Rupert Billingham, a pioneer in the field of organ transplantation, has died aged 81. In 1953 he was a co-author with the immunologists Peter Medawar and Leslie Brent of perhaps the most important paper in the history of the research that led to organ transplantation.
They showed it was possible to coax the body of an animal to accept foreign tissue transplanted from another. Skin taken from a white mouse could be accepted as "self" by the immune system of a brown mouse, if transplanted early in life, a condition defined as "immunological tolerance".
In a remarkable gesture, Billingham and Medawar decided that Leslie Brent, then a young PhD student, would present their astonishing findings, in what was to become a Nobel prize-winning paper, to the British Society for Experimental Biology at the Royal Society of Medicine.
Billingham and Brent also discovered later that in some cases a transplanted organ could reject its new body (in the process known as "graft-versus-host") that posed additional complications for bone marrow transplants.
Billingham, a dairy farmer's son, was born in Warminster and educated at the City of Oxford High School and Oriel College, Oxford. After wartime naval service, he returned to Oxford to become Medawar's first graduate student and long-term collaborator.
Successive attempts at human-to-human kidney transplantations were tried in the 1930s and failed. The reason for this was unclear until the second world war, when Medawar, then a young immunologist, was considering the problem encountered with skin grafting in severely burned servicemen.
He observed that initial skin grafts transplanted from one animal to another survived seven days; if an identical second graft was performed with the same two animals, the second set of skin lived a much shorter time. This phenomenon recognised that the immune system was responsible for the rejection of organ transplants; it was called the "second set response" and became the basis for the understanding of tissue incompatibility within species, as well as the body's ability to mount a host defence that ultimately destroys the transplanted tissue.
Although it was Medawar who received the Nobel prize for medicine in 1960 for the understanding of immunolog ical tolerance, he described in his memoirs the crucial collaboration that he and Billingham enjoyed of several years first at Oxford, and then at Birmingham and University College, London.
Medawar described in his Nobel prize acceptance lecture how he and Billingham revisited the discovery made by a veterinary geneticist, RD Owen, that most twin cattle were born with, and retained throughout life, a mixture of each other's red cells. This was the first known example of the phenomenon that became known as immunological tolerance.
The relevance of Owen's discovery arose when the pair were asked by scientists from the Agricultural Research Council if they could distinguish between fraternal and identical twins in cattle. The two immunologists believed the question could be settled by skin grafts; only identical twins would tolerate grafts. In practice, all the skin grafts were accepted, and Medawar and Billingham reasoned it was the effect of blood cells exchanged during development in the uterus.
They applied this knowledge in the experiments in Medawar's laboratory at University College. The trick was to coax tolerance in mice by first injecting lymphoid cells from a prospective donor strain into prenatal mice of another strain. When the intended recipient reached adulthood, the skin grafts were made and survived.
The discovery of the conditions when immunological tolerance could exist provided surgeons with the confidence to reconsider kidney transplants. In 1954 doctors transplanted a kidney from one identical twin to another, and in 1959 a kidney was successfully transplanted between fraternal twins.
In 1957 Billingham moved to the Wistar Institute in Philadelphia, and established a very successful kidney transplant centre. In 1971 he moved to the Southwestern Medical School in Dallas and his interest turned to reproductive immunology and understanding the most successful natural transplant of all, the foetus.
Researchers had little success using donor cells to inoculate humans who were going to receive transplants, and developed the use of immuno-suppressant drugs to stop the body's defences from rejecting a transplant. But the principle remains sound and might eventually answer the problem of a heavy burden on patients sometimes posed by the immuno-suppression therapy.
Although Billingham did not share a Nobel prize; Medawar shared the prize money with his collaborators. Billingham retired in 1986 and moved to Martha's Vineyard, with his wife of 53 years, Jean, who helped him and Medawar in their early work. She and their two sons and a daughter survive him.
· Rupert Everett Billingham, immunologist, born October 15 1921; died November 16 2002
