for opiates fell 44 percent. Physicians also started progressively lowering opioid doses for patients, a practice called tapering. A study tracking nearly 100,000 Medicare subscribers on opioids found that about 13 percent of patients were tapering in 2012, and that number increased to about 23 percent by 2017.
But some physicians may be too aggressive with this tapering strategy. About one in four people had doses reduced by more than 10 percent per week, a rate faster than the CDC recommends. The approach left people like Abayomi-Paul without the medication they needed. Every year, Abayomi-Paul says, her prescriptions are harder to fill. David Brushwood, a pharmacy professor who specializes in policy and outcomes at the University of Florida in Gainesville, says opioid dosing isn’t one-size-fits-all. “Patients need to be taken care of individually, not based on what some government agency says they need,” he says.
‘This is not survivable’
Health policy and disability rights attorney Erin Gilmer advocated for people with pain, using her own experience with chronic pain and a host of medical conditions as a guidepost. She launched an advocacy website, Healthcare as a Human Right, and shared her struggles on Twitter: “This pain is more than anything I've endured before and I've already been through too much. Yet because it's not simply identified no one believes it's as bad as it is. This is not survivable.”
When her pain dramatically worsened midway through 2021, Gilmer’s posts grew ominous: “I keep thinking it can't possibly get worse but somehow every day is worse than the last.”
The CDC revised its guidelines in 2022 after criticisms that people with chronic pain were being undertreated, enduring dangerous withdrawal symptoms, and suffering psychological distress. (Long-term opioid use can cause physical dependency, an adaptive reaction that is different than the compulsive misuse associated with a substance use disorder.) It was too late for Gilmer. On July 7, 2021, the 38-year-old died by suicide.
Last August, an Ohio district court ruling set forth a new requirement for Walgreens, Walmart, and CVS pharmacists in two counties. These pharmacists must now document opioid prescriptions that are turned down, even for customers who have no previous purchases at that pharmacy, and they’re required to share this information with other locations in the same chain. None of the three pharmacies responded to an interview request from Leaps.org.
In a practice called red flagging, pharmacists may label a prescription suspicious for a variety of reasons, such as if a pharmacist observes an unusually high dose, a long distance from the patient’s home to the pharmacy, or cash payment. Pharmacists may question patients or prescribers to resolve red flags but, regardless of the explanation, they’re free to refuse to fill a prescription.
As the risk of litigation has grown, so has finger-pointing, says Seth Whitelaw, a compliance consultant at Whitelaw Compliance Group in West Chester, PA, who advises drug, medical device, and biotech companies. Drugmakers accused in National Prescription Opioid Litigation (NPOL), a complex set of thousands of cases on opioid epidemic deaths, which includes the Ohio district case, have argued that they shouldn’t be responsible for the large supply of opiates and overdose deaths. Yet, prosecutors alleged that these pharmaceutical companies hid addiction and overdose risks when labeling opioids, while distributors and pharmacists failed to identify suspicious orders or scripts.
Patients and pharmacists fear red flags
The requirements that pharmacists document prescriptions they refuse to fill so far only apply to two counties in Ohio. But Brushwood fears they will spread because of this precedent, and because there’s no way for pharmacists to predict what new legislation is on the way. “There is no definition of a red flag, there are no lists of red flags. There is no instruction on what to do when a red flag is detected. There’s no guidance on how to document red flags. It is a standardless responsibility,” Brushwood says. This adds trepidation for pharmacists—and more hoops to jump through for patients.
“I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately,” Nicolson says.
“We now have about a dozen studies that show that actually ripping somebody off their medication increases their risk of overdose and suicide by three to five times, destabilizes their health and mental health, often requires some hospitalization or emergency care, and can cause heart attacks,” says Kate Nicolson, founder of the National Pain Advocacy Center based in Boulder, Colorado. “It can kill people.” Nicolson was in pain for decades due to a surgical injury to the nerves leading to her spinal cord before surgeries fixed the problem.
Another issue is that primary care offices may view opioid use as a reason to turn down new patients. In a 2021 study, secret shoppers called primary care clinics in nine states, identifying themselves as long-term opioid users. When callers said their opioids were discontinued because their former physician retired, as opposed to an unspecified reason, they were more likely to be offered an appointment. Even so, more than 40 percent were refused an appointment. The study authors say their findings suggest that some physicians may try to avoid treating people who use opioids.
Abayomi-Paul says red flagging has changed how she fills prescriptions. “Once I go to one place, I try to [continue] going to that same place because of the amount of records that I have and making sure my medications don’t conflict,” Abayomi-Paul says.
Nicolson moved to Colorado from Washington D.C. in 2015, before the CDC issued its 2016 guidelines. When the guidelines came out, she found the change to be shockingly abrupt. “I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately.’” Since then, she’s spoken with dozens of patients who have been red-flagged or simply haven’t been able to access pain medication.
Despite her expertise, Nicolson isn’t positive she could successfully fill an opioid prescription today even if she needed one. At this point, she’s not sure exactly what various pharmacies would view as a red flag. And she’s not confident that these red flags even work. “You can have very legitimate reasons for being 50 miles away or having to go to multiple pharmacies, given that there are drug shortages now, as well as someone refusing to fill [a prescription.] It doesn't mean that you’re necessarily ‘drug seeking.’”
While there’s no easy solution. Whitelaw says clarifying the role of pharmacists and physicians in patient access to opioids could help people get the medication they need. He is seeking policy changes that focus on the needs of people in pain more than the number of prescriptions filled. He also advocates standardizing the definition of red flags and procedures for resolving them. Still, there will never be a single policy that can be applied to all people, explains Brushwood, the University of Florida professor. “You have to make a decision about each individual prescription.”
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
When COVID-19 cases were surging in New York City in early spring, Chitra Mohan, a postdoctoral fellow at Weill Cornell, was overwhelmed with worry. But the pandemic was only part of her anxieties. Having come to the United States from India on a student visa that allowed her to work for a year after completing her degree, she had applied for a two-year extension, typically granted for those in STEM fields. But due to a clerical error—Mohan used an electronic signatureinstead of a handwritten one— her application was denied and she could no longerwork in the United States.
"I was put on unpaid leave and I lost my apartment and my health insurance—and that was in the middle of COVID!" she says.
Meanwhile her skills were very much needed in those unprecedented times. A molecular biologist studying how DNA can repair itself, Mohan was trained in reverse transcription polymerase chain reaction or RT-PCR—a lab technique that detects pathogens and is used to diagnose COVID-19. Mohan wanted to volunteer at testing centers, but because she couldn't legally work in the U.S., she wasn't allowed to help either. She moved to her cousin's house, hired a lawyer, and tried to restore her work status.
"I spent about $4,000 on lawyer fees and another $1,200 to pay for the motions I filed," she recalls. "I had to borrow money from my parents and my cousin because without my salary I just didn't have the $7,000 at hand." But the already narrow window of opportunity slammed completely shut when the Trump administration suspended issuing new visas for foreign researchers in June. All Mohan's attempts were denied. In August, she had to leave the country. "Given the recent work visa ban by the administration, all my options in the U.S. are closed," she wrote a bitter note on Twitter. "I have to uproot my entire life in NY for the past 6 years and leave." She eventually found a temporary position in Calcutta, where she can continue research.
Mohan is hardly alone in her visa saga. Many foreign scholars on H- and J-type visas and other permits that let them remain employed in America had been struggling to keep their rights to continue research, which in certain cases is crucial to battling the pandemic. Some had to leave the country, some filed every possible extension to buy time, and others are stuck in their home countries, unable to return. The already cumbersome process of applying for visas and extensions became crippled during the lockdowns. But in June, when President Trump extended and expanded immigration restrictions to cut the number of immigrant workers entering the U.S., the new limits left researchers' projects and careers in limbo—and some in jeopardy.
"We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened."
Rakesh Ramachandran, whose computational biology work contributed to one of the first coronavirus studies to map out its protein structures—is stranded in India. In early March, he had travelled there to attend a conference and visit the American consulate to stamp his H1 visa for a renewal, already granted. The pandemic shut down both the conference and the consulates, and Ramachandran hasn't been able to come back since. The consulates finally opened in September, but so far the online portal has no available appointment slots. "I'm told to keep trying," Ramachandran says.
The visa restrictions affected researchers worldwide, regardless of disciplines or countries. A Ph.D. student in neuroscience, Morgane Leroux had to do her experiments with mice at Gladstone Institutes in America and analyze the data back home at Sorbonne University in France. She had finished her first round of experiments when the lockdowns forced her to return to Paris, and she hasn't been able to come back to resume her work since. "I can't continue the experiments, which is really frustrating," she says, especially because she doesn't know what it means for her Ph.D. "I may have to entirely change my subject," she says, which she doesn't want to do—it would be a waste of time and money.
But besides wreaking havoc in scholars' personal lives and careers, the visa restrictions had—and will continue to have—tremendous deleterious effects on America's research and its global scientific competitiveness. "It's incredibly short-sighted and self-destructing to restrict the immigration of scientists into the U.S.," says Benjamin G. Neel, who directs the Laura and Isaac Perlmutter Cancer Center at New York University. "If they can't come here, they will go elsewhere," he says, causing a brain drain.
Neel in his lab with postdocs
(Courtesy of Neel)
Neel felt the outcomes of the shortsighted policies firsthand. In the past few months, his lab lost two postdoctoral researchers who had made major strides in understanding the biology of several particularly stubborn, treatment-resistant malignancies. One postdoc studied the underlying mechanisms responsible for 90 percent of pancreatic cancers and half of the colon ones. The other one devised a new system of modeling ovarian cancer in mice to test new therapeutic drug combinations for the deadliest tumor types—but had to return home to China.
"By working around the clock, she was able to get her paper accepted, but she hasn't been able to train us to use this new system, which can set us back six months," Neel says.
Her discoveries also helped the lab secure about $900,000 in grants for new research. Losing people like this is "literally killing the goose that lays the golden eggs," Neel adds. "If you want to make America poor again, this is the way to do it."
Cassidy R. Sugimoto at Indiana University Bloomington, who studies how scientific knowledge is produced and disseminated, says that scientists are the most productive when they are free to move, exchange ideas, and work at labs with the best equipment. Restricting that freedom reduces their achievement.
"Several empirical studied demonstrated the benefits to the U.S. by attracting and retaining foreign scientists. The disproportional number of our Nobel Prize winners were not only foreign-born but also foreign-educated," she says. Scientific advancement bolsters the country's economic prowess, too, so turning scholars away is bad for the economy long-term. "We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened," Sugimoto adds—because scientists will look elsewhere. "We are seeing them shifting to other countries that are more hospitable, both ideologically and in terms of health security. Many visiting scholars, postdocs, and graduate students who would otherwise come to the United States are now moving to Canada."
It's not only the Ph.D. students and postdocs who are affected. In some cases, even well-established professors who have already made their marks in the field and direct their own labs at prestigious research institutions may have to pack up and leave the country in the next few months. One scientist who directs a prominent neuroscience lab is betting on his visa renewal and a green card application, but if that's denied, the entire lab may be in jeopardy, as many grants hinge on his ability to stay employed in America.
"It's devastating to even think that it can happen," he says—after years of efforts invested. "I can't even comprehend how it would feel. It would be terrifying and really sad." (He asked to withhold his name for fear that it may adversely affect his applications.) Another scientist who originally shared her story for this article, later changed her mind and withdrew, worrying that speaking out may hurt the entire project, a high-profile COVID-19 effort. It's not how things should work in a democratic country, scientists admit, but that's the reality.
Still, some foreign scholars are speaking up. Mehmet Doğan, a physicist at University of California Berkeley who has been fighting a visa extension battle all year, says it's important to push back in an organized fashion with petitions and engage legislators. "This administration was very creative in finding subtle and not so subtle ways to make our lives more difficult," Doğan says. He adds that the newest rules, proposed by the Department of Homeland Security on September 24, could further limit the time scholars can stay, forcing them into continuous extension battles. That's why the upcoming election might be a turning point for foreign academics. "This election will decide if many of us will see the U.S. as the place to stay and work or whether we look at other countries," Doğan says, echoing the worries of Neel, Sugimoto, and others in academia.
Dogan on Zoom talking to his fellow union members of the Academic Researchers United, a union of almost 5,000 Academic Researchers.
(Credit: Ceyda Durmaz Dogan)
If this year has shown us anything, it is that viruses and pandemics know no borders as they sweep across the globe. Likewise, science can't be restrained by borders either. "Science is an international endeavor," says Neel—and right now humankind now needs unified scientific research more than ever, unhindered by immigration hurdles and visa wars. Humanity's wellbeing in America and beyond depends on it.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]
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.