Historical Reassessment of the Theoretical Genesis of Clonal Selection Theory

Andrea Grignolio
Center for Philosophy and History of Science - Boston University

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     Last modified: June 15, 2005
     Presentation date: 07/14/2005 11:00 AM in MACK 236
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Abstract
It is nowadays an accepted historical fact that Frank Macfarlane Burnet was the father of Clonal Selection Theory (CST). Historical reconstructions also claim that, apart from Talmage, Burnet arrived at this important discovery by reflecting on the excessive replicating capacity of tumoral cells and thereby replaced the Jerne’s humoral level of antibody selection with a cellular level in which antibodies can be correctly synthesized. Thus, the classical picture of CST discovery presents two isolated figures in the middle of the stage: Jerne as the one who put forward a selective mechanism to explain antibody diversity, and Burnet as the one who expanded the theory and, importantly, corrected the level of selection by focusing on the importance of cells for immune response. Shedding some light on a few historical oversights, this paper will offer a different historical reconstruction of the theoretical merits of CST.
First of all, Jerne’s article (1955) cannot be considered as turning immunology’s theory towards a selective model. In fact, he proposed a mechanism of antibody production that involves a partial enzymatic adaptation, a point demonstrated by a bibliography exclusively devoted to the advocates of this non-selective approach to protein synthesis. Thus, the concept of his paper is not written within a Darwinian construct. Further, well into the 50’s and 60’s, adaptive mechanisms were proposed to solve the problem of antibody diversity, for example ‘hybrid models’, both selective and adaptive.
The first proponent of a selective mechanism for the production of antibodies was Talmage (1957), who before Burnet also corrected Jerne’s article arguing that the antibody synthesizing units were the immune cells and that they were the actual targets of selective pressure. Fulfilling the basic postulates of CST, Talmage even claimed the importance of somatic replication, the homogeneity of the proteins produced by myeloma cells, and the reinstatement of both positive and negative memories in a Darwinian orientation.
According to this chronology, the contribution of Burnet to CST is limited to his emphasizing the homogeneity of lymphocyte production (1 cell: 1 antibody theory), the significant rhetorical role of catchy names (“clonal”, “memory”), and to broadening theoretical explanation of “self” and “tolerance”.
Burnet’s explanation of the discovery of CST (his autobiographical account) focused on the semi-malignant cell with other influences such as Lederberg’s presence during the CST formulation period, the R.A. Fisher approach to population genetics, and the role played by Burnet’s interest in information theory. Altogether, this reading of Burnet’s contribution to CST strongly suggest that more serious attention should be paid to Talmage’s contribution to the development of immunology’s selective theory.

Key words: Frank M. Burnet, Niels K. Jerne, David W. Talmage, Joshua Lederberg, clonal selection theory, template vs. selective theories of antibody formation, enzymatic adaptation, generation of diversity, tolerance, information theory, positive v. negative memory.