The Boy Who Loved Too Much Page 11

He came to the open-mic event. While Chelsea told stories, he accompanied her on guitar. Her classmates applauded politely when they finished. No one taunted her, but no one approached her after the event, either.

  Her father understood, from a developmental perspective, why Chelsea’s classmates distanced themselves from her. He didn’t see it as deliberate cruelty and tried not to take it personally.

  “So much of it is tied into their own identity,” he said. “At this age, they’re trying to navigate these social systems for themselves, to find their place. And as soon as they recognize something in her that doesn’t fit in, they want to dissociate before it becomes part of them.”

  Knowing that, and keeping it from breaking his heart, were two different things.

  * * *

  GAYLE’S HEARTBREAK FOR ELI WAS not quite the same. Eli never came home crying. He never complained about being different. He either didn’t realize or didn’t mind that he was unlike his classmates. He walked off the school bus singing every afternoon, whether or not he’d been teased.

  Gayle wasn’t sure whether Eli’s imperviousness to social slights meant that he was more intellectually disabled than some of his Williams peers or simply more happy-go-lucky. Either way, she wondered if he’d grow to become more self-aware—and whether she’d want him to. She knew that adults with Williams often struggled with anxiety and depression. Some researchers have theorized that this could be the result of accumulated social failures: years of opening their hearts to repeated rejection. The developmental psychologist and neuroscientist Helen Tager-Flusberg concluded, after interviewing countless children and adults with Williams, that a “more mature conception of self” often triggered the angst of adulthood.

  “With age, many of the individuals with Williams syndrome come to view their syndrome as socially disabling, or limiting their prospects and hopes for social integration, an attitude rarely seen in younger children,” she wrote.

  While Eli’s teachers, and Gayle herself, were pushing to help him gain a “more mature conception of self,” it gave Gayle pause that the insights she hoped he’d gain might also cost him the unburdened joy of his youth. He’d probably be happier if he stayed a child forever. Then again, she thought, wouldn’t anyone? Adolescence might be the most challenging stage of a life with Williams, but it’s also a challenge for every human being. Growing up is never easy. The reward isn’t necessarily happiness; it’s independence. But what Gayle wanted for Eli—what parents everywhere want for their children—was both.

  Nine

  Missing Genes, More Personality

  The paradox of a genetic deletion that can make people gifted storytellers and accomplished musicians with warm, charming natures once prompted Jonas Salk, the polio vaccine developer who founded the Salk Institute, to say of Williams syndrome, “I never knew talent was a birth defect.”

  The Salk Institute, one of the nation’s leading centers for genetics and neuroscience, has become a hotbed of Williams research. Here, Ursula Bellugi and the geneticist Julie Korenberg have spearheaded efforts to understand how twenty-six missing genes account for the Williams phenotype—the disorder’s observable features—and what brain abnormalities underlie its behavioral quirks.

  Years after researchers identified the elastin gene, the Salk team pinpointed two other genes on chromosome 7 that together play a role in the perception of spatial relationships. Their absence helps explain the trouble people with Williams typically have in drawing a simple picture, re-creating basic patterns with blocks, or finding their way through a maze. Korenberg, who has called Williams syndrome “a geneticist’s dream,” also led the way in tracing the characteristic elfin facial features of people with Williams to a cluster of adjoining genes.

  But Korenberg and her colleagues were even more determined to understand the genetic basis of the Williams personality: that combination of empathy, gregariousness, and trust that makes people with the disorder both so lovable and so vulnerable.

  Attempts to trace the biological roots of personality have been controversial ever since the Victorian psychologist (and eugenicist) Sir Francis Galton described the dichotomy between nature and nurture in 1869. The controversy has flared up again in recent years, especially since the Human Genome Project failed to fulfill hopes of pinpointing the genes responsible for traits such as intelligence and empathy, as well as for illnesses like cancer and autism. After researchers spent years—and billions of dollars—hunting unsuccessfully for those genes, some people called the quest a wild-goose chase. And some have argued that it would be reductionist in any case to view the stunning diversity of human personalities merely as differences in protein production dictated by our DNA. Detractors see the attempt to frame personality in genetic terms as a discredit to humankind, and one that underestimates our ability to shape our own lives.

  But it’s tough to argue with the premise that personality traits have a genetic basis: farmers and dog breeders have known it for centuries. Behavioral traits like intelligence, obedience, and gentleness can be transmitted genetically—and have been, through the selective breeding of livestock and dogs, since long before anyone understood the laws of genetics. Of course, scientists have established the heritability of behavioral traits in humans as well, largely through studies of twins, but the principle can be demonstrated easily enough by considering why Labrador retrievers make great pets, while wolves do not.

  Identifying the genes responsible for these traits, however, has proved much harder than breeding them in animals. One of the main failings of early research efforts was the presumption that there was a gene for any given trait. As geneticists have come to realize, the mechanisms behind heritability are much more complicated than that: whole systems, depending on entire networks of genes, are likely implicated in any one trait. That’s why the psychologist Eric Turkheimer has argued that all human traits are heritable—personality included—even as he added, in a 2014 article, that “the search for genetic mechanisms of human personality . . . will never bear fruit.”

  Korenberg and her colleagues believed that behavioral genetics could be fruitful if they turned the search on its head. Instead of tracking downward from, say, the social deficits of autism to genetic roots that could be anywhere in the vast wilderness of the human genome, they wanted to start with known genetic roots and work their way up. Williams syndrome offered the exhilarating opportunity to do just that. Limiting their search to the syndrome’s twenty-six missing genes dramatically narrowed the field on which to chase the wild goose of sociability. That still didn’t make it easy.

  The Salk team’s big break came in 2009, when they stumbled upon a nine-year-old girl whose genetic makeup was unusual even among the Williams population. She had the classic Williams facial features, its telltale heart defect, and the hallmark inability to process spatial relationships. However, her behavior was uncharacteristically reserved: she didn’t run up to strangers, lock eyes with them, or try to hug them. And although she was less outgoing, she was capable of more sophisticated social interactions than most people with Williams. In fact, to the researchers’ amazement, she easily formed meaningful connections with other kids her age. Korenberg and her colleagues wanted to know what made the girl so different.

  Using the same diagnostic test once given to Eli (the FISH test, which highlights DNA in fluorescent dye), combined with two even more sensitive procedures—a high-resolution imaging test that compared her DNA to her father’s, along with a technique called polymerase chain reaction, which can amplify a section of DNA by several orders of magnitude and is popular among forensic analysts—the team discovered that the girl was missing every Williams gene but one: the inelegantly named general transcription factor IIi (GTF2I) gene.

  It was a discovery with monumental implications for understanding human behavior, since GTF2I’s singular impact defied researchers’ predictions that a wide range of genes underlay the hypersocial behavior found in Williams. “It’s not simple,” Korenberg said,
“but it may be much simpler than we thought.”

  The Salk team needed to do more work to determine whether the correlation was more than a fluke, however. “It’s tempting to say that the gene she kept was related to that particular phenotype. But you have to be very careful, because it’s a single case, and how specific is the phenotype? Sort of specific, but not as specific as we might like,” Korenberg explained.

  While Korenberg and her colleagues could replicate the gene deletion in lab experiments by “knocking out” the GTF2I gene in normal DNA, they couldn’t test its effects on human subjects for obvious ethical reasons. Instead, they picked one of our primate relatives, the macaque monkey—a popular species among researchers because its brain structure and elaborate social systems resemble humans’ in key ways. The Salk researchers injected lab-modified DNA into a macaque embryo and raised a monkey that was missing the gene that seemed to have made such a difference in the girl they’d studied.

  The results confirmed their suspicion that GTF2I helped regulate the production of oxytocin, a hormone that plays a role in social activities from parent-child bonding to romantic encounters as well as trust, attachment, and friendship. It’s been called both the “love hormone” and the “trust hormone.” One of its neurological effects is to relax the amygdala, a power player in regulating our emotional responses. Oxytocin essentially allows this part of the brain to let down its guard so we can develop the feeling of closeness that is essential to attachment. It also stimulates the brain’s reward system, producing the feeling of pleasure in seeing a loved one’s face.

  Ordinarily, oxytocin is released by the pituitary gland in controlled, strategically timed doses. In monkeys without the GTF2I gene, however, the flow of oxytocin became a flood that went to all the wrong places. The same was true for vasopressin, a partner hormone to oxytocin that plays its own role in social behavior (and is involved in regulating blood pressure). Vasopressin, sometimes called the “fidelity hormone,” acts on part of the forebrain to create a sense of well-being that has been known to cement the feeling of closeness oxytocin helps facilitate.

  Watching these hormones course wildly through a macaque brain—which they did, again with the help of fluorescent dye—gave the Salk team a clue they hoped would help decipher some of the paradoxes of Williams.

  “People with Williams are overfriendly but anxious,” Korenberg said. “Oversocial, but without social judgment. They initiate and seek interaction, but have difficulty making friends. They can’t sustain a conversation. They’re engaging and gregarious, but they have a very limited, repetitive social repertoire. They’re often insensitive and inappropriate. We can trace this to very particular [neural] pathways in Williams syndrome that are abnormal.”

  Other geneticists have replicated some of the findings from Korenberg’s monkeys by manipulating the DNA of mice, whose genes correspond to more than 90 percent of those found in humans, including the region implicated in Williams. By removing a gene named Williams syndrome transcription factor (WSTF) from mouse DNA, scientists produced mice with tiny upturned noses and prominent ears: elfin-faced mice. Removing the mouse equivalent of GTF2I, they raised uninhibited mice that would wander brazenly through mazes. Instead of scurrying into corners, as mice normally do to escape detection by predators, these mice sauntered out into the open as if looking for a party. When a new mouse was introduced into their cage, they were much more interested in the stranger than were mice with unmodified DNA.

  To explore the role that unregulated oxytocin and vasopressin played in Williams, Korenberg teamed up with the behavioral neurobiologist Sue Carter, whose decades of research into social behavior have led to breakthroughs in understanding the hormone pair.

  Although scientists had long known that oxytocin played a part in maternal behavior—it induces labor contractions and aids in the release of milk after a baby is born—it was Carter who identified its far-reaching effects in the brain. She made the discovery by studying prairie voles, mouselike rodents that are anomalous for their highly social behavior and because they mate for life, raising their offspring as partners, while most mice and rats are promiscuous. What made prairie voles different from their polyamorous cousins, Carter found, was that their brains had a higher concentration of oxytocin receptors. So she conducted experiments with oxytocin and found that injecting it into rat brains made the rats more social. More of the hormone made them friendlier and less fearful toward other rats.

  Vasopressin, she found, played a crucial supporting role. When injected into the brains of a promiscuous breed of voles, it was found to promote pair bonding, and the male voles reformed from playboys to committed monogamists.

  So Carter, Korenberg, and other researchers were not astonished to discover that oxytocin and vasopressin ran rampant in the brains of people with Williams, although they were surprised by the degree. People with Williams, they discovered, have up to three times more baseline oxytocin than normal. And their studies demonstrated that higher levels of oxytocin correlate not only with increased social behavior but also with impaired visual-spatial skills and with increased imagination and creativity, including the abilities to pretend and to tell vivid stories.

  Higher oxytocin and vasopressin also seem to be tied to the extreme music appreciation that is nearly universal among people with Williams. Scientists have already found that their minds are, on a deeper level, wired for music appreciation. On average, the brains of people with Williams are 15 to 20 percent smaller than normal. But most of that lost mass comes from the occipital and parietal lobes—partly responsible for visual-spatial abilities—while the temporal lobes, which deal with language and music, are usually normally sized or even larger than normal. A brain imaging study led by Bellugi and her colleagues found that people with Williams process music much differently than other people and use much more of their brain to do so, including parts of the cerebellum, brain stem, and amygdala—more primal neural regions, sometimes called the “emotional brain”—that lie dormant when the rest of us listen to music.

  In one test, Korenberg and her team measured the amounts of oxytocin and vasopressin in the bloodstream of people with and without Williams while they listened to music. While the baseline levels for both hormones were higher in people with Williams, they jumped even more dramatically when music was played. So while music, considered a universal emotional stimulus, triggered an increase in oxytocin even in the control group, the torrent of hormones it elicited in the brains of people with Williams seemed to correspond with their exaggerated emotional response. Notably, a surplus of the two hormones also corresponded with a higher likelihood that they would approach strangers, and with the likelihood that their interactions would be considered overfamiliar and intrusive.

  “You had a person who might be running up to people and, once they get there, they’re not saying the right things,” Korenberg said. She speculated that too much oxytocin might increase our social drive but also cloud our judgment. Among other things, it might make us prone to displays of excessive and unreciprocated affection, alienating others instead of drawing them to us.

  By flooding the brains of people with Williams syndrome, this hormone—normally released only in the most intimate of moments, such as when mothers nurse their newborn children—creates a sense of closeness with everyone, turning strangers into trusted friends and instantly forging connections that most of us take months or years to build.

  * * *

  THE IMPLICATIONS OF THESE DISCOVERIES could be huge: by identifying the roots of these maladaptive behaviors, the Salk team opened the door to a search for possible treatments. And that could lead to effective therapy for other, more common social disorders, including autism and post-traumatic stress disorder. If too much oxytocin is partly to blame for the overly social behavior of Williams, then too little could play a role in social anxiety and withdrawal, and correcting the chemical imbalance could help with both.

  In fact, a 1998 study established that peop
le with autism had lower-than-normal levels of oxytocin in their blood. Around the same time that Korenberg was studying oxytocin in Williams, other researchers were designing experiments to test the therapeutic potential of oxytocin, given intravenously or via nasal spray, for improving the social skills of people on the autism spectrum. Two separate studies found that supplemental oxytocin helped people with autism and Asperger’s use nonverbal cues to successfully assess other people’s emotional states. (One asked them to identify emotions based on tone of voice, the other based on facial expressions.) And a study published in 2010 found that inhaling oxytocin gave high-functioning people with autism and Asperger’s an enhanced feeling of trust and connection with others, and helped them behave more appropriately in social settings. While oxytocin isn’t yet a mainstream treatment for autism’s social deficits, these researchers believe it could one day become a valuable therapeutic tool.

  Identifying oxytocin’s role in the brain could even lead to a greater understanding of social behavior in general, influencing everything from governing styles to financial policies. For example, in one neuroeconomics study, researchers gave people ten dollars to split with a stranger. They found that those given a spritz of oxytocin nasal spray were 80 percent more generous than those given a placebo spray. Oxytocin levels in the blood of those on the receiving end of the shared money also rose in proportion to the generosity of the giver, with higher levels corresponding to a feeling of warmth and trust toward the charitable stranger.

  Korenberg’s next goal is to trace the brain circuits and genes responsible for the anxiety common to people with Williams. If researchers can identify those systems, it could lead to treatments for anxiety in the general population.

  * * *

  GAYLE WAS DELIGHTED THAT WILLIAMS research might benefit the world at large. But like all parents of Williams kids, she was even more eager for advances that would improve the lives of people with the disorder, and soon enough to benefit her son. A treatment to address the social symptoms of Williams—an oxytocin eraser, perhaps—was near the top of her wish list. She dreamed of a day when her son’s irrepressible overfamiliarity would subside and when, like the nine-year-old girl in Korenberg’s case study, he’d be capable of forging a true, meaningful connection with someone other than his mother. Her dream come true would be his dream come true: he would finally make a friend.