Constança Carvalho, D. Alves, A. Knight, Luís Vicente
{"title":"Is Animal-based Biomedical Research Being Used in Its Original Context?","authors":"Constança Carvalho, D. Alves, A. Knight, Luís Vicente","doi":"10.1163/9789004391192_017","DOIUrl":"https://doi.org/10.1163/9789004391192_017","url":null,"abstract":"Since the second half of the twentieth century, non-human animals (herein after referred to as animals) have been widely used as models for researching human disorders. Historically, this occurred for two main reasons: a) animals are complex living systems; and b) it is considered less ethically-contentious as well as easier, quicker, and cheaper to use animals than humans. Their ben efit for biomedical advancement is assumed even though systematic evalua tions, though uncommon, suggest otherwise. It is crucial to evaluate whether animal-based biomedical research successfully benefits medical research even through indirect pathways-or if it is being used merely to justify further animal-based research. In this chapter we demonstrate that there is a lack of communication between animal-based research and clinical research. We dis cuss possible reasons for this and reflect on whether animal use in biomedical research is, indeed, fulfilling its primary purpose. Humans share a long evolutionary story with the rest of the animal king dom, which explains common physiological and behavioral traits and ad aptations. For example, basal ganglia, a set of subcortical nuclei involved in","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125585164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic Modification of Animals: Scientific and Ethical Issues","authors":"Jarrod Bailey","doi":"10.1163/9789004391192_020","DOIUrl":"https://doi.org/10.1163/9789004391192_020","url":null,"abstract":"The scientific method demands a willingness to correct and integrate previ ous knowledge, based on observable, empirical, measurable evidence and subject to laws of reasoning; yet, it has scarcely been applied to non-human animal (hereinafter referred to as animal) research. Nevertheless, animal use in science started declining in the mid 1970s, at least in the United King dom, resulting in a drop in the number of animals used approaching 50% be tween the mid-197os and mid 1980s (uK Home Office, 2016)-perhaps a tacit admission of problematic species differences that render animals poor models for humans. This trend was, however, reversed with the advent of genetically modified (GM) animals, animals whose genetic material has been deliberately altered in some way by insertion, deletion, or substitution of DNA. While the decline in use of non-GM animals continued steeply well into the new millen nium, overall numbers have been rising for some time, solely due to increased utilization of GM animals ( Ormandy, Schuppli and Weary, 2009 ). UK statistics for 2015 show that more than two million procedures involved the creation and breeding of GM animals, who were not subsequently used in further research (around 50% of the total); and there were 720,000 procedures on GM animals in further experiments, representing 35°/o of the total animals used in actual experiments (Hendriksen and Spielmann, 2014; UK Home Office, 2016). Trends in GM animal use for the rest of the world are difficult to determine due to different reporting requirements, but they are likely to be similar, with up to 50% of the approximately 13 million animals used annually in research in the European Union (Eu) (Taylor and Rego, 2016), and the estimated 115 million animals used globally (Taylor et al., 2008). This chapter aims to summarize and analyze this shift in the use of animals in experiments and, without being overly technical, to ask critically why GM","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131208018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Afterword: Evidence over Interests","authors":"J. Gluck","doi":"10.1163/9789004391192_030","DOIUrl":"https://doi.org/10.1163/9789004391192_030","url":null,"abstract":"After years of science education, teaching experience, and research practice, which focused on the use of non-human primates as potential models of human psychological disorders, a young student in my primate behavior class amiably, but insistently, suggested my preparation was incomplete. She asked me to read Peter Singer’s book Animal Liberation, which had been published two years earlier, in 1975. I had been lecturing in class about the effects of early experience on the rhesus monkey’s (Macaca mulatta) social and intellectual development, and my descriptions of the invasive research interventions and behavioral consequences encouraged her to make the book suggestion. I said I would try to find the time, but that I was busy. She handed me a fresh new copy of the book saying, “This is for you.” She made it clear that she was not loaning me her copy but wanted the book to be part of my professional library. Over the following weeks while describing this event to colleagues, many also involved in animal research, I asked them if they had read Professor Singer’s book. While some had heard of it, no one had actually read it. “Why should I do that?” was a common tone of the comments. After all, our experimental standards were quite clear and seemed self-evidently valid. That is, if any interesting and, therefore, valuable research question could not be tested in humans for ethical reasons, then it could be evaluated in animal models. Progress required risk, and progress was urgently needed. This powerful drive to know and understand nature, so as to improve the welfare of human beings, was what the bioethicist Paul Ramsey (1976) called, the research imperative, to emphasize its motivational dominance. In response to the student’s questioning looks as we saw one another in class, and out of respect for her serious intention, I did finally read Animal Liberation. The chapter titled, Tools for research or what the public doesn’t know it is paying for, quickly trapped my attention. Three of the assertions of the chapter were: (1) The raw descriptions of the experimental manipulations done to animals revealed a shocking emotional callousness on the part of investigators; (2) The extent of the harms, which the animals were required to absorb, seemed excessive in comparison with the many obvious or even trivial facts discovered; (3) It was estimated that after all the experimental effort and","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124014175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Behavioral Research on Captive Animals: Scientific and Ethical Concerns","authors":"K. Jayne, Adam See","doi":"10.1163/9789004391192_022","DOIUrl":"https://doi.org/10.1163/9789004391192_022","url":null,"abstract":"Behavioral research on non-human animals (hereinafter referred to as animals) can involve the study of their evolution and natural behavior, cognitive abili ties and psychological constructs, or welfare and response to stressors, among other areas of natural animal behavior. Behavioral research on animals is also carried out to model human behavior, for example in psychological studies and pharmacological models, as well as for comparative purposes to under stand differences and similarities between species. This chapter focuses on the former-where ethology moves into the laboratory environment to model the behavior of free living animals-however, some of the discussion is also rel evant to the laboratory animal model in general because of the very nature of using laboratory animals as \"models\". For further discussion on animals used to model disease or within pharmacology in particular, see the following chapters in this Volume: Archibald, Coleman and Drake (2019, Chapter 18); Bailey (2019, Chapter 19); Carvalho et al., (2019, Chapter 16); Greek and Kramer (2019, Chap ter 17); Pippin, Cavanaugh and Pistollato (2019, Chapter 20); and Ram (2019, Chapter 15). For more on animal models within psychology, see Shapiro (1998). In comparison to other scientific procedures, such as those within biomedi cal research, modeling the behavior of wild animals in the laboratory can involve","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128796535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Critically Evaluating Animal Research","authors":"A. Knight","doi":"10.1163/9789004391192_015","DOIUrl":"https://doi.org/10.1163/9789004391192_015","url":null,"abstract":"Researchers have sought to understand the mechanisms of human health and disease, for as long as the latter has existed. Serious interest in the structure and functioning of the human body has been evident at least since the ancient Greeks. However, the investigations of Greek physicians into human anatomy and physiology were greatly hampered by social taboos about dissecting hu man corpses (von Staden, 1989). But non-human animals (hereinafter referred to as animals), were not so revered or feared. Some dissected their corpses, while others, such as Alcmaeon of Croton (sixth-fifth century, BCE), prac ticed surgical or other invasive procedures on the living ( Court, zoos; Maehle and Trohler, 1990 ), and conducted some of the first animal experiments ever recorded. Almost two millennia passed before such social dogmas were seriously ques tioned. The Renaissance heralded a new era of scientific inquiry, during which Flemish physician and surgeon Vesalius (1514-1564) began to source human cadavers for dissection illegally. He discovered that a number of anatomical structures believed to exist, following animal dissections, were unexpectedly absent in humans. His highly accurate anatomical descriptions challenged the authoritative texts of classical authors (O'Malley, 1964). Throughout the seventeenth century the spirit of scientific inquiry grew and with it, experimentation on living animals. Some surgical investigations and demonstrations that predated anesthesia were infamously cruel and caused widespread social controversy. However, French philosopher, Rene Descartes (1596-1650 ), famously rebutted such critiques, claiming that animals were merely mindless automata, i.e., \"machine-like\" (Descartes, 1989 ); their cries were of no greater moral consequence than the squeals of a poorly-oiled machine. Nevertheless, by the end of the seventeenth century, the question of animal suffering and the acceptability of such procedures had become an increasingly","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123162691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modernizing Biomedical Training: Replacing Live Animal Laboratories with Human Simulation","authors":"J. Pawlowski, D. Feinstein, M. Crandall, S. Gala","doi":"10.1163/9789004391192_023","DOIUrl":"https://doi.org/10.1163/9789004391192_023","url":null,"abstract":"Hands-on skills training in biomedical education has traditionally relied on the use of more than g million live vertebrate animals each year in the United States (us) alone (Patronek and Rauch, 2007), and more in other countries around the world, ranging from performing minor surgical manipulations and pharmacological interventions to managing major traumatic gunshot wounds, bum injuries, and dismemberments. Recently, however, a paradigm shift has taken place that has seen the full replacement of animal use in civilian medical school curricula and skills-training programs in various countries, along with significant reductions and replacements of animal use in comparable military training drills. The embrace of simulation-based biomedical training has been spurred, in part, by improvements in technological realism that accurately mimics human anatomy and physiology, financial burdens involved with run ning animal laboratories, heightened public awareness and ethical objections","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122551062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Contesting Animal Experiments through Ethics and Epistemology: In Defense of a Political Critique of Animal Experimentation","authors":"Arianna Ferrari","doi":"10.1163/9789004391192_008","DOIUrl":"https://doi.org/10.1163/9789004391192_008","url":null,"abstract":"Generally, an animal experiment can be defined as an intervention on an animal, which causes suffering, harm, and distress, for scientific purposes. In this definition, animal experiments differ from more general scientific inves tigations concerning animals, such as observational studies in the wild in the fields of ethology or conservation, in which animals are involved but may not be harmed. Nowadays, the use of the term vivisection, in the case of animal ex periments, is very controversial. This term originally referred to the cutting of living bodies for scientific purposes and has a long conceptual history (Maehle, 1992 ). In ancient times, it was used for referring to experiments on animals as well as on humans. Only in modern times, it became a colloquial term for all animal experiments and was much used by opponents in the nineteenth century, as the criticism of animal experiments became organized in a politi cal movement (Maehle, 1990 ). Many opponents to animal experiments, nowa days, use the term deliberately in a political sense, connecting to past animal protection movements ( e.g., the international Citizens' Initiative Stop Vivisec tion, cf. Rippe, 2009 ). Animal experimenters, on the other hand, oppose the term on the grounds that there is no chirurgical exploration of living animals in experiments ( e.g., German Research Foundation, DFG, 2016). Currently, animals are used in different ways for scientific purposes: they are used in basic research; in education in a variety of biomedical disciplines, including veterinary medicine; as so-called disease models, to mimic different diseases, mostly human ones; as test subjects in different test settings; in vet erinary medicine; in behavioral and cognitive ethological studies; as bioreac tors to produce fluids or bodily parts which contain therapeutic substances for human beings (i.e., \"gene-pharming\"); and as sources of cells, tissues, and","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130205869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extrapolation of Animal Research Data to Humans: An Analysis of the Evidence","authors":"R. Ram","doi":"10.1163/9789004391192_016","DOIUrl":"https://doi.org/10.1163/9789004391192_016","url":null,"abstract":"The ethical arguments against animal experimentation remain ever-strong. In addition, the scientific case against the use of animals in research grows more compelling, with exponential progress in the development of alterna tive methods and new research technologies. The Dutch authorities recently announced an ambitious, but welcome, proposal to phase out \"the use of labo ratory animals in regulatory safety testing of chemicals, food ingredients, pes ticides and (veterinary) medicines\" by 2025, as well as \"the use of laboratory animals for the release of biological products, such as vaccines\" (Netherlands National Committee for the protection of animals used for scientific pur poses, NC ad, 2016 1 p. 3). National government departments ( e.g., the United Kingdom, UK, Home Office) have stated that alternatives to animals are now considered necessary for scientific as much as ethical reasons, also conceding that pressure exists within the research community to use animals in order to get published. Furthermore, only 20% of animal tests across the European Union (Eu) each year are conducted to meet regulatory requirements, with the vast majority carried out as basic research (including basic medical research) or breeding of genetically modified (GM) animals at academic institutions (European Commission, 2013b ). Despite the strength of both scientific and moral arguments, animal re search continues to increase worldwide, especially given the rising trend in use of GM animals. A Catch 22 situation also exists, with regulators largely refusing to break with tradition and continuing to accept only animal data, even when robust human-based data exists. Additionally, when new animal-free, human-relevant methods are developed, regulators often insist that research still be performed on animals; this is considered to be one of the major barri ers to achieving change and, in turn, results in an industry reluctant to invest","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"101 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127118047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Scientific Problems with Using Non-Human Animals to Predict Human Response to Drugs and Disease","authors":"R. Greek, Lisa A. Kramer","doi":"10.1163/9789004391192_018","DOIUrl":"https://doi.org/10.1163/9789004391192_018","url":null,"abstract":"Every year, and in countries around the world, significant time and resources are devoted to the noble cause of developing drugs to treat and cure human disease. With rare exception, drug interventions cannot reach commercial ization without safety and efficacy having first been demonstrated in animal models. The intention of regulations, which require the use of animal models in such contexts, is to ensure that only safe and effective drugs end up being used by patients. Similarly, it is standard practice for researchers to employ animal models in their attempts to understand the way diseases present and progress in humans. Unfortunately, there exist serious theoretical and empiri cal concerns regarding the standard practice of using non-human animals to model human response to perturbations, such as drugs and disease. These concerns are important because conducting disease research and drug devel opment in a manner that is not supported by science will have suboptimal implications for the humans who rely on that research, which encompass the entire population. Based on complexity science, modem evolutionary biology, and empirical evidence, we demonstrate that animal models have failed as predictors of human response. That is, animal models do not and cannot have acceptably high predictive value for human response to drugs and disease. By this we mean that animal modeling, as a methodology, is for all practical pur poses not predictive of human response to drugs and disease; and hence it should be abandoned in favor of human-based research and testing, such as personalized medicine, a new field that takes into account the unique genetic make-up of each individual patient.","PeriodicalId":138056,"journal":{"name":"Animal Experimentation: Working Towards a Paradigm Change","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126510682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}