Editing Neural Darwinism (section)

=== Antibodies and NCAM – the emerging understanding of somatic selective systems ===

Edelman was a medical researcher, [[physical chemist]], immunologist, and aspiring neuroscientist when he was awarded the 1972 [[Nobel Prize in Physiology or Medicine]] (shared with [[Rodney Porter]] of Great Britain). Edelman's part of the prize was for his work revealing the chemical structure of the vertebrate [[antibody]] by cleaving the covalent [[disulfide]] bridges that join the component chain fragments together, revealing a pair of two-domain light chains and four-domain heavy chains. Subsequent analysis revealed the terminal domains of both chains to be variable domains responsible for antigen recognition.{{sfn|Edelman|1972}}

The work of Porter and Edelman revealed the molecular and genetic foundations underpinning how antibody diversity was generated within the immune system.  Their work supported earlier ideas about pre-existing diversity in the immune system put forward by the pioneering Danish immunologist [[Niels K. Jerne]] (December 23, 1911 – October 7, 1994); as well as supporting the work of Frank MacFarlane Burnet describing how lymphocytes capable of binding to specific foreign antigens are differentially amplified by clonal multiplication of the selected preexisting variants following antigen discovery.

Edelman would draw inspiration from the mechano-chemical aspects of antigen/antibody/lymphocyte interaction in relation to recognition of self-nonself; the degenerate population of lymphocytes in their physiological context; and the bio-theoretical foundations of this work in Darwinian terms.

By 1974, Edelman felt that immunology was firmly established on solid theoretical grounds descriptively, was ready for quantitative experimentation, and could be an ideal model for exploring evolutionary selection processes within an observable time period.{{sfn|Edelman|1974}}

His studies of immune system interactions developed in him an awareness of the importance of the cell surface and the membrane-embedded molecular mechanisms of interactions with other cells and substrates. Edelman would go on to develop his ideas of topobiology around these mechanisms – and, their genetic and epigenetic regulation under the environmental conditions.

During a foray into molecular embryology and neuroscience, in 1975, Edelman and his team went on to isolate the first neural [[cell-adhesion molecule]] (N-CAM), one of the many molecules that hold the animal nervous system together. N-CAM turned out to be an important molecule in guiding the development and differentiation of neuronal groups in the nervous system and brain during [[embryogenesis]]. To the amazement of Edelman, genetic sequencing revealed that N-CAM was the ancestor of the vertebrate antibody{{sfn|Edelman|1987a}} produced in the aftermath of a set of whole genome duplication events at the origin of vertebrates{{sfn|Dehal|Boore|2005}} that gave rise to the entire super-family of [[immunoglobulin genes]].

Edelman reasoned that the N-CAM molecule which is used for self-self recognition and adherence between neurons in the nervous system gave rise to their evolutionary descendants, the antibodies, who evolved self-nonself recognition via antigen-adherence at the origins of the vertebrate antibody-based immune system. If clonal selection was the way the immune system worked, perhaps it was ancestral and more general – and, operating in the embryo and nervous system.