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If you like Thomas Starzl's story, you might also like:
Tenley Albright,
Keith Black,
Benjamin Carson,
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Jonas Salk and
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Thomas Starzl
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Thomas Starzl
Thomas Starzl
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Thomas Starzl Interview (page: 2 / 8)

Father of Modern Transplantation

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  Thomas Starzl

What did you learn from your early liver transplant trials that made you decide that you were going to stop the trials for the next several years?

Thomas Starzl: We just flopped. We failed. I describe in detail those first three cases, but I also mention we made two more attempts. So we had five human beings whose lives were terminated after liver replacement. And that to me was sufficient reason to say, "Stop. We've got to figure out what went wrong." But the actual chain of events was that I worked on liver transplantation for about five years before making those first attempts. But during years four and five I had used the kidney transplantation as a means of studying ways of preventing rejection. Those methods of preventing rejection I showed at the very beginning were common to all the organs. So if you could prevent rejection of a kidney reliably then you could do so with the liver. And the problem that evolved during that period of time -- when I was working on the liver there were attempts being made around the world, probably about 400 altogether to transplant the kidney. Almost all of those failed.

And toward the end ...

There were a small number of successes. The first one was at the Peter Ben Brigham Hospital in Boston. That was in 1959, using radiation as a way of preventing rejection. But that group was never able to duplicate that. And that particular case was a fraternal twin, not an identical twin. It was a fraternal twin, so there was some question about it. But then two groups in Paris coughed up four or five more cases, two each -- or two in one group and three in another -- again mostly failures. But by 1962 there had been in the world six cases of survival with kidney transplantation for at least one year. That is not the kind of record that you can have if you want to transplant a much more difficult organ, like the liver. So that was why what Bill and I said, "Nobody seems to be able to make the kidney work, we've got to dope that out, and once we succeed, we can do the liver." So back to the laboratory. We made some observations that was the key that unlocked the door for kidneys, and we went on a rampage of kidney transplantation, showed that not only could you make it work, you could make kidney transplantation an actual service, something that you could really offer a patient for the first time. So that was the first series in the world of successful kidney transplants.

[ Key to Success ] Perseverance

Once we had that in hand, we started working with the liver, thinking that this is going to be a pushover. And from the point of view of preventing rejection it was a pushover. I mean, it was just as easy, if not easier, to prevent rejection of the liver as we had accomplished with the kidney.

The liver was such a complicated operation and had so many other difficulties -- including the fact that liver recipients were always near death, destined in every case to die within 30 days -- that the illness itself probably was the greatest barrier to success. But that almost sounds too much like an excuse. The fact is that we tried five of those desperate cases and they all flopped. So that was plenty of reason to stop the liver program. But the kidney program was never stopped, and it was like gangbusters. At the time that all this occurred, there was actually only one program of kidney transplantation in the United States when we did this. That was the one at the Brigham. And a month or so after we started our kidney program, a guy named Dave Hume in Richmond started a program, but he was talking to me all the time, so I was giving him information that he was applying about our secrets. We were the third program. Those were the only kidney programs in the United States. But the kidney victory was so huge that within one year after the secrets got out, or we published them, there were 50 programs, replicas or downstream copies of what we had introduced. And in 1964, one year later, I wrote a book which was the bible for the organization of kidney programs all over the world. So the kidney drive never slowed down, it only accelerated. And the liver was left in the lurch. But not really, because just about every day we were in the laboratory investigating some problem or other that had contributed to the failures.

Did your success with the kidney remove some of the opposition you'd experienced when you were trying to gain acceptance for liver transplants?

Thomas Starzl: Our kidney results were our battering ram. No doubt, no doubt about it. Just doing those livers, if that were an isolated effort it would have been professionally ruinous. And it actually was, going beyond the kidney was not exactly the route to professional success. People were trying to recruit me to go elsewhere and take chairs and so forth. But they always -- or almost always -- said, 'We want you to come here and do kidneys, but you've got to promise that you won't do livers." So any time somebody said that, the game was over as far as considering a job.

[ Key to Success ] Integrity

Thomas Starzl Interview Photo
Thomas Starzl Interview Photo

By then did you believe that a successful liver transplant was inevitable?

Thomas Starzl: Well, yeah. We had been able to do it in dogs, all the time. And what you can do in dogs you can surely do in humans. I never had the slightest doubt that this was an attainable objective, not at any time. I would never have done a case simply as an experiment.

What did you learn from these failures that halted the trials in the early 1960s? Particularly about the phenomenon of chimerism, the coexistence of donor and recipient cells?

Thomas Starzl: Transplantation overall was a field that grew slowly at first, but then achieved monumental stature, actually changed the philosophy by which medicine is practiced, without knowing what was being accomplished. What were the mechanisms? What is the explanation? What finally brought some peace of mind, with the insight of knowledge, that transplantation actually could be -- and frequently was -- a curative operation. That that downhill slope of a graft being under constant attack and slowly, slowly losing ground until you were going to get a phone call. When it was finally discovered what the mechanisms were -- and they all surrounded the chimerism discoveries -- you realized that that was not an inevitable downhill slope. That transplantation was inherently a curative procedure that you could do on a child, like my grandson or a baby, and expect the child to grow up and go to college and have their own children. And that happened actually. Many of the transplant patients have had children who have had children. That early group of kidney patients that I did in 1962 and 1963, a group of 45 or 46, there are some still -- nine or ten of those patients -- still going with that original graft. That means that they're approaching 50 years now. In fact, they're in their 48th or 49th year right now. Those are the longest. Not a single case, but they are the longest patients in the world. And many of them have gotten off of (immunosuppressant) drugs. That is another unique observation. The longest surviving liver recipient in the world is in her 41st or 42nd year. And there are many following behind, you know. Like 35 to 40 years.

[ Key to Success ] Vision

So I suppose you could have seen those patients and just simply accepted the fact that, "Wow, I wonder what happened." But the question remained, "How did that happen?" Here was an observation that couldn't be explained.

In 1992 we set out to try to find out what the hell was going on. What were in fact the mechanisms by which it had been possible to successfully transplant organs and have them stick? Not only stay functioning, but to be able in the long run to get off drugs, in some cases. So that question was what drove the search for chimerism. And we found it in every surviving patient. Now if you had made the observation that we did in 1992, in isolation, it would have been dismissed as an artifact, perhaps even as an error, or as some kind of an epiphenomenon. You know, nothing. But armed with this memory bank of nearly a half century, the minute we found tumors, we found the chimeric cells. I was able to put every damn thing together that had been a mystery before, because transplantation in the conventional way that immunologists were viewing it was not only unsound, it was totally inexplicable. And the observations that were being made in the clinic about rejection, its reversal, and all the various complications and phenomenon, never could be explained. But suddenly with that discovery, you take all those little pieces, and just like magic, as if a magnet had pulled them together in exactly the right position, filled the whole picture out. And that piece of magic took place after I wrote The Puzzle People. It's one of the later printings, which you may not have, has the story, briefly summarized in four or five pages. I'll get that for you if you don't have it.

[ Key to Success ] Vision

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