Human Nature, Observed

By Douglas Starr, Science Magazine

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In 1987, Avshalom Caspi and Terrie Moffitt, two postdocs in psychology, had adjacent displays at the poster session of a conference in St. Louis, Missouri. Caspi, generally not a forward man, looked over at Moffitt's poster and was dazzled by her science. “You have the most beautiful data set,” he said. Not one to be easily wooed, Moffitt went to the university library after the meeting and looked up Caspi's citations. Yep, he'd do. “It was very nerdy,” Caspi recalls. “We fell in love over our data.”

It's been a personal and scientific love affair ever since. For nearly 30 years, Moffitt and Caspi have been collaborating on one of the more comprehensive and probing investigations of human development ever conducted. Launched in 1972, the Dunedin Multidisciplinary Health and Development Study is as fundamental to human development as the Framingham Heart Study is to cardiovascular disease and the Nurses' Health Study is to women's health. From detailed observations of the life courses of about 1000 New Zealanders, Dunedin has spun out more than 1200 papers on questions from the risk factors for antisocial behavior and the biological outcomes of stress to the long-term effects of cannabis use. Moffitt, who joined the study in 1985, and Caspi, who followed, have led much of the work. They “have done so much it's impossible to pigeonhole them,” says Brent Roberts, a psychologist at the University of Illinois in Champaign who has collaborated with the now-married couple.

One early finding, on the transient nature of most juvenile criminality, was cited in the U.S. Supreme Court's 2005 decision to prohibit the execution of underage murderers. Moffitt and Caspi did pioneering research showing that self-control in early childhood predicts health and happiness in adults. They detailed how the genetic makeup of certain individuals can make them vulnerable to specific stresses, elucidating the complex interplay between genes and life experience. And last year, the Dunedin team published a study that drew on decades of data to show that, contrary to conventional belief, the vast majority of people experience mental health problems over the course of their lifetime.

“Their work has transcended psychology to influence thinking in psychiatry, genetics, criminology, epidemiology, sociology, and many other areas,” the American Psychological Association said when it awarded Moffitt and Caspi its 2016 Award for Distinguished Scientific Contribution.

The field of psychology is rich with longitudinal studies, going back to 1946, when the United Kingdom's Medical Research Council began a survey of more than 5000 people from birth to old age. Other researchers have followed identical and fraternal twins over time to tease out the influence of nature versus nurture. Such studies, although slow, make it possible to observe phenomena in real time instead of having to reconstruct them from subjects' memories or medical records, or by comparing disparate groups.

Dunedin is the Goldilocks of longitudinal studies. It's not the biggest or the longest; but its high retention rate—about 95% of the original cohort has stayed with the study since it launched—and the intimacy of the data-gathering process make the group one of the most closely examined populations on Earth. Every few years, the team conducts intensive cognitive, psychological, and health assessments. They interview every member of the research cohort as well as their teachers, families, and friends and review their financial and legal records, promising them complete confidentiality in return for the fullest possible picture of their lives.

As a result, Moffitt, Caspi, and their colleagues have been able to tease out previously unseen patterns in human development. “It's been a remarkable resource,” Columbia University psychiatrist Ezra Susser says of the study. “There really is no equivalent,” Roberts adds. “Time after time they've anticipated where we've needed to go and done the work earlier than the rest of us.”

MOFFITT GREW UP in central North Carolina, where her Scotch-Irish ancestors had settled in the 1700s. She helped with farm chores and rambled in the woods, collecting arrowheads and catching fireflies, often in the company of her beloved Grandma Macon. “Respect is earned, not demanded,” Grandma Macon had taught her. “A woman's beauty is in her strength and in her laugh.”

Red haired and blue eyed, Moffitt was the first person in her extended family to attend college. Having come from a “low-quality high school,” she chose easy classes at the University of North Carolina in Chapel Hill, but when professors recognized her potential, she warmed to the challenge of advanced courses in psychology and behavioral pharmacology. She supported herself as a lab tech in nearby Durham's Research Triangle Park—a job she got because having grown up hunting rabbits and squirrels, she didn't feel queasy about sacrificing lab animals.

In graduate school at the University of Southern California in Los Angeles, working with the famed psychologist Sarnoff Mednick, she focused on the roots of criminal behavior. A few months before defending her Ph.D. dissertation, Moffitt and a few classmates decided to relax by taking skydiving lessons. It didn't go well. Moffitt broke her leg in several places. Confined to a wheelchair, she spent several hours entertaining a visitor from New Zealand who had come to speak about his study. Phil Silva had been tracking all 1037 children born in the Queen Mary Maternity Centre at Dunedin Hospital from April 1972 to March 1973, examining them every couple of years to assess their cognitive and psychological development.

Moffitt saw the population as a readymade laboratory to explore some of her ideas about early childhood and the roots of criminality. She joined the study when the children were 13 years old. Not long after earning her Ph.D., she made her first trip to New Zealand, gathering data about girls who got in trouble with the police. She presented her findings at that fateful St. Louis conference. Next to her was a guy with olive skin, soulful eyes, and brown hair in a ponytail.

Caspi, his hair now silver but still often in a ponytail, grew up on a tiny kibbutz in Israel's Negev Desert. The son of a Yemenite father and a Lithuanian mother, he was part of the “peopling” of the Negev envisioned by Israel's founding prime minister, David Ben-Gurion, who had retired to a cottage up the street. Every morning, Caspi and his five classmates would walk past Ben-Gurion's cottage on the way to their little school. “Shalom, David,” they'd call out to him. “Shalom yeladim [children],” Ben-Gurion would reply. Caspi was 10 when his family moved to Berkeley, California, where his father completed his Ph.D. in international studies. “The transition from a kibbutz to Berkeley was pretty amazing,” Caspi recalls. “This was the '70s, and I remember dodging riots with my dad.”

His experiences had made him curious about people and places, and he thought about becoming a journalist. But psychology won him over in college, and at Cornell University he did graduate work with sociologist Glen Elder, who wrote Children of the Great Depression: Social Change in Life Experience, a landmark study of how the economic environment influences human development. Caspi became fascinated by the interplay between people's dispositions and their social environment. He was presenting a study on how ill-tempered children become ill-tempered adults when a young woman with crimson hair set up her poster next to his.

A few years of long-distance courtship ensued, before the couple settled in at the University of Wisconsin in Madison. Colleagues warned against making their personal partnership a professional one, but they plunged ahead, and Caspi joined the Dunedin team.

His first collaboration with Moffitt involved a question that had long intrigued him: Do dramatic life events change people, or simply cement who they already are? The team focused on female puberty. Just over half of the Dunedin study subjects were girls, who by age 15 had been given physical and psychological exams since childhood. Previous studies showed that reaching puberty early is especially stressful, and Caspi and Moffitt found that the girls who had the most trouble adjusting to early adolescence were those who had shown behavioral problems in early childhood. That contributed to Caspi's “accentuation” hypothesis—that stressful transitions tend to accentuate who we basically already are. It was a radical notion in the early 1990s, when psychologists generally believed that situation, not temperament, was key to determining personality.

SINCE THEN, their work has often explored the darker side of human nature. Contrary to what the idyllic landscapes in the Lord of the Rings films might suggest, New Zealand is not heaven on Earth. Economic inequality is comparable to that of the United States, and addiction, suicide, and assault rates are similar. By promising strict confidentiality, the research team gets shockingly frank confessions from their subjects, including about brutality and criminal behavior. (A startling example: Women admitted to physically abusing their spouses as often as men, although they generally inflicted less physical damage.) “We have a policy of never interfering and never ratting them out,” Moffitt says. “And the New Zealand police, who understand the value of our research, have never asked.”

This long, intimate surveillance enabled Moffitt to track a troubled subset of the Dunedin cohort. Delinquent behavior is known to peak between the late teens and mid-20s, mostly in men. By 15, about a third of the study's boys took part in some degree of delinquency, Moffitt found, while a subset offended more frequently. When she looked at data from early childhood, she found that the habitual offenders had been making trouble from age 3, and had arrest records starting before their teen years.

Over the years, Moffitt reported in a series of papers that these boys did poorly in neuropsychological tests (such as verbal skills and verbal memory), measured high for impulsivity, and were likely to engage in substance abuse as they grew older. In 2002, she reported that at age 26 this same group was committing most of the crimes in the community—a pattern that persisted well into their 30s. In short, whereas many boys exhibited “adolescent-limited” criminal behavior, about 5% were “life-course-persistent” offenders. The work had important implications for social work and law, and won Moffitt the 2007 Stockholm Prize in Criminology.

In 2000, after Silva retired, Richie Poulton, a psychologist at the University of Otago in Dunedin, became project director, with Moffitt continuing as associate director. Every couple of years Moffitt and Caspi would visit Dunedin to spend a few months with Poulton collecting information, then return home to analyze data. (A few years earlier they had also initiated a study of 1100 U.K. families with twins that added prodigiously to their Dunedin data.)

The testing schedule in New Zealand, limited at first, expanded as they added new techniques and technologies, such as DNA analysis, retinal imaging (which can help gauge the brain's vascular health), and scans of brain activity. The study leaders trained staff to interview participants, their families, and associates, and they employed data managers to handle the masses of coded data. And they maintained a high retention rate by assiduously keeping track of the participants, a quarter of whom have emigrated from New Zealand, financing travel back to the study site, and visiting study members who were in prison or too sick to travel.

“They have gotten to know these people intimately, watched them age, get married, have children, and encounter the things that happen in middle life,” says James Tabery, a philosopher at the University of Utah in Salt Lake City who has written about the study. It can be harrowing, he says. “What do you do if one of them is on the verge of homelessness? Or if one of them is $1000 short on rent? It's like David Attenborough watching a giraffe get eaten but it's a giraffe you've come to know for 40 years.” Researchers can unburden themselves in a safe room after listening to upsetting information. Outside of that room, anyone who violates confidentiality will be fired.

THE STUDY'S FINDINGS mostly point to patterns, not mechanisms. But in the mid-1990s, Moffitt and Caspi joined a group at King's College London looking for genetic roots of behavior. The result was what may be the highest profile and most controversial of their claims.

It's commonly known that children who are abused often become violent adults. In the Dunedin group, for example, about half the boys with abusive childhoods grew into men prone to committing crimes. Moffitt and Caspi thought that studying this group could shed light on the classic nature versus nurture question: Do experiences alone produce a life of crime, or are some individuals naturally prone to it? The idea had come to them on safari in Namibia, where they noted how even in that mosquito-infested region many people did not get malaria, undoubtedly because of a genetic resistance. Could genotype play a role in behavior as well, making certain children psychologically resistant to abuse?

Earlier research had linked aggression to low levels of an enzyme called monoamine oxidase A (MAO-A), which breaks down certain neurotransmitters in the brain. Laboratory mice bred without the enzyme showed aggressive behavior, and in a famous human case, several male members of a Dutch family who were pathologically violent lacked the gene that encoded for the enzyme.

Moffitt and Caspi analyzed their study members' DNA for the gene. They found that among maltreated children, those who were genetically prone to make low levels of MAO-A were far more likely than their counterparts to become violent adults. It was the first substantial evidence that a specific gene could modulate the effect of a known cause of criminal behavior.

The finding, published in 2002 in Science, caused a media sensation, but some researchers questioned the utility of such studies. “Sure there's a genetic effect in people who have been exposed to violence,” says Dean Hamer, scientist emeritus at the National Institutes of Health in Bethesda, Maryland, who has written widely on genes and behavior. “But the effects are so small and so variable” as to be dwarfed by the dangers of childhood abuse.

Since then, investigators moved away from individual genes. “We're long past the low-hanging fruit of Mendelian genetics,” Tabery says. Geneticists now survey the genomes of thousands of people with a particular condition—asthma, for example—in search of gene/DNA variants whose small effects on risk combine. Often it turns out that hundreds or even thousands of genes contribute to the overall risk, not just one. Moffitt and Caspi have adopted that approach to search for genetic factors in conditions including tobacco addiction and obesity.

Recently, Caspi compared longitudinal research to farming—“sowing, nurturing, waiting, and harvesting.” It's an apt comparison, given that his and Moffitt's grandparents were farmers. Year after year they have harvested data, and new revelations about human development have emerged.

In 1987, Silva was among the first to recognize that children can experience hallucinations, when he detected them while interviewing 11-year-olds. As the subjects aged and the study accumulated data, an ominous connection emerged. Follow-ups at age 26 revealed that the kids with hallucinations had developed full-on schizophrenia at more than 25 times the rate of the general population. (Schizophrenia is so rare that the sample numbers were small, however.)

The work, reported in 2013, added support to the emerging practice of “prodromal” psychiatry, in which symptoms are identified and treated in their earliest stages, years before they blossom into disorders (Science, 17 November 2017, p. 856). “I've had mothers write me letters all the time saying, ‘My kid has some pretty crazy ideas, where can I go?’” says Moffitt, who describes the work as the most gratifying of her career. Now, she can direct them to clinics for treatment.

“It took a quarter of a century to see this unfold,” Caspi says. “You just have to be patient. Longitudinal research is a big exercise in delayed gratification.”

WHEN MOFFITT AND CASPI came back to the United States in 2007 to accept professorships at Duke University in Durham, it was a chance for Moffitt to return to her origins. They bought an old family property in central North Carolina, removed tons of old tires and debris, rebuilt structures, cleared trees, and built a new farmhouse.

Origins mean a lot in their work, which has shown that our nature as adults—our capacity for self-control, our propensity for violence—has deep roots in the children we once were. Recently, Moffitt and Caspi took a broad look at how their study members, now 45, are faring. It's a poignant time of life, when middle-aged adults face the reality that many of their youthful dreams won't come true. The Dunedin data showed that just over a fifth of the population accounts for the bulk of the social costs: crime, welfare payments, hospitalizations, cigarette purchases, fatherless child-rearing, and other indicators of social dysfunction.

What's wrong with these people? Moffitt and Caspi went back and looked at their data from age 3. The target group seemed cursed from the beginning: They scored low on early language skills, fine and gross motor skills, neurological health, and self-control. Often they also grew up in poverty and suffered maltreatment. All through life their disadvantages haunted them. “They didn't get a fair start right out of the starting block,” Moffitt says. “You can't expect people with this kind of childhood to do well.”

They even seem to age faster than those who had a better start. In their cohort, Moffitt and Caspi have been finding signs of aging starting in the 30s. They're particularly struck by the effects of stress at an early age. Childhood abuse seems to erode telomeres—the caps at the end of chromosomes, associated with cell preservation—and that, in turn, may accelerate aging.

Moffitt and Caspi offer no grand unified theory of human development: Humans are too complicated, too irrational, to sum up in a principle. What their research gives them is not so much a conclusion about humans as a particular point of view.

“All people are not created equal,” Moffitt says. “Some have real gifts and talents, and some have real problems right out of the starting block. Once we accept that, we can't dodge the responsibility for social action.”

Watching people's lives unfold over decades, she adds, “obliges compassion.”

Douglas Starr is co-director of the program in science journalism at Boston University.
Story originally published in Science Magazine on Feb. 2, 2018.


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