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Experimental Pharmacology and Therapeutic Innovation in the Eighteenth Century

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Experimental Pharmacology and Therapeutic Innovation in the Eighteenth Century -e: EXPERIMENTAL PHARMACOLOGY AND THERAPEUTIC INNOVATION IN THE EIGHTEENTH CENTURY by ANDREAS-HOLGER MAEHLE A thesis submitted for the degree of Doctor of Philosophy of the University of London University College London 1996 ProQuest Number: 10017185 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10017185 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT In the historiography of pharmacology and therapeutics, the 18th century is regarded as a period of transition from traditional, Galenistic materia medica to the beginnings of modern, experimental drug research. Ackerknecht (1973) characterized the pharmacotherapy of this period as a "chaotic mixture of chemiatric and Galenistic practices", yet acknowledged an "increasing tendency toward empiricism, partly even true experimentalism". This thesis explores this transitional phase for the first time in depth, examining the relations between pharmacological experimentation, theory-building, and therapeutic practice. Furthermore, ethical aspects are highlighted. The general introduction discusses the secondary literature and presents the results of a systematic study of pharmacological articles in relevant 18th-century periodicals. The identified main areas of contemporary interest, the spectrum of methods applied, and the composition of the authorship are described and interpreted. It is shown that lithontriptics ("dissolvents" for urinary stones), opium, and Peruvian bark were of major concern to 18th-century pharmacology. These substances are the subjects of three "case studies", which form the body of the thesis. Issues discussed here include, in lithontriptics, the role of proprietary remedies and links with analytical chemistry; in opium, the different interpretations of its mode of action, toxicity, and addictive properties; and in Peruvian bark, the widening of its therapeutic indications, changes in its pharmacological understanding, and problems of its quality assessment. The thesis provides evidence of a previously unknown wealth of 18th-century pharmacological works, which were characterized by an increasingly sophisticated methodology and critical discussions of their consequences for the theory and therapeutic uses of drugs. It argues in conclusion for a positive revision of current historical judgements about 18th-century pharmacology and therapeutics. ACKNOWLEDGEMENTS Research for the present study reaches back to 1990. I started it during my lectureship at the University of Gottingen, the main work was done at the Wellcome Institute for the History of Medicine in London, where I held a Wellcome Research Fellowship from 1991 to 1994, and it was completed in the beginning of my Wellcome University Award at the University of Durham. My foremost thanks go to Professor William F. Bynum at the Wellcome Institute, who has kindly and efficiently supervised my work throughout the years. I have greatly benefited from our "pharmacology discussions". I further gratefully acknowledge the generous and continuous support of the Wellome Trust. At Gottingen, Professor Ulrich Trohler gave advice on the original project outline. Dr Karl-Heinz Stubenrauch scrutinized with me seventeenth-century works on the viper, Marlies Glase and the late Dr Frank Dougherty lent their expertise in examining some eighteenth-century documents in the University Archive, and Axel Wolf kindly provided bibliographical assistance. In London, I also benefited from discussions with Professor Roy Porter and a group of young scholars then working simultaneously on other aspects of eighteenth- century medicine, especially Dr Philip Wilson, Dr Andrea Rusnock, Dr Javier Moscoso, and Dr Akihito Suzuki. Sally Bragg was always ready to help in practical matters. At Durham, Professor David Knight kindly read, and commented on, large parts of an earlier draft. Dr John Forrester was a perfect host and guide to the sources during a brief research trip to Edinburgh. My work with the sources was carried out in the Wellcome Institute Library, the British Library, and the university libraries of Gottingen, Newcastle, Durham, Edinburgh, Glasgow, and Freiburg. Thanks to the librarians of all these institutions for their friendly assistance. Preliminary findings have been presented in research seminars at the universities of Gottingen and Durham, in lectures at the University of Kiel and the Medical Academy of Magdeburg, at the Wellcome Symposium on the History of Medicine 'Narcotics, Drugs and Medicine* 1991 in London, and at the 1994 annual meetings of the Deutsche Gesellschaft fur Geschichte der Medizin, Naturwissenschaft und Technik in Halle and of the Pybus Society for the History and Bibliography of Medicine in Newcastle. Questions and comments at these occasions have contributed to my research. Kathleen Nattrass, Durham, and Dr Judith Schuler, Wasserburg, helped and advised in getting the word-processed text into its final shape. Last but not least thanks to Jillian for her understanding, when demands on my time became heavy in the final stages of this work. Andreas-Holger Maehle, Dr. med. habil. Durham, September 1996 CONTENTS Abstract 2 Acknowledgements 3 General Introduction 7 Tables 1-5 44 A. The Search for Lithontriptics 49 1. Introduction 49 2. Traditions 52 3. Early trials in vitro, animal experiments, and case histories 60 4. Mrs Stephens's remedies; evidence and evaluation 66 5. Reactions to Stephens's lithontriptic: criticism, more research, and a new theory 71 6. A "new" London and an Edinburgh lithontriptic: Jurin's soap-lye remedy and Whytt's lime-water 84 7. Continental ways: Carlsbad waters and the bearberry plant 99 8. Fixed air, mineral waters, and calculi: the impact of chemistry 108 9. Chemical analysis of calculi and the differentiation of lithontriptic therapy 119 10. Conclusions 132 B. Opium: Studies into an Ambiguous Drug 137 1. Introduction 137 2. The medical importance of opium 142 3. Seventeenth-century views on the pharmacology of opium and their basis 147 4. latromechanical interpretations around 1700 155 5. Some early therapeutic conclusions 165 6. Opium and the nervous system around 1750 176 7. Effects on the heart and irritability 194 8. Stimulant or sedative? 205 9. Pharmacology and therapeutics 215 10. Opium as a habit-forming drug 229 11. The identification of morphine 247 12. Ethical aspects 254 13. Conclusions 258 C. Peruvian Bark: from Specific Febrifuge to Universal Remedy 2 63 1. Introduction 263 2. Early controversy on the new febrifuge 267 3. Experiment and speculation: efforts to explain the bark's action around 1700 280 4. The Stahlian critique of cinchona treatment 301 5. A surgeons' matter: the bark in "gangrene" 305 6. New pharmacological experiments: the bark as astringent and antiseptic 323 7. Clinical inferences: the bark as a tonic 333 8. Early "clinical trials" 340 9. Which bark is best? 353 10. The isolation of quinine 366 11. Conclusions 370 General Conclusions 379 Bibliography 386 I. Primary Sources 386 II. Secondary Literature 433 GENERAL INTRODUCTION The origins of modern pharmacology and scientifically founded therapeutics are generally thought to lie in the first half of the nineteenth century. Often-cited landmarks are Friedrich Wilhelm Sertiirner's isolation of morphine from opium, i.e. the discovery of the first plant alkaloid, published in 1805; François Magendie's Formulaire pour la préparation et 1*emploi de plusieurs nouveaux médicamens (1821) as the first textbook on chemically pure drugs; and Rudolf Buchheim's creation of the first laboratory for experimental pharmacology at the University of Dorpat, where he had become professor of materia medica in 1847.’ The role of analytical chemistry and experimental physiology in the emergence of the science of pharmacology is usually - and rightly - emphasized. However, this focus on the nineteenth century has sometimes resulted in a lack of attention to developments in the older materia medica during the previous two centuries.2 From time to time historians of medicine and pharmacy have tried to remedy this. Studies into the beginnings of experimental pharmacology, which gave full attention to the eighteenth century, were carried out around 1960 by Melvin P. Earles. He traced the gradual recognition of ’ See for example Bo Holmstedt and Goran Liljestrand (eds), Readings in pharmacoloav. New York, Raven Press, 1981; John E. Lesch, Science and medicine in France; the emergence of experimental phvsiologv. 1790-1855, Cambridge, Mass. and London, 1984; Giinter Stille, Der Weg der Arznei von der Materia medica zur Pharmakologie, with contributions by M. H. Bickel and H. Going, Karlsruhe, G. Braun Fachverlage, 1994. ^ E.g. Gernot Rath, 'Zeiteinflüsse in der Pharmakologie des 16. bis 19. Jahrhunderts ' , Sudhoffs Archiv, 1963, 47.: 1-18, who argued that the transformation of pharmacology from a part of therapeutics to an experimental science did not originate from materia medica itself, but was induced by the development of pathology and physiology. pharmacological
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