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Organ transplantation: a paradigm of medical progress.

Organ Transplantation: A Paradigm of Medical Progress

Returning from Rome to Chicago recently in seat 23A of a Boeing 747 operated by British Airways I felt a magical sense of relief from the complexities of daily living. This world full of human beings seemed temporarily at peace from the vantage point of six miles up. It occurred to me that each one of us should, on occasion, pull back from the everyday intensity of moral decision-making and simply document certain human processes as they occur. A clear pattern of behavior would likely emerge. Given the wisdom of time and overview, we would all make fewer judgmental errors and moral definition would be better served. Such posture would be particularly suited to the evolution of biomedical technology of the past thirty years. Open heart surgery, organ transplantation, and development of biomechanical devices each illustrate the wisdom of exercising caution when drawing moral conclusions in the short haul. Many of my colleagues and I wonder if development of these technologies would even be possible in today's milieu of legal and ethical constraints. Yet each is contributing greatly to the welfare of mankind.

I should like to develop discussion of one particular technology, organ transplantation, simultaneously along three avenues. These include: transplantation as a technique and as a therapy - as an every-day reality. I want to discuss how it got here, why it is here to stay, and why there will be more of it in the future. Secondly, I want to consider transplantation as a science. Why much of the original work seemed doomed to fail; why science is forced to catch up with transplantation and how science has helped transplantation become a permanent fixture in modern therapy of end-stage organ diseases. Finally, I want to talk about transplantation as a social phenomenon. I want to consider the definition of death; distribution of resources; and imposed limitations on progress in this most visible of therapeutic realities. In addition, I would like to lace this discussion with enough examples to personalize transplantation for me as a physician and for you as philosophers. And I would like to share with you a few phrases such as "bioethical perspective" or another way of saying bioethical wisdom, and "predictive bioethics," which is another, if somewhat dangerous, way of approaching the question: What if? You may also want to contemplate "reactive bioethics" and all that term implies.

Please don't think that I in any way believe biomedical ethics is adversarial to medical and surgical progress. In fact. I strongly support philosophical interest in the direction biomedical scientists and practitioners are taking technology today. I believe professionals in biomedical ethics are and will continue to make an enormous impact on our understanding of how technology relates to the human condition. Bioethical perspective (or wisdom) may bring us full around from the sterile, so-called scientific method to the Hippocratic holism that reminds us all that we are, finally, human beings. I simply want to offer a few thoughts to see if you might relate to them in some way as being helpful in our joint assessment of organ transplantation as an example of medical progress.

When I arrived in the hotel in Chicago, there was a message requesting that I call Marsha Dunn, a wire service reporter. She was at another hotel in the same city covering an important meeting of transplantation specialists, and was just finishing a story on the dilemmas of anencephalic babies as organ donors that highlighted an infant friend of mine named Paul Holc. Paul is notable in the world of transplantation for being the youngest person ever to receive a solid organ transplant. More importantly and sadly, he remains the only person in history to be living with the transplanted heart of an anencephalic infant. There are many good, practical people on this planet who felt that transplanting Paul's heart was a wonderful and compassionate thing to do, both for Paul and his family and for the family of the donor. Anencephalics are potentially excellent infant organ donors and that, quite frankly, is what most of the individuals who conceived them would like them to be. I assured Ms. Dunn that we were still looking at anencephalics as potential organ donors and I felt confident that we would develop a method of carrying out their families' wishes to donate their vital organs. Meanwhile, Paul Holc is very much alive and well today, his little anencephalic heart working beautifully.

I don't need to remind anyone here of the debates that surrounded that transplant and questioned its propriety. Not a few ethicists, some sporting legal credentials, jumped at the anencephalic issue, and like the proverbial horseman, went riding off in all directions. We became embroiled in the definition of death - particularly as it relates to young infants. That missed the point. Most of us were having little if any trouble with the legal definition of death at any age. We seemed to slip so easily over the fact that an anencephalic's unfortunate little body is missing a brain and that if not dead by current definition, will be by any definition within a few short hours or days of birth.

Using transplanted organs from doomed anencephalics to save other infants lives was, some said, against Kantian ethics. In fact, I heard Immanuel Kant mentioned so often, I thought I should get better acquainted with him and his thoughts on the matter, and I did. I discovered that this venerable 18th century Prussian scholar was a master of the physical sciences, a great teacher, and a brilliant mind. What I like best about him was his willingness to comfront the imperialism of his time with the notion that old men had no business waging war with young men's lives. A suggestion for which he may have been beheaded had he not been quite so old when he made it.

A number of facts about Kant, however, recommend him far less as an authority on modern bioethical issues. He was born, grew up and to the best of my knowledge never really left the little town of Konigsberg, Prussia. His private life was mostly one of isolation, and his habits were so predictable that neighbors literally set their clocks by his behavior. He never married, though he apparently thought of it on two occasions. More to the point, he appears never to have produced or adopted a child and hence, was never a parent. Except for his courage in confronting the issue of whether war ought to be waged, there is little to recommend this individual to today's world of bioethical philosophy.

May I pressume to suggest that what is needed today is new, original, perceptive philosophical moorings against which to anchor our ship of medical progress? Kant was a purist and dealt in absolutes. Biology, by its very nature, is a practical, unpredictable science. One can play with it, push it around, and without even understanding it, succeed quite regularly in altering it. Organ transplantation is a perfect example. I seriously doubt transplantation ever crossed Kant's mind, and his Critique of Pure Reason has yet to make a sick human being whole again.

That transplantation even exists today is a tribute to the humanness of mankind. It derives from the compelling desire to help fellow human beings live, nothing more. Perhaps not everything about transplantation is quite that altruistic, but in the main, medical altruism, not science, fathered it. Like open heart surgery and biomechanical devices, organ transplantation is here to stay because it works. It is here to stay because it fulfills a basic human need to help, not because of any of the scientific developments that, like biomedical ethics, are desperately trying to catch up. Organ transplantation, perhaps more than any other one form of medical progress, has provoked bioethical dialogue. Nevertheless, biomedical ethics, in my view, is constantly scrambling to keep up with transplantation. This is not an indictment of ethics, just a simple matter of fact. The past can't help much, because where transplantation is concerned, we're not likely to repeat much or any of it as we approach the future. It is a soft and gentle science (George Bush might say a kinder science), and it deals with what little we know about unpredictable biologic systems. It's really all about human beings and other living things, and so calls more for bioethical wisdom, and, I would like to suggest, a whole new, if not dangerous, field of predictive bioethics. Where is this form of medical progress taking us? Based on what we've observed, what will organ transplantation be like in the year 2000? What if babies with monkey hearts or kidneys or livers are alive and well in the long-term? What if?

But let's refocus on organ transplantation. Human courage and compassion, not science, motivated three young surgeons in Boston to stitch a fresh cadaver kidney onto the arm of their acutely uremic and comatosed patient in 1947. This was done on the back ward of the Peter Bent Brigham Hospital using a couple of gooseneck lamps. The kidney immediately began to produce urine. Over the next couple of days, until it was rejected and lost function, the kidney cleared the uremic waste from the patient's blood stream and cleared her uremic symptoms. The experience with the transplanted kidney was just enough to allow her own kidneys to regain function and that individual left the hospital well. It was an unprecedented (if not terribly scientific) achievement, but I cannot help but wonder what today's bioethicists might have said about that remarkable experience. Additional kidney allotransplants to the groins of patients ended in only short-term success until a tiny ray of Mendelian science entered the picture. In 1954, again at the Peter Bent Brigham Hospital, a dying patient was given the kidney of his identical twin. That transplant worked. And thereafter, most, but not all, twin transplants worked. An occasional graft didn't work, leaving the donor with only one kidney and his or her sibling with none. And then occasionally, the donor twin developed the same kidney disease from which his sibling had died and then there were none, kidneys or twins. What would a modern ethics panel say about transplantation thus far? Would bioethicists in Boston in the early 50s have pulled the plug on organ transplantation?

Of course, science was doing its best to catch up and explain why some transplants worked and others didn't. the genes for human tissue uniqueness were discovered to exist on the short arm of your sixth chromosome. Crude, but exciting studies of tissue antigents began to appear in the scientific literature. It became possible, in a very limited sense, to type tissue, much as Landsteiner had demonstrated typing red blood cells in the 1940s. More important, a young zoologist in London, Peter Medowar, was demonstrating the mechanisms of allograft rejection, and in 1953, demonstrated the potential for the production of immune tolerance in transplanted animals. All of these scientific findings, while exciting enough in pure form, served to stimulate clinicians in a very dramatic way. Transplanters began to experiment with chemical means of suppressing the immune response and hence, prolong graft survival. Not all methods of immunosuppression were successful. In fact, some were really quite harmful. A whole series of patients subjected to whole body irradiation lost their lives to opportunistic infections. Nevertheless, it was clear to physicians that organ transplantation could improve the plight of their patients if not permanently, at least temporarily.

About this same time, the long-awaited heart-lung machine was used for the first time clinically at the Jefferson Medical School to repair an atrial septal defect in the heart of a young lady. It worked. At least it worked the first time. It failed miserably for the next several patients on whom it was used. There was, in fact, a period of four years when funding could not be obtained for development of a heart-lung machine because a group of scientific peers determined that "it could not be done." Again, I wonder what today's bioethicists would have said and done. Would we have foreclosed the development of open heart surgery?

Cadaveric organs were virtually unavailable in the 1950s and most of the 1960s because we did not know how to define death appropriately until just over twenty years ago - about the time The Hastings Center was conceived. Meanwhile, Tom Starzl in Colorado, James Hardy in Mississippi, and Keith Reemtsma in New Orleans were flying in the face of conventional wisdom and implanting primate organs into human beings. Most of these human beings died, but several of Reemtsma's patients with implanted chimpanzee kidneys survived for a number of weeks and even months. Rhetorically once again, what would today's bioethicists have said and done about this particular evolutionary rung in the ladder of transplantation?

And then a wonderful thing happened in 1968, stimulated by the pressures of transplantation reality. In December of 1967, a living, beating human heart was transplanted into another human being in Cape Town, South Africa, and then again in New York, and then California, and beyond. The incredibly dismal outcome of the approximately 100 heart transplants done in 1968 left two important legacies. First, brain death criteria were hammered out on the Harvard Campus in 1968, thus making possible a more reliable pool of cadaveric organs for transplantation. The second legacy had to do with the development of immunosuppression and refinements in the care of the transplant patient. What seemed most frequently overlooked was the fact that virtually all those 100 or so recipients of heart allografts would have died anyway in 1968 or 1969.

To their credit, surgeons in two institutions in North America, one in Europe, and one in Africa continued cautious investigation of human heart transplantation. They developed appropriate protocols for patient selection and post-operative management, and gradually developed heart transplantation as a clinical reality. Meanwhile, Starzl and a few others were experimenting with human liver transplantation and more and more kidney transplants were being performed with increasing success. During the early 1970s, heart transplantation carried a one-year survival of about 40 percent. Liver transplantation was even less successful and cadaveric kidney transplantation was hardly better. Patients were dying mainly of graft rejection or serious infection. And again I wonder what today's bioethicists would have said about transplantation in the early and mid-70s. Meanwhile, transplantation science was beginning to catch up and a whole field called transplantation immunology was developing. Science began defining the impressive balance between human immune suppression and aggression. Clinicians developed a better understanding of our use of immunosuppressive agents.

And then the drug cyclosporine was discovered by Jean Borel in 1976, and found to have significant immunoregulative capability. We knew enough science by the late 1970s to characterize the effect of cyclosporine on the human immune response. Introduction of this drug into clinical transplantation transformed the 1980s into a halcyon decade of organ transplantation with increasing numbers of transplants and markedly improved results. Heart and liver transplantation have increased thirtyfold during this decade. Heart-lung and lung transplantation were introduced and have shown steadily improving results. More and technically improved pancreas transplants are being accomplished. There has been a vast proliferation of centers performing transplantation throughout North America. Finally, Congress has established a central clearing house for organ distribution called the United Network for Organ Sharing. This was done to help assure fairness of organ distribution and competence of transplantation centers. And, of course, this has been a very stimulating decade for the profession of biomedical ethics.

In late 1984, my group at Loma Linda University transplanted a baboon heart into Baby Fae, an event that triggered enormous international interest and debate. In many ways, the compassionate effort to save an infant's life got lost in a quagmire of professional and public rhetoric. You'll recall how absurd it all seemed. Few noticed that she lived longer with the animal heart than did Mr. Louis Washkansky, Dr. Christiaan Barnard's first patient to receive a human heart in 1967. She also lived longer than Dr. Norman Shumway's original human-to-human heart transplant patients in 1968. Fewer still recognize Baby Fae's most important legacies, namely the fact that she did not reject her baboon heart, but rather died of an ABO incompatibility, a phenomenon that improved donor-recipient selection will prevent in the future. She would likely still be alive with her baboon heart had we been able to stay within the appropriate ABO grouping. Perhaps her most important legacy was to announce to the world that babies deserve the benefits of organ transplantation too. Subsequently, there has been an ever increasing flow of infant donors. During the years since her transplant, our group has accomplished human-to-human heart transplantation in forty-four additional infants under six months of age. Thirty-nine (89%) of those recipients are alive and well today. Since there have been no late deaths as yet, it would appear that newborns and young infants do benefit from heart transplantation. They may in fact, for a lot of reasons, be the best of all possible recipients of organ transplantation.

I suggest that the "reactive" bioethical rhetoric generated by Baby Fae might have easily destroyed further interest in infant heart transplantation. Much of what was said and written did not reflect well on the fledgling profession of biomedical ethics. It was all too quick, too ill-informed, too self-assured. Furthermore, some of it hurt my feelings. I have often compared the ethical rhetoric of those days to the phenomenon of "pack journalism," and have considered it "semi-ethics" - close, but not quite the real thing. What was missing was wisdom and a sense of perspective. And that's my main message: A plea for bioethical perspective. In 1984 and 1985, we learned a great deal about our professions and about each other. And I sense we're all better for it.

On balance, the story of organ transplantation is a paradigm of medical progress. Transplantation is the best its ever been and will get even better as the science develops and as donor resources improve. To be sure, there are many troubled areas of ethical concern to be ironed out, but that sort of thing takes time, or ought to. I for one am grateful for the enormous contributions biomedical ethics has made to organ transplantation. The standard of whole brain death has led to an ever increasing number of cadaveric organs for transplantation. We are more aware of the issues of recipient selection and fair distribution of donor organs. We are reminded of the economic impact on society. That's a whole other discussion. But our legitimate health care expenditures are among the best dollars this nation or any other nation spends out of its annual budget. We don't have to have organ transplantation or any other form of medical progress, but I'm convinced this great nation of ours wants it and deserves it. And so transplantation will continue because it offers hope in place of despair, because it's a very good and humane thing to do, because it makes an important statement about how human beings ought to relate to one another on this planet - with dignity and compassion. You and I as professionals must find ways to refine it, surely, but we must be very cautious in our attempts to limit transplantation or any of the myriad other areas of medical progress. To paraphrase a bumper sticker I see from time to time in California: "Progress Happens." Our mandate is not one of limiting medical progress, but one of wisely relating these exciting and beneficial new technologies to the human condition as it exists now and into the future.

Leonard L. Bailey is professor of surgery at Loma Linda University School of Medicine, Loma Linda, CA.
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Author:Bailey, Leonard
Publication:The Hastings Center Report
Date:Jan 1, 1990
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