Organ Transplantation. History

Organ transplantation is a specialized case of the transplantation of living body tissue. In the 1880s scientists and surgeons started developing a concept of organ replacement that formed the basis of the technique. According to this concept it is possible to treat complex internal diseases by replacing the lost function of a particular organ.

The roots of organ transplantation lay in the ever more sophisticated surgical strategy of removingdiseased tissues. Surgeons had noticed that the lack of particular organ tissue led to the development of specific disease phenomena, but reinserting the tissue into the body reversed disease development.

For the general acceptance of this concept it was significant that surgeons and physiologists were able to create and stop disease symptoms at will, using experimental animals under the controlled conditions of the laboratory. The first organ to be examined in this way was the thyroid gland. It was also the subject of the very first organ transplant by the Swiss surgeon and Nobel laureate Theodor Kocher in 1883.

The principle was then applied to other organs, starting with other endocrine glands—pancreas, testes, ovaries, and adrenal glands. In 1905 Alexis Carrel and C.C. Guthrie in New York City carried out the first heart transplant in a dog. In 1906 Mathieu Jaboulay in Lyons performed the first kidney transplant in a human being, using an animal kidney.

The technical aspects of organ transplantation were mastered in the first decade of the twentieth century when Carrel developed a reliable and effective technique for suturing blood vessels. Carrel was awarded the Nobel Prize in 1912 for his work on vascular surgery and organ transplantation. With growing technical perfection it became clear that organ transplants between different individuals (allotransplantation) normally failed because of some specific factor associated with the biological identity of individuals.

Some researchers ascribed the rejection of foreign tissue to the same mechanism that was also responsible for the body’s defense against infectious agents. In the 1920s the German surgeon Georg Scheine introduced the notion of transplant immunity to describe the phenomenon. However, all attempts to prevent the rejection of allotransplants by suppressing the immune reaction or by selecting suitable donors failed. As a result of the inability to overcome these difficulties, organ transplantation was gradually abandoned in the course of the 1920s.

In 1945 a new phase in the history of organ transplants was initiated when surgeons at the Peter Bent Brigham Hospital in Boston transplanted a kidney from a dead donor to a woman suffering from renal failure. Even though this and subsequent transplants failed, the American surgeons did not abandon their efforts. In 1954, again in Boston, a patient with renal failure was given a kidney from his identical twin brother.

The transplantation was successful, and in 1990 the operating surgeon Joseph E. Murray was awarded the Nobel Prize. In the latter case it was possible to avoid transplant rejection by the selection of an appropriate donor. In order to make allotransplanation applicable on a broader scale, however, surgeons had to pursue a different strategy, which consisted in suppressing the recipient’s immunological reaction against the transplant.

In the 1940s, Peter Medawar and Macfarlane Burnet had described the principles of immunological rejection, following wartime work on tissue grafting. Initial trials using x-ray radiation for immunological suppression proved too damaging for the recipient, so further attempts concentrated on chemical immune suppression. In 1962 the first successful kidney transplantation from a nonrelated donor was performed in Boston. Immune suppression had been achieved by the antimetabolic agent azathioprine.

This approach was subsequently perfected, one of its milestones being the introduction of the immune suppressor cyclosporine in 1982, which enabled more effective but simultaneously more selective suppression of tissue rejection. At the same time, efforts to select suitable organs from nonrelated donors were being made with the help of tissue typing using the human leucocyte antigen (HLA) system as a marker of compatibility. The allocation of transplants was organized by special organizations such as Eurotransplant, founded in 1967 to enable distribution in Austria, Belgium, Luxemburg and Germany.

Apart from kidneys, other organs were also soon transplanted in humans. Most spectacular was the first successful heart transplant in a human performed by Christiaan Barnard in Cape Town, South Africa in 1967. Because of technical and biological difficulties, however, heart transplantation was almost stopped during the 1970s, only to be resumed after the introduction of cyclosporine in the 1980s. At that time the transplantation of other organs, such as the liver, pancreas, and lungs were becoming more successful and therefore a more popular therapeutic option.

However, despite the development of new drugs for immune suppression and the introduction of immunological means to influence rejection (e.g., antilymphocyte globulines), the maintenance of long-term function of transplanted tissue is still considered an unresolved issue in the field. The other main problem concerns the procurement of organs. In the late 1960s, organ procurement from dead donors was regulated by formalizing criteria for the diagnosis of brain death.

Brain death is a state in which the brain has died, but the rest of the body is kept alive with intensive care measures such as artificial ventilation. Regulations were issued in different countries. For instance in the U.S. the so-called Ad Hoc Committee of the Harvard Medical School published a set of guidelines in 1968.

Nonetheless, donation rates in no way kept up with the demand for organ tissue. Living donor transplants, which would be a viable alternative, are largely restricted to the kidneys, though split liver transplants have been performed with hepatic tissue from living donors. Another strategy to relieve organ shortage is the use of animal tissue.

The procedure is called xenotransplantation and was tried from the very beginning of transplant medicine in the late nineteenth century. Results, however, were poor, and despite a number of research and development programs with pig organs in the 1980s and 1990s, xenotransplants do not seem to be a realistic option for the near future.

The idea of growing tissues or even whole organs, which had been pursued by Alexis Carrel together with the engineer and aviator Charles Lindbergh in the 1930s, became popular again in the 1990s and led to the development of the field of tissue engineering. However, even if surgery should overcome all technical obstacles, transplantation will continue to raise a number of relevant cultural and bioethical issues concerning personal identity and the definition of human life. Organ transplantation is, after all, a technology that transcends boundaries of the individual body that had previously been taken for granted.