Animals and Medicine E-Book

Regina Botting (editor)

• Herausgeber: Open Book Publishers
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2015

Beschreibung

Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease offers a detailed, scholarly historical review of the critical role animal experiments have played in advancing medical knowledge. Laboratory animals have been essential to this progress, and the knowledge gained has saved countless lives—both human and animal. Unfortunately, those opposed to using animals in research have often employed doctored evidence to suggest that the practice has impeded medical progress. This volume presents the articles Jack Botting wrote for the Research Defence Society News from 1991 to 1996, papers which provided scientists with the information needed to rebut such claims. Collected, they can now reach a wider readership interested in understanding the part of animal experiments in the history of medicine—from the discovery of key vaccines to the advancement of research on a range of diseases, among them hypertension, kidney failure and cancer. This book is essential reading for anyone curious about the role of animal experimentation in the history of science from the nineteenth century to the present.

Leseprobe

ANIMALS AND MEDICINE

Animals and Medicine

The Contribution of Animal Experiments to the Control of Disease

Jack H. Bottingedited by Regina M. Botting

http://www.openbookpublishers.com

© 2015 Regina Botting

This work is licensed under a Creative Commons Attribution 4.0 International license (CC BY 4.0). This license allows you to share, copy, distribute and transmit the work; to adapt the work and to make commercial use of the work providing attribution is made to the author (but not in any way that suggests that they endorse you or your use of the work). Attribution should include the following information:

Jack Botting, ed. Regina Botting, Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease. Cambridge, UK: Open Book Publishers, 2015. http://dx.doi.org/10.11647/OBP.0055

Please see the list of illustrations for attribution relating to individual images. Whenever a license is not specified, images have been released under the same license as the book. Every effort has been made to identify and contact copyright holders and any omission or error will be corrected upon notification to the publisher. In order to access detailed and updated information on the license, please visit http://www.openbookpublishers.com/isbn/9781783741175#copyright

Further details about CC BY licenses are available at http://creativecommons.org/licenses/by/4.0/

Digital material and resources associated with this volume are available at http://www.openbookpublishers.com/isbn/9781783741175#resources

ISBN Paperback: 978-1-78374-117-5

ISBN Hardback: 978-1-78374-118-2

ISBN Digital (PDF): 978-1-78374-119-9

ISBN Digital ebook (epub): 978-1-78374-120-5

ISBN Digital ebook (mobi): 978-1-78374-121-2

DOI: 10.11647/OBP.0055

Cover image: Pancreas and insulin (image B0007641). Wellcome Library, London, CC BY.

All paper used by Open Book Publishers is SFI (Sustainable Forestry Initiative), and PEFC (Programme for the Endorsement of Forest Certification Schemes) Certified.

Printed in the United Kingdom and United States by Lightning Source for Open Book Publishers

Contents

List of Illustrations

vii

Foreword

xii

Adrian R. Morrison

Introduction

xvii

Regina Botting

I.

Treatment of Infectious Diseases

1.

Smallpox and After: An Early History of the Treatment and Prevention of Infections

1

2.

Rabies

17

3.

Lockjaw: Prevalent but Preventable

29

4.

Pertussis Vaccine, Unfairly Maligned – At What Cost?

41

5.

Vaccination: The Present and Future

51

6.

The Conquest of Polio and the Contribution of Animal Experiments

57

7.

Diphtheria: Understanding, Treatment and Prevention

65

II.

Development of Life-saving Procedures

8.

Development of Dialysis to Treat Loss of Kidney Function

77

9.

The Contribution of Animal Experiments to Kidney Transplantation

87

10.

Cardiopulmonary Bypass: Making Surgery on the Heart Possible

103

11.

Artificial Heart Valves: From Caged Ball to Bioprosthesis

115

12.

Animals and Blood Transfusion

127

III.

Drugs for Organic Diseases

13.

Animal Experiments and the Production of Insulin

141

14.

Animals and Humans: Remarkably Similar

155

15.

Early Animal Experiments in Anaesthesia

161

16.

The Control of Malignant Hypertension

167

17.

Penicillin and Laboratory Animals: The Animal Rights Myth

177

18.

The History of Thalidomide

183

19.

Misleading Research or Misleading Statistics: Animal Experiments and Cancer Research

199

Index

211

List of Illustrations

1.1

Smallpox deaths in Sweden, 1774-1900.

6

1.2

Smallpox deaths in England, 1838-1900.

7

1.3

Smallpox incidence in Indonesia, 1966-1971.

10

1.4

Louis Pasteur (1822-1895), microbiologist. Wellcome Library, London, CC BY.

12

2.1

Study of a rabid dog from an oil painting by J.T. Nettleship. Wellcome Library, London, CC BY.

17

2.2

Slaying of a rabid dog. Wellcome Library, London, CC BY.

19

3.1

Incidence of tetanus per 1,000 wounded in the British Army, 1914-1918.

32

4.1

Studies on pertussis immunisation, 1937-1942.

43

4.2

Whooping cough notifications in England and Wales, 1940-1990.

44

4.3

Whooping cough in Fiji, 1950-1980.

44

5.1

Hib meningitis in Helsinki. Actual cases, 1970-1990.

51

5.2

Decline of Hib Meningitis in USA children under 5 years, 1980-1993.

52

6.1

The iron lung before vaccination, 1952? Image in the public domain.

57

6.2

Comparison of infant mortality rates and the incidence of poliomyelitis.

59

6.3

Deaths from poliomyelitis in the USA, 1948-1967. Data from Vital statistics of the USA; US Dept of Health, Educ. & Welfare.

62

6.4

Deaths from poliomyelitis in England and Wales. Data from A.M. Ramsey and R.T.D. Emond, Infectious Diseases, London: Heinemann, 1978.

62

6.5

Polio in Latin America, confirmed cases per year, 1969-1989. Data from Medical & Health Annual, 1991, Chicago: Encycl. Britannica Inc.

63

7.1

1909 photo of Emil von Behring (1854-1917). Wellcome Library, London, CC BY.

67

7.2

Effect of antitoxin on case mortality.

68

7.3

Diphtheria death rate in New York, 1920-1930.

71

7.4

Incidence of diphtheria in Birmingham (children 5-14 years), 1920-1935.

72

7.5

Diphtheria death rate in Great Britain, 1925-1955.

73

8.1

Kidney dialysis machine. © Science Photo Library, all rights reserved.

84

9.1

Alexis Carrel, 1912 Nobel Laureate in Physiology or Medicine. Wellcome Library, London, CC BY.

88

9.2

Carrel’s vascular anastamosis. From A. Carrel (1902), ‘La Technique operatoire des anastomoses vasculaire et la transplantation des visceres’, Medecine de Lyon, 98, 859.

89

9.3

Sir Peter Medawar, painting by Sir Roy Calne. All right reserved

92

9.4

The first long-surviving dog, Lollypop, treated with the immunosuppressant azathioprine following a kidney graft.All right reserved

97

9.5

A donor human kidney is perfused with saline prior to transplantation. © Science Photo Library, all rights reserved.

99

9.6

Surgeons performing a kidney transplant operation. © Science Photo Library, all rights reserved.

99

10.1

The recently transplanted heart of a baby boy, showing the tubing still connecting it to the heart-lung machine. © Science Photo Library, all rights reserved.

107

10.2

Heart-lung machine. © Science Photo Library, all rights reserved.

108

10.3

Effect of additives on recovery of rat heart from ischemia. Data from D. Hearse (1988) ‘The protection of the ischaemic myocardium: surgical success v clinical failure?’, Progress in Cardiovascular Diseases, 30, 6, 381.

110

10.4

Hypothermia and ischaemic injury. Data from Hearse (1988).

111

11.1

Diagrams from: ‘On Breathlessness, especially in relation to cardiac disease?’ An address given by Lauder Brunton to the Willesden and District Medical Society and published in The Practitioner in June, 1905. Image in the public domain.

116

11.2

Surgery to replace a mitral valve. © Science Photo Library, all rights reserved.

120

11.3

Artificial heart valves were successfully developed in animals.

121

11.4

The tilting disc aortic heart valve, with the tilting action shown in cross sectional profile. Picture courtesy of Medtronic, all rights reserved.

122

11.5

Tilting disc aortic heart valve. © Science Photo Library, all rights reserved.

122

12.1

Engravings showing transfusion in the neck and leg of a dog, from animal to man, and from man to man, by J. S. Elsholtz, 1667. Wellcome Library, London, CC BY.

128

12.2

Attempt at blood transfusion from lamb to man, depicted in an illustration dating from 1705. Wellcome Library, London, CC BY.

129

12.3a

Drawing of Blundell’s impellor. Wellcome Library, London, CC BY.

132

12.3b

Blundell’s apparatus in use. From J. Blundell (1828). ‘Observations on the transfusion of blood’, The Lancet, 2, 321. Wellcome Library, London, CC BY.

132

12.4

Today, the storage and transfusion of sterile compatible blood or blood constituents is a routine and life saving procedure. © Science Photo Library.

137

13.1

Photo of Frederick Banting, Charles Best and the dog Marjory, an early depancreatised dog treated with insulin, 1921. Wellcome Library, London, CC BY.

146

13.2

The effect of Collip’s highly-purified extract on the first patient to be successfully treated. Data adapted from F. Banting, C. Best, J. Collip, et al. (1922), ‘The effect produced on diabetes by extracts of pancreas.’ Transactions of the Association of American Physicians, 1-11.

147

13.3

Photographed in 1922, this diabetic girl, aged 13, weighed just 45lb before treatment with insulin. A few months later she had made a dramatic recovery. Wellcome Library London, CC BY.

148

14.1

Aspirin causes birth defects in rats, but not in people.

158

15.1

Watercolour of Henry Hickman by Richard Cooper, painted in 1912. Wellcome Library, London, CC BY.

162

15.2

Drawing of Sir James Young Simpson and friends by unknown artist, representing Simpson’s discovery of the anaesthetic properties of chloroform in humans. Wellcome Library, London, CC BY.

164

16.1

Deaths from hypertensive disease. Annual deaths per million population. Data from Paton et al. (1978) Highlights of British Science, Silver Jubilee Exhibition, Royal Society, and Compendium of Health Statistics, 8th edition, 1992 (Office of Health Economics).

171

16.2

Treatment of malignant hypertension with ganglionic blocking drugs. Comparison between 140 treated and 105 untreated patients, percent surviving against time after diagnosis. Data from Paton et al. (1978).

172

17.1

Effect of penicillin in normal and germ-free guinea pigs. Figures are number of animals per group. Data from S.B. Formal, G.D. Abrams, H. Schneider, and R. Laundy (1963), ‘Penicillin in germ-free guinea pigs.’ Nature, 198:712.

179

18.1

Columns represent the monthly incidence in Germany of births of children deformed because of ingestion of thalidomide by the mother. Data from W. Lenz (1988), ‘A short history of thalidomide embryopathy.’ Teratology, 38, 203-15.

190

19.1

Trends in cancer survival in the USA (male and female white), 1960-1963 and 1983-1988.

200

19.2

Trends in cancer mortality in England and Wales (males), 1950-1990.

201

19.3

Trends in survival of children under 15 in the USA, 1960-1963 and 1983-1988.

202

Dr. J.H. Botting, 6 January 1932-12 July 2012

Jack Howard Botting was born in Croydon, London and attended Selhurst Grammar School where he developed his lifelong passion for Rugby and captained the School First Fifteen. He graduated B.Pharm at Chelsea College in 1954 and immediately commenced postgraduate research under the supervision of Professor Mary Lockett.

On completing his Ph.D. in 1957, Jack entered National Service in the Royal Army Medical Corps and was posted to Army Operational Research Group. Seconded to the MRC Laboratories at Holly Hill, London he carried out research on acclimatization to heat and the assessment of stress in human subjects. In 1959 Jack returned to Chelsea as Lecturer in Pharmacology at a time when pharmacology was entering a golden age of drug research and discovery. Chelsea had many fine and dedicated teachers but Jack was exceptional in his eye for detail and in the pastoral care of his students. Liaison with industrial and government research centres was an important part of his responsibilities which allowed him to secure places for students in their third year intercalated research course. Many former students have spoken warmly of how Jack helped them obtain positions after graduating and how he would keep track of their careers.

Jack himself had a year’s sabbatical at the Sandoz Laboratories in Basel (1969-70) and returned as Senior Lecturer to Chelsea until 1989 when he became acting Head of Department prior and during the merger of Kings and Chelsea College. In 1990 he decided to retire from academic life and took the position of Scientific Director of the Research Defence Society until he finally retired in 1995.

Jack held many influential positions on academic committees in the University of London (as it was) including the chairmanship of the Board of Studies in Pharmacology. His major contributions to teaching pharmacology was recognised by the Society by the award of the Rang Prize in 2011.

Jack married Renia Botting, a fellow Chelsea student, in 1958 and Renia was still at his side when he left us in July 2012.

Foreword

http://dx.doi.org/10.11647/OBP.0055.20

Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease presents a detailed, scholarly historical review of the critical role experiments using animals have played in advancing medical knowledge. Laboratory animals have been essential, and the knowledge gained has saved countless human lives – and not only human lives. Animals, themselves, have benefitted. Unfortunately, those opposed to using animals in research, some even physicians, have presented doctored evidence that using animals has impeded medical progress. Therefore, the articles Jack Botting wrote for the Research Defence Society News from 1991 to 1996 have provided scientists – those willing to speak out – with the information needed to rebut such foolish claims.

Of course, animals are only used when necessary and other methods will not answer the question posed. It must be admitted that in days gone by attention to their welfare was not uppermost in the minds of some scientists. In the modern era, though, laboratory animal medicine has made major advances, and scientists are enjoined legally and morally to follow the principles of the 3Rs expounded by Russell and Burch: reduction (in numbers used); refinement (of experimental techniques to eliminate or reduce pain); and replacement (with alternative approaches when available).1 An extensive philosophical defence of the use of animals can be found elsewhere.2

It is tragic that Jack’s book had to be published posthumously. But thankfully, his efforts to put his many articles into book form were not initiated in vain because his wife, Regina, has carried his work on to publication. Because Jack and I had collaborated on a few articles more than fifteen years ago, she asked me if I would introduce the book.

Ours was a curious collaboration because we never had the pleasure of meeting face-to-face. But on the basis of one telephone call and numerous emails we wrote three essays. The first was written for an ill-conceived debate organized by Scientific American. Jack had been invited by the magazine to write an article defending the need for using animals in biomedical research.3 Jack thought that it would be best to have an American join him in the debate and chose me because I had been very active in the field.

Our opponents were to be two physicians, Neal Barnard and Stephen Kaufman, well-known for philosophical objection to using animals and their false claims that animal research has been wasteful and misleading. We knew that they had a history of depending on gross and clever distortions of medical history to support those claims, and what they wrote for the debate was no exception.4 Having joined together, Jack and I then tried to persuade the editor that his debate would be unwise and harmful because, as planned, there would be no chance for rebuttal. Our plea fell on deaf ears even after we had seen the contributions of our opponents prior to publication and had pointed out to the editor their various distortions of history requiring a reply.

The editor’s answer was that the issue was an important one and should be presented to the public as planned. But how was an uninformed public to sort out fact from fancy, we asked? Barnard and Kaufman’s philosophical objections to using animals in research had been melded into a supposedly scientifically sound presentation of medical history.

Regrettably, the debate was published; and, as we had predicted, reference to Barnard’s and Kaufman’s article in what had always been a legitimate journal began to appear in animal-rightist publications. Although one scientist whose work had been misrepresented wrote a letter to the editor describing how his statements had been presented wrongly, Jack and I thought that an extensive rebuttal had to be published somewhere. We found two outlets for presenting our rebuttal: an online journal, H.M.S. Beagle: TheBioMedNet magazine,5 and a guest editorial in The American Biology Teacher.6 The former is defunct, but science and medical journalist, Andrew A. Skolnick, is kindly hosting the article on his website.

We actually based our article in HMS Beagle, ‘UnScientific American: Animal Rights or Wrongs,’ on the several emails we had sent to the editor of Scientific American detailing Barnard’s and Kaufman’s distortions of medical history on several fronts. Our corrections focused on the development of the polio vaccine, stroke research, drug side effects, the birth defects induced by thalidomide, and the miracle of insulin. These topics are among the many that are discussed in this book in incredible detail.

Our guest editorial, ‘Confusion in the Ranks’ allowed us to present our arguments to an extremely important audience: biology teachers. Animal-rightist propaganda had been infecting young minds for many years so we thought it critical to counter these efforts. The misleading methods presented in Scientific American and elsewhere were listed

in no particular order of perversity [as we put it]:

Overemphasizing an ultimate clinical discovery while ignoring the dependence on years of dedicated background laboratory work of others or else dismissing the need to dissect mechanisms after a clinical observationEndowing a particular methodology, such as epidemiology, with exaggerated powersReporting experimental observations or even the opinions of scientists out of contextUsing faulty logicReversing the conclusions of a particular article by quoting a disjointed series of sentences as if they had appeared together in the originalBoldly listing supporting references even if they are not. (6, p. 388)

We then offered something positive: ideas for creating a curriculum module around the debate. First among them was the philosophical question of whether we are justified in using animals for purposes of our own health and well-being. If the answer is negative, is the individual prepared to live without benefitting from medical advances? We then suggested asking students how one would develop new drugs or surgical techniques without using animals in one or more stages of the process. Finally, we suggested researching one of the claims made in the Scientific American debate. We noted that the editor had received references from both sets of authors so that the magazine should be able to provide them on request. I hope some did follow through on this last suggestion. The foregoing illustrates how important Jack’s efforts were. I hope that many scientists will make good use of them in public education.

Adrian R. Morrison, DVM, PhDProfessor Emeritus of Behavioral NeuroscienceSchool of Veterinary Medicine, University of Pennsylvania Philadelphia, PA, USA

1 Russell W M S and Burch (1959), The Principles of Humane Experimental Technique. London: Metheun.

2 Morrison A R (2009), An Odyssey with Animals: Reflections of a Veterinarian on the Animal Rights & Welfare Debate.Oxford: Oxford University Press.

3 Botting J H and Morrison A R (1997), Animal research is vital to medicine. Sci Am 276 (2) 83-85.

4 Barnard N D and Kaufman S R Animal research is wasteful and misleading, Sci Am 276 (2) 80-82. http://dx.doi.org/10.1038/scientificamerican0297-80

5 Botting J H and Morrison A R (1998) UnScientific American: animal rights or wrongs: An op-ed. HMS Beagle: TheBioMedNetMagazine 25 (Feb 20) 1-7, http://www.aaskolnick.com/morrison/unscian.htm

6 Morrison A R and Botting J H (1997), Confusion in the ranks Am Biol Teacher 59 388-89. http://dx.doi.org/10.2307/4450341

Introduction

http://dx.doi.org/10.11647/OBP.0055.21

The Research Defence Society (RDS) was founded in 1908 by Dr Stephen Paget, son of the eminent Victorian surgeon, Sir James Paget. Its role was to defend scientists conducting medical research using animals and to inform the public about the importance of animal experimentation. In its first year it attracted a membership of 2000 which included scientists in the pharmaceutical industry, in academia and in research institutes. Past presidents of the Society include such distinguished figures as Lord Perry of Walton and Sir William Paton.

Dr Jack Botting joined the staff of the RDS as its Scientific Officer in 1991, at the height of the antivivisectionist activity being carried out by organisations such as the Animal Liberation Front (ALF), the National Anti-Vivisection Society (NAVS), the British Union for the Abolition of Vivisection (BUAV) and People for the Ethical Treatment of Animals (PETA).

One of the most damaging aspects of antivivisection campaigning was that they had started to hijack the scientific argument, claiming that animal experimentation was scientifically misleading, “a failed technology” etc., and that an examination of the research behind major medical advances showed that non-animal techniques were crucial and that the animal experiments had contributed nothing, or worse still, held up progress. Antivivisectionists were deliberately shifting the debate from the traditional “science vs animal welfare” argument to a “scientific” debate giving their arguments a cover of scientific respectability.

To respond to this style of campaigning, Jack was given the specific task of reviewing the research behind the major medical advances and writing non-technical reviews explaining the role played by animal experimentation. His work effectively put an end to this aspect of antivivisection campaigning. The articles which Jack wrote at that time have been collected in this book.

But the activists didn’t stop at spreading misinformation. Some extremist groups harassed, threatened and attacked scientists and laboratories involved in animal research, painting graffiti on the houses of researchers and even planting bombs under their cars. Colin Blakemore, Professor of Physiology at Oxford University, who was recognised for his research in early 2014 with a knighthood, was one of those targeted by these groups. A leading vision scientist who has used cats for his studies, he has received letter bombs, death threats against him and his family, had his car damaged and the windows of his home broken. The activists also agitated to close down laboratories which used animals and the facilities which bred them. Meanwhile, scientists were working to find ways to refine and reduce the use of animals in research, but their efforts did not appease the antivivisectionists who were determined to shut down animal research altogether.

These antivivisectionist groups vary in size and structure; PETA, for example, claims that their membership runs into millions. This particular group has a wide campaign portfolio: as well as vivisection, it also protests against the use of animals for fur farming, pet ownership, hunting and even for food. They and groups like them receive large donations from which they obtain a considerable income – PETA receives millions of pounds annually from their supporters.

The current animal rights movement, with its organised activities, has its origins in the publication of the book Animal Liberation in 1975, by Australian philosopher Peter Singer, which animal liberationists viewed as providing their founding philosophical statement of ideas. The following year saw the foundation of the ALF, followed in the 1980s by the Animal Rights Militia, which, as its name suggests, was an extreme group which sent bombs to politicians and animal researchers. In the early 1990s, they and other similar groups firebombed scientists and organisations engaged in medical research using animals.

One of the most well-known activists is Greg Avery, who founded Stop Huntingdon Animal Cruelty (SHAC) in 1999 and is an alleged member of the ALF. He was involved with a 10-month campaign that succeeded in closing down Consort Kennels, a facility which bred beagles for medical research. From 1996, Avery was in and out of prison on various charges before being jailed for nine years in 2008 after being convicted of conspiracy to blackmail; imprisoned along with him were his wife and ex-wife. Other protests achieved some success: 1999 saw the closure of Hillgrove Cat Farm, the last dedicated UK establishment which bred cats, its owner retiring after a sustained series of protests and attacks. In 2005 the Hall brothers, owners of Newchurch Guinea Pig Farm, shut up shop after a six-year campaign by activists; in one two-year period police logged 450 separate criminal acts. The victimisation culminated in the theft of the remains of Christopher Hall’s mother-in-law and, although no one was ever convicted of the desecration of the grave, four people were jailed for using the theft to blackmail the family.1

The degree of criminal behaviour exhibited by these groups led the British government to set up the National Extremism Tactical Coordination Unit (NETCU) which aimed to enable the police to deal effectively with animal rights extremism. In addition, legislation has been put in place to curb the activity of antivivisection groups. These measures, combined with more severe sentences handed down by judges, have notably reduced extremist action by such groups.

At the same time, the press coverage given to the more extreme cases led to public condemnation of the tactics animal liberation groups were using and along with this came an increase in awareness of the issues involved. While new animal rights campaigns were set up, other groups were formed, such as Speaking of Research, to counter them. In 2003, the work of the RDS was reinforced by the establishment of the Coalition for Medical Progress (CMP), which also engaged in pro-research communication. At the end of 2008, the two organisations merged to form Understanding Animal Research (UAR). The announcement of the building of a new animal research facility, the Oxford Biomedical Research Institute, resulted in animal rights extremists burning down student boathouses at Oxford University in protest. This action led to the formation at the beginning of 2006 of the Pro-Test committee and in February of that year they held their first rally, which saw over 800 students, scientists and members of the public marching through Oxford in support of animal research. Two subsequent rallies again attracted hundreds of people and, in 2008, Oxford University opened its new Biomedical Sciences Building.2

This tide of public support has been complemented by the pursuit of alternatives to animal research by the scientific community. The charity, Fund for the Replacement of Animals in Medical Experiments (FRAME), was registered in 1969 and has provided a blueprint for similar organisations throughout Europe and in the USA, advising the government on the Animals (Scientific Procedures) Act, passed in 1986. Medical research was still being regulated by the 1876 Cruelty to Animals Act, which was in need of updating. FRAME outlined a ‘Three Rs’ approach, advocating the replacement, reduction and refinement of experiments on animals and the work of the organisation, along with progress in scientific knowledge, has enabled the first of these to become a reality. The LD50 test has been substituted by the ED50 test which uses fewer animals; the Pyrogen Test using live rabbits has been supplanted by the Limulus Amebocyte Lysate (LAL) Assay which uses the blood of the limulus crab, and the potency of a batch of insulin is now determined by biochemical methods instead of the blood sugar levels of conscious rabbits.

Animal rights extremism has been significantly curbed due to the measures mentioned above, as well as the restraining or imprisonment of many of the most zealous activists. 2014 finally saw the end of the campaign against Huntingdon Life Sciences (HLS). The sustained attacks on Huntingdon had seen not only staff targeted but also investors; they received hoax bombs, had their cars torched and one US executive even had his boat sunk. Much of the energy of the activists has now been channelled into online campaigns, with antivivisection groups campaigning to stop airlines transporting primates, having already successfully prevented ferry companies transporting laboratory animals across the English Channel.3

The debates around animal experimentation will continue and animal rights activists will continue to campaign. However, the landscape has changed considerably and there are several organisations now engaged in countering the campaigner’s arguments and disseminating information. In the UK, the work of UAR is supported by the charitable organisation, the Biomedical Research Education Trust (BRET), which was originally set up by the RDS and which supports lectures for schools and societies interested in finding out the facts about animal research. In the USA, the groups Americans for Medical Progress (AMP) and the Foundation for Medical Research (FMR) perform a similar role. Even at the time of writing this introduction one of the recipients of the 2014 Nobel Prize for Physiology or Medicine, John O’Keefe, spoke in support of the use of animals. In an interview with the BBC he said “It is an incontrovertible fact that if we are to make progress in basic areas of medicine and biology, we are going to have to use animals.”4

This volume of Jack’s articles is supported by the trustees of BRET and their generosity is gratefully acknowledged. I would also like to thank Josephine Botting, Nina Botting Herbst and Mark Matfield for skilful editing and Ian O’Sullivan for invaluable technical help.

Regina Botting, Ph.D., October 2014

1 Illman J (2008) Animal Research in Medicine: 100 Years of Politics, Protests and Progress. The Story of the Research DefenceSociety. London: Research Defence Society.

2 Holder T (2014) ‘Standing up for Science: The Antivivisection Movement and How to Stand up to It.’ EMBO Reports 15/6, 625-30, http://dx.doi.org/10.1002/embr.201438837

3 The Independent on Sunday (2014) Animal rights group ends campaign, 24th August 2014.

4 BBC News Website, Interview with John O’Keefe by James Gallagher, 7th October 2014.

I. TREATMENT OF INFECTIOUS DISEASES

1. Smallpox and After: An Early History of the Treatment and Prevention of Infections

http://dx.doi.org/10.11647/OBP.0055.01

The scientific work that led to the discovery of the causes of infections was possibly the major biomedical advance of the nineteenth century. From it was derived the aseptic technique of Lister, the use of antitoxins and immunisation, and the ultimately successful search for chemicals selectively toxic to bacterial cells.

The conquest of most of the infectious diseases is, however, the field subjected to the most derisive attack by the antivivisectionists. The scourges that were responsible for the high childhood mortality up to the end of the nineteenth century were, it is claimed, defeated by improvements in sanitation, nutrition and housing, rather than knowledge obtained from animal experimentation.

Improvements in public health undoubtedly contributed to the reduction in death from infectious disease. Obviously the easiest way to avoid morbidity is to stay away from the cause. However, with one notable exception, the causes are still with us. The tubercle bacillus, streptococcus, poliovirus etc. could still, even in our sanitary environment, cause lethal or crippling conditions if there was no appropriate medical intervention. The fact that 50 million prescriptions for antibiotics are written per year in the UK is testimony to the continued prevalence of infective disease.

Pasteur and others, in the second half of the nineteenth century, attributed the cause of certain diseases to microbes that enter (or infect) the body. Pasteur’s subsequent work, on the examination of the relative virulence of microbes after in vitro culture, put a sound scientific basis beneath the empirical practice of smallpox vaccination that was current in Europe at the time.

Smallpox

Those who may harbour in their imagination an affinity for the romanticism of pre-Victorian times would find the historical descriptions of smallpox sobering reading. De la Condamine (1) wrote in 1754:

Every tenth death was due to smallpox, and one fourth of mankind were either killed by it, or crippled or disfigured for life. The disease was a river that everyone had to cross.

This severe scourge was endemic in China and other eastern countries centuries before Christ and was certainly present in Europe in the sixth century.

Bishop Gregory of Tours was surely describing smallpox when he wrote in 582 of the epidemic with vesicular eruption (lues cum vesicis) which began with sickness, fever and back pains. The fever abated with the copious eruption of hard, white vesicles which were very painful. Bad cases were fatal (amongst the young especially) on the 12th to 14th day.

The prevalence of the disease in these early times is indicated by the first clear description of smallpox by a physician. This was that of Isaacus Judaeus, or Isaac the Jew, who lived in the ninth century. Isaac theorised, since smallpox attacked everyone, that it was a natural fermentation of the blood in children in order to get rid of an impurity acquired in the womb. That smallpox continued to be a widespread scourge up to the time of the formal record of morbidity and mortality is evidenced by the quotation of De la Condamine (see above).

Against this background it is not hard to understand the development of the technique of inoculation (or variolation). This was the deliberate infection of pustular matter, collected during a mild epidemic, into an incision in a healthy child. This practice stemmed from the clinical observation that one attack of smallpox conferred protection against the disease and was long used by physicians of ancient China and India. It was introduced into Europe in 1721 by Lady Mary Wortley Montague, wife of the British Ambassador to Turkey. Although efficacious, the procedure was extremely dangerous, causing at least three epidemics on the continent and being fatal in at least 1-2% of cases (2). That individuals were prepared to accept discomfort and such severe risks attests to the inevitability with which people accepted smallpox in the era before any statistics were available.

Vaccination

Jenner’s experiments, published in 1798, obviated the need for variolation and set the scene for the eventual eradication of smallpox. The story is familiar. Jenner, like others before, was intrigued by the accepted belief that individuals who came into contact with the comparatively rare disease of cowpox were immune to smallpox. In his classic experiment Jenner inoculated a boy with pus from a cowpox lesion on the hand of an infected dairymaid. Two months later the boy was inoculated with pus from a smallpox vesicle but did not develop the disease. “Vaccination” with cowpox resulted in immunity to smallpox. Vaccination gradually spread throughout Europe during the next hundred years.