Transplant innovation and ethical challenges: What have we learned?
Panel discussion
Moderated by Mark Siegler, MD
WERE FINANCES A DRIVER OF EARLY TRANSPLANT INNOVATION?
Dr. Mark Siegler: It is clear that there are more ethical and less ethical ways to introduce innovations. I am reminded of an article in JAMA by Francis Moore in the late 1980s in which he warned that one of the things to look at for any new innovation was the ethical climate of the institution.4 He cautioned us to be very aware of the driving force behind an innovation. Is it to improve patient care? To save lives that otherwise would be lost? Or is it primarily for the self-aggrandizement of an investigator or the financial goals of an institution?
I also remember the chapter in Dr. Starzl’s book The Puzzle People5 about the anguish involved in introducing liver transplantation. It seems that financial considerations were not the driver of major steps forward in introducing liver transplantation, in Dr. Starzl’s case, or heart transplantation, in Dr. Cooley’s case. Would you comment?
Dr. Thomas Starzl: Actually, not only were we not driven by economic gain, we expected fi nancial penalty for focusing on transplantation. If ever there was a field that developed against the grain, that was costly to people who worked in it, whose engagement meant that for most of their career they would work for substandard income compared with their peers—even those peers in academic medicine, let alone those in private practice—it would be transplantation.
It was not until 1973, when the end-stage renal disease (ESRD) program began under Medicare, that cash for transplantation started to become available. The real cash streams did not start until the middle to late 1980s when nonrenal organs became the cash cows. To be fair, no new technology can be assimilated into the health care system unless it at least pays for itself. But you can go beyond that and create baronial kingdoms, and I think that is where you can go wrong.
Dr. Denton Cooley: I would add that those of us privileged to spend our entire career in academic settings have an opportunity that others may not have. A lot of brilliant people in private practice are capable of doing many things but do not have an institution to represent and protect them. I have also always felt that those of us in these positions have an obligation to become innovators. Surgeons who merely see how many appendectomies or cholecystectomies they can perform are being very derelict of their responsibility to the institution.
MEASURING SUCCESS IN HEART TRANSPLANTATION
Dr. Siegler: Dr. Cooley, what is the current success rate for heart transplants?
Dr. Cooley: Nationwide, around 90% of recipients survive 12 months. Of those, maybe half are still alive 5 years later. Of course, we do not know what the future will hold. It is interesting that the fi rst sign of rejection seems to be coronary occlusive disease. It is a different type of coronary occlusive disease than is seen in atherosclerosis: it is diffuse, involving the entire extent of the coronary circulation, and is not really amenable to coronary bypass or other interventional procedures.
Dr. Siegler: We are now at about the 40th anniversary of the first human heart transplants, an extraordinary and historic innovation. Dr. Cooley, do you think the timing was right in 1968 when you did the fi rst heart transplant in the United States? In retrospect, would you have done the first transplant sooner or maybe even a couple of years later?
Dr. Cooley: You can argue it both ways. Should we have waited for further developments? At the time, heart transplantation seemed to work fairly well in animals, but we never really know until it reaches the clinical level. It was probably as opportune a time as any. We knew something about organ rejection at the time, and we had immunosuppressive drugs, although they were not as effective as they are today. The news electrified the world. I think we were pretty well prepared for this spectacular event.
Dr. Siegler: When would have been the optimal time to do a clinical trial in order to achieve evidence-based medicine in heart transplantation? Would it have been during the big breakthroughs of Shumway, Barnard, and Cooley, or now, when we have the general strategy and can find out how we can do better?
Dr. James Young: I would not have done a randomized trial at that time. The patients who were getting transplanted then were nearly dead; all other management was futile. In 1970, Life magazine listed the 102 heart transplants that had been done around the world up to that point, and maybe only 2 or 3 of the patients were still alive. That prompted the moratorium that Dr. Cooley referred to.
As ethical clinicians, we are supposed to do our best to make our patients feel better and make them live longer. Sometimes you have to do something radical. On that basis, one can argue that we should not transplant “the walking wounded,” that instead we should save organs for patients who are truly terminal without some sort of ventricular replacement therapy. But today we are getting away from transplanting only dying patients, so we need randomized trials to find out how we are doing in transplanting outpatients. That is the setting in which trials are now needed.
THE ETHICS OF ‘LETTING GO’
Question from audience: Dr. Chen’s story [see previous article] raised the issue of the ethics of “letting go” of one’s patient. I wonder if in transplantation, especially when innovative procedures are involved, a commitment to the procedure itself might sometimes conflict with the need to let go of the patient.
Dr. John Fung: In the United States, we measure efficacy and benefits in different ways than people do in other parts of the world. Here, for a child with a biliary atresia—the most common reason for liver transplantation—we expend hundreds of thousands of dollars for a liver transplant, which is usually able to save the child’s life. But in China, a severely ill child is viewed as a medical and economic liability and will be allowed to die so the family can have another child.
It is also not only the ethics of letting go. We all deal with letting go, not just in transplant medicine. It is also the ethics of actually getting a patient into the system. In the case of transplanting a newborn, as in Dr. Chen’s narrative, should they even have embarked on that?
Dr. Pauline Chen: For me, the story illustrates the remarkable connection and profound attachment between a surgeon and his or her patient. The fact that three patients are really involved in transplantation—the donor, the recipient, and the patient still on the waiting list because the organ went to the recipient instead—also motivates the team with a sense of obligation to the two unseen patients.
If there is a lesson about the ethics of letting go, I think it is that we often fail to talk about these issues among ourselves. Perhaps if we had discussed end-of-life care or palliative care in Max’s case, we might have had more insight into the pressures we felt in considering the lives of three separate people. And those discussions might have—or might not have— changed the situation.
Dr. Starzl: I agree completely with the preceding comments. All kinds of motivations might cause a surgeon to cling too long—the ones that were mentioned as well as some ignoble ones, such as vanity, in terms of looking at one’s survival numbers.
I would also like to take a much larger view. Some years ago in Colorado, the governor at the time, Richard Lamm, thought that intensive care units (ICUs) were harmful—that they were economically draining, did not serve society, and prolonged suffering. My position, which was really the opposite, was that maybe he was right in his philosophy but transplantation had, in a sense, changed all that. Transplantation took desperate people who were in the ICU, with no chance of coming out, and dramatically returned them to wonderful health.
As procedures get better, this scenario happens more and more often. I agree that there is a time when you realize that no intervention will work and you should stop treatment. That is a bitter pill. But it is very hard to define when that moment occurs.
Dr. Chen: There also may be somewhat of a generational difference in approach.
Most surgeons will fully acknowledge that they stand on the shoulders of giants, and that holds particularly true in a field like transplantation. When I was training in liver transplantation, for example, 80% to 90% of the patients could fully expect to survive 5 years. For my vintage of surgeons, then, death and failure were rarities and they were truly a sort of enemy, whereas surgeons like Dr. Starzl and Dr. Cooley have seen so much more and are far more used to all the variations of outcomes. Because of that breadth of experience that you have, I think you are wiser than my generation of surgeons, for whom death often has to be ablated at all costs. I think it follows, then, that you would also have a better sense of when to stop.
Dr. Starzl: There is a generational change—there is no doubt about it.
IS TRANSPLANT ETHICAL WHEN A LIFE IS NOT AT STAKE?
Question from audience: What are the ethical implications of non-lifesaving transplants, specifically of the hand and face?
Dr. Young: I have been on many peer-review committees charged with looking at this issue. Although the ethics can be very troubling, I have resolved important questions in my mind by examining them through the context of human suffering. Our mission as physicians and caregivers is to relieve suffering, which can take the form of pain, a shortened lifespan, or even a debilitating disfigurement of the face or a severe limitation, such as after traumatic amputation. Looking at the issue this way, I am less troubled than I was initially, when I viewed these kinds of transplantations as simply altering physical appearance or extending ability.
Dr. Starzl: The next big movement in transplantation is going to be in composite tissue allotransplantation—that is, transplantation of the face, limbs, etc. Mechanisms of alloengraftment have recently been uncovered such that it is now possible to formulate protocols that use either very light immunosuppression (avoiding the 20% or 25% rate of renal failure at 5 years that we heard about from Dr. Young) or no immunosuppression at all.6 Without the heavy burden of immunosuppression, this type of transplantation can become worthwhile. Putting a new hand or face on someone is astounding: it changes the morphology of the brain, which can be observed with functional magnetic resonance imaging. It changes the soul, if that is what you want to think of when talking about the brain. I think it will be very important.
Dr. Siegler: This extraordinary panel has not only discussed events from 50 years ago; each of the panelists spoke of a future that is rich in promise and innovation—and in ethical issues. It reminds me of a remarkable letter written in 1794 by Thomas Jefferson to John Adams, which says, “We should never return to earlier times when all scientific progress was proscribed as innovation.” More than 200 years later, Jefferson’s insight remains modern and relevant.
