19 - A New Direction: Transplant Immunology

Summary

Differentiating Between Technical and Biological Causes of Failure

Although most allotransplantations done between the 1880s and the 1930s failed, the fact that some of them seemed successful led many surgeons to look for ways of making them work. As described in the previous chapter, surgeons first tried to improve surgical technique. Obviously factors such as blood supply, variations in transplantability of different tissues, and the technical details of transplant removal, interim storage, and implantation all had an influence on the outcome of an allotransplant. Many surgeons thought that their transplants died because of infections or from blood clots in the vascular linkups or within the transplanted organs themselves. Some researchers explicitly rejected the idea of some chemical obstacle that could not be overcome by surgical means and they predicted a great future for allotransplants. Thus the surgeon Aurel Avramovici in Bucharest believed, in 1924, that allogenic kidney transplantation was on the verge of its practical application. To him, success was a question of perfecting surgical technique; with good technique, one could transplant “almost anything,” he wrote.

Differences in surgical techniques, however, could not account for the striking contrast between the excellent outcomes of autotransplants and the poor outcomes of xeno- and allotransplants. By 1900 most researchers acknowledged the existence of an additional, nontechnical factor that explained these differences. This factor was apparently correlated to the biological difference between recipient organism and transplant—the only difference between auto- and allotransplantation—but none of this was clear from the start.

In 1908, Carrel therefore still found it impossible to decide why some of his experimental transplants failed while others succeeded. The systematic experiments he conducted in order to answer this question were a decisive step on the way to a general consensus among scientists and doctors at the time. Carrel began by perfecting his surgical technique to the point where he was able to achieve long-term success with autotransplants. By 1909 he had mastered the surgical aspects of kidney transplantation and achieved basically unlimited survival times in his autotransplants. When he used exactly the same techniques to do allotransplants, however, he found that, despite initial indications of function, all of his transplants eventually perished and showed indications of diffuse nephritis.