The Discovery of Insulin

by Michael Bliss

  THE

  DISCOVERY

  OF INSULIN

  Michael Bliss

  THE

  DISCOVERY

  OF INSULIN

  25TH ANNIVERSARY EDITION

  with a new Preface

  UNIVERSITY OF TORONTO PRESS

  Toronto London

  Copyright © 1982 by Michael Bliss.

  Published by arrangement with McClelland & Stewart Inc., Toronto, Canada. First published in 1982 by McClelland & Stewart Inc.; first paperback edition, 1984, and second paperback edition, 1996, published by McClelland & Stewart.

  Twenty-fifth anniversary edition 2007

  University of Toronto Press

  Toronto London

  Printed in the U.S.A.

  Reprinted 2011, 2012

  ISBN: 0-8020-8344-7

  Printed on acid-free paper

  Canadian Cataloguing in Publication Data

  Bliss, Michael, 1941-

  The discovery of insulin

  ISBN 0-8020-8344-7

  1. Banting, F.G. (Frederick Grant), Sir, 1891-1941. 2. Best, Charles Herbert,

  1899–1978. 3. Macleod, J.J.R. (John James Rickard), 1876–1935.

  4. Collip, J.B. (James Bertram), 1892- 1965. 5. Insulin – History.

  6. Pancreas – Secretions – Experiments – History. I. Title.

  QP572.I5B55 2000 616.462027 C99-932729-1

  University of Toronto Press acknowledges the financial assistance to its publishing program of the Canada Council for the Arts and the Ontario Arts Council.

  University of Toronto Press acknowledges the financial support of the Government of Canada for its book publishing activities through the Book Publishing Industry Development Program (BPIDP).

  Contents

  Preface, 2007/7

  Introduction: What Happened at Toronto?

  CHAPTER ONE A Long Prelude

  CHAPTER TWO Banting’s Idea

  CHAPTER THREE The Summer of 1921

  CHAPTER FOUR “A Mysterious Something”

  CHAPTER FIVE Triumph

  CHAPTER SIX “Unspeakably Wonderful”

  CHAPTER SEVEN Resurrection

  CHAPTER EIGHT Who Discovered Insulin?

  CHAPTER NINE Honouring the Prophets

  CHAPTER TEN A Continuing Epilogue

  Notes

  Sources

  Index

  For my father, Jim, Mona,

  Liz, Jamie, Laura, and Sally

  PREFACE

  The Discovery of Insulin was researched and written during a unique window of opportunity. The 1978 death of Charles Best, the last surviving member of the discovery team, happened to coincide with the release of the papers of Sir Frederick Banting. Suddenly it was possible to obtain access to complete documentation of the highly controversial events at the University of Toronto in 1921–23 that led to the isolation and emergence of insulin. At the same time, many individuals who had been witnesses to or participants in the discovery, and who were approaching the end of their lives, now felt free to speak frankly for the historical record. Working on this book, I not only uncovered many new collections of documents, but also found alive two of the original patients who had been treated with insulin in Toronto in 1922. Since publication, no significant new collections of documents have surfaced, but 66 of the 68 individuals I interviewed have died. No one can talk to them now, except through the notes of my interviews, which themselves are now part of the archival record.

  My family has been untouched by diabetes, but deeply involved in medicine. As a professional historian I first became interested in the insulin story at the suggestion of a brother who had been exposed by one of J.B. Collip’s colleagues to verbal accounts of the more dramatic incidents in the discovery saga. In 1978, fresh from publishing a biography of a major Canadian philanthropist/entrepreneur (Sir Joseph Flavelle), (and having been promoted to full professor at the University of Toronto, I decided that it should finally be possible to write the full story of the discovery of insulin.

  There were serious obstacles, including much skepticism about a mere historian’s qualification to write about advanced medical discoveries. Fully sharing that concern, I made a point of getting expert advice at every stage of the work, immersed myself in the history of endocrinology and diabetes, and worked and reworked my manuscript with more care and craft than I had ever applied to a project. The many people who helped me with the book have been thanked in earlier editions. Among those few who are still living, I feel particularly indebted to Richard Landon, who as head of the Thomas Fisher Rare Books Library at the University of Toronto, gave me crucial encouragement when it was most needed, and Dr. Anna Sirek, who, with her late husband Otto, gave me vital technical advice.

  The archival and personal adventures generated by this project were remarkable, exciting, and life changing. They culminated in several of the most exhausting and rewarding days of my life in Cambridge, England, with the late Sir Frank Young, a grand old man of diabetes research and British science generally, as he challenged not only my conclusions, but my spelling and commas, insisting that a book that would be read around the world and for many years be as perfectly argued and polished as possible. “Bliss,” he would say, “this book will be read by Fiji Islanders and Nobel laureates. You have to get it right.”

  The Discovery of Insulin received gratifyingly favourable reviews upon publication in 1982 and has remained in print since then and without need for significant revision or alteration. For this edition it has not been necessary to make any changes to the detailed narrative of the events of 1920–23. In addition to this new preface, it was, however, necessary to rewrite the final chapter, “A Continuing Epilogue,” because so much has happened in the world of diabetes in our time.

  Although I moved on to other work in the history of medicine and Canadian topics, I made a point of staying in touch with this subject, and expanded upon The Discovery of Insulin with a number of publications. The most important are Banting: A Biography (Toronto, 1984; 2nd ed., University of Toronto Press, 1992), and a scholarly article, “Rewriting Medical History: Charles Best and the Banting and Best Myth,” Journal of the History of Medicine and Allied Sciences, 48 (July 1993): 253–74. Read singularly or together, these publications underline the foolishness of believing that insulin was discovered by Banting and Best. As I believe I make clear in The Discovery of Insulin, it was a collaborative process, drawing on the talents of at least four people as well as the comparatively great research capacity of the University of Toronto, where for many reasons a field of medical dreams had been built. I should have been more explicit in suggesting that J.B. Collip ought to have shared the Nobel Prize for insulin with Banting and Macleod, and in criticizing the sad attempts at historical falsification engineered by Charles Best, a troubled soul.

  I also have published “Banting’s, Best’s, and Collip’s Accounts of the Discovery of Insulin,” Bulletin of the History of Medicine, 56 (Winter 1982–83): 554–68; and “J.J.R. Macleod and the Discovery of Insulin”, Quarterly Journal of Experimental Physiology, 74 (1989): 87–96, along with several condensed summaries of this book. In “Growth, Progress, and the Quest for Salvation: Confessions of a Medical Historian,” Ars Medica, I, 1 (2004): 4–14, I explain how The Discovery of Insulin relates to my 1991 study of smallpox, Plague, and to my 1999 biography, William Osier: A Life in Medicine. With the 2005 publication of Harvey Cushing: A Life in Surgery, I squared the circle, as it were, by writing about a surgeon who was both a true medical miracle worker and a great endocrinologist.

  A substantial article literature, locatable through standard search engines, has developed since 1982 about the early development of insulin. Robert Tattersall’s work on insulin i
n the United Kingdom is particularly noteworthy, as is the writing of Chris Feudtner in the United States, especially his book Bittersweet: Diabetes, Insulin, and the Transformation of Illness (2003). There now also exist biographies of the other members of the insulin team: J. B. Collip and the Development of Medical Research in Canada, by Alison Li (2003); J.J.R. Macleod: The Co-discoverer of Insulin, by Michael J. Williams (Royal College of Physicians of Edinburgh, Supplement to Proceedings, 1993); Margaret and Charley: The Personal Story of Dr. Charles Best, by Henry Best (2003). E.C. Noble, who lost the famous coin toss to Charles Best, finally receives attention in M. Jurdjevic and C. Tillman, “E.C. Noble in June 1921, and his account of the discovery of insulin,” Bulletin of the History of Medicine, 78, 4 (2004): 864–875. With the development of the Internet the University of Toronto has been able to make more than 7,000 pages of the original documents available on its “Discovery and Early Development of Insulin” website, http://digital.library.utoronto.ca/insulin. An Oxford-based British team has done marvelous work creating an oral history of patients’ experiences with diabetes, which may be accessed at www.diabetes-stories.com.

  Publication of The Discovery of Insulin dismayed and offended some of Fred Banting’s and Charles Best’s less critical admirers. Getting this history right has practical importance in Canada, for ceremonies and plaques, and in steering historical preservation priorities. Gradually, sometimes grudgingly, most devotees of Banting’s or Best’s legacies have come to accept most of my conclusions. Not so the scientific chauvinists in Romania, who have continued their noisy advocacy of Nicolas Paulesco, a campaign that substitutes repetition and agitation for scholarship. To dispute my findings without addressing them, one basic trick is to cite authorities who pronounced on credit before the evidence cited in The Discovery of Insulin became available.

  The central argument of this book has now been generally accepted. In several adaptations, the story told here has educated and, to my surprise and delight, inspired people whose lives have been touched by diabetes. The Discovery of Insulin has been read by diabetic teenagers, by their parents, by insulin sales representatives, by medical students, by research scientists, by historians of science, by Nobel laureates, and possibly by Fiji Islanders. It has inspired students to go into diabetes research and at least one researcher to revisit the potential of fish islet cells. In 1988 the story was made available to tens of millions of people around the world through Gordon Hinch/Gemstone Productions’ beautifully done 1988 television adaptation, “Glory Enough for All.”

  Of the books I have written, The Discovery of Insulin is my favourite. I hope it will still be read long after a cure for diabetes been found and no one needs to take insulin. I look forward to rewriting this preface on the centennial of insulin’s discovery in 2021–22, and to celebrating the occasion, once again, with my dear wife Elizabeth and our children and grandchildren.

  Toronto, October 31, 2006

  Michael Bliss

  INTRODUCTION

  What Happened at Toronto?

  The discovery of insulin at the University of Toronto in 1921–22 was one of the most dramatic events in the history of the treatment of disease. Insulin’s impact was so sensational because of the incredible effect it had on diabetic patients. Those who watched the first starved, sometimes comatose, diabetics receive insulin and return to life saw one of the genuine miracles of modern medicine. They were present at the closest approach to the resurrection of the body that our secular society can achieve, and at the discovery of what has become the elixir of life for millions of human beings around the world.

  This book is an attempt to re-create the discovery of insulin as accurately and fully as can be done in a single volume. It draws on a vast body of primary source material never before available to researchers. It reflects no point of view other than a professional historian’s obligation to be as objective and fair as possible. It is written to be read by anyone from a scientist to a high school student, and especially by those in between.

  Many readers will begin this book believing they have a reasonably clear understanding of the discovery of insulin. It is a story told in several books, in textbook accounts, in films, tapes and television programs. In broad outline, the conventional history is something like this:

  By the early years of the twentieth century it was understood that the disease named diabetes mellitus involves the body’s inability to metabolize or utilize its food, especially carbohydrates. It was also understood that the pancreas holds the key to carbohydrate metabolism. When experimental animals had their pancreases removed, they immediately lost the ability to utilize carbohydrates, the amount of sugar in their blood and urine rose sharply, and they soon died from severe diabetes. Various researchers speculated that the pancreas, which secretes digestive enzymes into the gut (its external secretion), must also produce another kind of secretion, one enabling the body to utilize its fuel. The search for the internal secretion of the pancreas had occupied a number of physiologists throughout the world, but by 1920 it had not produced any practical results.

  In the autumn of 1920 Frederick Banting, a young surgeon in London, Ontario, happened to be reading an article about the pancreas. Banting began thinking about the problem of the internal secretion, and late that night jotted down an idea for an experimental procedure – ligating the pancreatic ducts – that might be a way of isolating an internal secretion. He took his idea to his alma mater, the University of Toronto, where the Professor of Physiology, J.J.R. Macleod, was an internationally known expert in carbohydrate metabolism. Macleod was at first skeptical of Banting’s suggestion, but reluctantly agreed to give him a lab and some dogs for a few weeks during the coming summer. He assigned him a young science student, Charles Best, to do the chemical tests necessary for the work, and then went off to Scotland for his summer holidays.

  Banting and Best experienced a number of problems with their work in that summer of 1921, the story goes, but soon found that their approach was yielding remarkable results. With the extract of pancreas they had made from duct-ligated dogs they were able time after time to lower the blood sugar and remove other symptoms from diabetic dogs. Prof Macleod came home to a pair of excited researchers who, by the autumn of 1921, were keeping a severely diabetic dog, Marjorie, alive with their extracts. Marjorie eventually lived for seventy days before being sacrificed; until then diabetic dogs had died within a week or two of their pancreas being removed.

  By the winter of 1921–22 Banting and Best were giving their first papers on the internal secretion of the pancreas. They were also ready to test their extract on humans. In Toronto General Hospital a young boy, Leonard Thompson, became the first diabetic to receive insulin. His life was miraculously saved.

  Professor Macleod put his whole laboratory to work on insulin. An American drug firm, Eli Lilly and Company, was brought in to help prepare it in commercial quantities. At the same time, however, the University of Toronto patented the process in order to control the quality of insulin sold to diabetics. By 1923 insulin was being produced in virtually unlimited quantities, and was the stuff of life itself for thousands of diabetics.

  Late in 1923 the Nobel Prize was awarded for the discovery of insulin. It was awarded to Banting and J.J.R. Macleod. This raises what seems to be the single really controversial point about the discovery: why should Macleod have shared a Nobel Prize for work done in his lab while he was on holiday? It is fairly well known that Banting was dissatisfied with the Nobel Committee’s decision. He immediately announced that he was sharing his half of the award with Best. Macleod announced that he would share his half with J.B. Collip, a biochemist who had joined the team late in 1921 and worked on the development of the extract.

  There are several commonly held views about this problem of credit. Perhaps the Nobel Committee just made a mistake, possibly because Macleod’s name was on some of the early publications. Perhaps Macleod, a German-trained professor, held Teutonic-type notions about the head of a lab
meriting credit for everything done in his fiefdom. Perhaps it was a case of human weakness – perhaps Macleod deliberately tried to steal credit from the inexperienced young men who had actually made the discovery. Whatever happened, the judgment of history, at least in North America, has been to remember Banting and Best as the discoverers of insulin. And, of course, it was a magnificent discovery, a medical fairy tale come true of the lone doctor and his partner overcoming all obstacles to realize an idea and save the lives of millions and millions of people. Surely this is truth stranger than fiction, or it is the truth that makes fiction plausible.

  Even at first glance, however, we are left with some curiosities. For completeness’ sake, it would be interesting to know exactly why Macleod got his half of the Nobel Prize. More curious, come to think of it, who was J.B. Collip? Why did he end up with the same share of the Nobel Prize money that Banting and Best each got? More generally, why was insulin discovered by two inexperienced researchers in a city and a country which had no particular stature in the world of medical research? Was existing research so poorly developed that a total outsider could confound all the experts with a brilliant, untried suggestion? Or was there somehow a large element of chance involved? Perhaps the Canadians were just lucky.

  A few readers will know that some articles have already been written on the points raised by these and similar questions. Even most experts, though, will be surprised to know how early the controversy about the discovery of insulin actually began. The first attempt at serious historical assessment of the Toronto work was made almost immediately. In December of 1922 a physiological researcher in Cambridge, England, Dr. Ffrangcon Roberts, wrote a long letter to the British Medical Journal reviewing Banting and Best’s first publications. It was a scathing critique of the Toronto investigation. “The production of insulin,” Roberts concluded, “originated in a wrongly conceived, wrongly conducted, and wrongly interpreted series of experiments.”1