DOCSLIB.ORG

Sir Henry Dale and Autopharmacology: the Role of Acetylcholine in Neurotransmission

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sir Henry Dale and Autopharmacology: the Role of Acetylcholine in Neurotransmission SIR HENRY DALE AND AUTOPHARMACOLOGY: THE ROLE OF ACETYLCHOLINE IN NEUROTRANSMISSION 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 physiology. I intend to examine some of the details of his work as exemplified by his elucidation of acetylcholine as a neurotransmitter at sites in the autonomic nervous system, 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, endocrinology 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 London, 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 Ernest Starling, who with his brother-in-law William Bayliss had just discovered secretin, the first identified and named hormone. 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 .
Load more

Recommended publications
  • Bloomsbury Scientists Ii Iii
    i Bloomsbury Scientists ii iii Bloomsbury Scientists Science and Art in the Wake of Darwin Michael Boulter iv First published in 2017 by UCL Press University College London Gower Street London WC1E 6BT Available to download free: www.ucl.ac.uk/ ucl- press Text © Michael Boulter, 2017 Images courtesy of Michael Boulter, 2017 A CIP catalogue record for this book is available from the British Library. This book is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Attribution should include the following information: Michael Boulter, Bloomsbury Scientists. London, UCL Press, 2017. https://doi.org/10.14324/111.9781787350045 Further details about Creative Commons licenses are available at http://creativecommons.org/licenses/ ISBN: 978- 1- 78735- 006- 9 (hbk) ISBN: 978- 1- 78735- 005- 2 (pbk) ISBN: 978- 1- 78735- 004- 5 (PDF) ISBN: 978- 1- 78735- 007- 6 (epub) ISBN: 978- 1- 78735- 008- 3 (mobi) ISBN: 978- 1- 78735- 009- 0 (html) DOI: https:// doi.org/ 10.14324/ 111.9781787350045 v In memory of W. G. Chaloner FRS, 1928– 2016, lecturer in palaeobotany at UCL, 1956– 72 vi vii Acknowledgements My old writing style was strongly controlled by the measured precision of my scientific discipline, evolutionary biology. It was a habit that I tried to break while working on this project, with its speculations and opinions, let alone dubious data. But my old practices of scientific rigour intentionally stopped personalities and feeling showing through.
    [Show full text]
  • Independent Discovery in Biology: Investigating Styles of Scientific Research
    Medical History, 1993, 37: 432-441. INDEPENDENT DISCOVERY IN BIOLOGY: INVESTIGATING STYLES OF SCIENTIFIC RESEARCH by NICHOLAS RUSSELL * INTRODUCTION The fact that discoveries are often made independently is a commonplace of the history and sociology of science. Analysis of independent discovery has potential for evaluating the relative importance of social and individual components in the conduct of scientific research.' For instance, in a classic paper, Barber and Fox2 discussed the independent discovery of a bizarre phenomenon by two scientists. Aaron Kellner and Lewis Thomas both found that injections of the enzyme papain caused the upright ears of rabbits to droop over their heads like spaniels'. At first neither could find an explanation for it. Both abandoned the search and Kellner never returned to it, even though he went on to use the floppy ear response as a technical assay for measuring the potency of papain samples. Lewis Thomas did look into it again and discovered that papain completely altered the structure of the matrix of cartilage, not only in the ears but everywhere else in the animal as well. Both Thomas and Kellner had originally missed these changes because they had assumed that cartilage was a stable and uninteresting tissue. Barber and Fox concluded that Thomas persisted with the problem because it played a role in his developing research while the floppy-eared phenomenon was irrelevant to Kellner's interests. Barber and Fox hinted that more personal factors were involved as well, a theme expanded by Thomas in a later autobiographical essay.3 Thomas had found the collapsed ears amusing.
    [Show full text]
  • Development of Novel Synthetic Routes to the Epoxyketooctadecanoic Acids
    DEVELOPMENT OF NOVEL SYNTHETIC ROUTES TO THE EPOXYKETOOCTADECANOIC ACIDS (EKODES) AND THEIR BIOLOGICAL EVALUATION AS ACTIVATORS OF THE PPAR FAMILY OF NUCLEAR RECEPTORS By ROOZBEH ESKANDARI Submitted in partial fulfillment of the requirements for The Degree of Doctor of Philosophy Thesis Advisor: Gregory P. Tochtrop, Ph.D. Department of Chemistry CASE WESTERN RESERVE UNIVERSITY January, 2016 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of ROOZBEH ESKANDARI Candidate for the Ph.D degree *. (signed) Anthony J. Pearson, PhD (Chair of the committee) Gregory P. Tochtrop, PhD (Advisor) Michael G. Zagorski, PhD Blanton S. Tolbert, PhD Witold K. Surewicz, PhD (Department of Physiology and Biophysics) (date) 14th July, 2015 *We also certify that written approval has been obtained for any proprietary material contained therein. I dedicate this work to my sister Table of Contents Table of Contents ........................................................................................................................ i List of Tables .............................................................................................................................. vi List of Figures ........................................................................................................................... vii List of Schemes .......................................................................................................................... ix Acknowledgements ..................................................................................................................
    [Show full text]
  • Department of Physiology (Pages 158-181)
    Thomas Jefferson University Jefferson Digital Commons Thomas Jefferson University - tradition and heritage, edited by Frederick B. Wagner, Jr., MD, Jefferson History and Publications 1989 January 1989 Part II: Basic Sciences --- Chapter 5: Department of Physiology (pages 158-181) Follow this and additional works at: https://jdc.jefferson.edu/wagner2 Let us know how access to this document benefits ouy Recommended Citation "Part II: Basic Sciences --- Chapter 5: Department of Physiology (pages 158-181)" (1989). Thomas Jefferson University - tradition and heritage, edited by Frederick B. Wagner, Jr., MD, 1989. Paper 5. https://jdc.jefferson.edu/wagner2/5 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Thomas Jefferson University - tradition and heritage, edited by Frederick B. Wagner, Jr., MD, 1989 by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. CHAPTER fiVE Department of Physiology LEONARD M. ROSENFELD, PH.D. A physician:Js
    [Show full text]
  • Back Matter (PDF)
    INDEX to VOL. CII. (A) Absorption bands, wave-lengtli measurement of (Hartridge), 575. Address of the President, 1922, 373. a- and /3-rays, theory of scattering (Jeans), 437. a-particle passing through matter, changes in charge of (Henderson), 496. «-ray, loss of energy of, in passage through matter (Kapitza), 48. a-ray photographs, analysis of (Blackett), 294. Aluminium crystal, distortion during tensile test (Taylor and Elam), 643. Argon, ionisation by electron collisions (Horton and Davies), 131. Armstrong (E. F.) and Hilditch (T. P.) A Study of Catalytic Action at Solid Surfaces.— Part VIII, 21 ; Part IX, 27. Astbury (W. T.) The Crystalline Structure and Properties of Tartaric Acid, 506. Atmosphere, outer, and theory of meteors (Lindemann and Dobson), 411. Atmospheric disturbances, directional observations of (Watt), 460. Atomic hydrogen, incandescence in (Wood), 1. Backliurst (I.) Variation of the Intensity of Reflected X-radiation with the Tem­ perature of the Crystal, 340. Bakerian Lecture (Taylor and Elam), 643. Berry (A.) and Swain (L. M.) On the Steady Motion of a Cylinder through Infinite Viscous Fluid, 766. /3-rays, scattering of (Wilson), 9. Blackett (P. M. S.) On the Analysis of u-Ray Photographs, 294. Brodetsky (S.) The Line of Action of the Resultant Pressure in Discontinuous Fluid Motion, 361 ; ----- Discontinuous Fluid Motion past Circular and Elliptic Cylinders 542. Cale (F. M.) See McLennan and Cale. Campbell (J. H. P.) See Whytlaw-Gray. Carbon arc ultra-violet spectrum (Simeon), 484. Catalytic Action (Armstrong and Hilditch), 21, 27. Christie (Sir W.) Obituary notice of, xi. Clark (M. L.) See McLennan and Clark. Colloidal behaviour, theory of (Hill), 705.
    [Show full text]
  • Historical Development and Ethical Considerations of Vivisectionist and Antivivisectionist Movement*
    JAHR Vol. 3 No. 6 2012 UDK 179.4 Invited review Bruno Atalić* Historical development and ethical considerations of vivisectionist and antivivisectionist movement* Abstract This review presents historical development and ethical considerations of vivisectionist and antivivisectionist movement. In this respect it shows that both movements were not just characteristic for the past one hundred years, but that they were present since the beginning of medical development. It, thus, re-evaluates the accepted notions of the earlier authors. On this track it suggests that neither movement was victorious in the end, as it could be seen from the current regulations of animal experiments. Finally, it puts both movements into a wider context by examining the connection between antivivisectionism and utilitarianism on the one hand, and vivisectionism and experimentalism on the other hand. Key words: vivisectionism; antivivisectionism; bioethics; utilitarianism; experimentalism Introduction This review will try to present historical development and ethical considerations of vivisectionist and antivivisectionist movement in order to re-evaluate the accepted notions of the earlier authors. Firstly, it evaluates the Lansbury's notion that anti- vivisectionism was characteristic for the North European Protestant countries like England and Sweden, while vivisectionism was characteristic for the South Europe- an Catholic countries like France and Italy.1 Then, it proceeds to the Mason's over- 1 Lansbury C. The Old Brown Dog – Women, Workers, and Vivisection
    [Show full text]
  • Protection Against Dog Distemper and Dogs Protection Bills: the Medical Research Council and Anti-Vivisectionist Protest, 1911-1933
    Medical Historv, 1994, 38: 1-26. PROTECTION AGAINST DOG DISTEMPER AND DOGS PROTECTION BILLS: THE MEDICAL RESEARCH COUNCIL AND ANTI-VIVISECTIONIST PROTEST, 1911-1933 by E. M. TANSEY * The National Insurance Act of 1911 provided, by creating the Medical Research Committee, explicit government support for experimental, scientific medicine. This official gesture was made against a background of concern about some of the methods of scientific medicine, especially the use of living animals in medical research. Organized protests against animal experiments had gathered strength during the middle of the nineteenth century and resulted in the establishment of a Royal Commission to enquire into the practice of subjecting animals to experiments. The recommendations of that Commission led to the passing of the 1876 Cruelty to Animals Act, which governed all experiments calculated to give pain, and carried out on vertebrates. This paper will extend the examination of laboratory science and laboratory animals into a later period, the first decades of the twentieth century. It will focus on the use of one particular animal, the dog, in one specific laboratory, the National Institute for Medical Research (NIMR) in London, and will examine three related themes: the use and justification of the dog in experimental laboratory research into canine distemper at the Institute from its establishment in 1913 until the mid-1930s; this will be set against the protests of anti-vivisectionist groups and their use of the dog as a motif of animal suffering; and the moves by both opponents and proponents of animal experimentation to promote their views and to influence public opinion and members of the legislature.
    [Show full text]
  • Author Index
    Author Index Page numbers in italics refer to bibliography Aarsen,P.N. 501,506 Adkinson, N. F., J r., see Schellen­ Ali,S.y', Lack,C.H. 301,307 Aas,K.A., Gardner,F.H. 415 berg,R.R. 347,372 Alkjaersig, N., Fletcher,A. P., Abdullahi, M .l, see Whittle, Adler,R.D., see Grant,R. 630, Sherry,S.l. 449,450 H.C. 244,265 652 Allen, D. l, see Reimers, H .1. Abe,K., Watanabe,N., Kuma­ Adler,W.H., see Smith,R.T. 141,200 gai,N., Mouri,T., Seki,T., 322,330,341 Allen,F.H., Jr. 429, 450 Yoshinaga, K. 499, 506 Adolfs, M.J. P., see Bonta, I.L. Allen,F.H., lr., see Fu,S.M. Abell, C. W., Monahan,T.M. 554,562 428,454 306,307 Anggilrd,E. 409,410,415 Allen,J.C., Apicella, M.A. 257, Abercrombie, M. 114,129,206, Anggilrd, E., Larsson, c., 258,260 208,227 Samuelsson, B. 406, 408, 415 Allen,J.C., see Apicella,M.A Abercrombie, M., Ambrose, E. l Anggilrd, E., Samuelsson, B. 258,260 114,129 384,406,408,409,410,415 Allen,L.V. 622,649 Abercrombie, M., Heaysman, Anggilrd,E., see Nakano,1. AlIfrey,V.G., see Pogo,B.G.T. J.E.M. 114,129 412,419 323,340 Abercrombie, M., Heaysman, Agin,P.P., see Phillips,D.R. Alling,D.W., see Frank,M.M. J.E.M., Karthauser,H.M. 152,200 453 Allison,A.C. 98, 99, 212, 227, 114,129 Agudelo, C .A, see Schumacher, 276, 277, 288, 303, 304, 307, Ablondi,F.B., Hagen,J.J., H.R.
    [Show full text]
  • Receptive Substances'': John Newport Langley (1852±1925) And
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Medical History, 2004, 48: 153±174 ``Receptive Substances'': John Newport Langley $1852±1925) and his Path to a Receptor Theory of Drug Action ANDREAS-HOLGER MAEHLE* Introduction The concept of specific receptors that bind drugs or transmitter substances onto the cell, thereby either initiating biological effects or inhibiting cellular functions, is today a corner- stone of pharmacological research and pharmaceutical development. Yet, while the basic ideas of this concept were first explicitly formulated in 1905 by the Cambridge physiologist John Newport Langley $1852±1925), drug receptors remained hypothetical entities at least until the end of the 1960s. Without doubt, the development of receptor-subtype specific pharmaceuticalsÐespecially the beta-adrenergic receptor antagonist propranolol $intro- duced in 1965)Ðpromoted the acceptance of the receptor concept in pharmacology. It was only in the 1970s, however, that receptors began to be isolated as specific proteins of the cell membrane and that their composition and conformation began to be explored. During the last twenty years the modern techniques of molecular biology have helped to determine the genetic basis of receptor proteins, to identify their amino acid sequences, and to further elucidate their remarkable structural diversity as well as their similarities and evolutionary relationships. Numerous receptor types and subtypes have since been characterized.1 Unsurprisingly therefore, the origins of the receptor theory have attracted the interest of historians of medicine and science. In particular, John Parascandola has traced the beginnings of the receptor idea in the work of Paul Ehrlich $1854±1915) and J N Langley.2 More recently, the roots of the receptor concept in Ehrlich's immunological research, i.e.
    [Show full text]
  • History of Endocrinology
    EDITORIAL DOI: http://doi.org/10.4038/sjdem.v6i1.7295 HISTORY OF ENDOCRINOLOGY Siyambalapitiya S1 1 Diabetes and Endocrine unit, North Colombo Teaching Hospital, Ragama. Clinical endocrinology is a branch of Medicine that deals by himself. Later, the demonstration of blood glucose with the endocrine glands, the secreted hormones and lowering property of pancreatic dog extract by Von their metabolic effects. Hormones act on almost every Mering and Menkoski led to the discovery of insulin organ and cell type in the body and there are disorders during the early part of 20th century. However, the first that are entirely or largely related abnormalities of described hormone (1902) was a result of efforts by Sir hormone production. Type I diabetes and William Bayliss (1860-1924) and Ernest Starling (1866- hypothyroidism are such examples that entirely related 1927). In response to the delivery of acidic chyme from to abnormalities of hormones. However, there are so the stomach to the intestine, endocrine cells of the many other disorders such as osteoporosis and infertility, duodenum release secretin (an internal secretion) into the which are related to hormone dysfunction. bloodstream, which is responsible for the stimulation of exocrine pancreas to secrete bicarbonate to neutralize acid coming from the stomach. Secretin was the first History of endocrinology and study of hormone hormone to be identified and many more were found function dates back to 400 BC when Hippocrates and later. Although we have a substantial knowledge Galen introduced the concept of Humoral Hypothesis regarding these molecules, a lot of research is being where they describe as the four humors (body fluids) carried out to understand more about these substances.
    [Show full text]
  • Five ENDOCRINOLOGY
    Five ENDOCRINOLOGY 101 The doctor who sits at the bedside of a rat Asks real questions, as befits The place, like where did that potassium go, not what Do you think of Willie Mays or the weather? So rat and doctor may converse together. Josephine Miles “The Doctor Who Sits at the Bedside of a Rat” Since the Enlightenment, however, wonder has become a disreputable passion in workaday science, redolent of the popular, the amateurish, and the childish. Scientists now reserve expressions of wonder for their personal memoirs, not their professional publications. Katharine Park and Lorraine Daston Wonders and the Order of Nature Before going on to describe my research and academic career, I wanted to provide the reader with a short “course” in endocrinology, which I still, after all these years, think is wonderful. Let’s face it—the public, the media, and I love hormones. They do such wonderful things. For example, the sex hormones are responsible at puberty for turning on bodily sexual phenotype. A new born baby not secreting thyro- id hormone from its own thyroid will never show normal brain differentiation because crucial connections between neurons in the brain require the presence of this hormone to be completed. The mother’s thyroid hormones take care of the baby’s brain growth while the baby is still in the uterus, but after birth, the baby’s thyroid must secrete its own hormones. Unless treated before six months of age with thyroid hormone, this child will grow up severely dam- aged, what one used to call a “cretin,” with irreversible low intelligence and severe skeletal and muscular growth impairment.
    [Show full text]
  • Early Developments 19 1 1- 1944
    Chapter 2 The Founding of the Society: Early Developments 19 1 1- 1944 2.1 Formation of the Biochemical Club 2.2 Acquisition of the Biochemical Journal 2.3 Emergence of the Biochemical Society 2.4 Financial Position of the Society 2.5 General Developments 2.6 Honorary Members 2.7 Discussion Meetings 2.8 Proceedings 2.1 Formation of the Biochemical Club The events outlined in Chapter 1 which occurred in the first decade of this century made it clear that British biochemists needed a separate forum where they could develop their subject on a national level. The general criteria necessary for establishing a new discipline, summarized at the beginning of Chapter 1, were clearly already achieved. The time was thus ripe for the formation of a Society devoted to the furtherance of Biochemistry and, on 16 January 1911, J. A. Gardner (Fig. 2.1) and R. H. A. Plimmer (Fig. 1.2), after preliminary discussions with close colleagues, sent out invitations to fifty persons likely to attend a meeting to be held at the Institute of Physiology, UCL at 2.30 p.m. on Saturday, 2 1 January 191 1, to consider the formation of a Biochemical Society. Plimmer was evidently stung into action by an article in the press describing a new science, Biochemistry, which was making rapid progress on the Continent but was apparently unknown in Britain. The invitation, written on a postcard, read “Numerous suggestions having been made that a Biochemical Society should be formed in the Country, we shall be glad if you could make it convenient to attend a meeting at the Institute of Physiology, University College London, on Saturday 2 1 st January at 2.30 p.m.
    [Show full text]