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21 May 2009

Organ transplantation – a brief history

N L Tilney

Ann Transplant 2009; 14(1): 12-12 :: ID: 880518


The replacement of diseased or injured tissues or organs with healthy substitutes, either from distant sites of the body or from other individuals, has been a concept constant throughout human history. The Ancient Indians (1500 BC) covered the open site of amputated noses with skin flaps from the forehead. Gasparo Tagliacozzi in XVIth Century Bologna devised a pedicle flap from the upper arm as coverage of the facial defect - a method used to this day. Reports of the clinical application of such techniques appeared sporadically thereafter. The transplantation of vascularized organs was not considered, however, until Alexis Carrel in Lyon and then New York around 1900 perfected a surgical method to join blood vessels. Indeed, he and several European surgeons carried out a number of kidney transplants before World War I both in animals and humans, all technically successful but all failing within a few days. The subject lay fallow until after World War II with the exception of several transplants in the 1930s in patients by a Russian investigator, U U Voronoy - again all unsuccessful. A Chicago surgeon replaced a failed polycystic kidney with an organ from a deceased donor in 1950, the only transplant he ever attempted. To everyone's surprise, the patient lived over 6 years, probably because the new graft survived long enough to allow the remaining native kidney to regain some function. This single case stimulated surgeons in Paris and in Boston to perform 17 transplants by the middle of the decade. All patients died except one who was sustained by his graft for 5 months. At the end of 1954, Joseph Murray in Boston carried out the first successful kidney transplant between identical twins. The remarkable success of this procedure, resurrecting a terminally ill individual by replacing his failed kidneys with the healthy organ from his genetically identical brother, showed clearly the potential for such a radical step. Similar successes between twins stimulated investigations into means of transplanting kidneys from genetically dissimilar donor sources. By the end of the 1950s, a number of graft recipients in Boston and Paris had received total body radiation, the only means of immunosuppression available. While the transferred kidneys did not reject, all but two of the first 22 patients died of overwhelming sepsis. These two individuals lived normally for decades. It was clear, however, that radiation was too powerful and unpredictable for general use although the French persisted with the technique with some success. A new concept in immunosuppression was needed. In 1959 two Boston hematologists described that an anti-metabolite could inhibit the immune responses in rabbits. Roy Calne, a young British surgeon, came to Harvard to work in Murray's laboratory, bringing a chemical derivative of the drug. It worked well enough in dogs to attempt it clinically. The addition of maintenance steroids to Azathioprine, as the agent was named, became the linchpin of immunosuppressive therapy for decades. Transplant units burgeoned over the Western world. Professors Nielubovycz and Orlowski performed the first kidney transplant in Poland in 1966, for instance. Tissue typing, organ preservation, and the concept of brain death were introduced during the 1970s. In the 1980s a new drug, Cyclosporine A, appeared. Its superiority to prior agents was so obvious that the transplantation of other organs long under investigation - heart, liver, lung, pancreas -, became increasing possible. Agents introduced in subsequent years have improved results progressively. Transplantation has become routine treatment for the failure of a spectrum o vital organs. The relatively brief development and maturation of this unique field is a triumph of human persistence and ingenuity.

Keywords: Organ Transplantation

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358