Dr Vincent Dole

Pioneer of methadone treatment
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The Independent Online

Vincent Paul Dole, physician: born Chicago 18 May 1913; MD 1939; staff, Rockefeller Institute (later Rockefeller University) 1941-93, Professor 1955-93; married 1942 Elizabeth Strange (two sons, one daughter; marriage dissolved 1963), 1965 Marie Nyswander (died 1982), 1992 Margaret MacMillan Cool; died New York 1 August 2006.

Vincent Dole was a physician with a distinguished research record when he introduced the concept of treating heroin addiction with methadone, an idea that was taken up around the world with lasting success.

Dole developed his methadone maintenance programme in the 1960s at Rockefeller University, New York, in collaboration with his second wife, Marie Nyswander. Methadone was a synthetic variant of heroin, designed by German scientists during the Second World War when heroin had become unavailable for medical purposes, but it was rarely used medically because it was highly addictive.

Its value was that it could be administered in a single daily dose, could be taken by mouth (thus removing the health risk of reusing dirty needles), and locked onto the receptors in the body that heroin attaches itself to, thus blocking the action of any heroin taken in the following 24 hours. It satisfies the heroin craving while avoiding the frequent and extreme mood shifts that are characteristic of heroin addiction, so that addicts are able to live normal, productive lives.

The treatment's success was shown in a 15-year study by a New York state-funded research centre, which evaluated computer records on 96,000 addicts who entered maintenance programmes from 1964 to 1979.

Dole started his work on addiction in the early 1960s, when heroin use had become widespread in New York. At the time, addiction was usually regarded as a moral and legal problem. Addicts were often thrown into overcrowded prisons, where their addiction remained untreated. Few doctors were interested in the problem, though a handful of addicts had been treated with psychoanalysis or, in extreme cases, brain surgery. Dole saw addiction as a medical problem, and his research, including animal studies, led him to see that it was a physiological condition, and that, like diabetes, it could be treated, but not cured.

Dole was born in Chicago in 1913; his father was an importer of olive oil and his mother a schoolteacher. His schooling was at Loyola Academy in Chicago and Culver Military Academy in Indiana. In 1934 he graduated top of the class in mathematics at Stanford University, California, but wanted to solve human problems.

His aunt, a physician, introduced him to the Dean of Wisconsin University Medical School, and Dole mastered seven semesters of biology that summer in order to enrol. Two years later, seeking a more research-orientated course, he transferred to Harvard Medical School. He qualified with an MD in 1939 that included research in psychiatry and rheumatoid arthritis. His first scientific publication was on nerve regeneration.

He did his postgraduate medical training at Massachusetts General Hospital and was invited to join the Rockefeller Institute for Research, now Rockefeller University, in 1941. Working with Donald van Slyke, a founder of clinical chemistry, he did a huge amount of basic research in human metabolism and established our standard knowledge of renal failure.

During the Second World War, the Institute's hospital became a military hospital and Dole was drafted into the Navy, continuing to be based at Rockefeller. He helped develop the copper sulphate technique for measuring blood density in shock victims. The test enabled doctors in the field to estimate how much replacement fluid a patient needed when suffering from blood loss and the resulting shock. This test is still in use today, worldwide, to test blood donors for anaemia.

After the war, Dole returned to "Mass General" for a year in the arthritis clinic and spent a further year in Europe studying kidney diseases. He returned to Rockefeller in 1947 to study patients with high blood pressure. By feeding hypertensive patients the low-protein, low-salt diet given to renal failure patients, he found that sodium was the ion that contributed to high blood pressure, and that a low-protein diet contributed to loss of appetite and weight loss.

He then applied these observations to obese patients, curious to discover how fat moves to muscles when it is burned. He isolated free fatty acids from blood plasma and found that despite their low concentration they had a high turnover and were the major carrier of energy in the circulation. He traced their origin to triglyceride molecules in fat cells and showed how they interacted with insulin and carbohydrates. These findings underpin the understanding of arteriosclerosis.

Dole turned his attention to drug addiction in 1963, when it had become a problem around him in New York. He persuaded Detlev Bronk, the Rockefeller president, to establish an addiction clinic. This entailed administering illegal drugs to addicts without legal interference and performing thorough medical studies. Dole was profoundly influenced by a book, The Drug Addict as Patient (1956), by Dr Marie Nyswander, who ran a street clinic for addicts. The book suggested that psychotherapy, detoxification and prison were equally unsuccessful for addicts, though not because they lacked motivation.

Dole and Nyswander, who married in 1965, admitted tough, hard-baked addicts to Rockefeller Hospital and studied them as patients who needed medical help. They tested many drugs, of which methadone was substantially the best.

In 1983 Dole extended his work to study alcoholism, and established that it was impossible to establish a model of alcoholism in mice, because mice metabolise it eight times faster than humans, and therefore cannot become intoxicated, and that they cannot be persuaded to consume alcohol in preference to carbohydrates and fats.

He lectured world-wide on addiction, and methadone was taken up with success around the world far more rapidly than in the United States, where rigid official attitudes curtailed its use. He received honours including, in 1980, a Lasker Award, the next best thing to a Nobel prize. He officially retired at 80 but continued working at Rockefeller every day until he was 90.

His hobby was mountain climbing. Among other achievements, he reached the top of the Matterhorn.

Caroline Richmond

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