What It Means to Be Human

During the hot, humid summers spent on her grandmother’s farm in Randolph County, North Carolina, Terrie Moffitt witnessed the endless universal loop of creation and destruction. She and her fourteen cousins delighted in bottle-feeding calves and finding nests of baby rabbits, learned to spot snakes camouflaged in garden rows, suffered the painful curse of poison ivy. Nature, in all its majesty and violence, gave rise to discoveries both wondrous and frightening. Curiosity about the world and its creatures eventually led Moffitt to focus on the most complex, baffling species of all: human beings. From her pioneering work on the genetic implications of criminal behavior to pinpointing mechanisms that contribute to mental illness, Moffitt has become an internationally renowned researcher whose studies — often provocative, occasionally controversial — focus on the tantalizingly elusive nexus of nature and nurture.

At Duke, Moffitt is the Nannerl O. Keohane University Professor with appointments in three areas: psychology and neuroscience, psychiatry and behavioral sciences, and the Center for Genomic and Computational Biology. Along with Avshalom Caspi, her husband and research partner, she has won a slew of international honors and awards for her work, including the prestigious Stockholm Prize in Criminology.

Browse through her sixty-five-page curriculum vitae and you’ll get a sense of the breadth and scope of her research interests — how early-childhood adversity affects the body physiologically, why people with certain genetic predispositions do or don’t become addicts or habitual criminals, young women’s participation as perpetrators in intimatepartner violence, the correlation between heavy marijuana use in adolescence and a seemingly permanent decline in IQ.

Yet Moffitt’s path from playing in the rural countryside to becoming one of the most highly cited researchers in the world (more than 35,000 times and counting) was anything but linear. As her research has shown again and again, we all are born with a distinctive genetic profile and personality traits that predispose us for better or worse trajectories. But the unpredictable twists and turns of life push us toward (or repel us from) decisions and opportunities that shape our destiny.

For Moffitt, one of those life-altering moments happened with a single step at 5,000 feet.

TRAPPED IN A WHEELCHAIR

In the spring of 1984, Moffitt was a graduate student in clinical psychology at the University of Southern California. Her adviser, Sarnoff Mednick, had designed and conducted a seminal longitudinal study of adopted children in Denmark that linked environmental factors to the development of schizophrenia in at-risk individuals.

With nearly a dozen graduate students already using the study data to examine various aspects of schizophrenia, Mednick urged Moffitt to pursue a different focus. Her dissertation compared the role of parents’ mental health, and the extent of their criminal activity, with their offsprings’ tendency toward violence.

In the weeks leading up to her dissertation defense, Moffitt and several other graduate students commiserated about the daunting prospect of the looming oral exam. “We decided to take parachute jumping lessons,” she says, “because we reasoned that if we could overcome our fear of stepping out of an airplane, we could overcome our fear of defending our dissertations.”

The jump didn’t go as planned. Moffitt broke her leg in several places and was confined to a cast that extended from her waist to her toes. Her convalescence coincided with a visit from New Zealand psychologist Phil Silva, who was overseeing his own longitudinal research study on early-childhood development. “I was trapped in a wheelchair, and I couldn’t get away from this visitor,” she says with a laugh. “We ended up spending a lot of time together, talking about longitudinal studies. The Danish adoption study I’d used for my dissertation drew on medical and criminal records, but I was interested in actually interviewing people. And since I didn’t speak Danish or Swedish, I was looking for a longitudinal study that involved children or adolescents I could interview in English and follow into young adulthood.”

Silva was the founding director of an early-childhood assessment initiative involving 1,037 babies born in Dunedin, New Zealand, between 1972 and 1973. Silva’s original intent was to conduct a one-time study to gauge how those babies had flourished psychologically and developmentally (or not) by age three. But by the time Moffitt and Silva were comparing research notes, the study had been extended multiple times. Participants had continued taking part in screenings focusing on an array of physical and mental-health issues, social-development milestones, and age-specific criteria.

Temporary immobility notwithstanding, Moffitt knew even before Silva’s arrival that longitudinal studies beginning in early childhood were essential to teasing out the interplay between biological and environmental factors as they relate to cognitive development. Despite a lack of funding—Silva told Moffitt she’d need to secure her own fellowship, since they couldn’t afford to pay her—Moffitt joined the Dunedin study in 1985 as a National Institutes of Health-funded new investigator. Colleagues in the U.S. questioned her decision to travel half a world away to work on a relatively unknown study of New Zealand children.

Moffitt was undeterred. After all, she reasoned, it was just a two-year commitment, and it could be useful in her exploration of early-childhood brain growth. She had no way of knowing that the study would become the most ambitious, comprehensive, and groundbreaking longitudinal study of human beings in history— and that it would become such an integral and long-lasting component of her life’s work.

SHARING THEIR LIVES

The premise of the Dunedin Multidisciplinary Health and Development Study is both exquisitely intuitive and scientifically unprecedented: Follow babies throughout their lives and observe everything that happens to them, with the goal of learning fundamental truths about human behavior. Use multiple approaches and disciplines to assess health and well-being. Employ the latest technologies such as MrIs, retinal imaging, and genetic tests as they become available. And above all else, do everything possible to ensure that the participants stay committed to the study, no matter where life takes them.

Those New Zealand infants born in the early 1970s now are entering middle age. These men and women have been poked and prodded at the ages of three, five, seven, nine, eleven, thirteen, fifteen, eighteen, twenty-one, twenty- six, thirty-two, and, most recently, thirty-eight. They’ve been asked intimate questions about childhood trauma and sexuality, had their lung function tested and retinas scanned, divulged illegal activities and struggles with addiction, allowed credit checks and the release of hospital records, given blood and DNA.

Astonishingly, 95 percent of the original surviving cohort is still participating. They are flown back to Dunedin from wherever in the world they are living. The Dunedin researchers go to them if they are in prison or unable to travel. One man, incarcerated for a capital crime, told a study researcher that being part of the Dunedin study was his greatest accomplishment. “I haven’t done much with my life,” he said, “but at least I’ve done this.”

“Creating a culture of trust and confidentiality is important for retaining study members, but more important, it’s our ethical obligation,” says Moffitt, who became the study’s associate director in 1991. “These people are sharing their lives with us. We’re constantly asking study members how they feel about the research we’re doing, so that we can respond in real time to their fears. Without that mutual dedication between researchers and participants, we couldn’t have built these longitudinal data sets. There’s an extraordinarily huge amount of goodwill.”

Dunedin-study discoveries have been used to overturn a Supreme Court decision, inform public policy, and shape pediatric recommendations; been lauded by both sides of the marijuana legalization debate; and inspired a Sesame Street segment. The study even has captured the imagination of Nobel laureate and leading economist James Heckman, owing to its implications for improving global health and prosperity by reducing crime, poverty, and the soaring costs of health care for treating preventable diseases.

As the web of knowledge created by the Dunedin Study grows ever wider, one of its most significant conclusions is paradoxically unsettling and encouraging.

BIOLOGY AS DESTINY?

Moffitt traces her interest in the thin line between normal and abnormal brain development to her postdoc in clinical behavioral neuroscience at UClA’s Neuropsychiatric Institute. During biweekly rounds at a coma center, she honed her clinical diagnostic skills on people— mostly young men—with severe head injuries. “It was a medical warehouse with rows upon rows of beds,” she recalls. “Patients ended up there following brain trauma from sports injuries, motorcycle accidents, violence, or suicide attempts.” Every now and then, one of the patients would emerge from the dark depths of unconsciousness, and Moffitt watched the often excruciating struggles to recover cognitive function.

“People who were pleasant, loyal, and thoughtful before a prefrontal lobe injury would wake up as aggressive, disinhibited, and impulsive,” she says. She recalls one man who became so frustrated trying to unscrew the lid off a jar of peanut butter that he smashed the glass jar on a counter and started eating the shard-filled peanut butter.

Moffitt also worked with geriatric patients, observing the heartbreaking ways that dementia alters personality. “As Alzheimer’s dementia slowly destroys the brain, this often changes the loved one into someone who behaves totally out of character, and the effect of this on a family is shattering. These patients convinced me to study the role of brain integrity in mental health.”

As the Human Genome Project got under way in the mid-1990s, Moffitt and Caspi signed on with a fledgling consortium of psychologists and geneticists at london’s King’s College who were exploring how each discipline could inform the other around mental-health issues. By isolating the genomic location of variants associated with obesity or addiction, researchers can then investigate why some of those people do or don’t develop those conditions. What role might pre- or post-natal exposure to toxins have on fetal brain development, for example? How does childhood adversity—a negligent mother or abusive father—compound genetic factors?

“A very nihilistic or deterministic view would be, well those people are so damaged from such an early age that they will never contribute to society, so nothing can be done,” she says. “But the more optimistic view is that the early childhood years are a great time for intervention and preventive measures. We take great care when we write our papers to explain this to readers.”

Along the way, Moffitt has come to understand more about her own genetic tendencies. As a former smoker, she recognizes that she has genetic risk variants that predispose her to tobacco addiction. “Some people smoke an occasional cigarette at a party, or may just have one every few days. They’re called chippers; they can take it or leave it. Our research revealed that they actually have fewer addiction gene variants than do nonsmokers. But if I had one cigarette today, I would probably go ahead and smoke the whole pack, and I’d be addicted again. One of the things we’re looking at is why people who have identifiable genetic variants don’t go on to become addicted or develop conditions like diabetes or schizophrenia.”

Old habits die hard, and the tug of genetics is powerful. She sympathizes with fellow former smokers who figure they can resume puffing away at age sixty. “It takes about twenty years for heavy smoking to result in cancer, and the chances are that you’ll die of something else before the cancer gets you,” she says.

Although she successfully gave up smoking—she quit cold turkey at the funeral of her grandfather, who died of lung cancer—Moffitt admits that despite all she’s learned about health and wellness, she doesn’t work out or eat as well as she should. “You would think that having all this knowledge would have caused me to improve my diet and get more exercise, but I have to say it hasn’t.”

ANCESTRAL HARBOR

Despite the international acclaim, the multidisciplinary partnerships and policy- shaping discoveries, Moffitt is still, in many ways, that wide-open-to-the-world girl who picked violets and hunted for arrowheads, drawn equally to moments of transient beauty and tangible links to long-ago forebears. Her own life trajectory has brought her back to where shestarted, in North Carolina. She and Caspi, the Edward M. Arnett Professor of psychology and neuroscience at Duke, have built a 550-square-foot dogtrot-style house on the site of her family’s original 1920s farmhouse. (The corrugated metal and wood cabin, slightly modified from architect Stephen Atkinson’s plans, was featured in The New York Times.)

Moffitt keeps a close eye on surrounding parcels of land that might come up for sale, hoping to create a healthy buffer against the slow encroachment of developers. Her vision is both pragmatic and idealistic. Buying rural tracts of pristine farmland is a smart financial investment to be sure, but Moffitt also is preserving a familiar, familial home, a harbor in a world fueled by currents both benign and malignant. Those opposing forces of beauty and brutality, in nature and humanity, are what make life—and her life’s work—so compelling.

“I am always fascinated by the astounding variety of humanity,” she says. “I’m never shocked when people are at their most appalling, vile, and nasty, and I’m also enthralled when they accomplish something amazing and loving and beautiful. As a researcher, I’m driven by curiosity about the extreme ends of the human spectrum.”