Interview: Thomas Starzl
Father of Modern Transplantation

Dr. Starzl, you undertook your surgical training at a time when there were many new developments in surgery. Do you think that luck -- or perhaps timing is the better word -- was a major factor in the development of your career?

Thomas Starzl: Timing is everything. And I'm sort of inclined to go along with the word that you just swiftly bypassed: luck. The timing was lucky. How was that to join those up? I was very lucky about timing, not only because there were new fields emerging and they included open heart surgery -- this is pushing the clock forward a few years -- cancer was an infantile field at that time, and there were other great developments that were going on, five or six of them all together. But at the time I finally had to make a definitive decision, I was in my early thirties, and the two fields that looked like they could not be conquered, or hadn't already been spoiled by previous pioneers, were transplantation and cancer. People at that time, this was still in the '50s, were making pronouncements that the cure of cancer was right around the corner. I thought, well, I missed that one too. And so transplantation was a field that was thought to be a Jules Verne type of figment of the imagination. So I went into that field. But the other elements of timing were the massive amount of research money that became available after the Second World War. A decision had been made at a federal level that the United States, to stay current, would have to invest heavily in research. And so really for the first time, federal-supported research became available just at the right time for me to pick that, to get into that golden stream.

In your book, The Puzzle People, you talked about your experience as a young surgical resident in Miami. You were given an enormous caseload there. Did you leave because you couldn't do your research there? Was it the institution itself or just the caseload?

Thomas Starzl: I had so much work down there over a period of two years that I did something like 1,000 majors a year for two years. And normally you go through a surgical training program and if you end up doing 100 majors that would be considered quite enough. And most of those cases, I was doing what I was doing without any supervision. But I was prepared for that, because I had already spent four years at Johns Hopkins. I had already had the equivalent of a normal surgical training program. So I didn't have any uneasy feelings about shouldering the responsibility, but just the mere root volume was such that I got to the point where I really didn't want to operate anymore. And I never wanted to do high volume surgery from that time onward, even though I was eventually forced into that situation, most acutely after I had come here. When we were doing procedures that weren't being done any place else in the country, or for that matter in the world, now the volume came up again, just as it had way back then.

There was no period that wasn't highly fruitful, including the time I spent in Miami. But I didn't leave there for any non-specific reason. I didn't get along at all well with the Chairman of Surgery at the time, my boss. I don't want to say too much about that, because he's dead, or long dead. He died young, and he died actually from complications from the very reason that I didn't get along very well with him. He died of complications of alcoholism. And he was -- in fact when he was my boss -- he was an alcoholic. So you couldn't trust what you would get from him in response to any one of a wide range of circumstances, including performance in the operating room. So it was a good lesson. In fact, later on I had some kind of a reconciliation with him. I mentioned in that book how I met him after he had taken the inevitable spill that happens to people who have that lifestyle. I met him at a meeting of the American College of Surgeons in Atlantic City and had a long discussion with him. And I thought, "What a nice man this might have been," if he hadn't -- by luck or whatever you want to call it, timing, whatever -- taken a pathway that was beyond his reach.

What lessons did you take away from that experience that were most important to you professionally?

Thomas Starzl: I would almost have to say none, although...

You have to concede that the acquisition of skill is a big deal. And Miami was a place where the skill level went from -- and confidence level -- went from here up to here, especially when I had come to realize that I was getting as referrals -- I was a resident there, but I was getting referrals from people all over town, all over Miami -- of difficult cases, so that certain operations were available in Miami only if I did them. But that's just the acquisition of skill. The lasting trail that began in Miami was the research that I had done there in dogs, in a makeshift laboratory that was created by stealing stuff from -- the equipment maybe, and fluids for IV treatment -- and I did some experiments with the liver that eventually resulted in the development of liver transplantation. In fact, the first steps were taken in Miami. So as soon as I left Miami and went to Chicago I picked up where I had left off in Miami.

You worked on liver transplantation for many years, but there was a period in the early 1960s when you took kind of a break to work with the kidney. Was this an agreement you had with your chairman at the University of Colorado, Bill Wadell?

Thomas Starzl: Yes, actually we had that agreement before we ever did a liver.

I started working on liver transplantation in 1958. That was when I was still in Miami, as we discussed earlier. And then, when I went back to Chicago in June of 1958, I simply continued that and really expanded it, all the while taking a final year of thoracic surgery, heart and lung, but especially open-heart. It looked like that's where I was going. But on the side, as a hobby, I was pursuing the liver transplantation in the laboratory. And it was really weird, because I had been identified by Northwestern as one of their good prospects for a long-term academic career, and solely for that was the reason that Northwestern put me up for a Markle scholarship. Every university only got one candidate, and they picked their most promising young person. Okay, they picked me, thinking that naturally I was going into heart surgery, after all I was in my last year of training. But all the while I was over in the lab working on this liver project. And within a few months, I realized that I've got to finish this year in thoracic surgery and get my boards and maybe even practice thoracic surgery, which of course I did. But those jobs and those experiments were going to have to be followed. So when I went to be evaluated by the Markle evaluation committee, I didn't have a word to say about the heart, the lung, the chest. I proposed as a lifetime objective to do liver transplantation, which was kind of absurd, because no organ of any kind had ever been successfully transplanted in any species, in any animals, any humans. It just looked like a brick wall. And all this because I had a question about the portal blood, and a theory altering the portal blood flow to the liver might make diabetes better. Instead, it made it worse in the animals. Probably the need to explain that was the driving force that pushed me over onto the transplant side.

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.

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.

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.

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.

Who was Royal Jones, and how did he contribute to transplant research at Colorado General and the Veterans Hospital in Denver?

Thomas Starzl: Royal Jones was like a burr under the saddle, or like a guy that lit a match to the medical establishment that was doused with gasoline and was racing toward the nearest water hole, because...

When I went to Colorado, Royal Jones had just started kidney dialysis. And kidney dialysis -- chronic kidney dialysis -- was simply not available except -- or I should say with two possible exceptions. In 1962, the exceptions were the University of Washington, where a guy named Belding Scribner had a small group of beds where six people could be treated with dialysis three times a week, and Colorado had a guy named Joe Holmes, who was running a chronic dialysis service out of his back pocket. And Royal Jones was one of those lucky enough to get one of those slots. But the ability to give dialysis -- every time a dialysis was done you had to cut down on vessels, and you worked your way up one arm, down one leg, then the other. And after six months or a year, you used up all the vessels that you could use for dialysis and then that was end of it. So Royal was near the beginning of his way to the cross, if you will, and it was that kind of suffering. He dropped right in my lap. So we went into a rampage to find out -- by this time we've already covered that period of time. By his time, we'd come to realize that we had to make kidneys work first. Here was a kidney recipient, we were unprepared to do him. So we took about six months, with an enormous effort in the laboratory, and we made the discoveries about how to use these drugs in a way that would allow success, and applied them to Royal Jones for the first time. So Royal Jones, this little black boy with a very devoted mother who gave him a kidney, he ended up having a nice silver anniversary celebration 25 years later. But he was a perfect example of an otherwise lethal clinical situation in which there was a little hole of escape that might be available, but we had to know how to find it. And we found it just in time. So that was rather amazing. He did all this suffering during the preparation, while the place was going nuts trying to make discoveries. And he got through it and was back in school six weeks later.

If this boy hadn't been dying before your eyes, would things have happened that fast?

Thomas Starzl: They probably would have happened, because that was part of the game plan, but the time frame was three to five years, not three to five months. It was like everybody was on speed.

What was the catalyst for restarting the liver transplant practice in 1967?

Thomas Starzl: I think the fact that we had fully expected to succeed in 1963 and then fell on our butts -- all the humiliating failures -- was a devastating scar that had to be removed.

Take us back to 1967. You're going to start transplantation again. What were you looking for in a candidate for liver transplant? How much did you consider a potential candidate's disposition?

Thomas Starzl: Every case of liver transplantation required some specific recipient qualities, because everybody out there in a conventional practice, the mere thought or mention of transplantation promptly pronounced it to be folly, a pie in the sky, and without merit. So to actually get even to the point of candidacy required a proactive approach by the patient or by the patient's family. So there was really an ultra filter between having the disease and actually getting to Denver. So that was a culling, highly efficient and real culling device, just getting there. Once they got there they'd already demonstrated a strong disposition to live. And that was very important, because what lay ahead was like running a gauntlet.

When you started the trials again in '67 with those first patients, did you know it was going to be a whole different experience from the first day?

Thomas Starzl: We expected the first time that we would succeed. In the long run we knew precisely why we had failed, so we fully expected to succeed. In fact, it was a bit of a disappointment that we did not succeed more than we did. Once that was realized, which took about two years, I think by 1969 or 1970 we realized that we'd carved a new pathway, but this one was almost as lumpy as the one that had preceded it. That went on for about a dozen years. During that time, there was another program started in England by a guy named Roy Calne, but the only liver programs in the world for much of the next 12 years were the one in Denver and one at Cambridge, in England. And I think that if either one of those had caved in, probably the other one would have to stop also. So then, shortly after the livers, the first hearts were done. And there also, the results in terms of real patient service were not good enough to be generally used. So the heart transplant surgeons and liver surgeons were on a lonely road for much of that time. In some ways that halfway victory -- or you might call it a Pyrrhic victory and utter failure -- was somewhere in between maybe "waiting for Superman" syndrome, waiting for a super drug, a better drug. When the better drugs came, it was off and running.

Let's fast forward a bit to 1981 when you moved to the University of Pittsburgh, School of Medicine. You've overseen the largest transplant program in the world. Could you tell us about the goals and achievements of the University of Pittsburgh medical facility?

Thomas Starzl: There really was no program here at that time. I think the contribution to Pittsburgh shouldn't quite be so inward looking. The importance from a societal point of view, the important contribution was to train a large number of people thoroughly in multiple layers so that they could go out and disseminate a new technology worldwide. The technology that was taught wasn't just liver, although that was a particular item because it wasn't really being done anywhere else, but it was the training of people who could do kidneys. That always remained kind of the platform from the beginning that was continuous. It never was interrupted by a moratorium. Lungs, hearts, they all ate from a common trough. And then the first intestinal transplants ever done in the world. At first it was occasional, but ultimately intestinal transplantation became just as much of a service as the liver or kidney. The continued development of better and better ways of immunosuppression, anti-rejection therapy, all of those things stemmed from here. Not only stemmed from here, but were exported in the form of the fellows and trainees that came here in droves. So I don't think the size of this activity was half so important as its quality and of the cutting edge component of it. And the cutting edge component kept five years ahead of the pack for quite a long time, 20 years or so.

Let's go back to the beginning. Can you tell us about the town where you were born and grew up?

Thomas Starzl: I was born in Le Mars, Iowa, a town with a population of about 5,000 in Northwest Iowa.

What was it like growing up there?

Thomas Starzl: I think it was pretty normal, up to a certain point. That is, up until the time when the Second World War started. I was born in 1926. That means I'm just a few months short of being 85, and so this was long ago. I was in the Navy in 1944, 1945. But I think the social environment changed dramatically long before then. Pearl Harbor occurred in 1941, but even before that we were unofficially in the war. So there was a wartime ambience during most of my teenage years.

That must have been kind of poignant to a family that owned and ran a newspaper, keeping up on the details of World War Two?

Thomas Starzl: Well, I think it affected everybody.

This particular town, which is really a farm-based town, as most small towns in Iowa were then, and probably still are, there was a very high mortality in the Le Mars area, probably partly because there was a regional National Guard and we were on the tail end of a depression at the time. So there was a little income that came from belonging to the National Guard, and I think a very large fraction of the teenage population signed up. So they were off and they ended up all over the world. And during the war, if there was a death, a casualty that took place, the family got a Gold Star. So you could walk down the street, there were many -- too many -- Gold Stars in Le Mars, probably way out of proportion to that in most other places. So there was, I think, a pretty grim environment as a result of all that.

What about your school days? What was it like to go to school in Le Mars?

Thomas Starzl: We had very good teachers, wonderful teachers. That was a difference from today, because...

Up until the war almost no mothers, wives had jobs, worked. They raised their families. That was pretty much it. Their representation in the workplace was very small. Probably less than five percent of the jobs were held by women. But with the manpower shortage, there was this huge flood of women who got jobs now and had access to professions and all other kinds of jobs. Those women had represented an army, an enormous human resource whose only professional outlet was teaching. So in the book that I wrote, The Puzzle People, I named a lot of the ones that I remembered. They were of course profoundly influential. They were great teachers. But these were the kind of women that in today's environment would be presidents of banks and the heads of departments of surgery and doing all the things now that women do. Just as an example, this situation was just changing after the war. And after the war, when I went to medical school in 1947, at Northwestern there were classes of right around 120 or 125, but our class only had two women. That was pretty representative of the situation around the country. Nowadays the percentage of women in a medical school class is at least 50 percent. Here it's actually greater. Here at the University of Pittsburgh, it's actually greater than 50 percent. But that's every place now. But it was from that population, from the female population that the teachers were drawn. So we had top line people as teachers. They were all women. I didn't mention a single man in The Puzzle People, because there wasn't a single man who really fit that bill.

Was there a particular teacher or mentor that stood out during your early years? Someone who challenged you or inspired you?

Thomas Starzl: I named three or four in the book, and I can remember single figures from different grades, the first being a lady named Miss Mary Waddick. There were other names that followed, but they tended to be with succeeding grades. There was another nice feature. You usually kept the teacher for not just one year, but over a span of two or three years, so there was a good deal of continuity. They're now looking at that in charter schools as a very favorable situation, but it existed, automatically existed. I think I had an outstanding elementary and high school education in a small town in Iowa. Seventy years ago, Northwest Iowa was still a very primitive area. Not quite frontier land, but in 1926 we were only 40 years away from the Dodge City shootouts and the development of that part of the Middle West. It was really more West than Middle West.

Do you remember any books making a great impression on you as a young person? Was there anything you read that excited or inspired you?

Thomas Starzl: I had a great break, entirely I'm sure by accident, but when we lived off in the periphery of Le Mars, near the edge of the city when I was born. I have almost no recollection of the house that we were in. I went up and visited once in a while later on. It was near a cemetery and near a Catholic church, but we moved down more toward the center of the city, at about that age, four or five, right exactly across the street from a Carnegie Library, a good one. So I was exposed at an early time to the library, and by the time I left Le Mars I probably read every damn book in the library. So the library itself was almost like an extension of my house, of the house that we lived in, just walk right across the street. I probably was a bookworm, in a sense in that I was either playing football or doing something like that or sitting in the library. It wasn't necessary to sign out a book because it was like having everything right there. But I remember there was an encyclopedia that was called The Golden Book of Verse or something like that. It was multiple volumes. I read those with great interest, from end to end. So that was my home resource, the principal home resource. But the library was important. I can remember I was trying to learn words, and every time when I was reading something in the library I encountered a word, I wrote the word down and got a definition and went back and was starting to develop a large vocabulary.

Was writing something you enjoyed when you were in school? Were you pressured to excel at writing?

Thomas Starzl: No, I was not. Actually I was not pressured to excel at all by my parents. In fact, I think they somewhat resisted my forging ahead as fast as I could have. They wanted me to have a completely normal upbringing.

Would you say that you were a budding scholar as a child?

Thomas Starzl: That was the problem.

They had, in the state of Iowa at that time, they gave every child in the state one of these -- something -- Stanford Binet. It was the IQ test. They gave all the students the test, and then they published the ones that were outliers. They published it in the papers, so it was generally known. I had the great misfortune to have one of those high scores, in the top one percentile. They published them not only locally, but for the state. I was in that group, and probably I think at the top of that group, so this was well known. My parents didn't want me to be abnormal. They wanted me to be treated like everyone else. So the idea that I would be sequestered often in a corner reading books and not participating in the rest of life was something they did not want. In fact, as you know, my father had a newspaper and they wanted me to work and do all the normal things.

What about sports? Do you think sports helped you to develop motor skills or team building skills that are relevant in medical practice?

Thomas Starzl: I think the more important skills, manual skills, were developed more by being a printer. I learned how to be a printer. And 70 years ago, most typing, except for linotyping -- you wouldn't even know what that is, I'm sure, but linotyping was a process where you typed a script, whatever was going to be in the newspapers. But it was typed with a system different than a typewriter. So linotypers were very special people that had their own alphabet, their own keyboard. So I learned how to linotype, which in a way was a disadvantage because I learned a form of typing that doesn't exist today, is not the kind that people took up with their Olivettis.

So was it the linotyping you credit with developing these manual skills?

Thomas Starzl: I learned how to linotype. That required also mechanical skills. But the important mechanical training was with hand setting. The linotype was producing material that would be just about the same size as in the newspapers of today, because the lead slugs that came out for every line were the actual imprint, things that actually gave an imprint on paper, but anything bigger than that had to be set by hand. So you memorized, and here was an alphabet, and it too was in a strange organization -- not "a, b, c..." -- it had its own formulated structure, and you'd pick up letters and make your headlines or your subheads. That required a lot of technical skill. And there were other aspects of the printing and the newspaper publishing business that required skills. I did all the jobs from being a devil, which requires some explanation, all the way up to doing actual journalism work, or producing an atlas of a map of the county that we lived in. It was called Plymouth County. So there was sort of, when I was working in the newspapers I had to do many things. And of course, I also enjoyed basketball and football, and I was good at those sports. So I really had a very well-rounded life up to the age of 17.

Did you know what you wanted to be when you grew up? When did you choose a career in medicine?

Thomas Starzl: My mother had been sick and required some very serious orthopedic operations when I was probably about ten or something like that. These were high-risk procedures. She went to Sioux City for the operation and was gone for a long time, a couple of months or maybe longer than that. She also had been a nurse. She had a very high respect for the medical profession. And because I was fond of her, naturally that rubbed off. But her background was an interesting one in that she was one of that horde of women who, in order to get out of the kitchen, or do something other than sit around the house all day, had become a teacher. So she was a teacher first. And after doing that for a couple of years, several years, she went to nursing school. So she was a teacher first and then she was a nurse. Then she was a patient after that, so I had quite a bit of exposure to doctors of one kind or another.

There was a doctor named Wendell Downing whose son became a doctor and practiced -- probably still does -- in Des Moines, Iowa. But the older Dr. Downing, recognizing that I was interested in medicine and in surgery, invited me to come and watch operations, which I did, and observed operations that today are rarely done, like radical mastectomy for cancer of the breast and other operations. He taught me some details of anatomy that always stuck. It was always easy to remember the long thoracic nerve of Bell, because that was a nerve which one tried hard to preserve doing a radical mastectomy. So I spent quite a bit of time in the operating room, just watching surgery. I remember at first they were quite concerned that I might keel over and faint at the first sight of blood, but it didn't bother me.

A lot of people wonder how surgeons cope with this huge responsibility they have for the life and death of their patients. Have you ever experienced anything like stage fright or writer's block going into the operating room?

Thomas Starzl: Oh, I had that every time. That was a little bit unusual. I think most people who went into surgery become steeled to that responsibility, become hardened. Or maybe they don't even have to go through that process, just have a more conventional character and don't view it quite in such a lofty way as you've described.

But you did experience that?

Thomas Starzl: I was always worried. Of course there were textbooks describing operations. Even if I had done an operation 100 times, if I had an operation that I had done two days before, I'd go back and read the book and refresh books, which quickly became tattered and exhausted by constant use. But I think the great worries that tended to accumulate, so that they eventually became very heavy, were about what happened afterwards to the people. So if you operated on somebody with a cancer, you were always worrying that you were going to get that unwelcome phone call from somebody that they had a recurrence. Or in the case of the transplant patient, because the mechanisms of engraftment were not known, transplantation was a field in which big things were accomplished without knowing why and how. There was no reason to hope at the beginning of transplantation that those operations were cured. That is, if you could put a kidney and it had a chance of lasting for a lifetime. So instead the idea was that you had an alien, foreign organ in there that was under constant attack, and even though it lasted for a year, or a couple of years, that it was slowly, slowly going to go away. And if you actually came to know those patients, and I did, at a personal level in almost every case, you were sitting around like a parent watching over a child with an inevitably slowly advancing disease, and that you were going to get a phone call that the end had come. So if you had patients for whom you had a particular affection, and those uncommonly often were children, you just had an idea that you'd never see them grow up. So it was a deadly wait actually.

What did going through that stage fright, for lack of a better term, what did overcoming it teach you about yourself? Did it remove doubt from you?

Thomas Starzl: Well, I think the first thing it teaches you is not to get too puffed up about your importance. Maybe that's enough of a lesson all by itself.

From what you've said, it sounds like confidence in surgery grows with experience, and that confidence, in turn, allows you to take risks and gain more exeprience.

Thomas Starzl: That is absolutely true if you're in surgery, because you have to make decisions. Sometimes if you're not confident, you can reach a Y on the road, and there's an easy one that goes to the left that can be taken if you simply pronounce the objective to be unachievable. That's kind of a chicken way out, if in fact you're dealing with a problem that might be achievable, but only with great risk to yourself, risk of failure and professional disgrace. So if you're confronted with that kind of decision on a frequent basis, you can't take the tough road unless you're confident.

You've also learned from experiences that might have been judged as failures. After you moved to Denver, you experimented with treating diabetes by rerouting portal vein flow around the liver using portacaval shunts. That didn't work with diabetes, but it led you to eventual successes with transplantation. How do you deal with these apparent failures at the time?

Thomas Starzl: In that particular instance the first thing that you have to do right up front is to announce -- to yourself above all, but other people have to know right away -- that this was a dumb idea. And that's where writing, sitting down and actually writing a paper -- not in a deceptive way, in a very straightforward way -- becomes important. I don't know how many papers I've started pretty convinced of what a big boy I was and then, in the course of writing the paper, every word that is going in a false direction gives you heartburn, and it forces you back along lines of integrity. But that's just about a rather distant step down the line. You were asking about failures. That's a quite interesting question, at least from my point of view, because...

I never experienced any failures in life until I was fairly old, I mean until I was about 21 or 22, because everything had been so easy up to that point. I went through the Navy experience with no particular trauma, and going to school was easy, as I wrote in that book, because in order to get into the Navy with my parents' permission I had to skip a year of high school. No problem! Just go up and hire a few teachers and take the year in six weeks or so. So it was all easy, easy, easy. And then right around the age of 22, I woke up to the fact that I was going to have failures. I couldn't win all the time. It's kind of an experience that even the best professional athlete or boxer is going to have, discover somebody was smarter, stronger, out there somewhere, at least as it affected wherever specific enterprise was involved. So that's a bitter lesson. I learned that probably in my early twenties. Once you accept the fact that you can't always win, but you can always try, was an important turning point. I'm sure that because things still were pretty easy, and I advanced through life at a rapid rate, I always had that uneasy feeling that I didn't really deserve all this, that in some ways I was just a pretender with the shiny veneer, but without substance beneath. If you were to talk seriously to just about anyone who has done anything important you'll find that this concern, at some time, in many had a dominant force, and just trying to learn what your own true worth is. I think you keep pushing at that envelope maybe until you're 60, or maybe until you're 85. I don't know.

You took a reduction in your personal income from private practice in Chicago to come to the University of Colorado. What led you to this decision? Did you see greater potential for advancing liver transplantation at this facility?

Thomas Starzl: I didn't see how you could do transplantation in Chicago in any facility with which I was affiliated at the time. The teaching hospitals were all bread-and-butter private hospitals, Passavant and Wesley. I don't know whether you know the Chicago system, but Northwestern had at the time only two full-time members in surgery, was not at that time committed to research of one kind or another. So I was kind of a loony, and the people in private practice regarded me as a competitive threat, so they did everything they could to keep me out of the hospitals. And if you don't have a strong presence in the hospital it's foolish to think that you can ever bring anything from the lab to the hospital. I had a protocol to do kidney transplantation at the Cook County Hospital, which was a carefully thought out one. I went away on a weekend, for some reason or another, came back to find that all the people that I had gathered together to do this thing had run off and done one and messed it up so badly that there would never be another one done for years. So it just didn't seem like a place where the overall game plan or long-term plan for development was consistent with what I wanted to do.

I was exhausted by the life that I was leading, which -- I had left those mainstream hospitals, the society hospitals and had got practice privileges in a Northside hospital called Lutheran Deaconess Hospital, where the Sisters and the staff were willing to start cases at five in the morning, so I could do surgery and be out of there by nine o'clock and be in the lab and have a full day. But then, by having patients out there at the end of the day, I had to go back and make rounds, and I found myself getting two, three hours of sleep at night, if I were lucky at all. I was thinking at the time that I probably wouldn't make it to the age of 40, unless in some way I changed everything. So there's nothing noble about that, or mysterious. I couldn't conceive of getting done what I was supposed to do.

When you made your move from Chicago to Denver, there was a difference between the private practice of medicine and the work of full-time medical faculty in university hospitals. Has that changed over the years?

Thomas Starzl: There was this wall between private practice as a way of life and academia, which is where the research ideas were played out, were drummed up and played out into reality and exported. The salary differential between the two sides of the wall was enormous. Like the last year I was in Chicago I was quite busy. I can't remember how much money I made, but it was a lot, probably in the range of four or five times as much as the salary that I settled for to go to Colorado. If I said it was $100,000 in The Puzzle People, which I may have done, that would be, I probably wouldn't have been so indiscreet as to have done that. But if I had, that would be a correct, an approximately correct figure, because I had debts that had been accrued during this long period of training. Those were all paid off, so I was debt free for the first time in my life by the time I went to Colorado. So it was an exercise that I could -- it was a gesture, in fact -- that I could afford to make. And I'm describing 1960, 1961. What has happened, in my opinion, is that that wall broke down, and the university became a competitor with the people that are in private practice, and in so doing contributed to what I think is a very unfortunate situation that exists throughout the country, in which health care became an industry and we -- I'm talking about the United States -- became the only country in the world in which health care became a venture capital industry. I believe that to be a disgrace and a tragedy. You need to censor my remarks, somebody might actually hear them!

At one time, doctors in private practice volunteered their time to universities, and were a group apart from full-time medical school faculty. What was the difference?

Thomas Starzl: When I started practice, or when I went to medical school, or during essentially all of my training, there were two groups of people involved in my education. One consisted of a very small number of full-time clinical faculty. At Northwestern, I was one of two. At Johns Hopkins there may have been four or five, something like that. But most of the teaching and the surgery was being done by people who were in private practice. As years went by, at first slowly, but then in avalanche proportions, the group on the academic side, separated by a wall from those in private practice, became bigger and more and more like a group of practice physicians providing a full range of services: ENT, orthopedics and all brands of surgery. So in a sense, the people inside the ivy walls and those on the other side, as the wall went down, became much the same. The university became like a group practice. That situation exists here at the University of Pittsburgh and many others. The last holdouts, by the way, of the strict full-time faculty receiving the smaller fixed salaries, were the University of Colorado and the University of Chicago. Both of them have since imploded and have eliminated that functional distinction. So nowadays you have a full time faculty, and it competes with the private groups. A lot of the private groups have assembled multidisciplinary organizations, but it's been much easier of course to do that within the medical school.

Why did that system change, or implode as you said?

Thomas Starzl: I think it imploded because of money. Money drives just about every policy decision.

Do you think that staying in an institutional environment is necessary for a career in surgery?

Thomas Starzl: No, of course not. I don't think it's necessary to have a career in surgery to be within an institution within a university. You can have a very successful career in or out of the university. But the prestige element of a professional life is far more easy to follow within a university. There is a rewards system. But the ability for clinicians to do research, real research, has been not eliminated, but greatly reduced.

What do you think it takes to make a university competitive?

Thomas Starzl: Well, two things really. Innovation is one thing, but I think above all is competence, the ability to provide good care, day in and day out.

Let's talk about the classic axiom of the medical profession, "Do no harm." What do those words mean to you?

Thomas Starzl: That's an important rule. It's a self-explanatory statement. You don't want to treat somebody, or operate on somebody, or treat them in any way if the treatment can exacerbate their disease or increase their suffering or make them worse than they were when they came to you and made this moral contract that's called a doctor/patient relationship. So this is a warning from antiquity. "First..." The total statement is "First do no harm." That's in the Hippocratic Oath.

Looking back on your career, is there anything that you would have done differently?

Thomas Starzl: I doubt it. What I really regret is the penalty that was paid by my children, who lost their father for quite a long time. It was not much different than what happened when people went off after Pearl Harbor and didn't come home for six years.

As you see them, what are the pros and cons of the organ procurement process in the 21st Century?

Thomas Starzl: I'm not sure that I'm qualified any longer to comment on that, because I haven't actively practiced since I was 65. When I left the field, I just left and really stayed away from patient care and these mundane matters like where do the livers come from or where do the organs in general come from. But these problems were dumped in the lap of large groups of people with different agendas and different self interests. A great effort has been made, because there's been so much public scrutiny, to be fair, that was made possible by a system that was developed here and was then picked up and used as the national system. But in some ways it's a system that became so muscle-bound that there are delays -- very often very big delays -- where organs are just sitting around waiting to see where they should go. That's probably inevitable if you want to be fair. So the people that run the local procurement agency do a very good job. They are completely independent of control by the hospital. That's a big change, in what I hope was a fair and honest manner. We used to influence those activities much more than now. But because of the obvious conflicts of interest of the user and the provider, it was necessary to create distance. All of those things I think have come on in the last 20 or so years.

I think it's much harder to work today, and probably much more pedestrian than it was. But that is something that you automatically would say about almost any new field of medicine. And bear in mind, transplantation was not a small thing. It was a whole new discipline of medicine that didn't exist before. It's rather unusual for somebody to live for so long that they're able to participate in the birth and the adolescence and maturation and perhaps even the senescence of a field. But there are two people that I know that did that, and the only other one is Sir Roy Calne, the guy that I mentioned before.

That's quite an achievement.

Thomas Starzl: I realize I just gave you a taste of rhetoric, because I never really answered your question, but that's the best I can do.

Understanding that you've been out of the day-to-day minutiae of transplant practice for 20 years, we still appreciate your perspective on the competition for donors and for recipients.

Thomas Starzl: I know. It's too much like feuds going on all the time. It got that way fairly soon after I retired from practice. I think because so many people were trained here, that maybe I was a little bit like a center pole that could maintain amicable relationships for a long time. I wanted out, knowing that staying in would be worse than whatever problems might be entailed by getting out, and I didn't want to be a piñata.

If a young man or woman came to you for advice for what it takes to have this kind of career, what advice might you give to them?

Thomas Starzl: I would say that the thing to do would be to pick some question or objective that hasn't been addressed before, or has never been addressed in a satisfactory way, because if you really want to do something like I was able to do you have to start near ground zero. If you try to pick up and ride somewhere in that mushroom cloud that develops as things get bigger and bigger, there's really no... You might be able to make a lot of money and have a nice living even, but if you really want to ride a skyrocket you have to start on the ground, at the beginning.

What do you think will be the next frontier in transplantation, or other areas of medicine, in the next quarter century or so?

Thomas Starzl: By elucidating the mechanisms of engraftment, the tools have been handed on now that are going to make it possible to get people off (immunosuppressant) drugs more frequently or to use low doses of drugs more frequently. By understanding mechanism also, it may be possible to move into xenotransplant objectives, the use of animal organs. Or there is an interface, a powerful one, between transplantation and stem cell biology that might be exploitable. So I don't think that the lid is on transplantation. But with something new, the skyrocket goes here, and then it gets into a plateau which may be sustained on an upward trajectory, but it will never be straight up like it was at that time. With all its vicissitudes, I like the straight shot. It's a little bit like flying to the moon. That was a tremendous achievement in 1969, but it's slowly lost power, lost power, and in fact, even our participation -- at least moon exploration -- is coming to an end. We're turning it all over to the Russians. But there are planets out there beyond that, so there's room for more. But probably nothing will ever have the thrill of having some guy walking around on the moon.

What do you know about achievement now that you didn't know 50 or 60 years ago, when you were starting your career?

Thomas Starzl: I don't know that I can even give an answer to that, for one simple reason. I never thought of what I did as being an achievement. Even now I don't tend to categorize it in that way. I think self-evaluation is very unreliable and probably wrong either in one direction or another.

Do you have any advice for healthy living in the 21st Century?

Thomas Starzl: I have one cardinal rule or two; they're related. One is not to ever get caught up with substance abuse. That has ruined more people than any other factor, except one. The second is obesity. I do not understand what has happened in this country that makes everybody fat. It's just incomprehensible, because in fact obesity is a higher health risk than smoking. Take somebody like Shelly Winters. She probably doesn't mean anything to you...

We all know Shelly Winters.

Thomas Starzl: How can you start with this beautiful glamour girl and end up the way she ended? I just don't understand it.

It doesn't seem like Americans were the same size 30 years ago. Is this a new addiction? Has there been some change in our habits or lifestyle?

Thomas Starzl: I think there has been.

Looking back on World War Two personnel, or even thinking back on companions at that time, they were small. I weighed the same thing as I do today, 165 pounds, and I was considered big. I was one of the biggest kids on my high school basketball and football teams, one of the biggest kids on the college team. These are giants. Somebody who's 200 pounds is actually considered rather small in the pro football game. So I don't know what the hell happened, but it happened in a different way in Japan. And it's dietary. In Japan, the average height of Japanese women went up about a half a foot, from I think it was five to five feet six inches. Big Japanese women. The men also gained height, but not as much as the women. So what happened in Japan, they tend not to be fat, but their nutrition is good. But if you look at what happened, just follow the pro football players. I've been watching them almost since the game began. If you had somebody like Sam Huff -- you would probably know him, he was a West Virginia guy who played for the New York Giants, was supposed to be one of the great mid-linebackers of all time -- he weighed 200 pounds. And you know, they would be eaten alive today at that weight. So I don't know what the hell has happened. But the problem is that you have those examples of these... and you look at our soldiers now that are serving in Iraq and Afghanistan. They're big, muscular brutes, I'm just wondering if that is really an advantage. They're easier to shoot when they're so big. So I don't know what happened that made everyone fat, but I do know that it's a terrible health hazard.

Do you have a definition of the American Dream?

Thomas Starzl: No, I don't. It's a nice phrase, but there are many countries where these dreams can be fulfilled.

I think the American Dream has come to be distorted. The original American Dream was simply that we must have here a meritocracy where we don't inherit wealth, influence and power. It's come to mean, at least in political arguments, the right to get filthy rich. And I think that's a mistake. That is not the American Dream that our forbears had. That dream was to be free: freedom of expression and the right to climb as high in worthy causes as your abilities would enable you to do. It was pretty simple. It had nothing to do with money.

Could you tell us how organ transplantation reshapes the life of the surgeon?

Thomas Starzl: Well, it teaches you humility, for one thing, because there are failures, and as it existed when I was in practice it was all-consuming. It didn't leave a lot of room for other very worthwhile activities, such as tending more completely to your family, or carrying out other obligations that are time intensive. That was a different era, in which transplantation was more of a crusade then a business or an ordinary enterprise of any kind. So anything that I might say on that score would have to have an asterisk by it and that would be a "one-time-only" "at the beginning" notation.

Thanks very much, Dr. Starzl. It's been a pleasure.

Thomas Starzl: It's been great to talk to you.