A Short History of the Drug Receptor Concept (review)

[Erratum]

The receptor concept is so central to today's pharmacology that it is difficult to see its history as anything but a century of triumphant progress. We just know how the story turns out, so that in spite of the authors' explicit rejection of an old-fashioned "history of ideas" approach (p. 2), we know that it will begin with Paul Ehrlich's imaginary side chains of the 1880s and end with the cloning of the acetylcholine receptor in the 1980s.

But the authors try to place themselves within a modern network of historians who despise such technically detailed success stories as an "old style of writing." They draw, they say, on Jack Morrell's work on scientific schools and research networks and their effects on the social and cultural history of scientific concepts. They cite Morrell's essay of 1972, "The Chemist Breeders: The Research Schools of Liebig and Thomson" (p. 3),¹ that set off forty years of the study of new scientific disciplines and the networks that supported them. In this case, however, it is not so much the new scientific discipline of receptor-mediated drug activity that is so interesting but the old one that it was destined to replace. As the establishment background, the authors draw together a worldwide network of student-teacher and other influential relationships, beginning in mid-nineteenth-century Germany with the institutionalization of experimental physicochemical pharmacology. One of these influentials is said to have supervised eighty-six graduate theses. Among their heirs were the leading pharmacologists of Germany, Britain, and the United States, reaching well into the mid-twentieth century.

So it is not the beginning and the end but the middle part of this book that Jack Morrell would have liked, the period between, when physiologists, pharmacologists, and immunologists all worked with a range of physicochemical theories—gradients between the inside and outside of cells, adsorption on surfaces, physical solubility, and, I should add, the charge-based template theory of antibody production and the antigen-antibody reaction. None of this made any use of the receptor concept, and all of it was adequately supported by the quantitative methods of the time, usually the classic physiological experimental approach of applying a substance to an organ and recording the response. The physio-pharmacology of transmitters, the hormones and the sympathetic, and parasympathetic transmitter substances engaged all the most forward-looking workers.

The authors argue that this powerful modern movement left individuals who thought along different lines in a very weak position professionally. The American pharmacologist R. P. Ahlquist (p. 130), for example, who proposed two different types of adrenergic receptors with different effects, which he called a and b, had great difficulty in publishing his results and no positive feedback when he did. His 1948 paper was not seriously discussed until the 1960s. Ahlquist's rough tongue and rather mean behavior may have had something to do with his problems, though he did in fact get some recognition later on in the 1970s and 1980s. He is said to have believed that one of the Nobel officials was a personal enemy of his (p. 137). But of course, it is not clear which came first, the sourness or the scientific isolation. The authors' discussion of the network of pharmacologists and of why Ahlquist found his community unreceptive to receptors is the most interesting part of the book, the part that justifies their claim that theirs is not a simple progress story with lots of technical detail but a study of the cultural practice of science.

I would like to add just one critical point: this book has no illustrations. For a text that deals with something as visual as receptor theories, we would really have liked to have at least some of Ehrlich's famous...