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SPECIAL LECTURES

Acceptance speech by Joseph E. Murray

Murray, Joseph E. M.D.

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doi: 10.1097/01.TP.0000063278.33552.82
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I am overwhelmed to receive this honor.

My introduction to transplantation biology occurred 58 years ago during World War II. After a 9-month surgical internship at the Peter Bent Brigham Hospital, I was randomly assigned to Valley Forge Army Hospital in Pennsylvania, a plastic surgery center caring for war casualties from Europe, Africa, and the Pacific. There we took care of an aviator flying the hump between Burma and China who had been burned severely over 70% of his body. He was sent to our hospital, where we saved his life by using skin allografts to carry him over his nutritional and septic problems. This was the first person I had seen whose life was saved by using tissues from another person. He recovered well, began flying again, had a family, and now, at 83 years of age, is a close personal friend. He was my introduction to transplantation.

When I got out of the service after 3 years of active duty, I went back to the Brigham to complete my surgical residency. Dr. Thorn, the Chief of Medicine, was interested in treating end-stage renal disease and had asked Willem Kolff to come to Brigham to demonstrate his artificial dialysis machine, the rotating drum, which he had developed in the Netherlands when interned by the war. Dr. Thorn wanted to treat hypertension and thought that one way to do this was to get rid of the kidneys. Therefore he started a kidney transplant program at Brigham, and I joined it eagerly when I got out of the service. Nephrologist John Merrill and surgeon David Hume were already working as part of the team.

My first job was to establish that a renal transplant could be life sustaining. I did a series of kidney autografts in dogs and found they had perfectly normal long-term renal function; the nephrologists could not find anything wrong with them. These dogs showed that the results could be permanent. When a set of twins presented, one dying of kidney disease and the other a healthy, potential donor, we performed for the first time in humans, the renal transplant operation that we had developed for dogs. The recipient survived for 8 years but then developed chronic glomerulonephritis in the kidney. The full episode is described in my recent book Surgery of the Soul.

One of our patients during this time was a female identical twin. Both recipient and donor had been recently married, and we wondered about the dangers of future pregnancies. The female twins were operated on in May of 1956. Now, over 45 years later, they are both healthy, have normal renal function, have numerous children and grandchildren—my wife and I visit them yearly in Texas. The female recipient is the world’s longest living transplant recipient. Eventually we performed more than 20 identical twin transplants during the 1950s, which were reported to the American Surgical Association.

Echoing Dr. Roy Calne’s concern about donors, we have always been hesitant about removing organs from healthy donors. After discussions with clergy of all denominations and with physicians outside the hospital, we decided that it was worthwhile to proceed. This instance, however, involved careful soul searching and discussions. Today I am concerned about the increasingly casual attitude within some transplant teams toward using living donors in transplantation.

In January 1959, we operated on a set of nonidentical twins using sublethal total body irradiation to prevent rejection. The recipient survived some 28 years and succumbed to pericarditis, and his donor has just died. This was the first successful allogeneic transplant. Tom Starzl and I have had a running mild disagreement about the importance of this case. Tom, in his characteristically complimentary way, has said it is the single most important case in transplantation because it showed for the first time that the immunologic barrier could be breached. I thought it wasn’t that critical because we were able to achieve only one graft survivor of approximately 10 patients using total body irradiation protocol.

As Dr. Calne has said, he was sent to us by Sir Peter Medawar to work in our laboratory. There, he performed a series of dog experiments using bilateral nephrectomy in the donor and transplantation from an unrelated animal, treating the recipient with 6-mercaptopurine (6-MP). One of our early dogs survived for 38 days, which was a miracle to me because I had spent the preceeding 10 years unsuccessfully trying to get dogs to survive on all sorts of protocols. Guy Alexander came from Belgium to work with us after Roy left. Several other research fellows followed, including Allen Macdonald, Simon Simonian, Arnold Deithelm, and Ross Sheil, to mention a few.

Roy introduced us to George Hitchings and Trudy Ellion, who became friends and collaborators. They were frequent visitors to our laboratory, knew our dogs by name, and knew our patients, as well. In the lab, we had a wonderful time with all sorts of experiments trying to figure out how rejection occurred and how long we could keep a kidney in a dog before it was rejected. We transplanted rejecting kidneys back into the original donors and found that if we left the kidney in the recipient for more than 72 hr, we could not reverse the rejection, but under 48 hr we could sometimes get a rejecting kidney to reverse itself. In those years, you must remember that we did not even know of the existence of T cells or B cells, nor whether reversing rejection could be possible. From these experiments we learned a lot about the mechanisms of drug therapy. When one of the female transplanted dogs unexpectedly became pregnant, we wondered whether the drug therapy would cause fetal malformation. To our delight, the animal had a normal pregnancy, and this was the first indication that an immunosuppresive drug-treated kidney recipient could reproduce normally. I believe that David Hume was the first to have a drug-treated transplant patient with a normal pregnancy.

We could not get success in all our protocols, but we did one experiment in which we transplanted a kidney from two separate animals to see if both would be rejected at the same time. We found that one kidney could function well, whereas the other was rejected in the same recipient.

Roy, Trudy, George, and I would get together frequently and brainstorm at Burroughs Wellcome. I well remember driving on some of those snowy nights to New York from Boston. George and Trudy tried to construct an a priori concept to hit the rejection mechanism at different stages, investigating ways to use drugs to dissect the rejection process in a serial fashion.

I do not try to predict the future because, as George Eliot wrote in her novel Middlemarch, “Prophecy is the most gratuitous form of error.” If anyone had asked me 50 years ago whether transplantation would become a common worldwide procedure, I would have said that was impossible. So today I just accept the way transplantation has evolved.

Another favorite quotation of mine is by Albert Schweitzer: “To work for the common good is the greatest creed.” I believe that all of us in transplantation work for the common good and are privileged to be part of a scientific endeavor that combines science and humanity.

My last quotation was delivered by the dean of Harvard Medical School, at one of my very first faculty meetings. The American writer David Thoreau wrote, “If one advances confidently in the direction of his dreams, and endeavors to live a life which he has imagined, he will meet with a success unexpected in common hours.” I agree.

I accept this wonderful Medawar prize as a proxy for Doctors Francis D. Moore and George Thorn who were the inspiring and generous leaders of our group. Dr. Moore died this past year; Dr. Thorn is still living, at age 94. It is a real privilege, and I dedicate this gift to the memory of Dr. Francis D. Moore.

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