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    Instructive selection and immunological theory.
    Immunol Rev 2002 Jul;185:50-3
    Sackler Foundation at the Rockefeller University, New York, NY 10021, USA.
    The turning point of modern immunological theory was the advent of the clonal selection theory (Burnet, Talmage - 1957). A useful heuristic in the classification of theoretical models was the contrast of 'instructive' with 'selective' models of the acquisition of information by biological systems. The neo-Darwinian synthesis of the 1940s had consolidated biologists' model of evolution based on prior random variation and natural selection, viz. differential fecundity. While evolution in the large was by then pretty well settled, controversy remained about examples of cellular adaptation to chemical challenges, like induced drug-resistance, enzyme formation and the antibody response. While instructive theories have been on the decline, some clear cut examples can be found of molecular imprinting in the abiotic world, leading, e.g. to the production of specific sorbents. Template-driven assembly, as in DNA synthesis, has remained a paradigm of instructive specification. Nevertheless, the classification may break down with more microscopic scrutiny of the processes of molecular fit of substrates with enzymes, of monomers to an elongating polymer chain, as the reactants often traverse a state space from with activated components are appropriately selected. The same process may be 'instructive' from a holistic, 'selective' from an atomic perspective.

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