SIR HENRY DALE AND AUTOPHARMACOLOGY: THE ROLE OF IN

Tilli Tansey

This paper will focus on the work of Sir Henry Dale, the British physiologist who did so much to demonstrate the role of chemical mediation in integrative . I intend to examine some of the details of his work as exemplified by his elucidation of acetylcholine as a at sites in the , for which he was awarded the Nobel Prize in 1936. A great deal of his work, although not all of it, can be encapsulated in one word - 'autopharmacology'. Autopharmacology can be defined as the identification and examination of endogenous chemical substances, and it was the word Dale used as the subtitle for a collection of his scientific papers that was first published 40 years ago in 19531• The intricacies of Henry Dale's research, and the consequent pivotal role that his ideas and results had on the direction of others will be elaborated here as an extension of that prime focus. Henry Dale was born in 1875, and he died in 1968. His career in physiology thus spanned more than seven decades and epitomises many of the transitions that the subject went through, between the end of the nineteenth and the middle of the twentieth century. His life witnessed, and contributed to, enormous changes in the definition, conduct and pursuit of medical science: he was trained in the techniques of experimental physiological research, and always considered himself to be, primarily, a physiologist. With equal justification however he could be classified as a pharmacologist or biochemist; he was offered positions as a pathologist and bacteriologist; he played several major and influential roles as a medical administrator and as a politician of science2 • He also made substantial contributions to what we now call immunology, and the neurosciences. That is without mentioning his roles as a research director, as an administrator, or as a politician of science at both national and international levels. These labels - pharmacologist, endocrinologist, or immunologist reflect layers and diversifications implicit in physiology when he began his career, and explicit as that career ended. By looking at Dale's work on the autonomic nervous system I hope to convey some idea of the dynamics of the steps that led to that diversification and maturation. 180 Dale was educated in the Physiological Laboratory Cambridge, where he came under the particular influence of J.N. Langley, whose principal work was on the anatomy and physiology of the autonomic nervous system. After Cambridge and medical qualification at St Bartholomew's Hospital in , Dale was fortunate to be awarded a very rare postgraduate scholarship, the George Henry Lewes Studentship in Physiology3 • After consultation with Michael Foster, Dale elected to hold the George Henry Lewes Studentship in the Physiology Department of University College London. The department had a long and honourable history in experimental physiology, since the time of William Sharpey, who was appointed to the Chair of General Anatomy and Physiology in 18364 • Sharpey's successors, Michael Foster, John Burdon Sanderson, and Edward Schafer had maintained and extended the traditions started by Sharpey. When Dale arrived there in 1902, it was under the charge of , who with his brother-in-law William Bayliss had just discovered , the first identified and named . Secretin was liberated by cells in the wall of the duodenum, in response to acid secreted by the stomach and passed into the intestine with the bolus of digested food. Having been released in the duodenum, the secretin was then carried in the blood stream to the pancreas, where it stimulated pancreatic secretion. This was significant evidence for physiological regulation by means of chemicals, and Dale was offered an opportunity to examine the effects of secretin on the cells of the pancreas. Using standard histological techniques he examined changes in pancreatic cell structure after prolonged stimulation with secretin and observed that areas of the stimulated cells began to take on the appearance of the Islet of Langerhans cells, the function of which were then unknown. Dale concluded that the exocrine cells were converted, under the influence of secretin, into Islets of Langer hans cells, but his interpretation is now known to be incorrecf. The resultant paper was however published in the prestigious series Philosophical Transactions of the Royal Societl, although Dale always remained unhappy about it: "I never had any clear confidence, however, in my interpretations of these findings. It did surprise me, therefore, to find that they were soon to be completely outdated and discredited, by later and really convincing evidence about the cytology and the functions of the islets; but I think that this experience, even as emphasizing for me the proper method of conducting an investigation, and the proper criteria of significance in appraising its results, was not without its educational value"7 • Dale disliked his research project, he found practical histology and the routine cutting and staining of sections tedious and monotonous, but he found the lab was an exciting and congenial place to work. After all, this