Quantification and the Quest for Medical Certainty Quantification and the Quest for Medical Certainty J. Rosser Matthews princeton university press princeton, new jersey Copyright 1995 by Princeton University Press Published by Princeton University Press, 41 William Street, Princeton, New Jersey 08540 In the United Kingdom: Princeton University Press, Chichester, West Sussex All Rights Reserved Library of Congress Cataloging-in-Publication Data Matthews, J. Rosser, 1964– Quantification and the quest for medical certainty / J. Rosser Matthews. p. cm. Includes bibliographical references and index. ISBN 0-691-03794-9 1. Clinical trials—History. 2. Medicine—Research—Statistical methods—History. I. Title [DNLM: 1. History of Medicine, Modern. 2. Clinical trials— history. 3. Probability. WZ 55 M439g 1995] R853.C55M38 1995 619′.09—dc20 DNLM/DLC for Library of Congress 94-24091 This book has been composed in Utopia Princeton University Press books are printed on acid-free paper and meet the guidelines for permanence and durability of the Committee of Production Guidelines for Book Longevity of the Council on Library Resources Printed in the United States of America 13579108642 This book is dedicated to my mother and to the memory of my father CONTENTS Acknowledgments ix Introduction 3 Chapter One Probable Knowledge in the Parisian Scientific and Medical Communities during the French Revolution 8 Chapter Two Louis’s “Numerical Method” in Early-Nineteenth-Century Parisian Medicine: The Rhetoric of Quantification 14 Chapter Three Nineteenth-Century Critics of Gavarret’s Probabilistic Approach 39 Chapter Four The Legacy of Louis and the Rise of Physiology: Contrasting Visions of Medical “Objectivity” 62 Chapter Five The British Biometrical School and Bacteriology: The Creation of Major Greenwood as a Medical Statistician 86 Chapter Six The Birth of the Modern Clinical Trial: The Central Role of the Medical Research Council 115 Chapter Seven A. Bradford Hill and the Rise of the Clinical Trial 131 Conclusion 141 Notes 151 Bibliography 177 Index 191 ACKNOWLEDGMENTS As is often the case with one’s first academic book, this manu- script had its origin as a doctoral dissertation which, in this case, was completed at Duke University and awarded through the history department. As such, my most immediate scholarly and intellectual debts are to members of my doctoral committee for training me. For his knowledge of the history of science as well as for his critical and editorial comments on innumerable drafts (both as a disserta- tion and in the subsequent revision to a book), I acknowledge my doctoral supervisor Seymour H. Mauskopf. In addition, I would like to express my appreciation to the historians of medicine Michael R. McVaugh and Peter C. English for their comments on this study at various points in its evolution. I would also like to thank Allan M. Brandt for agreeing to be on my final doctoral defense committee and raising important issues that I hope I have been able to incorpo- rate in this revised manuscript. Various other teachers over the years have provided intellectual stimulation that, no doubt, had an impact on the views I express in this book. Among those I would like to single out specifically in this regard are Lloyd S. Kramer and Orest Pelech for their courses in graduate school which introduced me to some of the broader issues involved in attempting to understand (and write about) the history of “modern thought.” The intellectual inspiration for this study derives from the books, articles, and dissertations that have appeared in recent years on the history of probability and statistics by such contributors as Ian Hacking, Lorraine J. Daston, Stephen Stigler, Donald MacKenzie, Andrea A. Rusnock, Ulrich Tröhler, Harry M. Marks, the contribu- tors to the two-volume work The Probabilistic Revolution, and Theo- dore M. Porter. I would like to thank Theodore M. Porter specifi- cally for his comments, which helped transform this manuscript into a book. Several libraries and archives have provided indispensable help in my research on this book. Among the library staffs that have been the most helpful are the interlibrary loan office of Perkins Li- brary at Duke; Barbara Busse and Gayle M. Elmore of the Trent Col- lection in the history of medicine in the Duke University Medical Center Library; the National Library of Medicine, Bethesda, Mary- land; and the Library of the College of Physicians, Philadelphia, x ACKNOWLEDGMENTS Pennsylvania. I would like to acknowledge the following archives for permission to quote from papers housed in their collections: the American Philosophical Society—Raymond Pearl papers; the library of the London School of Hygiene and Tropical Medicine—Ronald Ross papers; and the Library, University College London—Francis Galton and Karl Pearson papers. In addition, I would like to ac- knowledge Major Greenwood’s grandsons Roger M. Greenwood and John M. Greenwood for their permission to quote from their grandfather’s correspondence in these various archives. I have made a “good faith” effort to locate the literary heirs of the other in- dividuals whom I cite; however, so far I have been unable to locate any of them. Several of my friends from graduate school have provided the in- tellectual, social, and emotional support that is indispensable in the production of scholarly research. Among the individuals who must be singled out are George Ehrhardt, Nancy Zingrone, and Carlos Alvarado. Finally, I dedicate this book to my mother, Barbara M. Matthews, and to the memory of my father, John R. Matthews, Jr. (1920–1992). It is hard to express my degree of appreciation to them except to say that, if I have succeeded academically, the reason is that there were two people in the world who have always believed in me. Any errors that remain are, of course, my own fault. Quantification and the Quest for Medical Certainty INTRODUCTION One of the most obvious contemporary examples of the effects of statistically based science both on public and on private life is the clinical trial. Since World War II, the trial has evolved into a standard procedure in the introduction of new drugs in most of the major Western industrial democracies. Its features include the use of a so- called “control” group of patients that do not receive the experimen- tal treatment, the random allocation of patients to the experimental or control group, and the use of blind or masked assessment so that the researchers do not know which patients are in either group at the time the study is conducted. Enshrined in public policy since the 1970s,1 the clinical trial nicely illustrates the desire of modern demo- cratic society to justify its medical choices on the basis of the “objec- tivity” inherent in statistical and quantitative data.2 Even though the clinical trial has moved to the forefront of medical research only within the past generation, the use of comparative sta- tistics in a therapeutic context has a much longer history, which this book will illuminate. My primary focus is three debates over the use of comparative statistics in a medical context, namely the dispute between the clinicians Risueño d’Amador and P.-C.-A. Louis before the Paris Academy of Medicine in 1837, the dispute between the mathematician Gustav Radicke and research physiologists con- ducted in the pages of the Archiv für physiologische Heilkunde during the 1850s, and finally the early-twentieth-century dispute between the British biometrician Major Greenwood and the bacteriologist Almroth Wright over the latter’s technique for diagnosing disease by measuring the opsonic index. My reasons for organizing this study around these three debates are multifaceted. One obvious benefit of comparing debates that were carried on in different countries and in different time periods is the opportunity for both cross-national and cross-temporal comparison.3 Further- more, the center of gravity of this study shifts to each country (France, Germany, Great Britain) at precisely the moment in time when that country was in a period of medical and/or scientific ascen- dancy. I focus on debates among early-nineteenth-century Parisian clinicians as they were attempting to forge (in Michel Foucault’s words) the “birth of the clinic.”4 In like manner, I focus on debates among German physiological researchers when they were attempt- 4 INTRODUCTION ing to create the modern physiological research institute. Finally, I focus on a British context wherein Karl Pearson and his associates at University College London gave birth to what became, in effect, the first modern department of mathematical statistics. This study thus not only illuminates important debates over the use of a statistical methodology within a medical context; it also uses these debates to cast certain epochal transformations within the history of Western science and medicine into especially bold relief. By analyzing how pioneering clinicians, physiologists, and bacteri- ologists viewed the “novel” method of statistical comparison, this study sheds new light on medical research and practice as a social and cultural activity5 and demonstrates that, despite the very real dif- ferences in outlook between the medical practitioner and the medi- cal researcher, both share an antipathy toward methods of quantita- tive or statistical inference. For both the medical practitioner and the medical researcher, the amorphous concept of “medical judgment” (whether that judgment is executed at the bedside or the laboratory bench) cannot be reduced to a set of