Animals and Medicine

Front matter

The Contribution of Animal Experiments to the Control of Disease

JACK BOTTING

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Contents

List of Illustrations Vii

Foreword xii

Adrian R. Morrison

Index

List of Illustrations

1.1

1.2

1.3

1.4

2.1

2.2

3.1

4.1

4.2

4.3

5.1

5.2

6.1

6.2

Smallpox deaths in Sweden, 1774-1900.

Smallpox deaths in England, 1838-1900.

Smallpox incidence in Indonesia, 1966-1971.

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

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

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

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

Studies on pertussis immunisation, 1937-1942.

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

Whooping cough in Fiji, 1950-1980.

Hib meningitis in Helsinki. Actual cases, 1970-1990. Decline of Hib Meningitis in USA children under 5 years, 1980-1993.

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

Comparison of infant mortality rates and the incidence of poliomyelitis.

viii

6.3

6.4

6.5

7.1

7.2

7.3

7.4

7.5

8.1

9.1

9.2

9.3

9.4

9.5

9.6

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

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

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

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

Effect of antitoxin on case mortality.

Diphtheria death rate in New York, 1920-1930.

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

Diphtheria death rate in Great Britain, 1925-1955.

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

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

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

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

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

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

© Science Photo Library, all rights reserved.

List of Illustrations ix

10.1 The recently transplanted heart of a baby boy, showing 107 the tubing still connecting it to the heart-lung machine. © Science Photo Library, all rights reserved.

10.2 Heart-lung machine. © Science Photo Library, all rights 108 reserved.

10.3 Effect of additives on recovery of rat heart from ischemia. 110 Data from D. Hearse (1988) ‘The protection of the ischaemic myocardium: surgical success v clinical failure?’, Progress in Cardiovascular Diseases, 30, 6, 381.

10.4 Hypothermia and ischaemic injury. Data from Hearse (1988). 111

11.1 Diagrams from: ‘On Breathlessness, especially in relation to 116 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.

11.2 Surgery to replace a mitral valve. © Science Photo Library, 120 all rights reserved.

11.3 Artificial heart valves were successfully developed in 121 animals.

11.4 The tilting disc aortic heart valve, with the tilting action 122 shown in cross sectional profile. Picture courtesy of Medtronic, all rights reserved.

11.5 Tilting disc aortic heart valve. © Science Photo Library, all 122 rights reserved.

12.1 Engravings showing transfusion in the neck and leg of a dog, 128 from animal to man, and from man to man, by J. S. Elsholtz, 1667. Wellcome Library, London, CC BY.

12.2 Attempt at blood transfusion from lamb to man, depicted in 129 an illustration dating from 1705. Wellcome Library, London, CC BY.

12.3a Drawing of Blundell’s impellor. Wellcome Library, London, 132 CC BY.

12.3b Blundell’s apparatus in use. From J. Blundell (1828). 132 ‘Observations on the transfusion of blood’, The Lancet, 2, 321. Wellcome Library, London, CC BY.

x Animals and Medicine

12.4

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

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

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.

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.

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

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

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.

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).

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).

List of Illustrations xi

17.1 Effect of penicillin in normal and germ-free guinea pigs. 179 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.

18.1 ColumnsrepresentthemonthlyincidenceinGermany ofbirths 190 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.

19.1 Trends in cancer survival in the USA (male and female 200 white), 1960-1963 and 1983-1988.

19.2 Trends in cancer mortality in England and Wales (males), 201 1950-1990.

19.3 Trends in survival of children under 15 in the USA, 1960- 202 1963 and 1983-1988.

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

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).' An extensive philosophical defence of the use of animals can be found elsewhere.”

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.

1 Russell W MS 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.

xiv Animals and Medicine

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.’ 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.’ 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

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

Foreword xv magazine,’ and a guest editorial in The American Biology Teacher.’ 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]:

1. 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 observation

2. Endowing a particular methodology, such as epidemiology, with exaggerated powers

3. | Reporting experimental observations or even the opinions of scientists out of context

4. Using faulty logic

5. Reversing the conclusions of a particular article by quoting a disjointed series of sentences as if they had appeared together in the original

6. Boldly 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

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 xvi Animals and Medicine 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.

School of Veterinary Medicine, University of Pennsylvania Philadelphia, PA, USA