Vincent P. Dole | Biography

In the 1960s Vincent P. Dole pioneered human studies on the biological basis of heroin addiction. He discovered that methadone can quell an addict's craving and that maintenance doses can return narcotics users to productive lives. Dole's innovative approach to studying addiction as a medical problem was conducted at the Rockefeller University Hospital in New York, a unique clinical research center where a scientific approach to this problem was possible. Dole has spent fifty years in biomedical research at Rockefeller and opened several areas of scientific medicine. His early contributions to understanding metabolic disturbances in patients with kidney disease, high blood pressure, and obesity provided the underpinnings of his seminal work in the biology and pharmacology of addiction.

Vincent Paul Dole, Jr., born in Chicago, Illinois on May 8, 1913, was named after his father, an importer of olive oil and olives. His mother, Anne Dowling, once taught school in the rural Wisconsin village where she grew up. Dole's only brother died in childhood. Young Vincent often went on long trips with his parents to visit his father's business interests. He spent the first two years of secondary school at Loyola Academy in Chicago and the final two years at Culver Military Academy in Indiana.

In 1934, he received a bachelor's degree in mathematics from Stanford University. While fascinated by math, Dole really wanted to explore the interplay of living systems. His aunt, a physician, introduced him to the dean of the University of Wisconsin's medical school, and Dole mastered seven semesters of biology that summer in time to enroll. Two years later, he decided to complete a more research-oriented program and transferred to Harvard Medical School. His M.D. from Harvard in 1939 included both clinical research in psychiatry and rheumatoid arthritis as well as laboratory studies in anatomy. His first scientific publication was on the regeneration of nerves.

Following an internship at Massachusetts General Hospital, Dole was invited to join the Rockefeller Institute for Medical Research in 1941. In the laboratory of Donald D. Van Slyke, a founder of clinical chemistry, Dole participated in hundreds of patient investigations. The clinical scientists in this group observed the effects of various diets on levels of albumin and lipids in the blood, measured the metabolism of proteins, amino acids and fats, and monitored the balance of salts in the body and its effects on edema. The team's work established the standard knowledge about nephrosis (kidney disease) for medical students and physicians.

When the institute's hospital became a naval research unit during World War II, Dole helped develop the copper sulfate method, a test that measures blood density in shock victims, and indicates how much fluid they need to have replaced. Blood banks continue to use this test to determine whether potential donors have sufficient hemoglobin to give blood.

After the war, Dole spent one year at the Massachusetts General Hospital arthritis clinic and another year in Europe studying kidney diseases. He returned to Rockefeller in 1947 to establish his own laboratory devoted to the study of hypertension. Using the hospital's resources to study selected patients, he monitored their metabolic state with many elaborate analyses. He tested the low-salt, low-protein diet recommended for kidney disease on these patients, and discovered that sodium was the salt ion contributing to elevated blood pressure. He also found that the diet's low-protein element contributed to diminished appetite and weight loss. Other studies related to hypertension led to Dole's characterization of human sweat gland physiology. Dole became curious about whether the experimental diet he used for hypertension could also treat obesity term="obesity" project="ntcs" type="index">. In further studies of patients, he discovered that obese people are not consistent overeaters and that their metabolism is abnormal when they lose weight. Dole's work pointed to obesity as a symptom of an underlying metabolic disease.

As he studied obese patients, Dole began to wonder about the function of their fat, whether it was needed, and how it moves from tissues to muscles where it is burned. In the mid-1950s, he made a significant contribution when he isolated free fatty acids from blood plasma. Despite their low concentration, he found their exceptionally rapid turnover was due to their role as the major carrier of energy in the blood stream. He traced their origin to triglyceride molecules in fat cells and showed how they interact with insulin and carbohydrates, findings that are basic to understanding mechanisms of arteriosclerosis (hardening of the arteries).

In 1963, Dole turned his attention to the epidemic of drug addiction he saw growing around him in New York City. At the time addiction had no place in organized medicine, and was assumed to be a sign of moral weakness that was often relegated to practitioners of psychopathology.

However, Dole persuaded Rockefeller president Detlev Bronk to establish the world's first research program on addiction at the university's hospital. This involved getting permission to treat addicts with long criminal records, administering illegal drugs to them without legal interference, and performing medical studies with an unprecedented degree of thoroughness.

Dole approached this novel problem as a physician and as a scientist. He was profoundly influenced by psychiatrist Marie Nyswander and her book The Drug Addict as Patient (1956). Her twenty years of working with addicts suggested that conventional psychotherapy, detoxification, or lock-up programs for chronic narcotic users failed, not through lack of motivation by the addict but for want of effective medical treatment. Physicians Dole and Nyswander (who were married in 1965) admitted tough, hard-core addicts to the Rockefeller Hospital and studied them as sick people. They learned from these patients that they suffered from an organic disease, one needing a medicine that would abolish the pathological craving for narcotics. They needed to restore the addict's neurochemical imbalance before social rehabilitation could even be addressed.

As clinical scientists, Dole, Nyswander, and Mary Jeanne Kreek traced metabolic factors and mechanisms of heroin's action to learn about the body's chemical appetite, tolerance, and physical dependence. They tested many drugs and discovered that a synthetic opiate called methadone--a narcotic in limited use as an analgesic and cough suppressant--had a normalizing effect and eliminated the compulsive narcotic hunger without producing euphoria. They later established that methadone acts as a buffer, and that its stabilizing effect is due to its slow elimination from the body.

Dole's initial studies were successful in treating addicts with daily doses of methadone. Like insulin for diabetes, methadone maintenance only corrects, but does not cure, and must be taken for life. More than two-thirds of those who discontinue methadone treatment return to illegal drugs. However, methadone is life saving, as it makes patients alert, healthy, and helps them resume fulfilling and socially productive lives, free of heroin use.

Within a year, Dole expanded his small clinical study, first to Beth Israel Hospital in New York City and then to the city's municipal hospitals. Methadone maintenance programs continue to have a major impact on reducing both crime and the spread of such epidemic infectious diseases as tuberculosis, hepatitis, and Acquired Immunodeficiency Syndrome (AIDS). "The simple fact is that it works," Dole told contributor Carol Moberg in an interview, and that this "treatment has survived challenge by professional skeptics, by ideologically hostile agencies, and by competitive modalities." Three decades after its beginning, 115,000 heroin addicts are being treated with methadone in 750 clinics in the United States, as well as thousands more in clinics worldwide.

In 1983, Dole broadened his research to study alcoholism, often a complicating factor in narcotic addiction, that afflicts an even greater segment of the population. Until Dole retired from lab work in 1991, he searched for a model of alcoholism in mice so that potential medicines could be tested that would benefit human alcoholics. However, his detailed report in 1986 discusses why he believes mouse metabolic data cannot be correlated with human alcoholism. He discovered that mice burn alcohol eight times faster than humans, so they cannot reproduce the high blood levels and symptoms of intoxication found in humans; also, mice prefer fats or sugars to alcohol when all are offered in their diets.

Dole's family includes three children from his first marriage in 1942 to Elizabeth Ann Strange: the oldest, Vincent, continues to run the family's olive oil business, Susan heads the Vermont Bar Association, and Bruce manages an electronics business. Marie Nyswander, his second wife and research collaborator, died in 1986. He married Margaret MacMillan Cool in 1992.

Dole was appointed a member of the Rockefeller Institute in 1951 and professor in 1954 when the institute became a graduate university. He has published nearly 200 scientific papers during his career and served as editor of The Journal of Experimental Medicine from 1953 to 1965. Dole has received many awards for his work on methadone and for his earlier lipid studies. He was elected a member of the National Academy of Sciences in 1972 and received an Albert Lasker Medical Research Award in 1988. Research into the biology of addictive diseases continues at Rockefeller, where Dole remains active in lecturing and writing.