3 SHARE NOBEL FOR MEDICINE

Author: By Judy Foreman, Globe Staff

Date: Tuesday, October 18, 1988
Page: 1
Section: NATIONAL/FOREIGN

Sir James W. Black, 64, of King's College Hospital Medical School in London, will share the prize money of nearly $400,000 with Gertrude B. Elion, 70, and George H. Hitchings, 83, both officially retired but still working every day at Burroughs Wellcome Research Laboratories in Research Triangle Park, N.C.

In awarding the prize to Elion and Hitchings, the Nobel committee at Stockholm's Karolinska Institute said their work is so important that each of the seven drugs for which they are being honored "could have won a Nobel."

Like many Nobel laureates, yesterday's honorees learned of the award through early morning telephone calls from journalists. At first, Elion simply could not believe it.

Seven hours later, she said in a telephone interview that "I'm just beginning to believe it," adding that, though she and Hitchings had been nominated before, she did not know they had been nominated this year. "I knew people thought Dr. Hitchings would get it, but I don't think I ever thought I would," she said.

Elion, a New York native who earned her bachelor's degree in 1937 from Hunter College and her master's from New York University in 1941, and whom friends in science describe as a "bubbling, enthusiastic person," took advantage of the spotlight to urge young people to go into science.

"It's the most rewarding form of life there is," she said. "I started at a time when women didn't go into science, when it was difficult enough for men to get a job, and even less likely for women. Quite frankly, it was the war that opened the door to women in science. Suddenly, there was a need for people and the men were gone."

Hitchings, a native of Hoquiam, Wash., said yesterday before a previously- scheduled speech at the Memorial Sloan-Kettering Cancer Center in New York that he was "trying to put my trousers on in my apartment at quarter to six in the morning" when the telephone calls began. Hitchings received both a bachelor's and a master's degree from the University of Washington, in 1927 and 1928 respectively, and a PhD from Harvard University in 1933.

A gentlemanly man with the manner of a country doctor, Hitching told reporters repeatedly throughout the day, "I've had a lot of honors, but the most important honors for me have been meeting patients whose lives have been saved by drugs I've invented."

Asked if he would work even more than his customary eight to 10 hours a day, Hitchings grinned and said, "I'm usually the first one at work, and it would be a little hard to work any harder."

The Nobel committee cited Hitchings and Elion for "important principles of
drug development."

"While drug development had earlier mainly been built on chemical modification of natural products, they introduced a more rational approach based on the understanding of basic biochemical and physiological processes," the committee said.

Elion and Hitchings analyzed the DNA or genetic material in normal human cells and the DNA in constantly-growing cancer cells, bacteria, protozoa and viruses, trying to figure out precisely how cells put together the building blocks of DNA.

The first breakthrough came in the early 1950s with an antileukemia drug called 6-MP, or 6-mercaptopurine.

Dr. Emil Frei, the chief physician at Boston's Dana Farber Cancer Institute, yesterday recalled the excitement about 6-MP, which turned out to be an "extraordinarily successful" drug still widely used. It "gives complete remission in 40 percent of children with leukemia" by blocking a cancer cell's ability to make viable forms of DNA, Frei said, adding that Hitchings' and Elion's Nobel honor is "fantastic. They are old and dear friends. Nobody could be more deserving."

Dr. Robert Gallo, head of tumor cell biology at the National Cancer Institute and often mentioned as a Nobel candidate himself for discovering the AIDS virus, said in reference to 6-MP's effect on a relative: "My own sister was one of the first to get at least temporary relief because of their work." He added: "They are also very nice people."

But 6-MP and another antileukemia drug, thioguanine, were just the beginning. As Frei recalls, Hitchings and Elion "immediately recognized" the importance of a side effect of the drugs, suppression of the immune system.

While a lowered immune response is detrimental to cancer patients, it is crucial in preventing rejection of transplanted organs. Hitchings and Elion, determined to exploit this effect, within a few years developed azathioprine, or Imuran, the drug that first made organ transplantation possible. Indeed, a plaque at Boston's Brigham and Women's Hospital, site of the world's first kidney transplant, honors Hitchings for this work.

The North Carolina team went on to develop a drug called pyrimethamine to fight malaria and another, allopurinol, against gout. In 1977, they developed acyclovir, the first effective treatment for herpes.

Erling Norrby, a Nobel committee spokesman, said yesterday that the team's work also led in a sense to the only US-approved AIDS drug, AZT, or azidothymidine, which tricks an infected cell into using phony building blocks for DNA, thus inhibiting reproduction of the virus. Norrby said the development of AZT capitalized on revelations by Hitchings and Elion on how chains of DNA are built.

Actually, AZT was developed as an anticancer drug in 1964 by Dr. Jerome Horwitz, chairman of the chemistry department of the Michigan Cancer Foundation in Detroit, who said his work was not directly related to that of Elion and Hitching. AZT did not work well against cancer, but several years ago it was shown by other researchers at Burroughs Wellcome and the National Cancer Institute to inhibit reproduction of the AIDS virus.

The British laureate, Black, won the prize for developing the first clinically useful beta blocker, propranolol, in 1964 for treatment of angina, heart attacks and hypertension. Propranolol acts on beta receptors in nerves leading to the heart, blocking the stimulating effect of the stress hormone, adrenaline. The Nobel committee proclaimed this "the greatest breakthrough when it comes to pharmaceuticals against heart illness since the discovery of digitalis 200 years ago."

Black, speaking at a press conference in London, quipped, "I wish I had my beta blockers handy."

Black was also cited for his 1972 discovery of a group of histamine receptors, molecules on the surfaces of cells to which other substances bind, that play a role in stomach ulcers. Black developed a drug called cimetidine to block these so-called H-2 receptors.

FOREMA;10/17 JOBE ;10/18,17:45 NOBEL18