Germs, hosts, and the origin of Frank Macfarlane Burnet's concept of "self " and "tolerance," 1936-1949.

In the early twentieth century, the living organism's ability to distinguish its "self" from foreign entities such as bacteria, viruses, transplanted tissue, or transfused blood was a major problem in medical science. This article discusses how the Australian immunologist Frank Macfarlane Burnet arrived at a satisfactory explanation of this problem through his 1949 theory of "self" and "tolerance." Burnet's theoretical work began from his study of diverse factors affecting the conditions of the host and the germ for the occurrence of infectious diseases. Among them, the host's age came to receive his attention as a crucial factor. This understanding was facilitated by his acceptance of cytoplasm inheritance theories, which emphasized the importance of the embryonic host's changing conditions according to its age. Based on this idea, he claimed in 1949 that the "self" of the organism was defined during its embryogenesis. Peter B. Medawar and his colleagues' demonstration of Burnet's claim became the basis for awarding Burnet and Medawar the Nobel Prize in Physiology and Medicine in 1960. While previous histories have focused on Burnet's "inductive reasoning" or "ecological perspective" to explain his conception of the theory of "self" and "tolerance," this article finds the origin of his ideas within an important line of modern medical research engendered through the development of germ theories--the studies of the host body and its relationship with parasites.