Germs, Hosts, and the Origin of Frank Macfarlane Burnet's Concept of "Self " and "Tolerance," 1936-1949

Abstract

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.

From infection to repair: Understanding the workings of our innate immune cells

“…The immune system is tolerant to the "self" entities but will be intolerant to the "nonself" entities and attack them. Burnet defined "self" as the entities distinguished during embryogenesis, but the definition of "self" has been challenged by multiple immunologists (Park, 2006). Immunologists have attempted to explain the "self" as entities encoded by one's genome, the entities encoded by inhabiting microorganisms, bodily proteins existing past a certain concentration threshold, or that it is composed of antigen-presenting cells (APCs; Matzinger, 1994;Mitchison, 1993;Zinkernagel et al, 1991).…”

Next Generation Cancer Vaccines—Make It Personal!

“…The concept that the body can differentiate between self and non-self tissue earned Macfarlane Burnett the Nobel Prize in 1960 [ 42 ] but a further half century of work was required to appreciate the complexity of how tumours coopt the immune system to ensure tolerance ( Figure 1 ). Antigens released by dying cancer cells are ingested by dendritic cells and presented to CD8 + T-cells on MHC class I molecules.…”

The forgotten successes and sacrifices of Charles Kellaway, director of the Walter and Eliza Hall Institute, 1923–1944

“…3,7 The resultant work on staphylococcal toxins helped build Burnet' s reputation as a talented bacteriological researcher, 27 while the immunological aspects of the tragedy are credited with sowing the seeds for his clonal selection theory. 28 Nevertheless, while the stigma of the Bundaberg tragedy took years to overcome, most practitioners were keen to accept the commission' s findings and move on, meaning Kellaway' s stewardship of this important investigation was largely forgotten. 5,6 An international scientific reputation built on venom research The 1920s were a halcyon decade for pharmacological and physiological research, and Kellaway' s Foulerton scholarship brought him into the laboratories of Britain' s leading researchers, especially Henry Dale.…”