History of Liver Transplantation

Abstract

Clinical liver transplantation began in the 1960s, but depended on key advances in immunology and experimental kidney transplantation over several preceding decades. Carrel described organ transplantation in animals in 1908, and was awarded the Nobel Prize in 1912 for pioneering the techniques of vascular anastomosis. In the 1930s, he worked on the extracorporeal perfusion of organs, collaborating with the famous aviator and inventor Charles Lindbergh to develop an apparatus that preempted the modern heart-lung machine. However, Carrel’s laboratory transplants and Voronoy’s attempts to transplant human kidneys in the late 1930s failed consistently from ischemic injury or the abrupt onset of rejection. Rejection was thought to be a nonspecific inflammatory process until Medawar’s groundbreaking work in the 1940s showed that it was an acquired and donor-specific response generated by the host’s immune system, possibly amenable to therapeutic manipulation. Medawar and others also established that rejection was predominantly lymphocyte-mediated, leading to experiments with whole-body radiation and donor bone marrow infusion, known to induce tolerance in animals, in the 1950s. These included human kidney transplants, which were aided by the introduction of hemodialysis, but results remained poor. By 1960, however, azathioprine and steroids had also been found to suppress cell-mediated immunity and several groups had established animal models of kidney and liver transplants to study immunosuppression [1].