By DENNIS HEVESI
Published: August 3, 2006

Dr. Vincent P. Dole, who along with a young researcher who later became his wife did the studies proving that the synthetic drug methadone blocks the cravings of heroin addicts, died Tuesday in Manhattan. He was 93.
The death was announced by Rockefeller University in Manhattan, where Dr. Dole and Dr. Marie Nyswander, his second wife, did their research in the mid-1960’s. The university was then the Rockefeller Institute for Medical Research.

Although Dr. Dole and Dr. Nyswander never considered methadone a silver bullet for heroin addiction, their work is credited with making it possible for thousands of addicts to lead normal lives.
“There are over a half-million people on methadone maintenance today,” said Dr. Mary Jeanne Kreek, director of the Laboratory of the Biology of Addictive Diseases at Rockefeller University. “That means they are on regular medication, just like anyone with a chronic disease.”

This view of heroin addiction as a medically treatable disease was shared by Dr. Dole and led to his frequent and forceful efforts to open methadone clinics in New York City and keep them open in the face of sometimes strong opposition.

In 1988, Dr. Dole received the prestigious Albert Lasker Medical Research Award for his work on methadone.

Vincent Paul Dole was born on May 18, 1913, the son of Vincent and Anna Dole of Chicago. He received a bachelor’s degree in mathematics from Stanford in 1934 and a medical degree from Harvard in 1939. In 1941, after an internship at Massachusetts General Hospital in Boston, he joined the Rockefeller Institute as an assistant in kidney research.

In World War II, Dr. Dole served as a lieutenant commander with the Naval Medical Research Unit at the Rockefeller Institute’s hospital. In 1947, he was named an associate member of the institute and, in 1951, a full member. When the institute became a graduate university in 1955, he was appointed a professor.

When Dr. Dole began planning to study the biology of addiction in the mid-60’s, he could find only one significant book on street addicts, “The Drug Addict as a Patient,” by Dr. Nyswander, who was then a psychiatrist treating addicts at a Manhattan storefront clinic. Dr. Dole asked her to join him in his research project. Within a year, he asked her to marry him. Dr. Nyswander died in 1986.

Dr. Dole’s first marriage, to Elizabeth Strange of Montreal, ended in divorce. A resident of Manhattan, Dr. Dole is survived by his third wife, Margaret MacMillan Cool; three children from his first marriage, Vincent, of Washington, Bruce, of St. Louis, and Susan, of Arlington, Va.; four stepchildren, John Cool, of Pelham, N.Y., Ellen Kwait, of Marblehead, Mass., Mary Lee Gupta, of Manhattan, and Adrienne Cool, of Oakland, Calif.; 13 grandchildren; and a great-grandchild.

It was in 1964 that Dr. Dole and Dr. Nyswander started testing methadone on addicts who had used heroin for at least 14 years and had been in and out of detoxification centers and, in many cases, in and out of prison.

Methadone’s origins go back to World War II, when German scientists synthesized it as a painkiller for wartime casualties. But in their research, Dr. Dole and Dr. Nyswander found that 100 milligrams of the drug blocked the effect of 200 milligrams of heroin — the equivalent of several highs.

Methadone has several advantages, many addiction experts say. It affects the brain’s receptors for 24 hours, blocking heroin’s three-minute euphoric rush. Its slow onset, as opposed to heroin’s spiky highs, eliminates mood swings, making an addict feel normal. It can be taken orally rather than injected, and it has a much lower risk of overdose.

But there are drawbacks. Methadone creates a physical dependence that can be as strong as heroin addiction, and many street addicts now also use cocaine, which methadone cannot block. Also, the purity of street heroin has more than doubled in recent years, requiring higher doses of methadone to block its effects.

Still, as Dr. Kreek of Rockefeller University said, thousands of methadone users “now live normal lives; they work, they pay taxes and their possibility of getting AIDS is reduced or eliminated because they are no longer injecting.”