Glances at the history of transplantation immunology

Abstract

THE aim of this presentation is twofold: to give a brief outline of the historical roots of present transplant immunology and to add a few remarks on how the merits of Felix Milgrom may be seen within this framework. The history of transplant immunology may be divided into two time phases, and the second phase into three branches, as outlined in Table 1. The early, nonimmunological phase begins, of course, with legends. Two examples may be given: (1) The medical Saints Cosmas and Damian allegedly lived as Christian missionaries in Rome in the third century. They treated a white patient by removing one of his legs and by grafting that of a black man who had died the same day (Fig 1A). A closer look at this painting reveals that these surgeons removed the wrong leg. What could be the message of this painting—that a really great physician would be one who can overcome the barriers of biological individuality; (2) Another legend of wishful thinking, regarding physical profits from another human being, was provided by Pope Innocent VIII, who reportedly tried rejuvenation by drinking the blood of three boys. Figure 1B shows how the blood may have been collected. The boys died, the Pope apparently received no benefit and died in 1492. Blood transfusions in man, directly from blood vessel to vessel, were, up to the end of the last century, so often lethal that in 1883 Berlin the influential German surgeon Ernst v. Bergmann felt himself forced to deliver a kind of funeral sermon to stop the use of this method. Only 17 years later, in Vienna, Karl Landsteiner (Fig 1C) began to discover the ABO blood group system and the laws of complication-free blood transfusion; the clinical value of which, however, only became understood by the surgeons more than 20 years later. The Nobel Prize was awarded to Landsteiner in 1930. Nowadays, besides transfusing human blood by gallons, we fractionate hemopoietic stem cells from peripheral blood to perform bone marrow transplantation. In this way, to my understanding, we now perform the biologically most fascinating of all transplantations (vide infra). The early trials of organ transplantation in this century were connected to the first Nobel Prize in transplantation medicine, which was awarded in 1912 to Alexis Carrel (Fig 1D), an experimental surgeon in Lyon, later in Chicago, for his pioneering work showing that organ transplantation is technically feasible. In the twenties and thirties of this century, many experimental transplantations, mostly in dogs and cats, were reported as successful—but the average survival times were just a few days, exceptionally up to 73 days. The first organ (kidney) transplantations in man were xenogeneic rather than allogeneic—for obviously the same reasons which initiated the recent rekindling of interest in xenotransplantation (see below), namely, the problems of organ allocation. Jaboulay (Lyon, 1906) grafted a pig kidney, thereafter a goat kidney, of course without success. Voronoy, in Russia, reportedly performed the first six allogeneic grafts from deceased humans (between 1933 and 1949) again, without success. Why no success? What were the old concepts on the mechanism of rejection? The leading idea in the first half of this century, beginning with suggestions of Paul Ehrlich (1906), was malnutrition of the grafted tissue as the prime cause. Those concepts may be summarized by saying: “Look for means to improve blood circulation and tissue metabolism—that will bring the solution to our transplantation problems.” This kind of reasoning has been maintained amazingly long—partly up to 1959, ie, one year before Peter B. Medawar was awarded the Nobel Prize for his, by then, widely reproduced pioneer work (see below).