The 1936 Nobel Prize in Physiology or Medicine was awarded to Henry Dale of London and Otto Loewi of Graz for their separate but synergistic discoveries of the role of acetylcholine in the transmission of neural impulses in the autonomic nervous system. It provided scientific authority and legitimacy to the concept of chemical neurotransmission. However it was to be a further two decades before the idea was widely accepted by more than a few faithful adherents, whilst many, if not most, neurophysiologists continued to believe that most, if not all, neural transmission was electrical. During the 1930s, 1940s and early 1950s, debates between these two groups frequently enlivened meetings of the Physiological Society, and became known jocularly as ‘Spark versus Soup’: hence the title of this book.
This volume records the history of much of the work on chemical neurotransmission, starting from the development of the neurone doctrine, through the Nobel Prize winning work, up to the modern day concepts of “first messengers” and neuromodulators, and with a final epilogue of historical reflections based on the author's active career of almost fifty years in neurobiology. Throughout there is a strong biographical emphasis on the main players, including Dale, Loewi, Walter Cannon, and their colleagues and successors, particularly Wilhelm Feldberg and John Eccles.
Early chapters set the scene by describing in particular the influence of the Cambridge department of physiology, especially that of John Langley and Walter Gaskell. The significance, or otherwise, of the work of Thomas Renton Elliott, often credited with the first articulation of chemical neurotransmission, is thoroughly discussed, and the importance of the autonomic nervous system emphasized. Gradually, the various pieces of the jigsaw puzzle of chemical neurotransmission are uncovered: Dale and Ewins' discovery of acetylcholine in an extract of the fungus ergot and their demonstration of its powerful depressor effect in the parasympathetic nervous system; Loewi's observations of vagusstoff and acceleransstoff, chemical substances apparently released on neural stimulation; Dale and Dudley's most important discovery, whilst looking for histamine, that acetylcholine was a normal constituent of the mammalian body; and the increasing evidence that vagusstoff was indeed acetylcholine. In 1933 came the arrival in Dale's laboratory of Feldberg, a refugee from Hitler's Germany, who brought with him the eserinized leech muscle preparation that finally provided a sensitive bioassay for acetylcholine. It was only a short matter of time before compelling evidence of acetylcholine release after nerve stimulation was compiled and the work was recommended by the Nobel Committee for the Prize. Meanwhile in Harvard, Cannon and his assistants, firstly the Belgian Zenon Bacq, and then the Mexican, Arturo Rosenblueth, were doing parallel work on the sympathetic nervous system. Here the work was complicated by the dual responses seen by stimulation of the sympathetic nervous system, excitatory in some systems, inhibitory in others. To explain this Cannon and Rosenblueth devised a complicated theory of sympathin-E (to account for the excitatory effects) and sympathin-I (to account for the inhibitory effects) secreted by sympathetic fibres. Although Dale always acknowledged Cannon's work in showing that a chemical was liberated from sympathetic fibres, he was never convinced by the sympathin theory, and on the whole it did not receive much support in the UK. It was Raymond Ahlquist, an unsung hero in the history of chemical neurotransmission and one who gets little attention here, who later unravelled the complexities of adrenergic receptors and their differential sensitivity to catecholamines, thus opening up the final elucidation of sympathetic neurotransmission. It was Ahlquist's work that finally discouraged the use of the confusing word “sympathin”, an important step more than matched by Dale's proposal, also glossed over here, of the words “cholinergic” and “adrenergic” to describe fibres by the kind of chemical (rather than the chemical itself) they might use, because “such a usage would assist clear thinking, without committing us to precise chemical identifications, which may be long in coming” (H H Dale, ‘Nomenclature of fibres in the autonomic nervous system and their effects’, J. Physiol., 1934, 80: 10–11).
Sadly, the book is riddled with numerous irritating small errors—for example, within just a few pages in the chapter on Henry Dale, Patrick Laidlaw is incorrectly identified (twice) as Peter; Dale did not head the Wellcome Trust Fund, he was Chairman of the Wellcome Trust; the novelist who founded the George Henry Lewes studentship was George Eliot, not Elliot. There is no such thing as the National Research Committee, it is not now the National Research Council, and Dale was not appointed to it in 1914. He became a member of staff of the Medical Research Committee (later the Medical Research Council) not a member of the Committee, and worked originally in the Central Research Institute that became the National Institute for Medical Research (NIMR) not the Institute of Medical Research, and it was not in Hampstead until 1919. There is no evidence that dissatisfaction at increasing calls to test Burroughs, Wellcome & Co's products led to Dale's departure from the Wellcome Physiological Research Laboratories, and indeed the suggestion that difficulties about the use of the word adrenaline encouraged him to consider other positions is plain wrong—that debate occurred in 1906, Dale shortly afterwards became the Director of the Laboratories, and remained there for another eight years. These errors, whilst individually small, are cumulatively irritating. Equally the insufficiency of some figure legends, and indeed of some of the figures themselves, detract from the presentation of one of the most riveting stories of modern neuroscience.