A talk with Sir Henry Dale (1960)

and am I correct insane but you're 85 years of age yes that's true Oh to be more precise I shall be if I live another few weeks and since your retirement for the Medical Research Council you found other interests as chairman of the Wellcome Trust oh yes that is so but you're mentioned of that now reminds me that it is more than 55 years since in 1904 as then still a youngish physiologist I began to get my first experience of research in pharmacology in the welcome to bellacor is where I remain for the next 10 years and that led directly to my major research opportunity in my service with the Medical Research Council for the next 28 years but my research is in that main period about some of which I expect you're in to ask me questions was largely derived from clues which I picked up in those earlier 10 years and now in your retirement well those you've already said I'm finding new kind of opportunity in bringing help to the researchers of other people as chairman of the trustees appointed by the will of the late Sir Henry welcomed these trustees draw their income you know from the pharmaceutical business which belonged to Henry welcomed himself when he lived and they use that income for the support of research and historical scholarship in the general field of medicine anywhere in the world and in 1936 I think Sir Henry you were awarded the Nobel Prize for medicine jointly with utterly yes that was Sir and may I say that each word gave me an additional pleasure in that the award was made jointly with my old friend professor Murphy who I'd known for I suppose about 60 years since he worked in London for the first time and in Cambridge near the beginning of this century and that award was given for the work that you did on the chemical transmission of the effects on nerve impulses that's it that's true yes but we ought to remember you know that 32 years earlier in 1904 the idea of such a chemical transmission of the effects of nerve impulses was actually proposed by another friend of mine professor TR Eliot while he was still working as a research student in Cambridge he put it forward to explain what he was then working on the remarkable correspondence between the effects of injecting adrenaline and those of stimulating the nerves of the true sympathetic system and it wasn't - 10 years later in 1914 that I came across acetylcholine in a peculiar text rate and was helped in identifying it by remembering that professor Reed Hundt of Harvard some years earlier but had that substance made for him artificially hadn't found but it has an extremely but inhibitory effect on the action of the heart it was that the early effect no when I came to really examine the effects of a sitar coating on the internal organs in general first I found that these correspondent in the most remarkable and significant manner with the effect of stimulating they are nerve supplies through the parasympathetic nervous system and beyond just as Elliot had found that the and written corresponding with those of stimulating the proof sympathetic nerve supplies but beyond all that I found also what was perhaps even more significantly the message are coded also stimulated all the cells in autonomic Ganga and the motor endplate some voluntary muscle fibers and then to jump some twenty years ahead later with a series of distinguished co-workers we succeeded in demonstrating that acetylcholine was actually liberated at these synaptic junctions in gondya and the endings of voluntary motor nerves to transmit the effects of the impulse to the motor end plate of muscle fiber and where does not endure becoming um earlier because Elliot's work with adrenaline in 1904 my own with acetylcholine in 1914 and as it were I think prepared the way for what was to come in 1921 when Otto burly gave the first and beautifully simple demonstration of such a transmission of nervous effects by liberation of chemical stimulators when he stimulated the doomed nerve suppliers to the isolated Hartman frog net and what then was the practical consequence of this work well I'm always a bit shy by frankly a see me to claim practical consequences in medicine for finding us and which I've been concerned in the laboratory but since you put the question I think it it is a fact that this discovery of this chemical mechanism for the transmission of effects at nerve junctions has had at least some effect on the clinical conceptions of nerve functions in general and of course of the disorders of those fetish and that in particular the application in treatment of now a whole lot missing drug some of the natural some of them artificial muslim artificial which either antagonize or directly accentuate the effect of one or another of these transmitters when they are liberated or on the other hand hinder the actual liberation of one of the other of them and while it was engaged in this series which i think you call the sympathy magnetic a means that you diverted your attention to noradrenaline yes remember fifty years ago that time noradrenaline was still a new synthetic curiosity it'll be made by one of the big German firms and have been made independently in this country by a man who was then a young research chemist who was to become another of my closest friends and retaken what I found about noradrenaline was that it not only as perhaps was to be expected reproduced effects of sympathetic nerve stimulation as Edwin land itself did but that it did so with a much closer accuracy of detail than everything did and what did that lead to well after many years do the recent discoveries that nor a dream then after all is not merely a synthetic curiosity but is an actual constituent of the living body and particularly of the sympathetic nervous system and that in many species including our own human species it does act as the principal transmitter of the effects of sympathetic nerve impulses those discoveries have been made largely by men who at one time or another have worked in my own laboratory but they've made them long after I myself retired now eighteen years ago and what about the old and liquid extract of ervis whose value the general practitioners had great belief although I think that belief was challenged by the pharmacologist and indeed by yourself yes well that's another story and one in which I had the privilege of being an interested spectator and perhaps to some extent a consultant rather than an active participant what happened was that the Medical Research Council had been passed to get paid accurate clinical comparison between two well-known alkaloids of Herbet for which rival claims were being made to be the essential obstetric constituent and they'd invited dr. chasuble who was then a keen young obstetrical registrar to undertake the comparison and he consulted with me and I perhaps helped him to obtain a suitable apparatus which he used to obtain objective records of the contractions of the fewer for all human uterus and with that he very soon settle the matter because he found no difference whatever between the actions on the human uterus of these two well-known alkaloids but he also found that neither of them had any distinct activity of that kind when it was given for the mouth yeah but where does the older liquid extract of earlier come in how in both ways because that law was given by the mouse and also it contains no recognizable traces of either of those alkaloids so that if the general practitioners and the obstetricians who used it had any good ground for their belief in its activity it must be due to something else well now Chesham buyer had at his disposal an ideal technique for putting that to the test and even think of the result which lost shell that the old liquid extracted administered in the conventional way by the mouse and a very potent and very valuable action on the activity of the human uterus and then the way was clear for him to cooperate with my native chemical colleague dr. Harold Dudley and they were at work for nearly three years until finally from the old liquid extract that they succeeded in isolating and there are two unknown alkaloid now known as Fermi critter recognized everywhere I think as the essential obstetrical invaluable constituent of herbage which I am and others have been looking for in vain for many years by the monitoring methods am I correct in supposing that your work on agate indeed led to many important further discoveries yes the number of discoveries are quite different kind for example some of my early experiments with Herbet I came across quite by accident evidence for the presence in the pituitary posterior lobe of a very potent oxytocin hormone now known as oxytocin and then histamine came to my notice though its occurrence in a peculiar extract of Herbet and Barger and I soon found that it was a natural constituent of the tissues of the body and then when we came to examine its activities in detail these showed the most remarkable correspondence to the chief features in different animal species of the then recently discovered and described anaphylactic reaction and now in recent years the generation after mine has been discovering that this amine is actually released in the anaphylactic reaction and all this evidence of course is naturally leading to an increasing application in therapeutics of substances which directly antagonize the actions of histamine and this work led to your interest in an update influence on the Biological standardization such as insulin well I suppose I did have some influence on that but chiefly I think by my insistence on the use of permanent stable standard substances in terms of which generally accepted units had to be defined a principle indeed which was already laid down as long ago as 1897 by the great power of Ali in his classical description of the standardization of the area antitoxin you were indeed a pupil for short are short time yes what strikes one cell forcibly so Henry is that your work has led to such important clinical results both for the benefit of the doctor and the patient oh well if that never has happened insofar as it happened of course it's been stimulus and an engagement to a laboratory worker but I think I ought to say that except in response to some official prompting I don't think I've ever worked with a consciously technical aim it's just happened that results which have fortunately been obtained in my laboratory on one thing or another have been recognized by other people as having useful clinical applications either for practice or theory and altogether you know I I have the feeling that in well in one way I've had more than my share of the good laugh