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.
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.
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.”
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
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
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
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.
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.
1. George CRP. John Jacob Abel reinterpreted: prophet or fraud? Nephrology. 2007;4:217–22
2. Abel JJ, Rowntree LJ, Turner BB. On the removal of diffusible substances from circulating blood by means of dialysis. J Pharmacol Exp Ther. 1913;5:275–316
3. Merrill JP. The artificial kidney. N Engl J Med. 1952;246:17–27
4. Kolff WJ, Berk HTJ. Artificial kidney, dialyzer with great area. Acta Med Scand. 1944;117:121–39
5. Heiney P The Nuts and Bolts of Life: Willem Kolff and the Inven tion of the Kidney Machine. 2003 Stroud, UK Sutton Publishing Ltd
6. Murray JE Surgery of the Soul: Reflections on a Curious Career. 2013 Canton, MA Science History Publications for Boston Medical Library
7. Hume DM, Merrill JP, Miller BF, Thorn GW. Experiences with renal homotransplantation in the human: report of nine cases. J Clin Invest. 1955;34:327–82
8. Merrill JP, Murray JE, Harrison JH, Guild WR. Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc. 1956;160:277–82
9. Stephen CR. Thomas K. Burnap. Anesth Hist Assoc Newsl. 1994;12:6–7
11. Tilney NL Transplant: From Myth to Reality. 2013 New Haven, CT: Yale University Press
12. Pope Pius XII. Allocution to anesthesiologists. Acta Apostolicae Sedis. 1957;49:1027–33
13. Healy GW. Transplantation of organs inter vivos: the pope ends fifty years of controversy. Landas. 1995;9:143–54
14. Cunningham BJ. The morality of organic transplantation. Doctoral thesis. 1944 Washington, DC Catholic University
15. Collins G Churchmen all in favor of transplants. 1967 Boston Globe:84
16. Jonsen AR The Birth of Bioethics. 1998 New York, NY Oxford University Press
17. Murray JE. Remembrances of the early days of renal transplantation. Transplant Proc. 1981;13:9–15
18. Eisendrath RM, Guttmann RD, Murray JE. Psychologic considerations in the selection of kidney transplant donors. Surg Gynecol Obstet. 1969;129:243–8
19. Starzl TE. Ethical problems in organ transplantation. Arch Int Med. 1967;67(S):132–6
20. Wolstenholme G, O’Connor M. Law and Ethics of Transplantation. 1966 London J & A Churchill Ltd
21. Vestal AD, Taber RE, Shoemaker WJ. Medico-legal aspects of tissue homotransplantation. Univ Detroit Law J. 1955;18:171–94
22. Masden vs. Harrison. No. 68651 Eq.Massachusetts Superior Judicial Court. 1957
23. Csete M. Donation after cardiac death and the anesthesiologist. Anesth Analg. 2010;110:1253–4
24. Leach G The Biocrats. 1970 New York McGraw-Hill
25. Vandam LD. Impressions of anesthetics past. Transplant Proc. 1981;13:61–4
26. Dripps RE, Eckenhoff JE, Vandam LR Introduction to Anesthesia: The Principles of Safe Practice. 1957 London W.B. Saunders Company
27. Desai SP, Desai MS, Wood DN, Maddi R, Leeson S, Tilney NL. A semi-centennial report on the participants depicted in Joel Babb’s portrait, “The First Successful Kidney Transplantation.” Am J Transplant. 2007;7:1683–8
© 2015 International Anesthesia Research Society
28. Edrich T, Cywinski JB, Colomina MJ, Jiménez López I, Xiong L, Sedaghati A, Pomahac B, Gilton A. Perioperative management of face transplantation: a survey. Anesth Analg. 2012;115:668–70