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Subject: R. E. Billingham, 81, Transplant Researcher

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Date Posted: November 29, 2002 2:34:46 EDT

Dr. Rupert E. Billingham, whose pioneering research into ways to coax the body to accept foreign tissue helped pave the way for organ transplants, died on Nov. 16 at Brigham and Women's Hospital in Boston. He was 81 and lived in Martha's Vineyard, Mass.

The cause was complications of Parkinson's disease, his family said.

In the years after World War II, when Dr. Billingham was a graduate student at Oxford, doctors were looking to the day when they might be able to remove a failing organ from a human patient and replace it with a healthy one from a donor. But they were deterred from trying it, aware of the body's tendency to treat transplanted tissue the way it does any invader, by marshaling its forces to fight it.

In 1953 Dr. Billingham wrote an article for the journal Nature with his mentor, Dr. Peter B. Medawar, and their colleage Dr. Leslie Brent, describing their success at grafting skin from white mice into brown mice.

The trick, the researchers wrote, was to inoculate the brown mice at birth, or even in utero, with cells from the white mice. The brown mice acclimated to the foreign tissue, much as a person with allergies can be desensitized by exposure to small amounts of an allergen, and when they grew up they accepted skin grafts from the white mice.

The article, with its suggestion that the rejection of foreign organs could be overcome, was the signal other researchers were awaiting. The next year, doctors transplanted a kidney from one identical twin to another, and in 1959 a kidney was successfully transplanted between fraternal twins.

By the mid-1960's, after Dr. Medawar had won the 1960 Nobel Prize in Medicine and been knighted, kidney transplants were becoming increasingly common. In the United States alone now, more than 20,000 organs of all sorts are transplanted each year.

The methods used, however, are not the ones described in Dr. Billingham's 1953 article. Researchers have had little success using donor cells to inoculate humans who are going to receive transplants. Only within the last year have researchers reported using the original technique in humans.

"The principle is sound, and is one that for the last half century a lot of people have been working at," said Dr. Clyde F. Parker, who was a postdoctoral fellow under Dr. Billingham and a professor of surgery at the University of Pennsylvania.

For now, doctors rely on another technique that Dr. Billingham developed during the same period: the use of immunosuppressant drugs to stop the body's defenses from rejecting a transplant. But the drugs can place a heavy burden on patients, in part because they do not allow the body to discriminate foes like infectious disease.

"The big problem we have now is, the immunosuppression is almost as bad as the disease itself," said Dr. J. Wayne Streilein, another former postdoctoral fellow under Dr. Billingham and a professor of ophthalmology at Harvard.

Rupert Everett Billingham was born in Warminster, England. He studied at Oxford and, after serving in the Royal Navy during the war, returned there to become Dr. Medawar's first graduate student. In the late 1950's he took a job at the Wistar Institute in Philadelphia, and later taught at the University of Pennsylvania and the Southwestern Medical School in Dallas.

Dr. Billingham retired in 1986 and moved to Martha's Vineyard, with his wife of 53 years, Jean Morpeth Billingham, who helped him and Dr. Medawar in their early work.

Dr. Billingham and another graduate student of Dr. Medawar's, Dr. Brent, have also been credited with discovering that in some cases, the transplanted organ can reject its new body. Known as graft-versus-host, the process poses a significant complication for bone marrow transplants.

In Dallas, seeking insight into ways to improve the body's acceptance of transplants, Dr. Billingham also conducted research into what happens when the body chooses not to fight off a foreign body, most notably in pregnancy.

Once an embryo is implanted, he discovered, the uterus undergoes a change that gives it "privilege" from the immune system.

Although Dr. Billingham did not share a Nobel Prize with Dr. Medawar, associates said Dr. Medawar shared the prize money with him and Dr. Brent.

"There are only two or three great transplantation immunologists in our lifetime," Dr. Streilein said. "He was one of them."

In addition to his wife, Dr. Billingham is survived by three children, John, of Brooklyn; Peter, of Dallas; and Elizabeth Billingham of Weston, Mass.

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