Organ transplantation is one of the most remarkable therapeutic advances in medicine. What started as a clinical experiment is nowadays a routine life-saving and cost-effective practice that brought about remarkable evolution in several medical fields – surgery, organ preservation, immunology, immunosuppression, infectious diseases, critical care medicine. Many are the major milestones of this multidisciplinary clinical science, and the challenges that organ transplantation still faces. Among these, such issues as the shortage of organ supply, graft longevity, the development of immunologic tolerance between host and graft, but also the threath of organ traffic, the promise of xenotransplantation, and of other innovative techniques that might make traditional transplantation surgery as we know it obsolete.

Organ transplantation has always been present in the mithology of many different cultures, but it was only in the second half of the 19th century that surgeons realised that diseased tissues could be removed and replaced without risking the patient’s death.

In July, 1883, Theodor Kocher transplanted thyroid tissue into a patient who had undergone radical thyroidectomy. This operation can be considered the first organ transplant of modern times.

Researchers used experimental animals under the controlled conditions of the laboratori and later began to use xenotransplants and allotransplants for treating patients.

In 1905, Alexis Carrel performed the first heart transplantation in a dog. Carrel’s technique of blood vessel suture made it possible to link up transplanted organs to their vascular connections in the host organisms.

Carrel noticed that the successful transplantation between individuals was blocked by a problem that could not be solved by surgical means, and that he called biological incompatibility.

A number of researchers undertook to study the effect of the immune system on the outcome of transplanted tissues. Among these, Sir Peter Medawar, now considered the father of transplant immunology, investigated why transplanted skin grafts so often failed. The descriptions of rejection, immunological memory, and tolerance earned him the Nobel Prize in medicine in 1960.

Meanwhile, in 1954, the team led by Joseph Murray in Boston, ushered in the modern era of organ transplantation with the first successful organ transplant between humans, a kidney transplant between two identical twins.

In December 1967, Christiaan Barnard performed the world’s first human heart transplant, after having become acquainted with the technique perfectioned in the US by Norman Shumway, who had done much of the pioneering research in the field.

In the same year, Thomas E. Starzl, in Denver, performed the first successful human liver transplant, which earned him the definition of “the father of modern transplantation.”

Physicians soon realized that tools were needed to prevent rejection. A dramatic change in immunosuppression came when Sir Roy Calne, drawing on laboratory work of Jean Borel, introduced cyclosporine A to clinical practice. This discovery was followed by a series of advancements including monoclonal antibodies, tacrolimus, mycophenolate mofetil, sirolimus, and polyclonal antilymphocyte preparations.

Technical avances have prompted the need for legal, ethical, and social changes. One of these was how to establish when someone was dead. The traditional concept of death as cardiopulmonary collapse became inadequate. In 1964, the concept of coma depasse was introduced, and in 1981, the Guidelines for the Determination of Death were published in the US, which declared that death was defined by the cessation of brain function.

The largest problem affecting transplantation today is the shortage of organs. Efforts are directed toward maximizing living donation. Many believe that xenotransplantation could become a reality and that the best source of potential organs would come from pigs, once hyperacute rejection is avoided. Two strategies that are also currently promising are mixed hematopoietic chimerism and costimulatory blockade.