Canine Models for Transplantation and Gene Therapy
I. HISTORY OF TRANSPLANTATION In 1902, Alexis Carrel perfected the technique of vascular anastomosis, and beginning in 1905, he reported the experimental transplantation of limbs, kidneys, and other organs. It quickly became apparent that autografts generally succeeded, and allografts almost always failed. He concluded that it was not possible to transplant tissue from one individual to another of different genetic origin without subsequent rejection. He received the Nobel prize for this work in 1912. It was not until after World War II that a group of biologists and immunologists led by Peter Medawar and Macfarlane Burnet provided the scientific base for graft acceptance and rejection. The observation by Owen (1) that nonidentical cattle twins with natural vascular anastomoses in utero were erythrocyte chimeras was the first evidence that rejection of genetically different cells need not always occur. Medawar and colleagues extended these studies and showed that such cattle were unable to reject one another’s skin grafts (2). This indicated that tolerance could be induced in utero and initiated a plethora of investigations to understand the phenomenon of immunological tolerance with the goal to overcome the immunological barrier. In 1955, Main and Prehn were the first to recognize the tolerance inducing ability of bone marrow transplants by showing successful skin allografts after the administration of high-dose irradiation and allogeneic marrow from donors that were syngeneic with the skin graft donors (3).