Animal Experimentation: Working Towards a Paradigm Change Human-Animal Studies Series Editor Kenneth Shapiro Animals & Society Institute, usa Editorial Board Ralph Acampora Hofstra University, usa Clifton Flynn University of South Carolina, usa Hilda Kean Ruskin College, Oxford, UK Randy Malamud Georgia State University, usa Gail Melson Purdue University, usa VOLUME 22 The titles published in this series are listed at brill.com/has Animal Experimentation: Working Towards a Paradigm Change Edited By Kathrin Herrmann Kimberley Jayne VOLUME 22 leiden | boston Cover illustration: Long-tailed macaque, Boo, was sent to an animal research laboratory in Europe together with her siblings, Betty and Baloo, where they were used in neurology experiments. Animal Defenders International rescued them in 2009 when they were due to be killed. They now live their lives free from suffering at Lakeview Monkey Sanctuary. We thank Australian contemporary realist artist, Anwen Keeling, for her kind contribution of the cover picture which she painted from a photograph taken by Animal Defenders International after Boo’s rescue. Library of Congress Cataloging-in-Publication Data Names: Herrmann, Kathrin, editor. | Jayne, Kimberley, editor Title: Animal experimentation : Working Towards a Paradigm Change / Edited by Kathrin Herrmann, Kimberley Jayne. Description: Leiden ; Boston : Brill, 2019. | Series: Human-animal studies, ISSN 1573-4226 ; volume 22 | Includes bibliographical references and index. Identifiers: LCCN 2018048693 (print) | LCCN 2018056495 (ebook) | ISBN 9789004391192 (E-book) | ISBN 9789004356184 (hardback : alk. paper) Subjects: LCSH: Animal experimentation. Classification: LCC HV4915 (ebook) | LCC HV4915 .H47 2019 (print) | DDC 179/.4--dc23 LC record available at https://lccn.loc.gov/2018048693 Typeface for the Latin, Greek, and Cyrillic scripts: “Brill”. See and download: brill.com/brill-typeface. ISSN 1573-4226 ISBN 978-90-04-35618-4 (hardback) ISBN 978-90-04-39119-2 (e-book) Copyright 2019 by The Authors. Published by Koninklijke Brill NV, Leiden, The Netherlands. Koninklijke Brill NV incorporates the imprints Brill, Brill Hes & De Graaf, Brill Nijhoff, Brill Rodopi, Brill Sense and Hotei Publishing. Koninklijke Brill NV reserves the right to protect the publication against unauthorized use and to authorize dissemination by means of offprints, legitimate photocopies, microform editions, reprints, translations, and secondary information sources, such as abstracting and indexing services including databases. Requests for commercial re-use, use of parts of the publication, and/or translations must be addressed to Koninklijke Brill NV. This book is printed on acid-free paper and produced in a sustainable manner. This is an open access title distributed under the terms of the prevailing CC-BY-NC License at the time of publication, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This book is dedicated to the non-human animals who suffer in the name of science and whose destiny we are determined to change. ∵ Contents Foreword xi Peter Singer Preface xiv Kathrin Herrmann and Kimberley Jayne Acknowledgements xvi Notes on Contributors xvii Introduction xxxiv Kathrin Herrmann and Kimberley Jayne Part 1 Why and How to Shift the Paradigm 1 Refinement on the Way Towards Replacement: Are We Doing What We Can? 3 Kathrin Herrmann 2 How to Evaluate the Science of Non-human Animal Use in Biomedical Research and Testing: A Proposed Format for Debate 65 Ray Greek and Lisa A. Kramer 3 How Can the Final Goal of Completely Replacing Animal Procedures Successfully Be Achieved? 88 Christiane Baumgartl-Simons and Christiane Hohensee 4 Disease Prevention with a Plant-based Lifestyle 124 Sabina V. Vyas Part 2 Politics and Legislation of Animal Experimentation 5 Political Campaigning: Where Scientific and Ethical Arguments Meet Public Policy 151 Emily McIvor viii Contents 6 Rethinking the 3Rs: From Whitewashing to Rights 168 Charlotte E. Blattner 7 Contesting Animal Experiments through Ethics and Epistemology: In Defense of a Political Critique of Animal Experimentation 194 Arianna Ferrari Part 3 Openness in Animal Experimentation 8 The Moral Status of Animal Research Subjects in Industry: A Stakeholder Analysis 209 Sarah Kenehan 9 Increasing the Transparency of Animal Experimentation: An Australian Perspective 224 Monika Merkes and Rob Buttrose 10 Wasted Money in United States Biomedical and Agricultural Animal Research 244 Jim Keen Part 4 The Ethics and Philosophy of Animal Experimentation 11 Ethics, Efficacy, and Decision-making in Animal Research 275 Lawrence A. Hansen and Kori Ann Kosberg 12 Beyond Plausibility Checks: A Case for Moral Doubt in Review Processes of Animal Experimentation 289 Mara-Daria Cojocaru and Philipp von Gall 13 Human Wrongs in Animal Research: A Focus on Moral Injury and Reification 305 Jane Johnson and Anna Smajdor ix Contents Part 5 Effectiveness of the Animal Model 14 Critically Evaluating Animal Research 321 Andrew Knight 15 Extrapolation of Animal Research Data to Humans: An Analysis of the Evidence 341 Rebecca Ram 16 Is Animal-based Biomedical Research Being Used in Its Original Context? 376 Constança Carvalho, Daniel Alves, Andrew Knight and Luis Vicente 17 The Scientific Problems with Using Non-human Animals to Predict Human Response to Drugs and Disease 391 Ray Greek and Lisa A. Kramer 18 Replacing Animal Tests to Improve Safety for Humans 417 Kathy Archibald, Robert Coleman and Tamara Drake 19 Genetic Modification of Animals: Scientific and Ethical Issues 443 Jarrod Bailey 20 Animal Research for Alzheimer Disease: Failures of Science and Ethics 480 John J. Pippin, Sarah E. Cavanaugh and Francesca Pistollato 21 Behavioral Research on Captive Animals: Scientific and Ethical Concerns 517 Kimberley Jayne and Adam See Part 6 Animal-free Education and Training 22 Modernizing Biomedical Training: Replacing Live Animal Laboratories with Human Simulation 551 John Pawlowski, David Feinstein, Marie L. Crandall and Shalin Gala x Contents 23 Humane Education: The Tool for Scientific Revolution in Brazil 567 Vanessa Carli Bones, Rita de Cassia Maria Garcia, Gutemberg Gomes Alves, Rita Leal Paixão, Alexandro Aluísio Rocha, Karynn Capilé and Róber Bachinski Part 7 The Paradigm Shift: Advanced Animal-free Approaches 24 Recent Developments in Alternatives to Animal Testing 585 Katy Taylor 25 The Changing Paradigm in Preclinical Toxicology: in vitro and in silico Methods in Liver Toxicity Evaluations 610 Fozia Noor 26 The Potential of Organ on Chip Technology for Replacing Animal Testing 639 Malcolm Wilkinson 27 When Is an Alternative Not an Alternative? Supporting Progress for Absolute Replacement of Animals in Science 654 Craig Redmond 28 Research and Testing Without Animals: Where Are We Now and Where Are We Heading? 673 Thomas Hartung Afterword: Evidence over Interests 689 John P. Gluck Index 692 Foreword Peter Singer From the time when I first became interested in the ethics of our treatment of animals, I have always regarded the use of animals in research as a more dif- ficult ethical issue than the use of animals for food. It is more difficult because we have a wide range of tasty and nutritious food to eat, and it is obvious that we can live healthy, flourishing lives without eating animals or animal prod- ucts. It is true, sadly, that not everyone in the world has the luxury of being able to choose what to eat. For the vast majority of people living in developed countries, however, there is no need to eat animals or any animal products; and the animal products they eat increase the risks to their health (see Chapter 4 in this Volume). Those who continue to eat animals do it out of habit or because they like the taste. On the other hand, some scientists tell us that to cease using animals in biomedical research would greatly impede medical progress and, in the long run, could lead to millions more premature deaths and additional human suffering. I am a philosopher, not a scientist, and my approach to issues relating to animals has always been from an ethical perspective. Some people think that taking an ethical approach to animal issues means that scientific claims about the benefits of animal research are irrelevant because, even if research on ani- mals could save many human lives, the end does not justify the means. That is not how I see the issue. Although Kantians, and some other deontologists, hold that the end does not justify the means, consequentialists regard the right action as the one that will bring about the best consequences, so they hold that the end can justify the means. I am a utilitarian, and utilitarianism is the best- known form of consequentialism, so I share that view. As we can see from this book, there is a case to be made for the view that continued animal research could, in fact, be impeding scientific progress. When it comes to protecting animals and giving proper consideration to their interests, utilitarians have always been in the lead. Jeremy Bentham, the founder of modern utilitarianism, wrote about animals, saying that, “The ques- tion is not, Can they reason? Nor, Can they talk? But, Can they suffer?”. Implicit in the utilitarian emphasis on the capacity to suffer, and to experience plea- sure, is the idea that all sentient beings have interests, and that similar inter- ests should receive equal consideration, irrespective of race, sex, or species. In contrast, the mainstream Abrahamic religions, Judaism, Christianity, and Islam, all treat humans as entitled to use animals more or less as they wish, xii Foreword often seeing this as stemming from a divine grant of dominion over other ani- mals. Christian teachings, from Augustine through Thomas Aquinas, and in- numerable others on into the twentieth century, take this line. Kant also said that we have no direct duties to animals, although the ground he gave for this harsh position is that they are not self-conscious and, so, are merely means to our ends. He does not explain why the absence of self-consciousness should be a sufficient reason for denying that we have duties not to cause gratuitous suffering to sentient beings. Suppose that research on non-human animals turned out to yield mislead- ing results, and only the use of one hundred human subjects, instead of the one hundred animals, would lead to the cure that would save thousands of lives. Defenders of animal research are loath to acknowledge that one im- plication of their defense of the use of animals in research might be that, in some circumstances, it would be justifiable to use humans. One objection to substituting humans for non-human animals would be that the greater self- awareness of the humans means that they have more to lose and, so, would suffer more from the knowledge that they are being experimented upon, than would the non-human animals. But not all human beings have more self- awareness than non-human animals. Anencephalic infants do not, nor do peo- ple who are brain dead, or in a persistent vegetative state from which they will never recover. The grounds on which Kant insisted that non-human animals are merely means to our ends, rather than ends in themselves, would seem to apply to these human beings as well. If they do not, why not? Should we give preference to human beings, irrespective of their consciousness, merely because they are biologically members of the species, Homo sapiens? How is that different to giving preference to members of one race or gender, merely because they are members of that race or gender? The institution of animal experimentation is clearly based on speciesism. Chapters 14 to 20 in this Vol- ume explore the difficulties in extrapolating findings from animals to humans. These difficulties sharpen the question why we are willing to perform painful or lethal experiments on non-human animals, who are clearly capable of suf- fering, while we are unwilling even to contemplate similar experiments on hu- man beings, who are not capable of experiencing anything at all. When I wrote Animal Liberation, which first appeared in 1975, it was shock- ingly easy to find accounts of horrific suffering inflicted on animals in the course of experiments. These were not accounts written by animal rights ac- tivists (there were virtually none at the time anyway). They were written by the researchers themselves and were published in leading scientific journals. All I had to do to make the case that the interests of the animals were being utterly disregarded was to quote from these journals, and I did so extensively. Since xiii Foreword then, there has been progress in reducing animal suffering. European Union Directive 2010/63/EU has been widely regarded as indicating that, at least in the EU, pain and suffering is kept to a minimum, and animals are being re- placed by non-animal-using methods wherever possible. The following pages contain evidence that strongly suggests this is not the case. Particularly telling are the observations, reported in Chapters 1 and 21 in this Volume, of abnormal behavior and signs of stress in animals caused simply by living in standard laboratory conditions. As these and other chapters show, even in Europe, there is no ground for complacency about what happens to animals in science. The situation is likely to be worse still in other countries. Nor should we neglect the cost of using money in ways that are not maximally productive of benefits. Chapter 10 explores the waste of United States public funds in research using animals and asks whether the benefits achieved by such research are sufficient to justify the cost. This Volume, with its many distinct critical perspectives on research with animals, is therefore very timely, particularly as I write this when Directive 2010/63/EU is under review. I hope it will transform discussion about the eth- ics and the science of research involving animals. Preface For close to a decade, I worked as a federal regulator, inspecting experiments involving non-human animals (hereinafter referred to as animals) in Germany. Because I had always been skeptical about the ethical and most of the sci- entific justifications given for conducting invasive research on animals, I felt that as a veterinarian I should work within the current system to scrutinize these practices and help improve the lives of individual animals used in the name of science. By inspecting numerous animal laboratories and breeding facilities, and assessing countless animal research proposals and their scien- tific outcomes (if they were published), I became exceedingly aware of the considerable harms involved and the flaws of animal-based research on all levels—ethical, scientific, legal, political, and economic. Alongside my work as an inspector, I carried out a PhD project, assessing the use of refinement, the last R of the 3Rs principles, in practice. Refinement refers to methods that ought to reduce animal suffering in the laboratory. I focused on experimental refinements in over 500 animal research applications com- prising recovery surgical procedures from around Germany. My results show that the majority of evaluated proposals did not take all possible measures to avoid needless suffering. They confirm the trends found in structured and systematic reviews of published animal studies from around the world. Being a member of the competent authority, I frequently experienced its limits in safeguarding animals due to the way it is set up: decentralized, understaffed, and with limited resources. Consequently, the political aims of reducing and replacing animals in science have remained political claims; and authorities are unequipped to ensure that only research projects that have a realistic potential to produce benefits, which outweigh the harms inflicted on the animals, are granted li- censes. The poor application of refinement methods in laboratories, and a malfunctioning regulatory body emphasized, for me, the urgency for a para- digm change, away from using animals in science. Fortunately, in some areas this change is already slowly happening. But to accelerate the shift, it is crucial to appraise animal experimentation critically, from all angles, and to publicly discuss the findings—a realization that led me to initiate this book project. The 51 experts who contributed to this volume critically appraise current ani- mal use in science, and they discuss innovative, human-relevant approaches to advance the life sciences and to accelerate the shift towards the replacement of animals in research, testing and education. – Kathrin Herrmann xv Preface I have more than a decade of experience in research and education, working in animal welfare and animal protection. Originally, starting my career in zoos and laboratories, I chose to specialize in animal behavior and welfare because I felt that science had a role in improving the lives of animals used by these industries. However, based on my personal experiences working in these en- vironments and hand-rearing animals to be used for behavioral laboratory research, my moral values shifted. With my increasing knowledge of animal behavior and welfare, I realized that these industries were seriously flawed, both scientifically and ethically. Increasingly, the scientific and educational re- search about animal behavior that I was exposed to on a daily basis informed me that the animals I was working with should not be used for these purposes. I now work as a Senior Scientific Researcher for an animal protection or- ganization that promotes phasing out animal use in these industries, particu- larly in the areas of animals used in research, education, and entertainment. The study of the behavior of all animals is fascinating; but only when the animals can express their natural behavioral repertoire, under natural condi- tions. I truly believe that furthering our understanding of wild animal behav- ior through non-intrusive means can help those campaigning and lobbying for greater animal protection, by enhancing appreciation for all species. Through generating more public support and using indisputable scientific rationale, which cannot be ignored, governments and policy makers can be influenced to make progress towards ending the use of animals in these environments. – Kimberley Jayne We first met back in 2014, at the University of Exeter, during a workshop that aimed to introduce perspectives from the humanities and social sciences to a dialogue with practitioners and stakeholders across laboratory animal science and welfare. Our mutual concerns about animals used in science led us to col- laborate on this book project. Since we both work closely with researchers, scholars, and campaigners, who are active in the fields of animal protection, animal replacement technology, and ethical philosophy, the project rapidly evolved into a 28 chapter-volume. Our aim is to not only transform science, education, and policy into a more inclusive environment, but to continue to work on projects that consider the impact of human behavior on all species. This book may be eye-opening for some and encouraging for others. Its ulti- mate goal is to motivate everyone to work together in order to end the suffering of our fellow animals. – Kathrin Herrmann and Kimberley Jayne Baltimore and London, August 2018 Acknowledgements We greatly appreciate the monetary contributions made by Lush Charity Pot, Cruelty Free International, Lush Prize, The American Fund for Alternatives to Animal Research, Ärztinnen und Ärzte für Tierschutz in der Medizin, Safer Medicines Trust, and a private donor, who have enabled us to make this book freely available online. We are also grateful for the input and suggestions made by anonymous peer reviewers. Contributors Daniel Alves studies the physiology of acoustic communication and has worked with in- sects and fish. He is currently completing his PhD at the University of Lisbon, Portugal. While a firm believer in the merits of animal experimentation, he believes that any improvement in the humaneness of animal experimentation is a desirable goal, and that science should always strive to ensure that animal sacrifice leads to advancements in human knowledge. Gutemberg Alves is a cell biologist with a PhD in biochemistry, and a professor at the Fluminense Federal University, Brazil. As coordinator of the Clinical Research Unit of the Antônio Pedro Hospital, he leads a research line in toxicological in vitro assays. Alves is a member of the Pyrogen Testing Consortium, in cooperation with the National Network on Alternative Methods (RENAMA). He is a founding member of the 1R Institute for Promotion and Research for the Replacement of Animal Experimentation (www.Instituto1R.org). As a member of Rede de Desenvolvimento Humano (Human Development Network), Alves also leads the development of strategies for teaching and using in vitro assays as alterna- tives in health and science classes. Kathy Archibald is the director of Safer Medicines Trust, United Kingdom. After graduating in genetics from Nottingham University, she worked in drug development for pharmaceutical and biotechnology companies (Searle Pharmaceuticals, Me- diSense). She then worked as a field teacher for a nature conservation charity, the Royal Society for the Protection of Birds ( RSPB ), and the children’s charity, Action for Children. In 2005, Archibald founded Safer Medicines Trust, to con- front the unspoken problem in pharmaceutical research of the poor relevance of much research (based on animals) to human medicine. Safer Medicines Trust exists to improve the safety of medicines for patients through an in- creased focus on human biology throughout the drug development process. Rober Bachinski studied biological sciences (2009), holds a Master’s degree in public health and environment with an emphasis on environmental toxicology, and a PhD in sci- ence and biotechnology (2015). He is dedicated to the study of new research xviii Contributors methods that do not use animals and is experienced in in vitro toxicological methods, cellular interactions, development and validation of analysis meth- ods, humane education, and animal ethics. Bachinski is also working to im- plement humane education in Brazil and end speciesism in science. He is a founding member and the current Director of the 1R Institute for Promo- tion and Research for the Replacement of Animal Experimentation (www. Instituto1R.org). Jarrod Bailey PhD, is the Senior Research Scientist at Cruelty Free International (formerly the British Union for the Abolition of Vivisection [BUAV]). His chapter on ge- netically modified animals in this volume reflects his background as a genetics researcher. He spent seven years investigating the possible causes of prema- ture birth in humans and has extensive experience in evaluating the scientific validity and ethics of animal experiments. Bailey has examined and reviewed the limitations of using animals in various fields, including the testing of substances that can cause birth defects and cancer; the use of non-human primates in various forms of medical research, including HIV/AIDS, cancer, and hepatitis; the use of genetically modified animals generally; and the use of dogs, monkeys, and other species in testing new human drugs. He has au- thored several substantial scientific petitions and submissions of evidence to a variety of inquiries into the validity of animal research worldwide and several book chapters by invitation. Christiane Baumgartl-Simons Dr. med. vet., is the deputy chairwoman of Menschen für Tierrechte – Bundes- verband der Tierversuchsgegner e.V. (People for Animal Rights Germany – Federal Association Against Vivisection). After studying veterinary medicine and completing her doctorate, Baumgartl-Simons worked in the curative treat- ment of large and small animals for 14 years. Animal experiments have been of particular interest to her since 1983. She has worked for People for Animal Rights since 1995 and her main focus has been animal experiments, animal- free methods, and lobbying. She is a member of several committees and boards including, German Federal Animal Welfare Committee, Committee Pursuant to Section 15 of the German Animal Protection Act, and Advisory Board for Animal Welfare. For several years, Baumgartl-Simons has considered the strat- egies for withdrawing from animal experiments. Her work has culminated in ideas for a masterplan in the form of five pillars. She is pleased to have the op- portunity to share her ideas in this volume. xix Contributors Charlotte Blattner is a postdoctoral fellow at Harvard Law School, Cambridge MA, working at the intersection of environmental law and animal law. Previously, she was a postdoctoral fellow at the Department of Philosophy at Queen’s University, Canada, where she explored the utility of thinking about animals as workers. She received a PhD in international and animal law from the University of Basel, as part of the “Law and Animals” doctoral program. In her PhD, Blattner developed ways in which states can respond to the ongoing regulatory race to the bottom in animal law, notably, through extraterritorial jurisdiction. She is a former visiting international scholar at Lewis & Clark Law School and has worked as a research fellow for the foundation Tier im Recht, based in Zürich, Switzerland. Blattner has authored numerous publications in animal law, in- ternational and trade law, as well as environmental law. The disconcerting un- derdevelopment of animal law and the need to evaluate law critically, in light of our growing knowledge of the non-human animal world, prompted her to explore means for a paradigm change for animals in research. Vanessa Carli Bones is a postdoctoral fellow at the Federal University of Paraná, Brazil, with an em- phasis on the welfare of animals used in laboratories. She studied veterinary medicine at the Federal University of Santa Maria and completed her Master’s degree and PhD in veterinary sciences at the Federal University of Paraná. In her Master’s and PhD studies, she focused on the welfare of laboratory animals and methods to replace them. During this time, Bones had opportunity to par- ticipate in several scientific events in this area, including the World Congress on Alternatives and Animal Use in the Life Sciences. She is experienced in the areas of animal welfare, animal ethics, and alternatives to the use of labora- tory animals. At present, she is trying to identify legal violations in the use of animals in laboratories in Brazil and is working as a technical advisor to the Regional Council of Veterinary Medicine of Paraná, Brazil. Robert Buttrose has an honors degree in philosophy and a Master’s degree in cognitive science from the University of New South Wales, Sydney, Australia. He has worked for the Australian Commonwealth Government, universities, and the private sec- tor. Buttrose is a member of the Victorian Schools Animal Ethics Committee and the management committee of Humane Research Australia, the coun- try’s largest anti-vivisectionist organization. He has written articles (in col- laboration with Monika Merkes) about animal experimentation, animal ethics