Wellcome Witnesses to Twentieth Century Medicine PEPTIC ULCER: RISE AND FALL The transcript of a Witness Seminar held at the Wellcome Institute for the History of Medicine, London, on 12 May 2000 Volume 14 – November 2002 CONTENTS Introduction Sir Christopher Booth i Witness Seminars: Meetings and publications;Acknowledgements E M Tansey and D A Christie iii Transcript Edited by D A Christie and E M Tansey 1 Biographical notes 113 Glossary 123 Appendix A Surgical Procedures 127 Appendix B Chemical Structures 128 Index 133 List of plates Figure 1 Age-specific duodenal ulcer perforation rates in England and Wales. 13 Figure 2 Map of India showing areas of high duodenal ulcer prevalence. 24 Figure 3 The distribution of maximal gastric secretion in control and duodenal ulcer subjects. 28 Figure 4 The risk curve of duodenal ulcer in relation to maximal gastric secretion. 28 Figure 5a The Hermon Taylor gastroscope. 44 Figure 5b The Wolf–Schindler gastroscope. 44 Figure 6 A prescription written for a duodenal ulcer patient in 1912. 54 Figure 7 ‘Active’ medical treatments for peptic ulcer before 1976. 56 Figure 8 John Wyllie with engorged conjunctivae, following histamine infusion. 69 Figure 9 The first duodenal ulcer patients in the world to receive a dose of cimetidine in 1975. 72 Figure 10 Roy Pounder recording the results of the first 24-hour acidity study. 72 Figure 11 Jelly babies used in lectures around the world by Roy Pounder, to explain a mathematical model of ulcer relapse and healing. 74 Figure 12 The first advertisement for a histamine H2 receptor antagonist, in November 1976 (Smith Kline & French). 78 Figure 13 Some of the first duodenal ulcer patients in the world to receive doses of omeprazole at the Royal Free Hospital. 86 INTRODUCTION Peptic ulcer has unquestionably been a disease of the twentieth century. Rare before the end of the previous century, peptic ulcer became increasingly frequent, reaching a peak during the next 50 years and afflicting as many as 10 per cent of men. There were two types of peptic ulcer: gastric ulcer, which appeared to be due to damage to the lining of the stomach, and duodenal ulcer, which was associated with excessive acid secretion by the stomach. Such ulcers did not occur if there was atrophy of the gastric mucosa, when no acid is secreted by the stomach. The aetiology of peptic ulcer was fiercely debated. Not unnaturally, in those post-Freudian days, psychosomatic influences were for long thought to be the cause of peptic ulcer, stress being the major culprit. The complications of peptic ulcer were an important cause of death, severe haemorrhage being common and perforation, particularly of duodenal ulcers, being a frequent surgical emergency. Obstruction of the stomach by pyloric stenosis might also occur. The treatment of many cases of peptic ulcer was undertaken by the GP. Antacids were the mainstay but in more severe cases hospitalization and ‘medical’ treatment with a wide range of bland diets or with milk drips prevailed (see pages 10, 53, 55–56). There were always such patients languishing in bed in hospital wards throughout the country. When such measures failed, as frequently they did, the only recourse was surgery. For many years gastroenterostomy (for example, pages 18, 29, 58–59, 110–111) was considered to be the mainstay of surgical treatment, until it became apparent that the procedure was often followed by stomal ulceration. Partial gastrectomy then came to enjoy strong support, until the complications of dumping syndrome (see pages 59 and 60) and nutritional deficiency brought such procedures into disrepute. Vagotomy had been introduced as a means of reducing acid secretion but gastric stasis often resulted, encouraging surgeons to combine vagotomy with pyloroplasty or gastroenterostomy to facilitate gastric emptying. Vagotomy, however, was often followed by troublesome diarrhoea. As Dr John Ford1 has reminded me, for the GP there were often difficulties in persuading surgeons to operate even when those practitioners knew that there might be unpleasant after-effects. Patients were expected to ‘earn’ their operations, by enduring years of unsuccessful ‘medical’ treatment. There was also the problem that many surgeons lost interest in the patients who developed complications, leaving the GP to deal the situation as best he could. A totally new dimension to the treatment came with the introduction in the 1970s, by Sir James Black, of the H2 receptor antagonists. Ulcers would now heal without 1 Dr John Ford’s comments are written in a letter to Dr Daphne Christie, 8 June 2002, and will be deposited with the records of the meeting in Archives and Manuscripts, Wellcome Library, London. i recourse to surgery and remain healed if drug treatment was continued. These developments greatly reduced admissions to hospital as well as the workload of gastric surgeons. At the same time, enormous profits were earned by the pharmaceutical firms involved in H2 receptor antagonist manufacture. The aetiology of peptic ulcer, for so long a matter for whimsical speculation, was suddenly illuminated in the early 1980s through the discovery by Barry Marshall and his colleagues in Perth, Western Australia, that a microorganism adhering to the mucosa of the stomach and duodenum was of major importance. The organism, Helicobacter pylori, was cultured from biopsy specimens and, when introduced into his own stomach, Marshall produced extremely unpleasant dyspeptic symptoms, which were relieved by appropriate antibiotic treatment. Never in their wildest dreams would many gastroenterologists have imagined that peptic ulcer might be an infectious disease. There remains, however, an enigma. The prevalence of peptic ulcer has fallen during the later decades of the twentieth century, irrespective of the introduction of effective treatment. This apparently spontaneous fall remains to be explained. Nevertheless, the discovery that peptic ulcer may be an infectious disease raises the question, posed by James LeFanu,2 that there may be other diseases of unknown aetiology such as coronary arteriosclerosis and rheumatoid arthritis which may also have an infective origin. Sir Christopher Booth Wellcome Trust Centre for the History of Medicine at UCL 2 See LeFanu J. (1999) The Rise and Fall of Modern Medicine. London: Little, Brown and Company, 382–389. ii WITNESS SEMINARS: MEETINGS AND PUBLICATIONS1 In 1990 the Wellcome Trust created a History of Twentieth Century Medicine Group, as part of the Academic Unit of the Wellcome Institute for the History of Medicine, to bring together clinicians, scientists, historians and others interested in contemporary medical history. Among a number of other initiatives the format of Witness Seminars, used by the Institute of Contemporary British History to address issues of recent political history, was adopted, to promote interaction between these different groups, to emphasize the potential of working jointly, and to encourage the creation and deposit of archival sources for present and future use. In June 1999 the Governors of the Wellcome Trust decided that it would be appropriate for the Academic Unit to enjoy a more formal academic affiliation and turned the Unit into the Wellcome Trust Centre for the History of Medicine at University College London from 1 October 2000. The Wellcome Trust continues to fund the Witness Seminar programme via its support for the Centre. The Witness Seminar is a particularly specialized form of oral history where several people associated with a particular set of circumstances or events are invited to meet together to discuss, debate, and agree or disagree about their memories. To date, the History of Twentieth Century Medicine Group has held over 30 such meetings, most of which have been published, as listed in the table on pages v–vii. Subjects for such meetings are usually proposed by, or through, members of the Programme Committee of the Group, and once an appropriate topic has been agreed, suitable participants are identified and invited. These inevitably lead to further contacts, and more suggestions of people to invite. As the organization of the meeting progresses, a flexible outline plan for the meeting is devised, usually with assistance from the meeting’s chairman, and some participants are invited to ‘set the ball rolling’ on particular themes, by speaking for a short period of time to initiate and stimulate further discussion. Each meeting is fully recorded, the tapes are transcribed and the unedited transcript is immediately sent to every participant. Each is asked to check their own contributions and to provide brief biographical details. The editors turn the transcript into readable text, and participants’ minor corrections and comments are incorporated into that text, while biographical and bibliographical details are added as footnotes, as are more substantial comments and additional material provided by participants. The final scripts are then sent to every contributor, accompanied by forms assigning copyright to the Wellcome Trust. Copies of all additional correspondence received during the editorial process are deposited with the records of each meeting in Archives and Manuscripts, Wellcome Library, London. 1 The following text also appears in the ‘Introduction’ to recent volumes of Wellcome Witnesses to Twentieth Century Medicine published by the Wellcome Trust and the Wellcome Trust Centre for the History of Medicine at University College London. iii As with all our meetings, we hope that even if the precise details of some of the technical sections are not clear to the nonspecialist, the sense and significance of the events are understandable. Our aim is for the volumes that emerge from these meetings to inform those with a general interest in the history of modern medicine and medical science; to provide historians with new insights, fresh material for study, and further themes for research; and to emphasize to the participants that events of the recent past, of their own working lives, are of proper and necessary concern to historians.