In a monumental review of the development of ideas in immunology in the first half of the 20th century, Silverstein in 1989 carefully traced the origins of the clonal selection theory and the roles of Paul Ehrlich, Niels Jerne, David Talmage, and Burnet. 9 Recently, the immunologists Cruse and Lewis pointed out that “Talmage never received the recognition he deserved for his seminal contribution” and they attempted to “rectify this oversight”10(pp919-924). Their article is in two parts. The first part gives a historical outline similar to Silvertein’s; the second is a transcript of a conversation with Talmage.
It is of interest that, although mentioning Ehrlich and his work, in neither his 1957 account6 nor his 1959 book does Burnet actually cite Ehrlich in his reference list. In his autobiography Burnet devotes a chapter to clonal selection. He states that: “I regard the development of the clonal selection theory of immunity as my most important scientific achievement. ” 1) Interferon Discovery and Antibody Response Interferon referred to any of a group of antiviral proteins produced by animals, including humans, in response to infection by viruses.
It was first recognized in chick embryo cells by British virologist Alick Isaacs16(p225) and his Swiss colleague Jean Lindenmann in 1957, interferons were found to block further viral infection of body cells. The active antiviral substance is not the interferons themselves, but proteins that interferons cause other cells to produce. Some of these proteins have been identified, but their manner of operation is not yet well understood. It is clear, however, that interferons play a role in the body’s most important defenses against viruses, and that they help fight bacteria and other disease-causing agents.
Interferons may be grouped into three categories. Alpha (leukocyte) interferons are made by white blood cells, beta (fibroblast) interferons by skin cells, and gamma (immune) interferons by lymphocytes after stimulation by antigens. During the 1960s physicians attempted to use interferons to treat virus-caused human diseases, especially colds, but the therapy was determined impractical due to the enormous cost of obtaining minute quantities of interferons from human white blood cells. Researchers then tried to stimulate the body to make its own interferons with inducers such as synthetic nucleic acids.
These chemicals worked, but the body quickly became tolerant of them, and they lost their effect. In 1980, however, interferons were made available in sufficient quantities through genetic engineering techniques, and trials testing dosage levels and side effects were begun the following year. One of the significant lines uttered by Talmage was taken in a review early in 195711 saying that “it is tempting to consider that one of the multiplying units in the antibody response is the cell itself. According to this hypothesis, only those cells are selected for multiplication whose synthesized product has affinity for the antigen injected.
This would have the disadvantage of requiring a different species of cell for each species of protein produced, but would not increase the total amount of configurational information required on the hereditary process. ” He discussed supporting evidence from 1) the kinetics of the antibody response, 2) immunological memory, and 3) the fact that myeloma tumours often result in what Putnam and Udin had described as the: “massive production of one globulin randomly selected from the family of normal globulins”. 12