Organ Transplantation History
Deutsch: Beinwunder der Heiligen Cosmas und Damian aus Ditzingen, Kreis Ludwigsburg
Entstanden in Stuttgart (?), Anfang 16. Jahrhundert (dem Meister des Stettener und Schnaiter Altarretabels zugeschrieben)
Württembergisches Landesmuseum Stuttgart, Inv. 989
English: Legendary transplantation of a leg by Saints Cosmas and Damian, assisted by angels.
Successful human allotransplants have a relatively long history; the operative skills were present long before the necessities for post-operative survival were discovered. Rejection and the side effects of preventing rejection (especially infection and nephropathy) were, are, and may always be the key problem.
Cosmas and Damian miraculously transplant the (black) leg of the Ethiopian onto the (white) body of Justinian. Ditzingen, 16th century.
Several apocryphal accounts of transplants exist well prior to the scientific understanding and advancements that would be necessary for them to have actually occurred. The Chinese physician Pien Chi\'ao reportedly exchanged hearts between a man of strong spirit but weak will with one of a man of weak spirit but strong will in an attempt to achieve balance in each man. Roman Catholic accounts report the third-century saints Damian and Cosmas as replacing the gangrenous leg of the Roman deacon Justinian with the leg of a recently deceased Ethiopian. Most accounts have the saints performing the transplant in the fourth century, decades after their deaths; some accounts have them only instructing living surgeons who performed the procedure.
The more likely accounts of early transplants deal with skin transplantation. The first reasonable account is of the Indian surgeon Sushruta in the second century BC, who used autografted skin transplantation in nose reconstruction rhinoplasty. Success or failure of these procedures is not well documented. Centuries later, the Italian surgeon Gasparo Tagliacozzi performed successful skin autografts; he also failed consistently with allografts, offering the first suggestion of rejection centuries before that mechanism could possibly be understood. He attributed it to the \"force and power of individuality\" in his 1596 work De Curtorum Chirurgia per Insitionem.
The first successful corneal allograft transplant was performed in 1837 in a gazelle model; the first successful human corneal transplant, a keratoplastic operation, was performed by Eduard Zirm in Austria in 1905. Pioneering work in the surgical technique of transplantation was made in the early 1900s by the French surgeon Alexis Carrel, with Charles Guthrie, with the transplantation of arteries or veins. Their skillful anastomosis operations, the new suturing techniques, laid the groundwork for later transplant surgery and won Carrel the 1912 Nobel Prize for Medicine or Physiology. From 1902 Carrel performed transplant experiments on dogs. Surgically successful in moving kidneys, hearts and spleens, he was one of the first to identify the problem of rejection, which remained insurmountable for decades.
Major steps in skin transplantation occurred during World War I, notably in the work of Harold Gillies at Aldershot. Among his advances was the tubed pedicle graft, maintaining a flesh connection from the donor site until the graft established its own blood flow. Gillies\' assistant, Archibald McIndoe, carried on the work into World War II as reconstructive surgery. In 1962 the first successful replantation surgery was performed - re-attaching a severed limb and restoring (limited) function and feeling.
Transplant of a single gonad (testis) from a living donor was carried out in early July 1926 in Zaječar, Serbia, by a Russian emigr?surgeon Dr. Peter Vasil\'evič Kolesnikov. The donor was a convicted murderer, one Ilija Krajan, whose death sentence was commuted to 20 years imprisonment and he was led to believe that it was done because he had donated his testis to an elderly medical doctor. Both the donor and the receiver survived, but charges were brought in a court of law by the public prosecutor against Dr. Kolesnikov, not for performing the operation, but for lying to the donor. (v. Timočki medicinski glasnik, Vol.29 (2004) #2, p.115-117 ISSN 0350-2899 article in Serbian)
The first attempted human deceased-donor transplant was performed by the Ukrainian surgeon Yu Yu Voronoy in the 1930s; rejection resulted in failure. Joseph Murray performed the first successful transplant, a kidney transplant between identical twins, in 1954, successful because no immunosuppression was necessary in genetically identical twins.
In the late 1940s Peter Medawar, working for the National Institute for Medical Research, improved the understanding of rejection. Identifying the immune reactions in 1951 Medawar suggested that immunosuppressive drugs could be used. Cortisone had been recently discovered and the more effective azathioprine was identified in 1959, but it was not until the discovery of cyclosporine in 1970 that transplant surgery found a sufficiently powerful immunosuppressive.
Dr. Murray\'s success with the kidney led to attempts with other organs. There was a successful deceased-donor lung transplant into a lung cancer sufferer in June 1963 by James Hardy in Jackson, Mississippi. The patient survived for eighteen days before dying of kidney failure. Thomas Starzl of Denver attempted a liver transplant in the same year, but was not successful until 1967.
The heart was a major prize for transplant surgeons. But, as well as rejection issues the heart deteriorates within minutes of death so any operation would have to be performed at great speed. The development of the heart-lung machine was also needed. Lung pioneer James Hardy attempted a human heart transplant in 1964, but a premature failure of the recipient\'s heart caught Hardy with no human donor, he used a chimpanzee heart which failed very quickly. The first success was achieved December 3rd 1967 by Christiaan Barnard in Cape Town, South Africa. Louis Washkansky, the recipient, survived for eighteen days amid what many saw as a distasteful publicity circus. The media interest prompted a spate of heart transplants. Over a hundred were performed in 1968-69, but almost all the patients died within sixty days. Barnard\'s second patient, Philip Blaiberg, lived for 19 months.
It was the advent of cyclosporine that altered transplants from research surgery to life-saving treatment. In 1968 surgical pioneer Denton Cooley performed seventeen transplants including the first heart-lung transplant. Fourteen of his patients were dead within six months. By 1984 two-thirds of all heart transplant patients survived for five years or more. With organ transplants becoming commonplace, limited only by donors, surgeons moved onto more risky fields, multiple organ transplants on humans and whole-body transplant research on animals. On March 9th 1981 the first successful heart-lung transplant took place at Stanford University Hospital. The head surgeon, Bruce Reitz, credited the patient\'s recovery to cyclosporine-A.
As the rising success rate of transplants and modern immunosuppression make transplants more common, the need for more organs has become critical. Advances in living-related donor transplants have made that increasingly common. Additionally, there is substantive research into xenotransplantation or transgenic organs; although these forms of transplant are not yet being used in humans, clinical trials involving the use of specific cell types have been conducted with promising results, such as using porcine islets of Langerhans to treat type one diabetes. However, there are still many problems that would need to be solved before they would be feasible options in patients requiring transplants.
Recently, researchers have been looking into steroid-free immunosuppression. This type of immunosupporession is being pioneered on large scale at Northwestern University in Chicago and other smaller institutions, while steroid minimization is being employed at the University of Wisconsin at Madison and other smaller institutions. This would avoid the side-effects of steroids. While short-term outcomes are outstanding, long-term outcomes are still unknown.
In addition, calcineurin-Inhibitor-Free Immunosuppression is currently undergoing extensive trialing, the result of which would be to allow sufficient immunosuppression, without the nephrotoxicity associated with standard regimens that include calcineurin inhibitors. Positive results have yet to be demonstrated in any trial.
An FDA approved immune function test from Cylex has shown effectiveness in minimizing the risk of infection and rejection in post-transplant patients by enabling doctors to tailor immunosuppressant drug regimens. By keeping a patient\'s immune function within a certain window, doctors can adjust drug levels to prevent organ rejection while avoiding infection. Such information could help physicians reduce the use of immunosuppressive drugs, lowering drug therapy expenses while reducing the morbidity associated with liver biopsies, improve the daily life of transplant patients, and could prolong the life of the transplanted organ.
Many other new drugs are under development for transplantation.
Timeline of successful transplants
1905: First successful cornea transplant by Eduard Zirm
1954: First successful kidney transplant by Joseph Murray (Boston, U.S.A.)
1966: First successful pancreas transplant by Richard Lillehei and William Kelly (Minnesota, U.S.A.)
1967: First successful liver transplant by Thomas Starzl (Denver, U.S.A.)
1967: First successful heart transplant by Christiaan Barnard (Cape Town, South Africa)
1981: First successful heart/lung transplant by Bruce Reitz (Stanford, U.S.A.)
1983: First successful lung lobe transplant by Joel Cooper (Toronto, Canada)
1986: First successful double-lung transplant (Ann Harrison) by Joel Cooper (Toronto, Canada)
1987: First successful whole lung transplant by Joel Cooper (St. Louis, U.S.A.)
1995: First successful laparoscopic live-donor nephrectomy by Lloyd Ratner and Louis Kavoussi (Baltimore, U.S.A.)
1998: First successful live-donor partial pancreas transplant by David Sutherland (Minnesota, U.S.A.)
1998: First successful hand transplant (France)
2005: First successful partial face transplant (France)
2005: First successful penis transplant (China)