Ehrlich's "Beautiful Pictures" and the Controversial Beginnings of Immunological Imagery

The History, Landscapes, Metaphors and Ghosts Around the Concept of Specificity

“…From our point of view, this reflection may have diverse readings, although the principal reading provided by the history of immunology in with respect to the strict instructionist character of the formation of antibodies, that is, the antigens are the pattern directing the formation of the antibody. However, we consider that a new reading of this proposal in other directions, above all in the light of the historical retrospection we have made herein and that of other authors [26,[28][29][30][54][55][56], allows compatibility among many of the problems regarding the concept of specificity dealt with in the present work [77]. For example, Ludwik Fleck in his famous book Genesis and Development of a Scientific Fact compared "antitoxins" with "states" rather than with "substances chemically defined" [25,26], that is, he proposed speaking of states or structures rather than of substances.…”

“…Unlike the receptors whose functions are more limited: the ligands are generally not enzymes, or operators of neuronal networks. Specificity, then, depends not only on the chemical structure of the reactant molecules and much less on only the composition and the chemical structure of the receptor, but also on the structural characteristics of both molecules [21], on the conformational state (molecular pre-stress) of the ligand-receptor [22], on the connectivity of the ligand-receptor with each other [23] and with the environment [24], as well as on the observer's conceptual and experimental framework [15,25,26].…”

“…Koch's perspective of discontinuity and separation among bacterial species, which implied a relationship of one to one, or specific, between the microorganism and the infectious illness, was not only transferred to the context of the Abs and Ags; it also introduced within the notion that specificity was no longer a gradual matter [30,75]. Within the framework of this mental landscape, Ehrlich proposed his famous "side chain theory" of the formation of antibodies, which is based on an analogy between the iconography of benzene molecules and the cell, the latter being a kind of giant molecule with a ring of benzene in the core (which corresponds to protoplasm) and chains of atoms (interpreted as "side-chains" or, later on, "receptors") extending outward from the central ring (protoplasm) [26], that is, the cell itself was conceived as a rigid structure. This theory in turn gave birth to the chemical-static metaphor of key-lock for the enzymes and receptors, which matches a type of Ab with each type of Ag, and in which there is an absolute specificity.…”

“…This theory in turn gave birth to the chemical-static metaphor of key-lock for the enzymes and receptors, which matches a type of Ab with each type of Ag, and in which there is an absolute specificity. This means that a particular "side-chain" or "receptor" may or may not react at all with some given "poison" or "toxin", as a result of the presence or absence of mutually adjusted chemical groups [26]. Ehrlich proposed that .…”

“…[54]. However, Bordet attacked Ehrlich's proposal, postulating that it was "irrational" to assume the existence of a given (fixed, narrow) characteristic, that endows an antibody with particular atomic groupings inscribed in its molecule [26]. According to the foregoing, Bordet had opted for a more diffuse mechanism, postulating that the "agglutination" was due to the complex and contextual interaction among all the substances present in the solution [26].…”