genetics of IQ – WIRED

Skip Article Header. Skip to: Start of Article. Barely out of his teens, Zhao Bowen is leading a multimillion-dollar research effort to solve a genetic mystery: What makes people like him so smart? And how can we make more of them? David Hogsholt

Zhao Bowen is late for a Satanic heavy metal concert. After haggling the doorman down to half price, he pushes into a Beijing bar with a ceiling low enough to punch. He follows the shriek of guitars down a corridor and into a mosh pit lit by strobe lights. Its hot as hell and looks like it too: Men onstage made up as demons are slashing through a song about damnationthe lyrics are in Englishwhile headbangers worship at their feet. Zhao dives in.

The strobes capture midair collisions of bodies, sprays of sweat. Someones glasses fly off and are crushed underfoot. Over the faces of the onlookers spreads that distinctive look of thrill and fear that tends to presage a riot. But just then the song climaxes in a weird screamgasm and the band takes a break. The crowd responds with the ultimate compliment, chanting Niu bi! and pumping their fists. The phrase can be roughly translated as fuck yeah! but it literally means cows vagina.

Zhao blends right in with all the Chinese teenagers in this sweltering rock dungeon. He has big wide-set eyes framed by dark eyebrows and a pair of silvery geek glasses. It makes him look like a friendly cartoon character, and the effect is enhanced by full cheeks that make his head look spherical. He is neither strikingly handsome nor unattractive. Zhao is of average height, average weight.

But he is far from average. After being identified early as a science prodigy, Zhao raced through Chinas special programs for gifted students and won a spot in Renmin, one of the countrys most elite high schools. Then, to the shock of his friends and family, he decided to drop out when he was 17. Now, at 21, he oversees his own research project at BGI Shenzhenthe countrys top biotech institute and home to the worlds most powerful cluster of DNA-sequencing machineswhere he commands a multimillion-dollar research budget.

Zhaos goal is to use those machines to examine the genetic underpinnings of genius like his own. He wants nothing less than to crack the code for intelligence by studying the genomes of thousands of prodigies, not just from China but around the world. He and his collaborators, a transnational group of intelligence researchers, fully expect they will succeed in identifying a genetic basis for IQ. They also expect that within a decade their research will be used to screen embryos during in vitro fertilization, boosting the IQ of unborn children by up to 20 points. In theory, thats the difference between a kid who struggles through high school and one who sails into college.

Zhao doesnt talk about work tonight. He dives in and out of the crowd. He makes small talk with a girl, bums a cigarette off her. Tonight Zhao is a normal young adult. Tomorrow he will return to his multimillion-dollar experimentone whose success could complicate the whole idea of what it means to be normal.

Some people are smarter than others. It seems like a straightforward truth, and one that should lend itself to scientific investigation. But those who try to study intelligence, at least in the West, find themselves lost in a political minefield. To be sure, not all intelligence research is controversial: If you study cognitive development in toddlers, or the mental decline associated with Alzheimers disease, thats treated as just normal science, says Douglas Detterman, founding editor of Intelligence, a leading journal in the field. The trouble starts whenever the heritability of intelligence is discussed, or when intelligence is compared between genders, socioeconomic classes, ormost explosivelyracial groupings.

Since the 1990s, when a book called The Bell Curve (coauthored by a psychologist and a political scientist) waded into this last morass, attempts to quantify or even study intelligence have become deeply unfashionable. Dozens of popular books by nonexperts have filled the void, many claiming that IQwhich after more than a century remains the dominant metric for intelligencepredicts nothing important or that intelligence is simply too complex and subtle to be measured.

For the most part, an IQ testthe most common of which today is called the Wechsler Adult Intelligence Scaleis a series of brainteasers. You fit abstract shapes together, translate codes using a key, sort numbers or letters into ascending order in your mind. Its a weirdly playful exercise, the sort of test you would expect to have no bearing on anything else. But studies make it clear that IQ is strongly correlated with the ability to solve all sorts of abstract problems, whether they involve language, math, or visual patterns. The frightening upshot is that IQ remains by far the most powerful predictor of the life outcomes that people care most about in the modern world. Tell me your IQ and I can make a decently accurate prediction of your occupational attainment, how many kids youll have, your chances of being arrested for a crime, even how long youll live.

Critics claim that these correlations are misleading, that those life outcomes have more to do with culture and environmental circumstances than with innate intellectual ability. And even IQ researchers are far from in agreement about whether scores can be validly compared between groups of peoplemen and women, blacks and whiteswho experience very different environments even within the same country. Variations within groups are often greater than the variations between them, making it impossible to draw conclusions about someone based on their group.

But on an individual level, the evidence points toward a strong genetic component in IQ. Based on studies of twins, siblings, and adoption, contemporary estimates put the heritability of IQ at 50 to 80 percent, and recent studies that measure the genetic similarity of unrelated people seem to have pushed the estimate to the high end of that range.

This is an idea that makes us incredibly uncomfortable. People dont like to talk about IQ, because it undermines their notion of equality, Detterman says. We think every person is equal to every other, and we like to take credit for our own accomplishments. You are where you are because you worked hard. The very idea of the American dream is undermined by the notion that some people might be born more likely to succeed. Even if we accept that intelligence is heritable, any effort to improve or even understand the inheritance process strikes us as distasteful, even ghoulish, suggesting the rise of designer superbabies. And given the fallout that sometimes results when academics talk about intelligence as a quantifiable conceptsuch as the case of Harvard president Lawrence Summers, who in 2006 resigned after suggesting that science is male-dominated due not to discrimination but to a shortage of high-IQ womenits no surprise that IQ research is not a popular subject these days at Western universities.

But in his lab at BGI, 21-year-old Zhao has no such squeamishness. He waves it away as irrational, making a comparison with height: Some people are tall and some are short, he says. Three years into the project, a team of four geneticists is crunching an initial batch of 2,000 DNA samples from high-IQ subjects, searching for where their genomes differ from the norm. Soon Zhao plans to get thousands more through Renminhis former high schoolas well as from other sources around the world. He believes that intelligence has a genetic recipe and that given enough samplesand enough timehis team will find it.

Zhaos improbable rise at BGI began in the summer of 2009, when one of the firms founders, a geneticist named Wang Jian, noticed a skinny stranger lurking in the hall. Hey, what are you doing here? Wang asked the high school student with a spiky mess of hair. Zhao was 17, and he was there taking part in BGIs science summer camp. Why arent you in class? Wang pressed.

Its boring, Zhao said.

Wang took an immediate liking to him. On a hunch, he pushed Zhao into the hands of Li Yingrui, a recent college dropout who was already one of BGIs leading scientists. Do you know any Perl? Li asked him. Perl is a programming language often used to analyze genomic data. Zhao admitted he did not; in fact, he had no programming skills at all. Li handed him a massive textbook, Programming Perl. There were only two weeks left in the camp, so this would get rid of the kid for good.

A few days later, Zhao returned. I finished it, he said. The problems are kind of boring. Do you have anything harder?

Perl is a famously complicated language that takes university students a full year to learn. So Li gave him a large DNA data set and a complicated statistical problem. That should do it. But Zhao returned later that day. Finished. Not only was it finishedand correctbut Zhao had even built a slick interface on top of the data.

The next morning Li marched into Wangs office. This guy is a genius, he said. You have to keep him. So Zhao dropped out of high school, said good-bye to his mother and fatherhe is an only child, like most Chinese of his generationand moved to Shenzhen to begin a new life.

Despite Wangs open-door policy for young dropouts, BGI doesnt provide much of a safety net for its incoming prodigies. Zhao had a rough arrival. His starting salary was minimal. He had no friends. It was hard, he admits. It was also crazy. Zhao didnt drop out of just any high school. He dropped out of Renmin, one of the best prep schools in China. He had won his place there by acing a series of academic tests when he was in sixth grade. Zhao seemed to be forfeiting his future. He asked his parents for their blessing and they agreed, but with one condition: He had to get permission from Renmin.

The Renmin principal, Liu Pengzhi, had watched Zhaos growth with pride; she had identified him early as one of the schoolsand hence the countrysmost gifted science students. She flew down to Shenzhen to tour BGI and meet Wang in person. Only then did she give Zhao her official approval, as well as a parachute: If you change your mind, you can come back to Renmin and finish your studies anytime, she told him.

Ask Zhao what draws him to IQ as a research subject and invariably he talks about the mysteries of the brain. Hes driven by a fascination with kids who are born smart; he wants to know what makes themand by extension, himselfthe way they are. But theres also a basic pragmatism at work. By way of explanation, he points to the International Mathematical Olympiad, a tough competition that has helped define Chinas approach to math. Two-thirds of students train for it, he says, and its judgment of the talent is so respected that for years high scorers were allowed to skip gaokao, the traditional college entrance exam. But only a tiny fraction of people have the mathematical gifts to be competitive, Zhao says, and this basically comes down to IQ. You cannot ask a kid with low IQ to just work hard and then become a really talented mathematician, he says. Its impossible. And yet, Zhao says, thats what is currently expected in China. He wants to stop the vast majority of Chinese students from wasting their time.

Three years after arriving at BGI, Zhaos messy mop of hair is gone, replaced by a dark shadow across his shaved scalp. His project, meanwhile, has grown up along with him. Just a week before my visit, thousands of DNA samples arrived at the institute, each containing the genome of a person with extraordinarily high IQ. They were collected from volunteers around the world by Robert Plomin, a behavioral geneticist at Kings College London who is now one of the projects main collaborators. Once these samples are processed, BGIs battery of DNA sequencers will decode them.

The project has already weathered at least one serious false start. Zhaos original plan made sense on paper: Get IQ scores and DNA samples from a large number of smart people, compare their genomes to normal people, and after some statistical magic, voil! The genetic markers for IQ would pop right out. So Zhao returned, naturally, to Renmin, the high school he had just abandoned. He worked with Yang Rui, a brilliant Renmin graduate who had worked on the human genome project at BGI as a teenager. Zhao knew nothing about psychometrics, the branch of psychology behind the IQ test. Yangs psychometric research at Yale and Brown universities made her the perfect collaborator.

But they ran up against an unexpected problem: There was no Chinese IQ test, and Renmin students English skills werent consistent enough to conduct the test in English. Moreover, the IQ test is supposed to be given as a one-on-one interview, so when Zhao and Yang tried to administer it to whole classes of students at once, the result was chaos and useless data. Worst of all, getting blood samples from students proved nearly impossible, as wary parents began to raise alarms. Principal Liu had to call a meeting with parents to calm their nerves. The collaboration with Renmin was quietly put on hold.

The fortunes of the research effort changed in October 2010, when Zhao met Steve Hsu, a professor who was spending a year in Taiwan while on sabbatical from the University of Oregon. (He is now vice president for research and graduate studies at Michigan State University.) A theoretical physicist who likes to apply his mathematical muscles to a wide range of complex problems, Hsu was intrigued by a news article about BGI that briefly mentioned Zhaos project. A few emails later, he flew over to give a talk at BGI and soon became a permanent collaborator and adviser to the team.

Since most of the variation in IQ is heritable, scientists have long searched for genetic differences that might account for it. The reason we havent found them, Hsu theorizes, is because there arent any single genes or even a handful of genes with a big effect on IQ. Instead, the thinking goes, there are as many as 10,000 different locations in the genome where a mutation can affect IQ. According to Hsus rough model, all humans carry a few hundred of those 10,000 possible mutations, and each mutation has a tiny negative cost to IQ, on the order of half an IQ point.

If this is right, then the difference between a brilliant 150-IQ person and an average 100-IQ person comes down to DNA typos at perhaps 100 of those 10,000 places. Other traitslike height, for exampleseem to work the same way, and an ongoing study into the genetics of height has begun to find relevant mutations. Most geneticists who have studied intelligence agree with this theory in broad strokes. At the very least, says Kevin Mitchell, a geneticist at Trinity College Dublin in Ireland who studies brain development, Hsus basic theory of many deleterious mutations is far more plausible than the alternativethat is, more plausible than the idea that the mutations are building up IQ, not knocking it down.

The only way to unravel the genetics of a trait scattered among 10,000 possible DNA variants is to use something called GWAS (genome-wide association study). Rather than identifying the variants that cause a trait, as can be done with so-called Mendelian traits like finger length or earwax type, you find the variants associated with the trait.

Butand this is crucialthe implications of this math are that it will take far more than a few thousand genomes to solve the puzzle of intelligence. Given the small sample size they have so far, Hsu hopes theyll start by finding one or two genes associated with intelligence. A recent Dutch study required more than 125,000 genomes to isolate three variants associated with educational attainment; to create a genomic predictor of IQ, Hsu says, it could take 1 million or more.

The good news for Zhao is that cheap DNA sequencing, together with more creative ways of obtaining DNA, means that a million genomes could be in reach within five years. The genomes dont all need to be geniuses, because the IQ-affecting genetic markers theyre looking forDNA typos that drag down intelligenceare more often carried by the 100-IQ people. That is, its a relative dearth of these mutations that gives people higher IQ, according to the theory.

Assuming Zhao and his team succeed, there are implications that will trouble many people. Hsu is confident that through embryo screening during IVF, any genetic markers for intelligence that their team discovered would inevitably be used to select for more intelligent babies. Children tend to fall within a spread of 13 IQ points above and below the average IQ of their parents. But sometimes the apple can fall twice as far from the treethat is, two parents with 100 IQs producing a child with an IQ of 126. Hsu puts the chance of such a positive outlier at around 2 or 3 percent, and it depends mostly on which sperm meets which egg.

If parents use IVF to conceive, then a genetic testan extension of the screening tests for genetic diseases that are already routinely done on embryoscould let them pick the smartest genome from a batch of, say, 20 embryos. Its almost like there are 20 parallel universes, Hsu says. These are all really your kids. Youre just choosing the ones with the greatest genetic potential for intelligence. But effectively, you could be giving an unborn child a boost in IQ above their parents. As Hsu sees it, this is no Faustian bargain. Arent we doing them a great service? Over the long term, he proclaims, this would improve the average IQ of the species by quite a bit. He hopes governments will even provide it for free; Singapore, he predicts, would be the first to sign up.

Even if Zhao and his team do get enough DNA, the genetics of IQ could prove to be a thornier problem than Hsu and Zhao expect. For example, theres the question of epistasis, or the interaction of genes with one another. Hsu is convinced (based on his reading of the existing data) that IQ mutations are essentially additive, such that the negative pull of each persons DNA typos can simply be tallied up. But its likely that the effect of some genes will depend on the presence or absence of others, making it much trickier to predict IQ from birth. The reality, says Mitchell, the Trinity College geneticist, is probably somewhere in the middle between simple additivity and complex epistasis; and just where that balance lies will determine whether a genetic IQ prediction machine is ever possible. Even if Mitchells skepticism is borne out, and the answer is somewhere in between, it still means that an embryonic test could allow parents a significant degree of influence over their offsprings intelligence.

In Shenzhen, when I meet two members of Zhaos teamChris Chang, a 35-year-old Chinese American statistician, and Laurent Tellier, a 30-year-old Danish bioinformaticistI ask them the unavoidable question: Would they, as parents, take advantage of this service? Their responses are radically different. Yes, absolutely, Tellier says, adding that he had decided this years ago after seeing the film Gattaca. (It probably wasnt the takeaway that the filmmakers of that dystopian tale had intended.) Chang, meanwhile, gives a definite no. He declines to give a reason; he just shakes his head.

The last time I see Zhao, I put the same question to him. Its a freezing day in November when he swings through Boston, near where I live, and I meet him at a bar. Hes not old enough to legally drink in the United States, but no one cards him. He had spent the afternoon with a Harvard scientist who studies prosopagnosia, a condition that makes it difficult for a person to recognize faces. Theres evidence that the disease is strongly heritable, so Zhao and the scientist discussed sequencing the genomes of afflicted families to find the genes. Over our drink, I pose my earlier question to Zhao: Would he use his research to have more intelligent offspring of his own? His response is nuanced. I understand both positions, he says. But I will have to respect my wife. Its not only my child. It will be hers too. He worries that some neurological complications, such as Aspergers syndrome, might be genetically tied to IQ.

Not all the ramifications of Zhaos success would be frightening. If studies like this end up shedding light on the genetic architecture of the brain, it could transform mental health, revealing genes that go awry in diseases like schizophrenia and bipolar disorder. Diagnoses could happen earlier; treatments could become more effective. In any case, Zhao prefers to think of his work as basic research, drawing an analogy to physics from a century ago. You could make something bad, like atomic bombs, or you could make something really good, he says. But the science itself is neutral, and it has to move on.

Human intelligence is encoded in our genes, he believes, and someones going to find it. Why not a boy genius?

John Bohannon (gonzo@aaas.org) wrote about a reality-TV show for Arab inventors in issue 20.02.

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genetics of IQ - WIRED