'Like Joining a Select Club'

John Keats has vividly described his excitement on seeing for the first time Chapman's translation of Homer. I had a somewhat similar experience in 1942. During my early surgical training in Australia, the only grafts I learned about, apart from blood transfusion, were autografts of skin, bone and fascia, and allografts (called homografts in those days) of cornea. I was iguorant of the numerous attempts by surgeons to use allografts of skin, and of the long controversy about whether these did or did not behave like autografts. I assumed, if I thought about it at all, that autografts were used simply as a matter of convenience, except in the case of cornea where this was obviously impossible. Therefore it came as a complete surprise when, as a prisoner of war in Singapore, I happened to read, in a copy of Rodney Honor Maingot's Postgraduate Surgery that we had managed to salvage from the medical school library after the fall of Singapore in February 1942, that skin grafts transplanted from one person to another often took initially but did not survive permanently. How could anyone distinguish between his own skin and that of someone else, yet happily accept a corneal allograft? I resolved that, if I survived the war, I would investigate the matter. Three and a half years later, when the war ended, I learned of the work of Tom Gibson and Peter Medawar with human skin allografts, and Medawar's subsequent experiments with skin grafts in rabbits. Although this work established that allograft rejection was an immunological phenomenon, Gibson was a plastic surgeon and Medawar an experimental biologist, and for a long time much of the research on transplantation was undertaken by people who were not professional immunologists. For a year after the war I was fully occupied in becoming readjusted to civilian life, getting married and resuming my interrupted surgical training, but my long-awaited opportunity arrived when, in September 1946, I took a junior appointment in the Department of Surgery in the University of Sheffield. We managed to obtain a passage to England, where my having to take the final examination for Fellow of the Royal College of Surgeons and to rewrite a report about deficiency diseases in Changi, Singapore, for the Medical Research Council caused a brief delay in plans. Shortly thereafter I became immersed, insofar as surgical and teaching duties allowed, in transplantation research. This was like joining a select club, for at that time only a few dozen people in the world were working in the field, among them Medawar and Peter Gorer in England and Converse, Hume and H.S.N. Greene in the United States. Greene was interested in the behavior of allografts in immunologically privileged sites, and after reading his papers my wife and I embarked on a study of the behavior of thyroid grafts in the anterior chamber of the eye in guinea pigs. This work sufficiently impressed Charles Kellaway, a former teacher of mine who was now director of the Welicome Research Laboratories in London, for him to offer to communicate it to the Royal Society, and it was subsequently published in Philosophical Transactions B. It seemed an auspicious beginning. There was a lot of reading to be done, and I became acquainted with Leo Loeb's book, The Biological Basis of Individuality, and J.B. Murphy's remarkable monograph, "The Lymphocyte in Resistance to Tissue Grafting, Malignant Disease, and Thbercubus Infection," published in 1926 by the Rockefeller Institute. Murphy's book made me decide to try to raise an antibody against lymphocytes, in the hope that it would have immunosuppressive properties. Another person who greatly influenced me was MacFarlane Burnet. He was a friend and colleague of my father in Melbourne, and in 1949, just after we had moved from Sheffield to Aberdeen, he and his wife stayed in our home for a few days. We talked about his prediction that an animal would become tolerant of antigens it encountered during early embryonic life, and my wife and I set out to test this by grafting a minute piece of allogeneic skin to rat fetuses in utero and challenging the survivors with a donor-strain graft when they were a few weeks old. None of our rats showed any degree of tolerance, doubtless because our initial graft did not provide an adequate tolerogenic stimulus. It was disappointing at the time, and somewhat humiliating to learn later from Medawar and his colleagues how the experiment should have been performed. People soon began to think seriously about the possibility of organ transplantation. Some surgeons became impatient, and began transplanting kidneys, but for more than a decade without success except, as Murray and his colleagues in Boston showed, when donor and recipient were identical twins. During this time the foundations for a new era were being laid by patient research, due in no small measure to people who managed to maintain a foothold in both the clinic and the laboratory. The fruits of this research include the development of chemical immunosuppression and tissue matching; the enticing prospect of being able, one day, to make prospective recipients nonreactive to donor tissue; and an extraordinary spinoff in fundamental immunology. But that, as they say, is another story. A pioneer of tissue transplantation, Sir Michael Woodruff is Emeritus Professor of Surgery at the University of Edinburgh, Scotland. Born in 1911, he was educated at the University of Melbourne and served in the Australian Medical Corps during World War II. In 1951, recording his observations as a prisoner of war, he jointly authored Deficiency Diseases in Japanese War Camps. During the early 1960s, Woodruff found he could overcome the body's rejection of transplanted tissue by using serum containing antibodies against the white blood cells (lymphocytes) that otherwise attack foreign cells. Prepared by injecting human lymphocytes into a horse, "anti-lymphocyte serum" proved useful in facilitating the grafting of kidneys before the immunosuppressive drug cyclosporin was introduced some years later.

'Like Joining a Select Club'

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