When most lights in the dormitory went out, David Kupfer’s stayed on. A history and economics major at Yale College, Kupfer, M.D. ’65, couldn’t understand why his peers needed so much sleep. At the time, he didn’t realize sleep would influence his career—that he would become a leader in sleep, depression and bipolar disorder research—and that observing two cases of narcolepsy would set him on this path.While in medical school and still undecided about a specialty, Kupfer saw two patients at Yale-New Haven Hospital (YNHH) who suffered from an extreme exhaustion called cataplexy that results in a complete loss of muscle control. Both were also diagnosed with narcolepsy.Seeing these two patients solidified Kupfer’s decision to study sleep, but two encounters with a Yale professor molded his career. As a second-year student he met Thomas Detre, M.D., then chief of psychiatry at YNHH, whose interests included recurrent depression, violence and aggression in children, biologic aspects of mental disorders and the budding fields of psychobiology and psychopharmacology. At a time when there was little understanding of mental diseases, Detre felt that understanding the body could lead to better treatment of mental illness.During Kupfer’s third year, a last-minute trade with a classmate led to a chance reunion with Detre and solidified Kupfer’s decision to pursue psychiatry. The night before beginning his psychiatry rotation at the VA hospital in West Haven, Kupfer agreed to switch rotations with a classmate who wanted to work at the VA. Kupfer was back at YNHH with Detre. They soon realized they had a lot in common—both were high-energy and stayed up late. Detre expected diligence and Kupfer delivered.“Some people have considered [Detre] a tough taskmaster because he was so persistent. I found him loyal and supportive and clever. He gave me freedom,” Kupfer said.After medical school, Kupfer trained at the National Institute of Mental Health (NIMH), then returned to Yale in 1969 as an NIMH investigator and assistant professor of psychiatry. Kupfer’s career was blossoming at Yale, but Detre asked him to join him at the University of Pittsburgh and its Western Psychiatric Institute and Clinic (WPIC), which Detre felt he could transform to better treat patients with mental illness. In 1973, Kupfer went to Pitt as an associate professor of psychiatry and director of research. In 1983, he became director of the WPIC and chair of the Department of Psychiatry when Detre became senior vice chancellor for health sciences. In 1994, further cementing the connection between these remarkable colleagues, Kupfer was named the first Thomas Detre Professor of Psychiatry.Finally retired from his 23-year career as vice chancellor, Detre now serves as a professor emeritus of psychiatry and is teaching a course to residents on psychiatric diagnosis. He sits on the boards of two software companies in Pittsburgh and is also on the scientific advisory board of PsychoGenics, a New York-based company that tests neurological drugs.At Pitt, Kupfer stressed the importance of determining the biological underpinnings of psychiatric disease and led a research revolution by earning a number of NIMH grants for research on sleep disturbances, depression and bipolar disorder. The number of faculty and beds increased, along with the reputation of Pitt’s psychiatry program. “From 1983 to 1993 the department went from Number 4 to Number 1 in federal research funding,” Detre explained.With his wife, Ellen Frank, Ph.D., Kupfer co-directs the Bipolar Disorder Center for Pennsylvanians, created with a $5 million grant from the commonwealth. He is principal investigator of several studies, including one on the pharmacogenetics of bipolar disease.“You’re going to laugh when I say this—writing is very difficult for me,” he said. He has written 800 articles, books and book chapters. His latest book, written for a general audience with Helena Chmura Kraemer, Ph.D., and Karen Kraemer Lowe, M.S., is titled To Your Health: How to Understand What Research Tells Us About Risk, and stresses the importance, throughout medicine, of designing more rigorous clinical trials and clearly defining the results. As a case in point Kupfer cites media reports of studies that appeared to show a high risk of suicide among young children on antidepressants. According to Kupfer, many of the studies poorly defined the risk.Kupfer hopes that someday more physicians will value the relationship between mental and physical illnesses. Research has shown that depression, for example, makes people more susceptible to other illnesses, like diabetes. Kupfer feels that many doctors treat the diabetes rather than exploring the link between the depression and diabetes. He hopes this paradigm changes soon—patients who receive poor mental health treatment face serious health risks, just like patients who receive the wrong medical care.It might keep Kupfer up at night, but that’s when he does his best work.