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Interview With Dr Joseph Murray

2002; Elsevier BV; Volume: 2; Issue: 9 Linguagem: Inglês

10.1034/j.1600-6143.2002.20901.x

1600-6143

Francis L. Delmonico,

Organ Transplantation Techniques and Outcomes

The Editors asked Dr Delmonico to interview Dr Joseph Murray, winner of the Nobel prize in Medicine 1990 for performing the first successful renal transplant, to record recollections of the issues of the 1950s, when clinical transplantation was born, on Dr Murray's medical career in transplantation, and on some contemporary issues. The Editors asked Dr Delmonico to interview Dr Joseph Murray, winner of the Nobel prize in Medicine 1990 for performing the first successful renal transplant, to record recollections of the issues of the 1950s, when clinical transplantation was born, on Dr Murray's medical career in transplantation, and on some contemporary issues. I visited with Dr Murray on a bright New England Sunday morning, January 6, 2002, as Dr Murray had returned from St. Paul's Church. If Dr Murray is not traveling, everyone in his parish knows they can find him at the 7:30 AM Mass, sitting in the same pew where he has on Sunday morning for the past 40 years. Many an impromptu medical consultation has been given at the conclusion of church services. Since his retirement, Dr Murray usually proceeds from church to breakfast and then to a local gym. But on this Sunday, we talked at the kitchen table of his home in Wellesley, Massachusetts. Dr Murray's wife 'Bobby' was with us, adding a verifying comment to the places and events of Dr Murray's recollection. My assignment was to record some aspects of transplant history unique to Dr Murray's experience, regarding the first successful kidney transplant between identical twins in 1954, and the development of the brain death diagnosis in 1968. My previous conversations with Dr Murray over the years have shown him to be very consistent, comfortable, and secure with his own perspective. This consistency is a measure of his wisdom and his contribution to the transplant community today. Dr Murray recalled that his career interest in transplantation had been propelled at Valley Forge during World War II by the plight of the burned victims returning from battle. There is the extraordinary story of war hero and aviator Charles Woods in Dr Murray's book Surgery of the Soul, which had an enormous impact upon Dr Murray's career and his devotion to reconstructive surgery (1Murray JE Surgery of the Soul: Reflections of a Curious Career.. Science History Publications, Canton, MA2001Google Scholar). His experience as a military surgeon stimulated Dr Murray's goal of controlling the rejection of 'foreign' skin. It was this interest in the biology of rejection that made his assignment to the kidney transplantation project at the Brigham so appealing, and led him to perform the first successful kidney transplant between identical twins on December 23, 1954. The Brigham team was not apprehensive about personal failure but upon its hopes for the living donor and his recipient, and the impact that a widely reported medical disaster would have upon the field. Dr Murray observed that the same is true today with right lobe liver transplantation from a living donor. Importantly, the 1954 kidney donor and the recipient were secure to proceed, also aware of the successful experimental results. I asked a biological question regarding how assured Dr Murray was that the initial live donor was indeed a genetically identical sibling and that the recipient would not reject the transplant. Dr Murray replied that even though the Brigham team had assembled '17 identifiers of a genetic match, including the finger printing of the twins at the Roxbury police station', he was not ready to undertake the transplant until skin grafts were exchanged compatibly between the donor and the recipient. 'This was the indisputable evidence of their identity.'FIGURE 2Harvard Medical School Transplant Research Team.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In neither the first successful kidney transplant nor the brain death diagnosis did Dr Murray (or his colleagues) forecast its impact upon medical history. They did not anticipate either that clinical circumstance would become commonplace or so widely accepted. Thus, Dr Murray was surprised to learn that the annual number of live kidney donors in the United States had exceeded the number of cadaver donors in 2001 (2The United Network for Organ Sharing. Richmond VA.Google Scholar). He immediately expressed his concern about the probability of risk to the live donor, with so many being performed. However, our conversation then brought us to the predictions of Dr Murray's Surgical Chief and life‐long friend, Dr Francis D. Moore ('the great oak of American Surgery' as Dr Murray referred to him, who had died only days before this interview). Dr Moore had written years ago that, as a result of Dr Murray's accomplishment, the ethical assumption of physicians to first do no harm would be forever challenged (3Moore FD Three ethical revolutions. ancient assumptions remodeled after under pressure of transplantation.Transplant Proc. 1988; 20: 1061-1067PubMed Google Scholar). Indeed, the focus of the 1954 transplant was the ethical underpinning of the procedure. The decision to proceed was only given after the community was completely engaged, including discussions with prominent clergy of all faiths and legal scholars. Dr Murray recalled that the institutional attitude of the Brigham was clearly supportive because of its first‐hand knowledge of all of the experimental work that had been carried out successfully in dogs. However, the medical community of Boston and elsewhere dismissed the clinical procedure as an isolated event, especially considering the donor was an identical twin. As the field of transplantation developed, Dr and Mrs Murray recalled that there was no ringing endorsement of the Brigham live donor program at international scientific meetings. On the contrary, Dr Starzl had subsequently stated categorically that the report of a donor death had 'so shaken him' that he (Dr Starzl) would never sanction the use of a live organ donor for the remainder of his career (4Starzl T The Puzzle People: the Donors and the Organs Memoirs of a Transplant Surgeon.. University of Pittsburgh Press, Pittsburgh1992: 147Google Scholar). It was not envisioned at these early scientific meetings that live organ donation would evolve to the acceptance of virtually any person medically suitable and irrespective of a genetic relationship between the donor and the recipient. I discussed with Dr Murray the concerns about complications, coercion, and compensation that are in the mix of live organ donation today. He gave this comment directly: 'We are the last bulwark of a profession that separates itself from being a business'. Dr Murray emphasized the nobility of a live donor to give altruistically what is sacred – life. There is also the nobility of our medical profession, whose primary mission is the care of fellow man. It is this nobility that is offended, for example, by the insinuation of a sole profit motive or by advertisements for live organ donors by transplant centers in the media. Dr Murray remembered a comment by one of the initial donors, as told to him by his medical colleague John Merrill, when the donor was turned down because of medical reasons. The potential donor told Dr Merrill: 'I hope this satisfies the family'. Thus, the possibility of donor coercion especially within a family was evident to the Brigham team even from the outset. Dr Murray noted that his policy was to decline to perform such donor surgery if he was aware of the donor being coerced. I brought to attention the recommendation of the national live donor conference, that ideally the live organ donor should have an independent advocate (5Live organ donor consensus group. Consensus statement on the live organ donor..JAMA. 2000; 284: 2919-2926Crossref PubMed Scopus (414) Google Scholar). However, we also noted that there might be instances in which the donor may hide from the transplant team the issue of coercion into donation. It may also be difficult for the transplant center to ferret out an illegal donor sale. We then discussed the black market for organs that now exists in the Middle East, the Philippines, and the use of organs 'harvested' from executed prisoners in China. In response to these observations, Dr Murray showed me a paper sent to him by his Nobel friend, Joshua Lederberg, as they gathered recently for the 100th anniversary of the Nobel Prize. Dr Lederberg had written as early as 1963 of 'the potential dehumanizing abuses of a market in human flesh' (6Lederberg J Biological future of man. In: Man and His Future.. UK Churchill Ltd, London1963: 263-273Google Scholar). Dr Murray expressed his unequivocal opposition to monetary payment for human organs. In response to a recent 48‐h news documentary on the issue of organ sales from the poor, produced by Columbia Broadcasting System, Dr Murray wrote this message: 'We are physicians and surgeons caring for patients, not in a business with customers and clients.' Dr Murray's concern for the well being of the live donor remains as strong today as ever. We turned our attention to the development of the brain death diagnosis and its conceptual origins. In October 1967, Dean Robert Ebert of the Harvard Medical School had convened a group of physicians, ethicists, and legal scholars at the Countway Library, chaired by Doctor Henry Knowles Beecher (an anesthesiologist at the Massachusetts General Hospital), to examine the characteristics of a permanently nonfunctioning brain (7Beecher H Adams R Barger A et al.A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to examine the definition of brain death.JAMA. 1968; 205: 337-340Crossref PubMed Scopus (1445) Google Scholar). Dr Murray was a member of that committee, which included famed neurosurgeon William Sweet, neurologist Raymond Adams, and legal scholar William J. Curran. At the time French clinicians had proposed the concept of a condition that was 'beyond coma', exhibited by patients with nonviable cerebral hemispheres and a nonviable brain stem (8Mollaret P Goulon M Le coma depasse (memoire preliminaire).Revue Neurologique. 1959; 101: 3-15PubMed Google Scholar). However, Beecher's group sought to define such patients as dead, despite the presence of a heart beat. Dr Murray recalled that the Committee had the clinical impression that comatose patients hospitalized for weeks after cardiac bypass or head trauma were dead. Ventilatory assistance was a new technology, and the legal and medical obstacles 'to turning off the respirator' were before the Harvard Committee to consider. The Committee's goal was to develop consistent criteria that could be applied prospectively to declare death. Dr Murray's religious background presented no obstacle to his participation in either the ad hoc Harvard Committee or in organ recovery surgery. Operating upon a brain dead donor for Dr Murray was 'the start of an autopsy'. However, there were prominent physicians in Boston who disavowed this procedure. Moreover, Dr Murray was aware of the professional criticism given privately by some colleagues. The Harvard Committee accomplished its objective in the development of criteria, but it also introduced a concept of death by absence of brain function, a departure from the classical assessment of life. Dr Sweet later commented in the New England Journal of Medicine: 'It is clear that a person is not dead unless his brain is dead. The time honored criteria of stoppage of the heartbeat and circulation are indicative of death only when they persist long enough for the brain to die' (9Sweet W Brain death.N Engl J Med. 1981; 299: 410-412Crossref Scopus (26) Google Scholar). This formulation was the impetus for the development of brain death statutes, ultimately the Uniform Determination of Death Act (UDDA) in 1981 (10President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research.. U.S. Government Printing Office, Washington, DC1981: 166Google Scholar), and widespread acceptance of the diagnosis (11Wijdicks EF The diagnosis of brain death.N Engl J Med. 2001; 344: 1215-1221Crossref PubMed Scopus (512) Google Scholar). Nevertheless, the standard of brain death as a determination of death has been challenged and defended repeatedly (12Bernat JL A defense of the whole‐brain concept of death.Hastings Center Report. 1998; 28: 14-23Crossref PubMed Scopus (166) Google Scholar, 13Youngner S Arnold R Philosophical debates about the definition of death.J Med Philos. 2001; 26: 527-537Crossref PubMed Scopus (58) Google Scholar, 14Delmonico FL Murray JE A medical defense of brain death.Ethics Medics. 1999; 24: 1-2Crossref PubMed Google Scholar). I discussed with Dr Murray the significant criticism that has been directed to the Harvard Committee report over the years, namely that it did not separate a redefinition of death from the objective to obtain organs legally from a 'dead' donor. For example, this objective was obviously central to the introduction of heart transplantation. Dr Norman Shumway has written: 'It appeared by the time of the Clinical Congress of the American College of Surgeons in October, 1967, that clinical heart transplantation might be justified if the concept of brain death could be legally recognized' (15Shumway N Thoracic transplantation.World J Surg. 2000; 24: 811-814Crossref PubMed Scopus (14) Google Scholar). Thus brain death was defined by medical necessity, and this aspect of its development has been a reason for some skeptics to doubt its validity (16Shewmon DA Recovery from brain death: a neurologist's apologia.Linacre Quarterly. 1997; 64: 30-96Crossref PubMed Scopus (105) Google Scholar). We observed that as more patients are dying in the intensive care unit following the withdrawal of futile treatment, it has been argued that the brain death diagnosis might become rare if a sufficient supply of organs for transplantation was derived from pigs. Although the Harvard Committee settled upon a brain death diagnosis that included brain stem as well as cortical function, Dr Murray's perspective to this day is to distinguish the loss of cortical brain function from the function of the brain stem. Unlike many, he has no objection to the removal of organs from an anencephalic baby. He was quick to comment, however, that death has a social context, and he could readily understand the difficulty to declare death of any individual breathing spontaneously. He had no personal misgivings of the Harvard group's conclusion to require an apnea test to determine death. Dr Murray suggested that it would be unlikely for society to adopt any revisions in the brain death determination in the near future to either expand the concept of death to only a consideration of cortical function or to diagnose death for an individual in a persistent vegetative state (13Youngner S Arnold R Philosophical debates about the definition of death.J Med Philos. 2001; 26: 527-537Crossref PubMed Scopus (58) Google Scholar). He is opposed to either development. Finally, Dr Murray underscored the importance of the Harvard criteria, by which organs cannot be recovered from an individual unless he or she is declared dead, and from which the 'dead donor rule' has been consistently applied since the Harvard proclamation (17Robertson J The dead donor rule.Hastings Center Report. 1999; 29: 6-14Crossref PubMed Scopus (212) Google Scholar). Brain death must also be the standard for the nonheart beating donor: organs should only be recovered when the brain is dead. Dr Murray considers a unifying concept to death, whether the mechanism of death is by the cessation of heartbeat or by a direct injury to the brain. That unifying concept is the irreversible (meaning cannot be recovered) loss of brain function. The importance of this concept for Dr Murray is that a nonheart beating donor is dead when it is reasonable to assume that brain function cannot be recovered. Kidney transplantation remained Dr Murray's primary research responsibility from 1949, when David Hume departed Boston for military service, until 1971. In 1971, seven years after his first cadaver donor success, Dr Murray requested that Dr Moore pass the leadership of the transplant service to Dr Richard Wilson. Dr Murray dedicated the remainder of his career to advancing the field of plastic surgery. In 1990, Dr Murray was awarded the Nobel Prize in Medicine for the first successful transplantation of a kidney from a genetically identical twin, from a non identical twin, and from a cadaveric donor. In his Nobel presentation, Dr Murray remarked: 'In the course of many laboratory experiments on canine renal transplantation, a reproducible operation was developed that became the universal transplant procedure since that time'. It was the reproducibility of the procedure that captured the Nobel Prize. We discussed the circumstances shaping Dr Murray's early career, and what areas would interest him if he were startinghis career today. He highlighted the benefit he derived from Dr Moore, who provided a departmental environment that was enriching and conducive to scientific investigation. Dr Murray observed that the chairman of a department of surgery today does not have the economic flexibility that Dr Moore enjoyed. Without committed departmental support, scientific innovation from a surgeon would be difficult to achieve to the degree that it was experienced in the development of transplantation. Nevertheless, Dr Murray noted that stem cell research would be the most attractive field to pursue, because of its obvious potential to change the lives of so many. As a community, we now enter a phase of our history in which the pioneer leaders and early contributors to the field are passing: Francis Moore, Amir Tejani, Felix Rappaport, and Robert Corry; our colleagues of the past 40 years are no longer with us. We are fortunate to have these reflections of Dr Murray's experience and wisdom to shape our perspectives today.