"I think that transplantation as Dr. Fitts has pointed out has really contributed to the medical world in ways, which perhaps not all of us necessarily think about. But, all of this business about cell biology and understanding about what goes on inside cells really came about as a result of kidney transplants."
Dr. Charles Zukoski performed the first kidney transplant at Vanderbilt University in 1962, thus initiating clinical efforts at a program which has grown over five decades. Ultimately moving to Tucson where he was the Emeritus Professor of Surgery at the University of Arizona College of Medicine, Dr. Zukoski was best known for pioneering work in immunosuppression. At the Medical College of Virginia, in laboratories of Dr. David Hume, Zukoski learned that azathioprine and its derivative products would prolong kidney allograft survival in dogs. Serving through a long career in transplantation and general surgery at the Medical College of Virginia, Vanderbilt, North Carolina, and the University of Arizona, Zukoski was recognized by Vanderbilt in 2007 at the 45th Anniversary of the establishment of its transplant program. He passed away in August 2009.
Charles Zukoski: I am Charles Zukoski and I got interested in organ transplantation in 1961 when I went on a fellowship to the Medical College of Virginia to study the relationship of the hypothalamus to gastric secretion and I worked on putting electrodes down into the hypothalamus and creating gastric pouches innervated and not innervated, and I got tired of collecting gastric juice and stimulating brains and started in on helping Dr. Hume and Dr. Igdall in their studies on whole body irradiation and kidneys.
We finally came to a big push to get a whole bunch of kidneys transplanted in dogs and Dr. H.M. Lee, who is a former President of the ASTS; he and I took 24 dogs and a trailer to Bethesda, Maryland from Richmond and used the Naval Medical Hospital’s four part whole body irradiation machine to irradiate those 24 dogs. We anesthetized them, put them into the tube and gave them 1000 rads, 1,500 rads, and 2,000 rads. Put them all back into the truck and went back to Richmond and transplanted kidneys all night and the next morning finished up the rest of them. Then at varying periods of time after that we sacrificed the animals and they all showed marked signs of rejection and Dr. Hume went off to the American Surgical Association and presented that paper with those experimental results.
Then I read an article by Schwartz and Damishek that talked about creating “tolerance in rabbits to bovine serum albumin following the injection of one large dose of 6-mercaptopurine into the rabbits. That intrigued me so I called the Burroughs Welcome Corporation and asked them to send me 5 pounds of 6-mercaptopurine and they said they did not have that much in stock to send me. So, we agreed on a little less than that, the box arrived, and we started transplanting kidneys with 6-mercaptopurine. We got some rather interesting results in October, November, and December and by that time we had had several dogs that had lived longer then 100 days with their kidney transplants and this was really the first time that anything had created an animal model that allowed kidneys to survive for that length of time.
Thomas Peters: Can you tell us about the first human transplants at MCV and can you weave into that a little bit about Dr. Hume?
Charles Zukoski: Well, the first kidney transplant at MCV and when I was there they did only did whole body irradiation transplants. They only did one while I was there. So there were no kidneys transplanted in 1961 or 62 using 6-mercaptopurine at the Medical College of Virginia. Dr. Hume, I owe a great deal to him because, and we could show the picture about here, that he gave me an opportunity to work in the laboratory. I did not have any grant support for what I was doing and I do not know who paid for what I did, but Dr. H.M. Lee and I transplanted an awful lot of kidneys in 1961 and 62, to 59 to 61 we did it, to work on that.
It was a great opportunity to do that. Early the next year, Sir Roy Calne, M.D., in England published a paper on 6-mercaptopurine and survival of great lengths of time for dogs. His paper came out before mine did, but we had been working on the problem separately for all that length of time.
Thomas Peters: Tell us where you went from the Medical College of Virginia and how you developed the transplantation services.
Charles Zukoski: Well in 1961, I finished my second year of my fellowship, and I moved to Vanderbilt at the Veterans Hospital in Nashville and continued working. It was a marvelous place to work because I could operate on humans in the morning and I transplanted kidneys in dogs to Bach, Beethoven and Mozart all afternoon. We studied prednisone and how it affected kidney transplants there and then on October 24, 1962, Dr. H. William Scott was head of the department of surgery there, called me and said he had a patient that needed a kidney transplant and he had a kidney and would I come over to the Vanderbilt Hospital and help him transplant it.
It was a pediatric kidney and under the circumstances that we were, we tried several times to vascularized the kidney in the groin of this particular patient and we were unsuccessful in re-vascularizing the kidney. After that, I became more interested in going to transplant kidneys in humans and we learned about what Dr. Starzl had been doing in Denver.
He bankrupted the Veterans Hospital in Denver by transplanting so many kidneys with Dr. Waddell and they had to be billed out by the central central office because they did that.
But, you know when you come back to what was going on in 1962; there were so many things that went on. The T-cells and B-cells had not been invented by that time. We had not organ procurement, we had not dialysis in my hospital. The first patient that was dialyzed on a regular basis waiting for a kidney, we had two operating rooms with a door between the two rooms, and I was doing pneumonectomies and gastric resections in one room and a patient was being dialyzed in the next room with a nurse because I did not know any other way and I wanted to be available in case something happened to the dialysis. I did all the access, ran the patients and we began to get several patients who needed dialysis, but we did not have a nephrologist to help use to really do this inside the system.
We dialyzed them with twin coil kidney machines and I knew so little about cellophane and blood that the first patient that I dialyzed had filled up to bottles to transfuse him, the next time we were going to fill the coil to start and when I got ready to run the blood out of the bottles into the tubes, it has all clotted because I put it together with Heparin and not citrate. So everybody had a big laugh at ole Charlie because he did not know how to dialyze anybody.
Thomas Peters: But eventually there were people who knew how to dialyze folks in Nashville and a long-standing program began. Can you tell us about some of the early players in Nashville and how the program emerged?
Charles Zukoski: Well to try to help us support it Dr. Earl Gang was recruited to come to Nashville to help us with our renal program and he became a great support and developed a large dialysis program where we had patients sent to us from the Veterans Administration from over the southeastern part of the United States. We struggled, we did I don’t know, 5 or 6 kidneys that never functioned, but finally one day we got a kidney in good enough shape from some place and transplanted it and we had our successful transplant. It moved on slowly in never any great volume, but we had enough to sort of keep us going.
Thomas Peters: Tell us your memory of the early period of transplant organization in America.
Charles Zukoski: Well, I had a great difficulty in finding a place to publish my results from the dog lab because Surgery, Obstetrics and Gynecology did publish my first paper on 6-mercaptopurine in survival of kidneys, but after that time it really took several years before we developed any great program like that. Most of my work was published at the Surgical Forum at the American College of Surgeons meetings in the fall each year to go along with that. American Society of Transplant Surgeons developed and I became a member for that. The first meeting that I went to that was a congress on transplantation was the Paris meeting in 1967 of the International Transplant Society in Paris.
Thomas Peters: Who are some of the outstanding people in your memory in the early days of transplantation?
Charles Zukoski: Well, when I was at Richmond, of course Dr. Hume was the driving force in as far as those types of things were concerned, but there was a fellow and I am not sure I can tell you his name right now, but in Cooperstown, New York, who won the Nobel Prize with Dr. Murray who was interested in transplanting bone marrow who ended up in Washington state. He did a great deal to, not in whole organ transplants, but he was much more interested in bone marrow transplants. Of course, Dr. Starzl did a great deal of this and two other people who I think did a great deal for us was Roy Calne and Joseph Murray. Calne came to the Brigham in 1961 and they did some kidney transplants with 6-mercaptopurine in humans, but pretty soon gave up on that and then Burroughs’s welcomed Gertrude Elion and George Hitchings created Imuran for them which is a 6-mercaptopurine with an imidazole derivative they put on it which allowed the blood levels of 6-mercaptopurine to remain high for longer periods then just 6-MP because the Imuran had to go through the liver and have the mercapto radical removed before it became an active 6-mercaptopurine.
Thomas Peters: Tell use when you became principally a clinical transplant surgeon, a kidney transplant surgeon. Where was that…what was your life like at that time?
Charles Zukoski: Well I am afraid to say that I am not sure; I never earned a living just transplanting kidneys or worked at an institution were enough kidney transplants were being done to say that was the principle feature. I think that it is a loss to me that I was not able to create the type of organization that allowed kidney transplants to develop. I started three transplants programs at Nashville, Chapel Hill, and Tucson, and I was never able to get enough interest in any of those places, to really allow us to move forward in a real fashion.
Thomas Peters 2: But you might add that they are all still open.
Charles Zukoski: Yes, they are. I left Chapel Hill in 1969 and we had done two or three kidney transplant programs there and then Dr. Stanley Mandel came and continued the program, I understand, after I left. In Tucson we did the first transplant there on July 24, 1970, and transplanted there until about 1989 when the program sort of died and then other people have come in and we have got a new Chairman of the department of surgery, Dr. Grossner from Minneapolis who has started the program again.
Thomas Peters: Any other questions for Charlie?
Thomas Peters 2: Charlie is there anything you want to say?
Charles Zukoski: Well there is one thing if I could. I think that transplantation as Dr. Fitts has pointed out has really contributed to the medical world in ways, which perhaps not all of us necessarily think about. But, all of this business about cell biology and understanding about what goes on inside cells really came about as a result of kidney transplants. When Dr. Starzl transplanted his first 100 patients, he had 67% survive for one year. That really crammed transplantation down the crow of the immunologist who had said it was a great big farce and it would never survive. Then they started looking for what made the lymphocyte tick and along came interleukin 1 and 2 and now we are up to 22 or 29, I do not know. I do not keep up with it any longer, but those early studies have allowed, I attended a meeting yesterday morning about intra and vascular diseases and it was worse than the Roosevelt administration, NRA, and all those other things, I just could not understand what was being said, I am so far behind. It has led to all of this and now has gone on to allow us to understand genes and how it works. I think that is almost as big a contribution to medicine and the development of medicine as the fact that we are successful transplanting organs today.
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