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Medical and Ethical Challenges During the First Successful Human Kidney Transplantation in 1954 at Peter Bent Brigham Hospital, Boston

Leeson, Stanley MB, FRCA; Desai, Sukumar P. MD

doi: 10.1213/ANE.0000000000000521
General Articles: Special Article
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BACKGROUND: The first successful major organ transplantation, a kidney transplant, took place on December 23, 1954, at Peter Bent Brigham Hospital, Boston, Massachusetts. This was the beginning of major organ transplants commonly performed today, heralding one of the most significant achievements of medicine. A half-century later, heart, liver, limb, and even face transplants have become standard practice. In this report, we explore details of the preparations, the ethical dilemmas and the unknowns, and how these issues were addressed and overcome.

METHODS: Published works, hospital records, personal notes, and conversations with the individuals who participated in this event allowed us a unique opportunity to collect, analyze, and interpret the events.

RESULTS: Several factors converged at Peter Bent Brigham Hospital to enable success. The department chair in medicine was committed to studying renal hypertension who then recruited others to work in this area. The department chair in surgery was committed to research, including making research results clinically useful. The chair of the anesthesia division was a technically skilled clinician, able to manage a previously unknown procedure. Finally, a suitable candidate for kidney transplant happened to have an identical twin brother, eliminating the issue of possible rejection. These factors aligned at the right time and place to transplant the first human kidney.

CONCLUSIONS: Medical and ethical challenges dominated the scene of the first successful major organ transplant, which began the remarkable advance in transplant medicine, an advance that occurred very rapidly between 1947 and 1951.

From the Department of Anaesthesia, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts.

Accepted for publication September 9, 2014.

Funding: Intramural funds only.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Sukumar P. Desai, MD, Department of Anaesthesia, Harvard Medical School, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. Address e-mail to sdesai@partners.org.

Chronic renal failure affects almost 1 million patients in the United States, and kidneys are the most commonly transplanted organ. Each year approximately 15,000 kidneys are transplanted in the United States. The first successful kidney transplantation occurred at Peter Bent Brigham Hospital (PBBH) in Boston on December 23, 1954. Operative surgeon Joseph Edward Murray (1919–2012) was awarded the Nobel Prize in Medicine and Physiology in 1990. This pioneering procedure was full of challenges. The perioperative team had to plan carefully and be prepared for the unexpected. In this article, we provide firsthand information about events that led to success for Murray and medicine on that historic day.

Subsequent teams of physicians and surgeons have encountered and overcome challenges associated with transplanting organs such as the heart, lungs, liver, limbs, and face. The events we describe paved the way, an achievement that has saved many lives. Personal interviews, primary source documents, and other published material were used to conduct this investigation.

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ADVANCES BEFORE RENAL TRANSPLANTATION

In the absence of dialysis and transplantation, chronic renal failure was uniformly fatal in the middle of the 20th century. The concept of dialysis had been proposed at Johns Hopkins University as early as 1913 after pharmacologist John Jacob Abel (1857–1938) had successfully removed toxins from animals using a dialysis exchanger.1 He was interested in extracting hormones from plasma, and although his equipment may have worked in animals, it was never successful in humans.2,3

Dutch physician Willem Johan Kolff (1911–2009) was motivated to develop a treatment for renal failure after he had watched helplessly as a young man died of renal failure. He successfully assembled a simple hemodialysis machine in Holland during World War II using materials such as sausage wrappers, tins, and washing machine parts.4 During the war, he saved 800 people from Nazi labor camps by hiding them in his hospital in Kampen, The Netherlands. It was in this hospital that he set up Europe’s first blood bank. After the war, in 1945, he saved the life of a woman in renal failure. She was a 67-year-old Nazi sympathizer imprisoned after World War II, who went into coma from kidney failure. Kolff placed her on experimental hemodialysis treatment for a longer duration than ever tried before. She woke up from the coma, and a new treatment for renal failure was born.5 He went on to develop the membrane oxygenator leading to the heart lung machine and with Robert Jarvik (born 1946) developed the first artificial heart, thereby earning the title “father of artificial organs.”

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THE TEAM AT PETER BENT BRIGHAM HOSPITAL

In 1942, PBBH’s brilliant young Chief of Medicine, Soma Weiss (1898–1942), died suddenly. Many staff had enrolled for military service or taken up positions at other institutions. The hospital desperately needed to find a suitable replacement for Weiss. George Widmer Thorn (1906–2004) was the ideal candidate to take over as chief, but he was serving as a major in the Army Medical Corps. One of the hospital’s trustees was personally acquainted with President Franklin Delano Roosevelt (1882–1945). By appealing directly to the President, the trustee cleared the path for Thorn’s discharge from the Army, allowing him to accept the appointment as Hersey Professor of the Theory and Practice of Physic at Harvard Medical School and Physician in Chief at PBBH. A keen interest in renovascular hypertension led him to establish a medical unit that specialized in treatment and research on hypertension and renal disease.

Thorn appointed John Putnam Merrill (1917–1984), a young cardiologist, to develop and lead a program in renal dialysis and transplantation. He also invited Dutch dialysis pioneer Willem Kolff to lecture at the Brigham in 1947. Kolff provided details about the dialysis machines he had used. The resulting collaboration between Kolff, Merrill, and surgeon Carl W. Walter (1905–1992) resulted in the development of the first hemodialysis machine at PBBH in 1949—the Kolff-Brigham dialyzer.5 The dialysis machine was quickly incorporated into management of acute reversible renal insufficiency.

Under Thorn’s leadership, a kidney obtained from a just-deceased patient was attached externally to the forearm of a young woman by Charles Anthony Hufnagel (1916–1989), a surgical resident. Although the transplanted organ produced only a small amount of urine, and had to be removed, the patient did eventually recover. Thorn and Merrill concluded that the artificial kidney could perform the excretory, but not the metabolic, functions of the kidney. This provided impetus to conduct research into renal transplantation.

In 1948, Francis Daniels Moore (1913–2001) was appointed Surgeon-in-Chief at PBBH and Moseley Professor of Surgery at Harvard Medical School. Moore’s studies on body fluids and electrolytes made him famous as an “academic surgeon.” As Chief of Surgery at PBBH, Moore was a constant guide and source of encouragement to members of the renal transplant group.6 Moore supported the efforts of the medical team and directed members of the surgical department to focus their attention on making renal transplantation a reality. Upon completion of surgical training at PBBH in 1951, David Milford Hume (1917–1973) was appointed Director of the Laboratory for Surgical Research. Over the next 3 years, Hume and Merrill performed 9 renal transplants in patients with terminal renal failure. Although technically successful, none of these operations altered the outcome of renal failure because none of the patients survived >6 months. They were forced to conclude, “At the present state of our knowledge, renal homotransplant does not appear to be justified in the treatment of human disease.”7 Elsewhere they state, “It seemed possible that since we had transplanted a sick kidney into a sick donor, that this might in some way have modified the immune response.”7 “It seemed possible that the transplanted tissue or the host or both might be incapable of the violent rejection response which characterizes the immune response in a healthy host.”7 The experience gained from these patients encouraged the team to persevere in this endeavor.

In 1951, surgeon Joseph Edward Murray joined the staff of PBBH and the Brigham transplant team. He assumed responsibility for experimental work on animals and humans when Hume was called to serve in the Korean War. Murray successfully transplanted a kidney into the pelvis in a dog model.8 These experiences confirmed that although renal transplantation was technically feasible, success could only be achieved by controlling rejection of the transplanted organ. From their experience, they prepared a list of conditions that would have to be met to make the transplant successful.7 It included the location of the graft and vascular and ureteral anastomoses, among others, but there was 1 question that they did not know the answer to, the duration of ischemia that could be tolerated by the transplanted organ to remain viable.

Leroy David Vandam was appointed Chief Anesthetist at PBBH on July 1, 1954 (Fig. 1). Vandam had a reputation as an excellent clinician, partly reflecting that he initially trained as a surgeon. The other anesthesiologist, Thomas Kelvin Burnap (1924–1975), had worked at the hospital for several years (Fig. 2).9 At that time, anesthesia services were a division within the Department of Surgery. Vandam and Burnap were acquainted with ongoing research into human renal transplantation.

Figure 1

Figure 1

Figure 2

Figure 2

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THE STARS ALIGN

Just as the team at PBBH had developed technical expertise as well as an understanding of the biology of kidney transplantation, and the first hemodialysis unit was established at PBBH, Richard Herrick (1931–1963) sought care for severe hypertension at the United States Public Health Service Hospital in Boston. Mr. Herrick, a 23-year-old man, was the ideal transplantation candidate. His admitting physician, David C. Miller (1917–1997), suggested the possibility of transplantation from his twin brother. Miller had trained as an epidemiologist at Harvard School of Public Health, located adjacent to PBBH, and was familiar with the work and research interests of the Brigham team.

On October 26, 1954, Mr. Herrick was admitted to PBBH in severe distress. He had developed all the signs of malignant hypertensive syndrome: retinal hemorrhages and exudates, marked cardiomegaly, and peripheral as well as pulmonary edema. Tests established beyond reasonable doubt that Richard Herrick and Ronald Herrick (1931–2010) were identical twins: eye examination and matching of fingerprints and blood group matching. However, because there was no way to manage rejection of the kidney, it was felt that the best test was to explicitly confirm that transplanted tissue would survive. The novel proposal was to transplant a skin graft between the 2 brothers.

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INFORMED CONSENT AND ETHICAL ISSUES

At a meeting with the medical and surgical teams, Ronald Herrick (the donor) inquired whether physicians at PBBH would be prepared to guarantee all of his future medical and surgical needs. Joseph Murray referred the question to urologist John Hartwell Harrison (1909–1984), who replied that they could not assume responsibility for all his subsequent health needs but did assure him that the medical staff would not refuse to help to the best of their abilities. The medical and surgical teams also assured the brothers that although long-term success had not been achieved with renal transplantation, circumstances were optimal to perform this pioneering effort.

Moral and ethical issues were raised because the use of living donors involved a major surgical operation for the donor, with a known risk of morbidity and mortality. For the healthy donor, there is no physical benefit. Indeed, he would face the risk of hypertension and renal failure if his sole remaining kidney became injured or diseased. The risk might even be quite high, since his genetically identical brother had renovascular hypertension. The members of the medical team had to make a significant qualitative shift in their approach and actions because they were subjecting a healthy, normal subject to an extensive surgical procedure and compromising the central and well-accepted medical injunction: first do no harm.

The first human transplantation was full of ethical dilemmas. Willem J. Kolff risked his own life by helping Nazi labor camp prisoners and hiding them in his hospital. John P. Merrill was the flight surgeon on the Enola Gay, the Boeing B-29 Superfortress bomber that dropped an atom bomb on Hiroshima, Japan, on August 6, 1945. Joseph E. Murray served during World War II and took care of many soldiers with extensive burns. He had transplanted skin, but knew that the skin would peel off after a few days. In a 50-year posttransplant interview on National Public Radio, Murray reflected somberly that this was the first time a team would be performing a major operation on a subject who would derive no personal medical benefit, but instead be exposed to unknown risks of losing 1 kidney.10

Skeptical surgical colleagues warned Murray that he would be jeopardizing his career by embarking on such a risky venture.11 The operation posed religious,12–16 ethical,17–19 and legal20–22 challenges. In a rare display of social responsibility and consideration, the team consulted members of several religious denominations. The details of the opinions received are not available. Additional ethical challenges included the unknown results from a hitherto never performed operation on an extremely sick recipient and the absence of legal precedent for transplantation from a living donor.

Controversies about organ transplantation exist to this day, and even a brief discussion of the many concerns is beyond the scope of this article. These include identifying who owns rights to a deceased body, the sanctity of the human body, dismemberment of an organ from a living person, the potential harm to the donor, psychological pressure on the donor to participate in a procedure that offers no personal physical benefit, and the controversial practice of donation after cardiac death.23 In the end, the surgical team justified their recommended course of action on the basis of the low known risk to the donor compared with great potential benefits to the recipient.6,17,22 On December 23, 1954, Murray and Merrill took “a major ethical leap,”24 launching medical ethics into previously uncharted territory.

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PREOPERATIVE COURSE

On November 10, 1954, a skin graft was transplanted from Ronald to Richard under local anesthesia. The procedure was tolerated well. On December 12, Richard developed severe left heart failure. A chest radiographic examination showed marked cardiomegaly and right pleural effusion. Drainage of 350 mL turgid fluid and transfusion of 3 units packed red blood cells resulted in symptomatic relief. However, the onset of heart failure was worrisome and made the prognosis uncertain, even if the skin graft were successful. On December 17, the transplant margins of the skin graft were biopsied and found to show no evidence of rejection by Chief Pathologist Gustav Dammin (1911–1991).8

Problems persisted regarding inexperience with the proposed operation. Murray and Moore were especially worried about technical difficulties. No member of the team had placed a transplanted kidney in the pelvis, with vascular anastomoses to iliac vessels. On December 20, 1954, Murray and Moore received word that a cadaver was available so they welcomed this opportunity to conduct a “dry run.” When this went well, Murray scheduled the first renal transplantation for December 23, 1954.

On the eve of the operation, Richard wrote an urgent note to his healthy brother Ronald, who was still a student, “Get out of here and go home,” to which Ronald replied, “I am here and I am going to stay, and that’s it.” Remarking to National Public Radio on the 50th anniversary of the event, he recalled, “It was something that hadn’t been done before, you knew nothing about it. So I thought about it a long time. . . . My stomach was churning many a morning going to school.”

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ANESTHESIA CONCERNS

Although the medical and surgical teams had been preparing for this event for years, the earlier kidney transplants reported by Hume were performed under local anesthesia. Vandam was confronted with a challenging situation because he could not possibly have had the benefit of conducting a dry run.

The poor medical condition of Richard Herrick raised many anesthetic concerns. Patients in terminal renal failure rarely underwent elective major surgery. Problems including uncontrolled hypertension, recurrent episodes of heart failure, pleural effusion, severe chronic anemia, and hyperkalemia, among others, presented a formidable challenge to the anesthesia team. After reviewing the condition of Richard Herrick, Vandam concluded, “I doubt that anyone before that time had been asked to give anesthesia for an elective operation under those circumstances or that any other kind of major procedure would have been countenanced even as an emergency.”25 The psychological stress on Vandam and Burnap was likely exacerbated by the death earlier that week of a patient from a cardiac arrest after administration of succinylcholine. Succinylcholine was introduced into clinical practice in 1951, but more than a decade would elapse before the risks of hyperkalemia and malignant hyperthermia were understood.

Recognizing that no anesthetic or operation can ever be guaranteed to be completely free of risk, Burnap and Vandam were greatly concerned that the donor nephrectomy poses as little risk as possible to Ronald Herrick, a healthy young man. Burnap and Vandam decided that general anesthesia with diethyl ether would be the best option. It carried the favorable attributes of excellent analgesia, good muscle relaxation, minimal respiratory depression, and indirect support of the circulation.25

Vandam felt that regional anesthesia would be the best option for Richard Herrick. Compared to general anesthesia, regional anesthesia would avoid the cardiovascular and respiratory perturbations caused by tracheal intubation, induction of general anesthesia, fluid overload, pleural effusion, and extubation. Continuous spinal anesthesia had been used in many situations where regional anesthesia was clearly preferred over general anesthesia, especially if the procedure was lengthy or of unknown duration. Moreover, continuous spinal anesthesia avoided the rapid hemodynamic changes brought about by single-injection spinal anesthesia. Postdural puncture headache was common because of the larger needle used for inserting the catheter during continuous spinal anesthesia. Vandam considered the choice of continuous spinal anesthesia via catheter as logical and prudent. This would provide predictable anesthesia that could be titrated gradually to minimize cardiovascular compromise and, at the same time, permit good operating conditions for the surgeon. Moreover, vasodilation would be a favorable side effect in a patient with uncontrolled hypertension. The excellent immediate postoperative analgesia would also minimize the likelihood of hypertension and tachycardia. Since there was no previous experience with such a surgical procedure and the duration of the operation was unknown, continuous spinal anesthesia would permit extended operating time. He chose tetracaine as the local anesthetic drug for its prolonged duration of action and rapid metabolism in plasma.26

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OPERATIVE MANAGEMENT

Anesthetic techniques and monitoring in the 1950s were primitive by our present standards. It was primarily the clinical acumen of the anesthesiologist that assured a good outcome. Writing several years later, Vandam observed, “At that time determining the patient’s condition during anesthesia and operation depended on antiquated methods. The only criterion usually measured accurately is the respiratory rate. The heart rate can be correctly counted provided there is no discrepancy between the cardiac rate and that of the palpable pulse waves reaching the periphery. Many of the other methods by which a patient’s condition can be judged had not yet been found practical in an anesthetized patient, including the electroencephalograph, the electrocardiograph, oxygen and carbon dioxide analyzers, intra-arterial and intravenous pressure recorders, and other similar devices. Circulation was monitored by feeling the pulse, assessing perfusion of the skin, and auscultatory measurement of the blood pressure.”26

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DECEMBER 23, 1954

The surgeon for the donor was J. Hartwell Harrison and Thomas K. Burnap was the anesthesiologist. The surgeon for the recipient was Joseph E. Murray and Leroy D. Vandam was the anesthesiologist.27

Operations began on the donor and recipient concurrently in adjacent operating rooms at 8:15 AM. Communication and coordination between the 2 teams were critically important. Murray briefly visited the donor operating room to review the anatomy of the renal vasculature. At 9:50 AM, an hour and a half into the operation, Murray was ready to receive the organ from Harrison. Murray told Harrison to proceed with clamping of the renal artery. Blood was allowed to drain from the kidney, and shortly thereafter the renal vein and ureter were clamped, after which the vessels and ureter were transected. Moore, who helped coordinate the operations, transported the kidney to the recipient’s room 3 minutes later at 9:53 AM. The arterial anastomosis between the cut end of the hypogastric artery and the renal artery was completed at 10:40 AM. It took another 35 minutes to anastomose the renal vein to the common iliac vein before the transplanted organ was reperfused. At 11:15 AM, there was a collective hush in the operating room as Murray gently removed the clamps from the vessels newly attached to the donor kidney. As blood flow was restored, Richard’s new kidney became engorged and turned pink. After an ischemic interval of 1 hour and 25 minutes, urine freely flowed out of the ureter. Merrill had wondered how long a kidney could remain ischemic and retain functionality. Here was the first answer in a human.

The joy in the recipient operating room was offset by panic in the donor operating room. Surgery had proceeded uneventfully up to the point that the kidney was handed off to the recipient team. To provide maximal length of the renal artery for the recipient team, Harrison had clamped the renal artery at its origin on the aorta before dividing it. The vascular clamp on the arterial stump of the donor slipped off, resulting in a brisk arterial bleed. After loss of a liter of blood, Harrison was able to apply a Pott’s clamp to control the bleeding and repair the aorta. Fortunately, Ronald Herrick did not need a blood transfusion. Burnap had been very concerned about minimizing the risk to the donor. Not only had the donor had a healthy kidney removed, but Burnap had to resuscitate his patient during hemorrhage and unclamping of the aorta.

Both operations were completed within 4 hours. The brothers did very well postoperatively and were discharged from the hospital without postoperative complications.

Richard, the recipient, developed severe hypertension resistant to medical treatment. He underwent 2 nephrectomy operations in 1955 to control renovascular hypertension. He remained relatively stable until 1963 when he developed pneumonia and, soon after, died from a myocardial infarction. When asked to comment about this event, Murray remarked, “The young man’s death was not related to the historic kidney operation 8 years ago.” Ronald, the donor, lived a long healthy life complicated decades later with hypertension. He died from complications after heart surgery on December 27, 2010, at the age of 79.

Murray continued his transplant practice for 20 years but devoted the rest of his career to his true passion, plastic surgery. Murray was awarded the Nobel Prize in Medicine and Physiology in 1990 not only for the first successful transplant but also for his other studies on the problem of rejection and use of drugs to counteract rejection.6

Vandam’s seminal role in devising an anesthetic for a critically ill patient undergoing a “first in man” procedure has been reprised by other anesthesiologists in landmark surgeries, including the first successful heart, lungs, liver, organ combinations, limbs, and even face transplants.28 In retrospect, Vandam’s choice of a continuous spinal anesthetic was brilliant. Had the patient received a general anesthetic and displayed cardiorespiratory instability during the perioperative period, the outcome could have been very different. In a letter to Brigham transplant surgeon Nicholas Tilney shortly before he died, Vandam stated, “so far as the recipient was concerned I could only safely give him a continuous spinal anesthetic—he was in such tough shape chemically—high K+ which was usually elevated by succinylcholine.”

Vandam remained the Chairman of the Division of Anesthesia until the late 1960s, when the division became the Department of Anaesthesia at Harvard Medical School. Vandam was an effective spokesman for our specialty at the Harvard Medical School and at PBBH. He also served as Editor-in-Chief of the journal Anesthesiology and on the editorial boards of many anesthesia journals and the New England Journal of Medicine.

In the late 1980s, Vandam, Murray, and Moore commissioned artist Joel Marvin Babb to create a 70″ × 88″ oil painting, entitled “The First Successful Kidney Transplantation” (Figs. 3 and 4). It was presented by the team to Harvard Medical School and currently adorns the lobby of the Francis A. Countway Library of Medicine.27

Figure 3

Figure 3

Figure 4

Figure 4

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CONCLUSIONS

Major medical breakthroughs rarely occur without team support. In this case, a constellation of scientific, medical, surgical, and anesthesia stars aligned to facilitate the first renal transplant. The role of chance cannot be underestimated. It was pure coincidence that Richard Harrick had an identical twin brother. If the patient, a naval serviceman, had reported to another hospital for treatment, and the admitting physician had not been aware of PBBH’s interest in renal transplantation, he may never have secured the referral. Without the ideal patient, the stars would not have aligned.

We conclude by acknowledging the critical contributions of an ideal patient, Richard Herrick, and his loving and altruistic brother, Ronald Herrick. Their contributions to medical practice must be recognized. Too often we laud the physicians as heroes, ignoring the contributions of pioneering patients whose courage advances the practice of medicine. The courage of the Herrick brothers benefited hundreds of thousands of patients in the half-century since their 1954 surgery changed their lives, and the history of medicine.

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DISCLOSURES

Name: Stanley Leeson, MB, FRCA.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Stanley Leeson approved the final manuscript.

Name: Sukumar P. Desai, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Sukumar P. Desai approved the final manuscript.

This manuscript was handled by: Steven L. Shafer, MD.

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