Historical
perspective
Since early times the idea of tissue and organ transplantation has
captured the imagination of successive generations, and over the centuries
numerous fanciful descriptions of successful transplants have been recorded.
One of the most widely cited early examples is that of the Christian Arab saints
Cosmas and Damien. They were reputed, around 300 AD, to have successfully
replaced the diseased leg of a patient with that from a black man who had died
several days earlier (Fig. 11.1). The modern era of transplantation began in the
1950s and relied on surgical techniques for anastomosing blood vessels which had
been developed at the beginning of the twentieth century by Mathieu Jaboulay and
Alexis Carrel. The first successful kidney transplant was a living donor
transplant performed between identical twins in 1954 at the Brigham Hospital in
Boston by Joseph Murray and colleagues.
This and other kidney transplants between identical twins demonstrated the
technical feasibility of kidney transplantation, but attempts to perform renal
transplantation when the donor and recipient were not genetically identical failed
because no effective immunosuppressive therapy was available (Fig.
11.2). Then,
in 1959, Schwartz and Dameshek discovered that 6-mercaptopurine had
immunosuppressive properties, and Roy Caine showed that azathioprine, a
derivative of 6-mercaptopurine, prevented rejection of canine kidney
transplants. From the early 1960s, a combination of azathioprine and
corticosteroids was used with success in the clinic to prevent graft rejection
after kidney transplantation. These chemical agents were sometimes
supplemented with a polyclonal antilymphocyte antibody given at the time of
transplantation as immunoprophylaxis or used to treat an episode of graft
rejection. The cyclosporin era began in the late 1970s following the discovery
of the new agent by Borel at the Sandoz laboratories in Basle and the
demonstration, by Caine, of its potent immunosuppressive properties in
clinical studies. The introduction of cyclosporin was a major advance and
cyclosporin (usually given together with azathioprine and steroids) not only
improved the results of renal transplantation but also allowed transplantation
of the heart and liver to be undertaken with acceptable results. Organ
transplantation is now well established as an effective treatment for selected
patients with end-stage organ failure. Transplantation of the kidney, liver,
pancreas, heart and lungs are all routine procedures, and transplantation of the
small intestine is becoming more widely practised. Today, transplant activity is
limited only by the shortage of cadaveric organs.