"Transplantation offered me something that I really desired. It offered me the ability to be a very good physician and a surgeon. I was always trained that a surgeon is a doctor plus, and there is really no other field than transplantation that requires you to be a good nephrologists, hematologist, infectious disease expert, radiologist. You really have to practice total medicine and practice it well, plus you have to be a reasonably good, if not an excellent, surgeon, and have good clinical, surgical judgment."
Mark Hardy, MD, attended medical school at the Albert Einstein College of Medicine in New York City. He trained in surgery at Strong Memorial Hospital in Rochester, and thereafter returned to New York City where he founded the Transplant Program at New York Presbyterian Hospital/Columbia University Medical Center. He is the Founding Director and Past President of the New York Organ Donor Network, and was a founding ASTS member. He served the Society as its 21st President in 1994-95.
Mark Hardy: I’m Mark Hardy, and I’m at Columbia University in New York. My path to transplantation has been an interesting one, I think. I started out in medical school, and at that time, I decided to be a neurosurgeon. I change my mind about the second year after seeing a patient who was on their way to dying, and I just couldn’t tolerate it. Then, by the time I graduated, I was definitely going to be a cardiac surgeon. I went into general surgery training up at Strong Memorial, and then because of the times, the Vietnam War, I went into the navy for two years. When I came out, I didn’t want to go back to Rochester, where it was pretty cold and pretty lonely. Although, Charles Robb was a wonderful teacher, and Sy Schwartz was there.
But I went back to New York to Einstein and resumed the residency at the third year. And then, it was still going to be a cardiac surgeon, and that was the time when datascope was working on intra-aortic balloons, and I had a fellowship, and I was ready to really roll.
I got the…American Heart Fellowship, at which point, my Chair at that time, since I was a newcomer now into the program, told me, essentially, “You either go into my lab, or you can leave.” That was Dave State, and he told me that I go into transplantation lab; if I’m interested in heart, then may as well transplant hearts. But his laboratory was focusing on intestinal transplants. So I ended up doing a lot of intestinal transplants in dogs in various forms, and absorption of…f various oleic acids and so forth, radioisotopes.
And he actually reached a point where we did three-month-old baby intestinal transplant after the first one was done in Minnesota. We did one; the child died within 18 hours, because of really, no fluid replacement and so forth and… inadequate fluid replacement. That’s…That was 1967.
And from there, I got very interested in basic immunology, and started working on thymic hormones with basic immunologists and biochemists, at which point, there was an opportunity to get an NIH scholarship to go into, spent some years in research. It was very valuable because it offered an extra $3,000 in salary, compared to the resident’s salary, which at that time, was about $18,000. And I didn’t really want this in. I had one baby… one child on the way at the time, and I just wanted to finish, go with my cardiac or vascular surgery.
But my colleague decided to come to the lab from his flying lessons, and when he came and learned that I was trying to make up my mind, he said, “Well, Mark, this is an investment. If you want to…This is a new field. Why don’t we…Why don’t we do it?” at which point, he convinced me pretty quickly that we would have fun and that it was enjoyable to do research, and I started looking for a quick job, and actually called up Rupert Billingham, and …who was at Wistar at the time, and tried to get a job. We…I was…I was coming with a salary and some research support at the time. So, I was really quite desirable. And he said, “Sure,” and I said…And asked me, “When can you come?” I said, “Well, this July,” and this was March, and he said, “No. Sorry. We don’t have anything for three years.” [laughter] At which point, I changed my mind and became Tony Monaco’s first Fellow in Boston.
And I as very fortunate in that Tony Monaco, at that time, start…was just starting a transplant program at a new site, at the Harvard Division of Boston City Hospital, plus doing all his work with antithymocyte globulin and antithymocyte serum at the time. And I went up to Boston and spent a year with him, helping to organize the transplant program, the dialysis program, and started doing clinical transplants in a very adventurous way, in that the donors came to us. We had cadaver donor in the middle operating room and two recipients on either side; two transplants going on simultaneously, really almost with no really cold ischemia time of any significance. This is the way that transplants were done. They were…The preservation was just starting. Actually, the people, the…Chief of Orders apparatus at the time visited us and want us to conduct preliminary studies, and we said, “Well, why should we do that? We don’t need any preservation. We just take the kidneys and put them in!”
Goran Klintmalm: So, tell me how little transpired. You had the donor. And how you…I mean, these were cadaveric donors…to be, and this happened very quickly. How did the timing come in, and the patients…
Mark Hardy: Well, you had a patient that was thought…declared brain dead. If you recall, the brain death something that actually originated at Mass General in Harvard with various committees and the concept of what constitutes brain death was born there. There was a certain degree of partiality to at the Boston schools to accept brain death, more so perhaps than in the rest of the country. Nevertheless, there were very many demands, and to be fulfilled, but once a patient was declared dead, then they went, they could go to the operating room, we’re actually they were extubated, and where…had to have a cardiograph before the organs were removed. But the cardiac arrest was a controlled, really very well controlled, cardiac arrest, to the point where actually, the warm ischemia time was relatively short.
We’re trying to remove kidneys very rapidly, and we could do that, really quite rapidly, and we cooled them. Meantime, the recipients were already opened and ready to receive organs in two other rooms. So, it was actually better than what we do now probably in terms of profusion, reperfusion injuries and the like. But of course at that time, we had only Imuran and high doses of steroids. We had a mortality, at one year, of about 50%. We had the most exotic collection of pulmonary infections, fungi, with the mucomycosis and candida and pneumocystis was almost routine. There were no drugs for these things at the time.
Pentamidine…we actually found pentamidine vial in a laboratory in the back refrigerator one time. I remember distinctly when I was in Boston as a Fellow, there was a very bad snowstorm. I got on the skis and actually went on, cross-country skiing to Mass General to get the ampoule of Pentamidine, brought it back and gave it to the patient. It’s one of the memorable experiences. Patiently covered, actually, and it preserved the kidney. So this, these were the kind of adventures we went through.
Then, when I came back to Einstein after finishing the fellowship, doing a lot of work with ATG, and eventually taking it into patients with Tony Monaco…We actually had gave it to patients and gave it to about 20 patients, and probably the infection rate was associated with the use of those things. But I came back, and I was hooked. I liked the field, but there was really…The market for transplantation was not very large, and when you have to support a family…And when I finished my fellowship, having been trained a pretty well by that time (in my last year, I did almost every…all year, of really vascular surgery) so it was a pseudo-fellowship. We do not have formal vascular fellowship. And I did general surgery, vascular surgery, and then started the transplant program at Einstein as, really as more…as a hobby than anything else; it was out of interest.
Goran Klintmalm: What would you say are your biggest triumphs?
Mark Hardy: Well, I think organizing the transplant program at Einstein was a triumph, particularly since it would have to be focused primarily on children because it was one of the best nephrology, pediatric nephrology programs, in the world at that time, and we have very many children. So, I ended up doing 25 transplants in children in the first year, which was really an extraordinary number. And it was a very exciting time to work on the children. A few living donors, many cadaveric donors, and the satisfaction, obviously, was enormous, the adventures there were…were very exciting, but seeing children recover from being so ill was an extraordinary, satisfying experience. The individual stories are very numerous, both sad and happy! The…And some very unusual. I remember one young man I transplanted. He was 15 or so, and he did very badly afterwards. The kidney shut down after a week or so, and we were sure it was rejection. We didn’t do routine biopsies. There was no ultrasound; there was only an x-ray. We treated him for rejection, massive dose of steroids, three, four days; nothing really happened. Finally, he got this bit mass over the kidney. It turned out he had an obstructing lymphocele. Well, we were smart enough. We drained the lymphocele to the outside, not to the inside. The patient recovered remarkably well and went on to keep the kidney for 40 years until he died, actually of unrelated causes. At that time, I was sort of…triggered my idea that when they…when patients have an injured kidney, and you really give them a lot of immunosuppression, somehow you turn off the switch, and maybe you actually cause some form of tolerance.
But this continued on, and I actually made a living doing general surgery and vascular surgery and continued to develop transplants at a relatively slow pace, about 20 transplants a year. And then there was a political struggle at Einstein between two adjoining institutions, and at the same time, Keith Reemtsma came to Columbia University, interested in transplantation and a pioneer in the field, and recruited me from across the island of Manhattan, more or less. And I came to Colombia, and there was no transplants and nothing else, and no dialysis in fact. There was an attitude, anti-dialysis, and anti-transplants, as being useless modalities of treatment. This was enunciated primarily by the group of nephrologists at that time. So I took everything over, the dialysis and transplantation. This is what was given to me, and they were very generous. They built a new unit with a new dialysis unit and nurses and everything else, and I started doing transplants at Columbia, it the same time, continuing to do that still are surgery, to really make a living.
Goran Klintmalm: Could you ever have foreseen what we have with transplantation today?
Mark Hardy: Yes. I could foresee, but I didn’t think how large it would become and how important. And I think the real major progress and the inkling of, that this was going to be a modality of treatment that’s going to be paramount in many instances, was with the advent, really, of the newer immunosuppressive drugs. Cyclosporine N-84, then obviously, tacrolimus, serolimus and so on and so forth. But at that time, when we still dealt with steroids and Imuran, more and more with some form of anti-lymphocyte sera, the success was better than 50%; it got up to 70%, 75%. But still, the mortality was high. Complications were very significant. The patients walking around with the Cushingoid appearance were not very happy. The bony defects and so forth that came along made patients unhappy if they lived long enough to do it.
So I think that the revolution came with the new immunosuppressive drugs, and then I became much more convinced that this was going to be it. But I was pretty convinced to persist in that, to the point actually where, with a lot of pushing from my chief, who is Keith Reemtsma. We organized a heart transplant program when everyone else was closing it down, except for Shumway. And we opened one that grew and really was reasonably successful. And in an 19---, with the advent of cyclosporine, became one of the largest, most successful programs in the country under the direction of the cardiac surgeons, Reemtsma first, then Eric Rose…
Goran Klintmalm: Please tell me any… if there is a story, stories that…
Mark Hardy: Well, there are very many stories that probably shouldn’t be told now be either. So, but I will reserve some that may have some historical interest. One I think that’s an interesting story in terms of ASTS, for example, is when it was the first meeting, thinking about organizing this, sort of led by Tom Starzl, with Merckel and Barnett and a few others, speaking more or less, for Tom Starzl, in a back room, a long back room at the Meeting of The American College of Surgeons in Miami. Just the volunteers came, people interested and so forth. And then there was a call for volunteers for various subcommittee type things, just to get going. I ended up on the bylaws committee, and obviously, one of the bylaws issues was who should be members of the Society. Tom Starzl through himself and…and through his colleagues, really made it very clear that this has to be a society for surgeons only. There were few members on the bylaws committee who felt that it really should be open to immunologists and biologists and so forth. They were sort of suppressed and the Society grew to become a society only of surgeons.
This actually had serious consequences around ’95, ’94, ’95, when the issue came to fore because there was, at that time, a society of transplant physicians, and there were issues of merger or not merging, and the initial reaction to our exclusion of physicians, transplant physicians, nephrologists particularly, eventually hepatologists and cardiologists, and particularly scientists, immunologists, people involved…and immunogeneticists. When this came up originally, there was really a question of how exclusively should be. And there was an outcry from the others about belonging, and I happened to be good friends with some of them, and they called me up and said, “How can you do this?” I said, “Well, you know, it’s a democracy. We vote, and these surgeons decided to do this, and there’s really…we welcome you to come to our meetings and present and so forth and so on, but right now we can’t do it.” So they went ahead and organized the American Society of Transplant Physicians, which
was non-exclusive. And then you can see what happened over the years, and eventually, there were many discussions, some amicable, some not so amicable. But now, we sit together at the same meetings, and this sort of came around…oh about 2000, I guess.
Goran Klintmalm: How has transplantation been part of your life? How much of your life has been transplantation?
Mark Hardy: Transplantation offered me something that I really desired. It offered me the ability to be a very good physician and a surgeon. I was always trained that a surgeon is a doctor plus, and there is really no other field than transplantation that requires you to be a good nephrologist, hepatologist, infectious disease expert, radiologist. You really have to practice total medicine and practice it well, plus you have to be a reasonably good, if not an excellent, surgeon, and have good clinical, surgical judgment. Plus, it allows you, really, to step into the field of research, where it…which was evolving when I started. We just started, really. We didn’t know about T4 cells and all this sort of thing. They were just getting the names in those days. So, it allowed basic science, and it allowed individuals involved in this to go on to translation science. We were able, literally, to go from the bench to the patient. We could do this with various immunosuppressive, with diagnostic tests, with islet transplants, where we did islet transplants in rats for 15, 20 years, and we used to actually meet…, have a political consortium on the east coast with Clyde Barker and Keith Reemtsma. And Keith Reemtsma used to hold these in one of his,… in his penthouse apartment over a giant billiard table, and we talked islet transplants, and it was always, we’ll do a clinical islet transplant on Monday. Well, Mondays took many, many, many years. [laughter] But eventually, it was done. And so, we were able to go from the rat and the monkey to men, and you could do this with many different aspects in transplantation, which is a…extraordinarily satisfactory experience, because you grow with the experience, and you can translate it to the wellbeing of the patient. And that was really a very, very worthwhile experience. I enjoyed other disciplines in surgery. I enjoyed doing vascular surgery for many years.
And clearly, my major goal always has been my family, and now, grandchildren and…and …meeting people around the world who are interested, who share the interest and who are extraordinarily fascinating people with whom I have established frequently very close relationships and close friendships. And I think that transplantation contributed to that clique, essentially a starting clique that grew to hundreds, and in some cases, I guess, in thousands. In my case, to hundreds of people. So, it was a very exciting part of my overall career.
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