A Study of Heterologous Antibodies in the Serum of Poliomyelitis Patients

The enunciation and impact of Macfarlane Burnet's clonal selection theory of acquired immunity

“…No supporting findings were found for this concept but much contrary evidence accumulated. In the first edition of ‘ Production of Antibodies’ , 1 Burnet discussed the many aspects already known about antibody production that did not support the direct template theory. This included a logarithmic rise in the antibody titre during the immune response.…”

“…Meanwhile, with the growing recognition of the role of enzymes in biology, Burnet suggested that an antigen might induce modifications of those enzymes involved in globulin synthesis so that a protein with the required specificity might be formed 1 . In the second edition of the monograph, 2 Burnet considered another possibility—that an antigen might somehow influence the genomic machinery of the cell, leading to the synthesis of a specific antibody.…”

“…As a virologist with a very high international status, he had been nominated in the 1930s for a Nobel Prize for his work in Virology. He maintained a strong interest in immunology, and in 1941, published a monograph on the production of antibodies 1 . In the second edition (1949), he proposed that tolerance to self‐antigens would be learned during foetal life 2 .…”

Frank Macfarlane Burnet as I Knew Him

“…He interpreted this to mean that antibody‐producing cells were reproducing at a relatively constant speed somewhere within the body. To Burnet's surprise, his paper was not accepted by the British journal to which he had sent it, so he decided to publish in an unrefereed monograph published by the Hall Institute 9 . Essentially, this rendered the Haurowitz–Mudd–Pauling ‘chemical’ theory of antibody production obsolete 10 …”

Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory

“…From the early 1940s, Burnet had attempted to develop a comprehensive, cohesive and concise view of the workings of the immune system—a theory of everything immunological. This effort resulted in the publication of a series of papers and books on the subject, including his two popular monographs titled The Production of Antibodies 2 , 3 and culminated in his drafting of the clonal selection theory, which was introduced in a brief monograph 4 and subsequently explored in some detail in a published series of lectures presented to the Vanderbilt University in 1958 5 . The development and implications of this model have been discussed in detail elsewhere, including by one of us 6 …”