In 1979, Thomas R. Insel had just finished medical school and three years of training in Jungian psychoanalysis. That was when the psychiatrist became a clinical associate at the National Institute of Mental Health in Bethesda, the federal government's top institute for the study of mental illness.
It was partly an accident -- Insel replaced someone who had dropped out at the last minute.
On Monday, Insel will return to the NIMH -- but this time it is no accident. He will arrive as director of the agency and its $1.3 billion annual research program. Along the way, sticking to a penchant for variety, Insel has made breakthroughs in the treatment of obsessive-compulsive disorder, managed one of the nation's largest AIDS vaccine primate research programs and figured out why some rodents are monogamous.
The range of Insel's interests does not mean, however, that the institute's focus is to become diffuse. Just the opposite. Insel's recent work has focused on basic questions about brain biology and the influence of genes on behavior. The decision to appoint him director seems to be a clear statement about where psychiatry is headed: Both Insel and his field have spent the past quarter-century moving steadily away from psychoanalysis and the legacy of Sigmund Freud, and increasingly into the arms of neuroscience.
While Insel's plans for the NIMH are still coalescing, one thing is certain: Under his watch, the institute will intensify its focus on basic brain biology, especially in areas that have hitherto been largely the purview of psychoanalysts, sociologists and anthropologists.
"For psychiatry, the basic science should get at complex social behaviors. The neurobiology of social hierarchy, the neurobiology of loss," said Insel in a recent interview at his offices at the Center for Behavioral Neuroscience at Emory University School of Medicine.
Unlocking Complex Mental Disorders
While a debate still rages over whether such complex behaviors can be understood through the mechanisms of the physical brain, Insel's research has convinced him that focusing on genes and neurobiology will help unlock some of the most complex mental disorders.
Insel's research on voles, a species of mammals similar to mice, received much attention in 1999. Insel identified a family of neuropeptides -- chemicals in the brain found in species from humans to invertebrates. Brain receptors for these chemicals are found in different parts of the brain in different species. Insel found that among voles, the placement of these receptors determined whether the voles were monogamous.
"One group of voles are highly social, they huddle all the time," he said. "The non-monogamous species avoid social contact."
Uniquely in the brains of monogamous voles, Insel found that the receptors were in the reward centers of their brains. When Insel and his team engineered the non-monogamous voles to have receptors in the same area, they seemed to become somewhat more social.
"It was the first example in neuroscience where we go from variation in genes to cellular expression in the brain to behavior and social organization," he said. "It gave us a model on how we can go from genes to behavior."
The discovery sparked tremendous journalistic interest around the world, with several reports immediately drawing the irresistible -- but wrong -- conclusion that Insel had discovered a "cure" for infidelity in humans. Insel and other scientists tried to point out that the behavior of human beings is considerably more complicated than that of voles, with culture and the environment playing at least as important a role in the development of personality as brain structures do. The scientists said that, unlike voles, humans don't seem to have the receptors scattered in a wide range of brain locations and that, in any case, monogamy in voles is less related to sex and more to a commitment to raise offspring.
The real impact of the research, Insel said, is that it could offer a better understanding of human disorders such as autism. Autistic people are often unable to form reciprocal social relationships, he said, and there is strong evidence that the disorder has a genetic and neurological basis.
Insel believes that research along the lines of his work can unearth a number of genes and brain chemicals that could each have a small effect on the development of complex disorders such as autism, depression and anxiety.
"In the post-September 11 world, how do events lead to post-traumatic stress disorder?" he asked. "How do certain memories become traumatic? Most of us extinguish traumatic memories. . . . [We] should study what it takes to forget a traumatic event. There is neurobiology to it."
Human Genome's Yellow Pages
Insel describes the completion of the human genome project as a central landmark, comparing it to the telephone directory's white pages. But while an alphabetical listing is comprehensive, it doesn't help in the quick search for a plumber. Insel said the NIMH will help write the genome's yellow pages -- identifying and clustering genes according to what they do -- and make it possible to identify which genes are involved in specific brain activities.
Insel's subordinates would be wise to quickly learn a motto he adopted when he first came to the NIMH more than two decades ago: "There are two things to do to be successful," he declared. "Do something no one else is doing, and do something that has an impact."
Shortly after coming to the NIMH in 1979, for example, Insel found that most of his colleagues were studying depression. Following the precept of "plowing a field that hadn't been plowed," he turned his attention to obsessive-compulsive disorder, a condition in which patients are overwhelmed by their own compulsive rituals.
Insel conducted a trial in which drugs that boosted the level of a brain chemical called serotonin seemed to help such patients. The discovery has led to widespread treatment along similar lines.
He believes his background in clinical practice, combined with his expertise in basic science, is what prompted his appointment as director of the NIMH.
And what about the early influence of psychoanalysis?
"It's a long way from Jungian analysis," he said, with a smile, of his current work. "I'll never get back there."