Addiction is a formidable research subject, involving long-elusive brain mechanisms and a murky line between the biological and the psychological. The moral stigma often associated with addiction long provided an equally obdurate hindrance to those who wished to understand and help drug-addicted people. Studying one of the most formidable addictions — heroin — Vincent P. Dole, a physician-scientist at The Rockefeller Institute for Medical Research, overcame these obstacles and ultimately developed a treatment that not only ended heroin use in most patients but also provided an entirely new way of approaching addiction — as a medical problem, with a medical answer. For his development of methadone maintenance therapy, Dr. Dole received the 1988 Albert Lasker Clinical Medical Research Award.
By the early 1960s, heroin addiction had become the biggest public health issue affecting New York City, where approximately half of the country’s heroin addicts lived. As chair of the committee on major medical problems for the Health Research Council of the City of New York, Dr. Dole found himself at a crossroad when he discovered that very little basic clinical research on opiate addiction existed. Though he had firmly established a research path in obesity and related metabolic disorders, Dr. Dole changed the focus of his laboratory in 1963 and created the world’s first medical research program to study drug addiction. By the following year, he had begun clinical tests with methadone treatment.
Though its chemical structure bears no resemblance to the natural opiates, methadone, a synthetic painkiller developed in 1937, triggers the brain’s opioid receptors and thus produces many of the same effects as heroin or morphine, though without the same euphoria or debilitating physical side effects. For this reason, some in the medical community had theorized that it may be useful in mitigating the effects of heroin withdrawal syndrome. Dr. Dole, along with his colleagues Marie Nyswander (later his wife) and Mary Jeanne Kreek, recruited 22 heroin-addicted subjects to test the effects of replacing heroin with regular methadone treatment. Observing the metabolic effects of various dosage levels and administration methods, the researchers discovered that not only does methadone substantially ease the pain and distress of heroin withdrawal, but it promotes stability during the detoxification process through its very slow elimination from the body. Perhaps most crucially, they found, methadone can also be cross-tolerant: Treated with a high enough dose, the brain stops responding to other opiates.
Within a few short years, Dr. Dole’s methods were being successfully applied by physicians treating addicts. Because methadone is significantly longer lasting than other pharmaceuticals in its class and is comparatively inexpensive, public treatment programs were a highly feasible option, and by the early 1970s, methadone maintenance programs were being established in clinics across the country. Though it is not a curative and must be administered to patients indefinitely, sociological studies have shown that in conjunction with other psychological therapies, methadone programs also definitively reduce the larger effects of heroin addiction on communities, including health care costs, criminality and transmission of infectious diseases through sharing of injection equipment.
Dr. Dole’s success with methadone maintenance effected the beginning of a cultural shift by positing drug addiction as a medical disease rather than a character flaw. The National Institute on Drug Abuse, the first federal research agency to focus on addiction, was established in 1974. Dr. Dole’s work also resulted in the partial legalization of opiate maintenance therapy in the United States, which had been made illegal outside of cancer treatment in 1914. By 2006, when Dr. Dole died, over one million patients worldwide were receiving methadone maintenance treatment. To this day, it remains the most empirically studied and most successful pharmaceutical used for the treatment of drug addiction.
Born in Chicago in 1913, Dr. Dole was educated at Stanford University and Harvard Medical School, receiving his M.D. degree from Harvard in 1939. He joined The Rockefeller Institute in 1941, following an internship at Massachusetts General Hospital. During World War II, he served as a lieutenant commander in the Naval Medical Research Unit established at Rockefeller. After the war, he continued his research at Mass General and in Europe, returning to Rockefeller and establishing his own laboratory in 1947. He became a full member of the institute in 1951 and a professor in 1955 when the institute began its graduate studies program. He served as editor of The Rockefeller University Press’s Journal of Experimental Medicine from 1953 to 1965. Dr. Dole was a member of the National Academy of Sciences. He retired in 1991, and died in 2006.