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A History of Organ Transplantation

A History of Organ Transplantation: Ancient Legends to Modern Practice

David Hamilton
Clyde F. Barker
Thomas E. Starzl
Copyright Date: 2012
Pages: 640
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  • Book Info
    A History of Organ Transplantation
    Book Description:

    Foreword by Clyde Barker and Thomas E. Starzl

    A History of Organ Transplantationis a comprehensive and ambitious exploration of transplant surgery-which, surprisingly, is one of the longest continuous medical endeavors in history. Moreover, no other medical enterprise has had so many multiple interactions with other fields, including biology, ethics, law, government, and technology. Exploring the medical, scientific, and surgical events that led to modern transplant techniques, Hamilton argues that progress in successful transplantation required a unique combination of multiple methods, bold surgical empiricism, and major immunological insights in order for surgeons to develop an understanding of the body's most complex and mysterious mechanisms. Surgical progress was nonlinear, sometimes reverting and sometimes significantly advancing through luck, serendipity, or helpful accidents of nature.The first book of its kind,A History of Organ Transplantationexamines the evolution of surgical tissue replacement from classical times to the medieval period to the present day. This well-executed volume will be useful to undergraduates, graduate students, scholars, surgeons, and the general public. Both Western and non-Western experiences as well as folk practices are included.

    eISBN: 978-0-8229-7784-1
    Subjects: Health Sciences

Table of Contents

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  1. Foreword
    (pp. vii-x)

    David hamilton has been a senior transplant surgeon at the Western Infirmary, Glasgow, Scotland, and also the first director of the Wellcome Unit for the History of Medicine at Glasgow University. In addition, he is steeped in the lore and the basic science of the field because of his early training under the great transplantation biologist Peter Medawar. Thus, it is no surprise that he has written a history of transplantation that is unmatched in its scope, perceptiveness, and readability.

    The masterly account he has crafted comes at an appropriate time, since organ transplantation has now become widely accepted as...

  2. Introduction: Toward the Impossible
    (pp. xiii-xx)

    It is usually thought that within the general advance of medicine, tissue and organ transplantation has a short history. Certainly the modern successful era started only in the 1950s, but there was earlier, much earlier, interest. Even the surgical records from 600 BCE contain accounts of plastic surgery, and the question of the use of tissue from donors appears in surgical works of medieval times. And many outside of surgery were interested from the first in the replacement of lost tissue. In medieval times, numerous shrines to the saints Cosmas and Damian and images of those twin physicians showed them...

  3. 1 Early Transplantation
    (pp. 1-30)

    To early humans, as to all their descendants, the possibility of restoration of lost or mutilated parts of the body was a lively issue. To make good such losses incurred by war, disease or punishment, ancient humans had recourse to local help and healers. But they also looked for supernatural help, because legends told them that such powers could be used to make the injured part whole again. And there may have been an additional imperative to ancient humans to be restored to normal. If after death the body went in a mutilated, deficient state to the afterworld, subsequent resurrection...

  4. 2 The Eighteenth Century
    (pp. 31-48)

    The subject of human tissue grafting disappeared from surgical and literary texts in the early 1700s, but some experimentation continued. Two individuals in particular, Abraham Trembley and John Hunter, took an interest in grafting in order to gain insight into the fundamental mechanisms of animal life. Their work focused on tissue vitality, regeneration, and adhesion. Only later did Hunter turn to human studies.

    Of these two noted investigators, the first to achieve fame was the Belgian naturalist Trembley (1710–1784), who in 1736 became tutor to the sons of the Comte de Bentinck in the Netherlands. Trembley added to his...

  5. 3 The Reawakening
    (pp. 49-64)

    The ancient craft of plastic surgery was revived in Europe in the early nineteenth century. With the discovery of early Indian surgical methods, which were still in use there, and the realization that Tagliacozzi’s works, when read in the original language, had merit, human skin replacement was performed in Europe for the first time in two centuries. The techniques quickly became part of surgical routine.¹

    The awakening began when European colonists in India observed local practitioners performing practical plastic surgery using methods that were long established.² The colonists were in India largely because of the East India Company, and through...

  6. 4 Clinical and Academic Transplantation in Paris
    (pp. 65-87)

    Germany was the first nation to nourish and broaden the revival of the old techniques of plastic surgery, but it was mid-nineteenth-century French surgeons who can be credited with finding the simple solution to the problem of grafting detached skin. The solution was for the graft to be very thin, and although this simple discovery may have been an entirely empirical surgical venture, the talented group of biological investigators led by Claude Bernard had some input.¹ As this history has already shown, such surgical advances had important consequences for tissue transplantation from donors.

    Claude Bernard (1813–1878) initially worked under...

  7. 5 The Beginning of Organ Transplantation
    (pp. 88-104)

    At the start of the twentieth century, the new methods of blood vessel surgery allowed experimental and human organ transplantation to commence, and some order returned to the understanding of tissue transplantation. Increasingly, the famous European surgical centers took up tissue grafting studies and did so carefully and critically. With increasing confidence, surgeons and scientists concluded that animal-to-human grafts always failed, and there followed a slow acceptance that most homograft transplants, from human-to-human or between experimental animals, did not survive. The haphazard use of homograft slices and fragments of graft tissue was slowly, though reluctantly, abandoned.

    The new experimental transplant...

  8. 6 The “Lost Era” of Transplantation Immunology
    (pp. 105-125)

    Awareness of the phenomenon later called “immunity” existed in ancient times.¹ After epidemics, those who recovered from the disaster seemed naturally protected from future outbreaks of the illness. Possibly in India or China, early peoples learned to induce a state of immunity to smallpox by inoculation—placing a small amount of material from mildly affected patients onto scratches in the skin of others at risk, who later usually did not experience the full effects of the disease. The strategy was observed in use in Turkey in the early 1700s and was brought back to Europe and used with success. To...

  9. 7 Anarchy in the 1920s
    (pp. 126-153)

    The impressive gains in transplantation immunology research and the technical expertise developed in experimental and human transplantation were largely forgotten in the wake of World War I. War, which often gives birth to medical advances, was in this instance the assassin. Although academic studies in mainstream humoral immunology, particularly in antibody structure, continued to progress, these were increasingly unrelated to clinical needs, especially with regard to tissue transplantation. This research trajectory veered sharply away from the “lost era’s” immunological developments with transplant applications, and this gap has broad importance in medical history.¹

    The war in Europe certainly played a role...

  10. 8 Progress in the 1930s
    (pp. 154-172)

    By the early 1930s, after the muddles of the previous decade, the prewar European experimental transplant work was revived in small ways. There was some activity in Lyon.¹ In Germany, there was a modest restoration of studies on immunosuppression. In the Soviet Union, there was impressive innovation in blood transfusion, corneal grafting, and tissue transplantation. In the United States, after the uncritical skin and organ grafting of the 1920s, good surgical science was quietly gaining some ground. In his St. Louis laboratory, Leo Loeb returned unostentatiously to build on his solid earlier immunological achievements by detecting and correcting a flaw...

  11. 9 Understanding the Mechanism
    (pp. 173-194)

    The emergence of a new and lasting interest in tissue transplantation is usually dated to 1943, the year of publication of a reinvestigation by the surgeon Tom Gibson and biologist Peter Medawar. Entitled “The Fate of Skin Homografts in Man,” thisJournal of Anatomypaper emerged from studies at the Royal Infirmary in Glasgow.¹ The conclusion from this careful work reaffirmed that homografts in general did not survive and that the mechanism of graft loss was an immunological one, a view now regarded as self-evident but one that was not yet widely accepted then. Their central finding was that after...

  12. 10 Experimental Organ Transplantation
    (pp. 195-220)

    At this time in the late 1940s, some surgeons renewed their interest in experimental organ transplantation, attempting to transplant not only kidneys but also the heart. As described earlier, these efforts had started in Europe before World War I and largely ceased when the war began, but the growing interest in transplantation immunology now encouraged another look. Organ and tissue preservation now became important, and in clinical work the artificial kidney found a routine place in treating acute renal failure.

    Four groups began experimental kidney transplantation studies, two in Paris, one in Denmark, and one in London. In Paris, the...

  13. 11 Transplantation Tolerance and Beyond
    (pp. 221-253)

    During the early 1950s, while human and experimental organ transplant attempts were under way, in the laboratory steady progress was being made toward understanding graft rejection, and the advance of great significance resulted. In 1949, Peter Medawar met Hugh P. Donald, an Edinburgh veterinarian, at a scientific conference in Stockholm, and he asked for Medawar’s help in solving a familiar problem: distinguishing at an early stage between identical and nonidentical twin cattle—that is, between mono- and dizygote twins. Dizygote, or nonidentical twins, when one was male and the other female, could look very similar, since the female twin had...

  14. 12 Hopes for Radiation Tolerance
    (pp. 254-268)

    The first hesitant steps that marked the start of the modern, continuous period of human organ transplantation were taken in 1958, when attempts were made to thwart organ graft rejection in humans. The strategy used came from radiobiology—the study of the effects of lethal radiation and its treatment using bone marrow infusion. An infusion of an animal’s own bone marrow allowed it to survive the effects of radiation, but a surprise was that “foreign” marrow cells from donors would also be effective. After recovering, the test animals had marrow of donor origin and would accept grafts from this donor...

  15. 13 The Emergence of Chemical Immunosuppression
    (pp. 269-295)

    In the early 1960s, the approach to organ transplantation changed, allowing attempts with radiation to be put aside in favor of progress by other means. Immunosuppressive drugs appeared, and they proved to be more controllable and more effective than irradiation, and the surgeon’s assumptions changed from hoping for “one-shot” tolerance to accepting the use of long-term, continuous medication. Soon after this shift, in the mid-1960s, rapid developments in tissue typing showed promise for close and beneficial matching of the recipient and donor, either within the family or with a deceased donor organ. There was also at this time rapid growth...

  16. 14 Support from Hemodialysis and Immunology in the 1960s
    (pp. 296-313)

    In 1960, the medical community made significant progress toward a full understanding of cell-mediated immunity. Most notably, researchers uncovered the central role of the thymus and defined the two types of lymphocyte and their links with cell-mediated immunity. Also in 1960, Peter Medawar was awarded a Nobel Prize for his work on tolerance, a signal that transplantation immunology had come of age. And 1960 was also the year in which regular dialysis was first used to sustain patients in end-stage renal failure. Dialysis and kidney transplantation were to be closely linked thereafter.

    Beginning in the mid-1950s, the use of the...

  17. 15 Progress in the Mid-1960s
    (pp. 314-339)

    The technical side of kidney transplantation was now well established, and there was growing confidence with the surgical management. Policy shifted to encourage the use of cadaveric organs, thus removing the concerns associated with living-related donation. The only source of kidneys for transplantation so far had been from patients dying in those hospitals interested in transplantation, but as the results improved, more doctors and more hospitals were prepared to consider helping with donation.

    Experience with both living and cadaveric grafts yielded one very important observation about the comparative results. Although cadaver grafts could do well, living-related kidney donation within the...

  18. 16 Brain Death and the “Year of the Heart”
    (pp. 340-358)

    A major change in hospital practice occurred in the mid-1960s when gravely ill or injured patients could receive respiratory support on a ventilator. This shift transformed resuscitation into a focused, successful strategy. Intubation and ventilation of patients, followed by care in the orderly calm of the new intensive care units, constituted an increasingly standard procedure if recovery was deemed possible.

    The pioneers of intensive care were encouraged by outcomes in the Denmark polio epidemic of 1953, when respiratory support for a period of time allowed some patients to survive. Traditional anesthetic practice taught that prolonged anesthesia was dangerous, but, with...

  19. 17 The Plateau of the Early 1970s
    (pp. 359-379)

    In the early 1970s, there was a hesitation in the development of organ transplantation. The results of kidney transplantation had been encouraging in the late 1960s, but thereafter the pace of improvement stalled.¹ The numbers of kidney transplants also leveled off after 1972, and the results then got mysteriously worse. After the major promise of anti-lymphocyte serum had faded, the hunt for new drugs ensued, and there was but brief enthusiasm for each new agent tried.² The hopes for a dominant role of tissue typing in cadaveric kidney transplantation declined, and the matter became problematic. The development of liver transplantation,...

  20. 18 The Arrival of Cyclosporine
    (pp. 380-412)

    After the uncertain and at times discouraging events of the middle 1970s, the mood in the transplant world changed. In 1976, a possibly useful immunosuppressive agent made its first appearance in a pharmaceutical company laboratory and then slowly made its way into transplant management. Cyclosporine (CsA) was a difficult drug to use, but it was to bring fundamental change to transplantation, making most forms of organ grafting routine and noncontroversial.¹ The grafting of each organ increasingly had its own management routine, immunosuppression protocols, training, and interdisciplinary linkages.² With this expansion came new challenges and, above all, growing shortages of donor...

  21. 19 Waiting for the Xenografts
    (pp. 413-422)

    The 1990s were a time of continued, steady improvement in the results of organ transplantation. In the United States in mid-decade, 250 hospitals carried out kidney transplants, 160 reported heart grafting, and there were 70 liver transplant units. Cyclosporine was still important, but a number of new agents began to rival its dominant and lucrative position. Alternatives to azathioprine also appeared, and, as a result, there was an active and aggressive new commercial interest in immunosuppression.¹ The variety of immunosuppressive agents available gave doctors considerable flexibility, allowing them to individualize treatment, and different strategies evolved for different organs or tissues...

  22. Conclusion: Lessons from the History of Transplantation
    (pp. 423-430)

    The many landmark events in the development of tissue transplantation offer data useful not only for their own sake but also for analyzing the more general mechanisms of clinical and scientific innovation. Looking at what happened and how it happened, rather than how it ought to have happened according to theory, is illuminating. The history of surgery is usually presented simply as steady technical progress in skilled hands, but the story of transplantation is a more complex one. The story has a rich mother lode of themes, topics, incidents, and case histories which offer rich pickings for historians of medicine....