A History of Organ Transplantation: Ancient Legends to Modern Practice

10 Experimental Organ Transplantation

195 10 Experimental Organ Transplantation A t this time in the late 1940s, some surgeons renewed their interest in experimental organ transplantation, attempting to transplant not only kidneys but also the heart. As described earlier, these efforts had started in Europe before World War I and largely ceased when the war began, but the growing interest in transplantation immunology now encouraged another look. Organ and tissue preservation now became important, and in clinical work the artificial kidney found a routine place in treating acute renal failure. Four groups began experimental kidney transplantation studies, two in Paris, one in Denmark, and one in London. In Paris, the physician Jean Hamburger’s unit reconvened after the war and reported on their experience in 1947.¹ The other group in Paris included the surgeons René Küss, J.Oudot, and J.Auvert.² By the early 1950s, this laboratory experience had prepared both French groups to attempt human kidney transplantation.³ But the most detailed experimental studies were done elsewhere—by Morten Simonsen and William “Jim” Dempster. Morten Simonsen In Denmark, Morten Simonsen (1921–2002) started kidney grafting in 1948. Newly qualified from medical school in Copenhagen, he was fulfilling a necessary house-surgeon post in Ålborg before looking for a full-time research post. He had developed an interest in organ transplantation after a medical student friend died from chronic renal failure, and Simonsen persuaded a local surgeon to help him with some kidney grafting experiments in dogs. Simonsen then obtained a post in the university department of bacteriology in Copenhagen and continued with this unusual type of work, reporting it from 1949 to 1953. He confirmed the old finding that transplanted kidneys worked well for a while, then failed. He found that a second kidney homograft from the same donor was rejected more 196 Experimental Organ Transplantation promptly than the first and thus supported the “acquired immunity” theory , then regaining favor, and, like others, he hoped to find the missing antibody responsible for graft loss. Simonsen also had some extra information. He was aware of the pioneering finding by Astrid Fagraeus in Stockholm in 1947 that plasma cells were the likely producers of antibodies, and he found plasma cells (and lymphocytes) not only markedly in the rejecting kidneys but also in the host spleen at the time of graft loss. He noted that “in experiments with successive transplantations from the same donor this proliferation was even more pronounced. Adherents to the plasma cell theory for antibody production will hardly hesitate to interpret this as a sign of antibody production against the homotransplant.” Although Simonsen had faith that an antibody might be found, he had some doubts and pointed again to the puzzle that some human diseases also showed clear evidence of an immune response, but without a responsible antibody: “The weakest point in the theory of acquired immunity [in explaining graft rejection] is that it never has been possible to demonstrate the active antibodies by serological means. This is a shortcoming that transplantation biology shares with eczematous allergy.”⁴ Simonsen, like others at the time, was unaware that Loeb had solved the problem. Later Simonsen discovered the Murphy-Loeb work and graciously made belated amends. But the sentiment of the day, as taught by physiologists, was that lymphocytes and plasma cells were immobile, con- fined to the bloodstream or connective tissue. To explain the florid reaction in the graft, Simonsen resorted to a tortuous explanation. He suggested that the lymphocytes in the failing graft came from within, that is, they were donor lymphocytes. He proposed that these “passenger” lymphoid cells in the graft were activated and reacted against soluble host antigens in the blood reaching the kidney. Simonsen was wrong, and he was absolved from this error later when lymphocyte mobility was at last recognized and the simpler host invasion explanation resulted. Simonsen’s suggestion was not in vain. He went on to show later that this kind of destructive mechanism did exist elsewhere and that this graft-versus-host (GvH) reaction was important. Ironically, this component of the immune response, prominent later in clinical bone marrow transplantation, was not a major clinical feature of human organ transplantation , but had a more subtle role.⁵ William Dempster at Hammersmith Also involved in experimental organ transplantation in the early 1950s was William J.Dempster, a surgeon in London at the Royal Postgraduate Medi- Experimental Organ Transplantation 197 cal School at...