Immunosuppression

Correspondence between Joseph Murray and Roy Calne, a British surgeon. The correspondence contains discussions of cadaveric kidney transplantation, including Murray's likely description of the first successful cadaveric transplantation, in April of 1962, using the immunosuppressive drug Imuran (azathioprine).

Despite their successes with transplantation in twins, Murray and his colleagues were intially unable to supress a recipient's immune system sufficiently so that it would not reject a kidney from a non-twin or a cadaver. Attempts at utilizing total-body irradiation to achieve immune suppression largely failed. In 1959, doctors at Tufts Medical Center published a paper on the immunosupressive effects of an anticancer drug, 6-MP. This drug had been developed by George Hitchings and Gertrude Elion at Burroughs Wellcome in New York.

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Kidney transplant protocols developed by Joseph Murray and John Merrill at the Peter Bent Brigham Hospital, utilizing the immunosuppressive drug Imuran (azathioprine).

In London, Dr. Roy Calne had been using the drug for canine kidney transplants, with encouraging results. Calne came to Boston as a Research Fellow in the Surgical Research Laboratory, where he and Murray continued to work with Hitchings and Elion. They ultimately settled on a derivative of 6-MP called azathioprine (Imuran).

Letter from Peter Mawdsley of Burroughs Wellcome and Company to Joseph Murray, informing him that the immunosupressive drug Imuran (azathioprine) has received FDA approval for commerical release, to help prevent organ rejection after transplantation.

On April 5, 1962, the first successful cadaveric transplantation was performed on a 23 year-old accountant named Mel Doucette. Murray and John Merrill disagreed about the correct protocol for administering the Imuran. Merrill preferred higher doses along with small doses of whole body irradiation, while Murray sought to keep the doses of Imuran small. They utlimately decided to follow Murray's recommendations.

Joseph Murray (far right) with Roy Calne (second from left), future 1988 Nobel Laureates Gertrude Elion and George Hitchings (third and fourth from left, respectively), and surviving transplant dogs on the Harvard Medical School Quad.

The successful transplantation of an organ from a deceased donor revolutionized transplantation. 16,812 kidney transplants took place in the United States in 2012, 11,043 of which came from cadaveric donors.