{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:38:40Z","timestamp":1776465520814,"version":"3.51.2"},"reference-count":204,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2013,3,19]],"date-time":"2013-03-19T00:00:00Z","timestamp":1363651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The use of non-human animals in biomedical research has given important contributions to the medical progress achieved in our day, but it has also been a cause of heated public, scientific and philosophical discussion for hundreds of years. This review, with a mainly European outlook, addresses the history of animal use in biomedical research, some of its main protagonists and antagonists, and its effect on society from Antiquity to the present day, while providing a historical context with which to understand how we have arrived at the current paradigm regarding the ethical treatment of animals in research.<\/jats:p>","DOI":"10.3390\/ani3010238","type":"journal-article","created":{"date-parts":[[2013,3,19]],"date-time":"2013-03-19T12:33:57Z","timestamp":1363696437000},"page":"238-273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Animal Experiments in Biomedical Research: A Historical Perspective"],"prefix":"10.3390","volume":"3","author":[{"given":"Nuno","family":"Franco","sequence":"first","affiliation":[{"name":"Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2013,3,19]]},"reference":[{"key":"ref_1","unstructured":"von Staden, H. (1989). Herophilus: The Art of Medicine in Early Alexandria, Cambridge University Press."},{"key":"ref_2","unstructured":"Anderson, S. (2005). Making Medicines: A Brief History of Pharmacy and Pharmaceuticals, Pharmaceutical Press."},{"key":"ref_3","unstructured":"Rupke, N.A. (1987). Vivisection in Historical Perspective, Croom Helm."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Finkel, I.L., and Geller, M.J. (2007). Disease in Babylonia, Brill.","DOI":"10.1163\/ej.9789004124011.i-226"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guerrini, A. (2003). Experimenting with Humans and Animals: From Galen to Animal Rights, Johns Hopkins University Press.","DOI":"10.56021\/9780801871962"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"O\u2019Malley, C.D. (1964). Andreas Vesalius of Brussels, University of California Press.","DOI":"10.1525\/9780520310230"},{"key":"ref_7","unstructured":"Regan, T., and Singer, P. (1989). Animal Rights and Human Obligations, Prentice Hall. [2nd ed.]."},{"key":"ref_8","unstructured":"Prioreschi, P. (1998). A History of Medicine, Volume 3: Roman Medicine, Horatius Press."},{"key":"ref_9","unstructured":"Prioreschi, P. (1996). A History of Medicine, Volume 2: Greek Medicine, Horatius Press. [2nd ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0306-9877(94)90091-4","article-title":"Experimentation and scientific method in the classical world: Their rise and decline","volume":"42","author":"Prioreschi","year":"1994","journal-title":"Med. Hypoth."},{"key":"ref_11","unstructured":"Prioreschi, P. (1996). A History of Medicine, Volume 5: Medieval Medicine, Edwin Mellen Press. [2nd ed.]."},{"key":"ref_12","unstructured":"Montague, B. (1842). The Works of Francis Bacon: Baron of Verulam, Viscount St. Albans, and Lord High Chancellor of England, Carey and Hart."},{"key":"ref_13","unstructured":"Regan, T., and Singer, P. (1989). Animal Rights and Human Obligations, Prentice Hall. [2nd ed.]."},{"key":"ref_14","unstructured":"Rupke, N.A. (1987). Vivisection in Historical Perspective, Croom Helm."},{"key":"ref_15","unstructured":"Boden, M.E. (2006). Mind as Machine: A History of Cognitive Science, Oxford University Press."},{"key":"ref_16","unstructured":"Zalta, E.N. (2011). The Stanford Encyclopedia of Philosophy, Center for the Study of Language and Information, Stanford University. [Summer 2011 ed.]."},{"key":"ref_17","unstructured":"Moya, G.J.D. (1991). Rene Descartes: Critical Assessments, Routledge."},{"key":"ref_18","first-page":"219","article-title":"Descartes on animals","volume":"42","author":"Harrison","year":"1992","journal-title":"Philosoph. Quart."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1468-5914.2011.00464.x","article-title":"Descartes: The smear and related misconstruals","volume":"41","author":"Leiber","year":"2011","journal-title":"J. Theory Soc. Behav."},{"key":"ref_20","first-page":"691","article-title":"Animal consciousness: What matters and why","volume":"62","author":"Dennett","year":"1995","journal-title":"Soc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1515\/agph.1998.80.3.268","article-title":"Descartes on the moral status of animals","volume":"80","author":"Steiner","year":"1998","journal-title":"Arch. f\u00fcr Geschichte der Philosophie"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Steintrager, J.A. (2004). Cruel Delight: Enlightenment Culture and the Inhuman, Indiana University Press.","DOI":"10.2979\/1445.0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1177\/003591575004301102","article-title":"Ren\u00e9 Descartes, 1596\u20131650. A short note on his part in the history of medicine","volume":"43","author":"Bayon","year":"1950","journal-title":"Proc. Roy. Soc. Med."},{"key":"ref_24","unstructured":"Gaukroger, S., Schuster, J., and Sutton, J. (2000). Descartes\u2019 Natural Philosophy, Routledge."},{"key":"ref_25","unstructured":"Steiner, G. (2010). Anthropocentrism and its Discontents: The Moral Status of Animals in the History of Western Philosophy, University of Pittsburgh Press."},{"key":"ref_26","unstructured":"Spinoza, B. (2006). The Ethics, Echo Library."},{"key":"ref_27","unstructured":"Locke, J. (1778). Some Thoughts Concerning Education, Walker."},{"key":"ref_28","unstructured":"Schneewind, J.B. (1997). Lectures on Ethics, Cambridge University Press."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1017\/S0031819100063312","article-title":"Kant\u2019s treatment of animals","volume":"49","author":"Broadie","year":"1974","journal-title":"Philosophy"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Linzey, A. (2009). The Link between Animal Abuse and Human Violence, Sussex Academic Press.","DOI":"10.2307\/jj.4116413"},{"key":"ref_31","unstructured":"Gregory, A. (2001). Harvey\u2019s Heart: The Discovery of Blood Circulation, Icon Books Ltd."},{"key":"ref_32","unstructured":"Conrad, L.I., Neve, M., Nutton, V., Porter, R., and Wear, A. (1995). The Western Medical Tradition: 800 BC\u20131800 AD, Cambridge University Press."},{"key":"ref_33","unstructured":"Shackelford, J. (2003). William Harvey and the Mechanics of the Heart, Oxford University Press."},{"key":"ref_34","first-page":"491","article-title":"Anatomy of a physiological discovery: William Harvey and the circulation of the blood","volume":"88","author":"McMullen","year":"1995","journal-title":"J. Roy. Soc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cohen, I.B. (1994). Interactions: Some Contacts between the Natural Sciences and Social Sciences, MIT Press.","DOI":"10.1007\/978-94-017-3391-5_1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physiolgenomics.00117.2005","article-title":"Computational modeling of physiological systems","volume":"23","author":"Beard","year":"2005","journal-title":"Physiol. Genom."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Grene, M.G., and Depew, D.J. (2004). The Philosophy of Biology: An Episodic History, Cambridge University Press.","DOI":"10.1017\/CBO9780511819018"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/jhmas\/XII.4.167","article-title":"The Echo of Harvey\u2019s de Motu Cordis (1628) 1628 to 1657","volume":"XII","author":"Weil","year":"1957","journal-title":"J. History Med. Allied Sci."},{"key":"ref_39","first-page":"1405","article-title":"From the discovery of the circulation of the blood to the first steps in hemorheology: Part 2","volume":"28","year":"2009","journal-title":"Revista Portuguesa de Cardiologia"},{"key":"ref_40","first-page":"91","article-title":"Descartes and the heart beat: A conservative innovation","volume":"Volume 11","author":"Buchwald","year":"2005","journal-title":"Wrong for the Right Reasons (Archimedes-New Studies in the History and Phylosophy of Science and Technology)"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2307\/2709897","article-title":"Mind-body dualism and the Harvey-Descartes controversy","volume":"55","author":"Gorham","year":"1994","journal-title":"J. History Ideas"},{"key":"ref_42","unstructured":"Frank, R.G. (1980). Harvey and the Oxford Physiologists: Scientific Ideas and Social Interaction, University of California Press."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1177\/014107689809100316","article-title":"Palpitation: Brain, heart, and \u2018spirits\u2019 in the seventeenth century","volume":"91","author":"Wooley","year":"1998","journal-title":"J. Roy. Soc. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"420","DOI":"10.7326\/0003-4819-132-5-200003070-00023","article-title":"Richard Lower: Anatomist and physiologist","volume":"132","author":"Felts","year":"2000","journal-title":"Ann. Int. Med."},{"key":"ref_45","unstructured":"Wootton, D. (2006). Bad Medicine: Doctors Doing Harm Since Hippocrates, Oxford University Press."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Park, K., and Daston, L. (2006). The Cambridge History of Science, Volume 3: Early Modern Science, Cambridge University Press.","DOI":"10.1017\/CHOL9780521572446"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"French, R.K. (1994). William Harvey\u2019s Natural Philosophy, Cambridge University Press.","DOI":"10.1017\/CBO9780511628245"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Van der Worp, H.B., Howells, D.W., Sena, E.S., Porritt, M.J., Rewell, S., O\u2019Collins, V., and Macleod, M.R. (2010). Can animal models of disease reliably inform human studies?. PLoS Med., 7.","DOI":"10.1371\/journal.pmed.1000245"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Maehle, A.-H. (1999). Drugs on Trial: Experimental Pharmacology and Therapeutic Innovation in the Eighteenth Century, Editions Rodopi.","DOI":"10.1163\/9789004333291"},{"key":"ref_50","unstructured":"Boyle, R. (1660). New Experiments Physico-Mechanicall, Touching the Spring of the Air, and its Effects (Made in a New Pneumatical Engine): Written by Way of Letter to the Right Honorable Charles, Lord Vicount of Dungarvan, Eldest Son to the Earl of Corke\/by the Honorable Robert Boyle, Esq., Printed by H. Hall."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/japplphysiol.00759.2004","article-title":"Robert Boyle\u2019s landmark book of 1660 with the first experiments on rarified air","volume":"98","author":"West","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1152\/jappl.1984.57.3.635","article-title":"Stephen Hales: Neglected respiratory physiologist","volume":"57","author":"West","year":"1984","journal-title":"J. Appl. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/014107689308600613","article-title":"The impact of Stephen Hales on medicine","volume":"86","author":"Smith","year":"1993","journal-title":"J. Roy. Soc. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1136\/bmj.2.6103.1656","article-title":"Stephen Hales, DD, FRS","volume":"2","year":"1977","journal-title":"Br. Med. J."},{"key":"ref_55","unstructured":"Conrad, L.I., Neve, M., Nutton, V., Porter, R., and Wear, A. (1995). The Western Medical Tradition: 800 BC-1800 AD, Cambridge University Press."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00415-006-0998-x","article-title":"Albrecht Von Haller (1708\u20131777)","volume":"253","author":"Frixione","year":"2006","journal-title":"J. Neurol."},{"key":"ref_57","unstructured":"Duffin, J. (2010). History of Medicine: A Scandalously Short Introduction, University of Toronto Press. [2nd ed.]."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1017\/S0025727300015362","article-title":"William Harvey and the foundation of modern haemodynamics by Albrecht Von Haller","volume":"14","author":"Buess","year":"1970","journal-title":"Med. Hist."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/clc.4960180513","article-title":"Albrecht von Haller","volume":"18","author":"Fye","year":"1995","journal-title":"Clin. Cardiol."},{"key":"ref_60","first-page":"393","article-title":"Albrecht Von Haller medical encyclopedist","volume":"48","author":"Bay","year":"1960","journal-title":"Bull. Med. Library Assoc."},{"key":"ref_61","first-page":"51","article-title":"Animal experiments: The long debate","volume":"121","author":"Festing","year":"1989","journal-title":"New Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S0025727300050250","article-title":"Literary responses to animal experimentation in seventeenth- and eighteenth-century britain","volume":"34","author":"Maehle","year":"1990","journal-title":"Med. Hist."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Maehle, A.-H. (1999). Drugs on Trial: Experimental Pharmacology and Therapeutic Innovation in the Eighteenth Century, Editions Rodopi.","DOI":"10.1163\/9789004333291"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.resuscitation.2008.09.020","article-title":"Luigi Galvani and the foundations of electrophysiology","volume":"80","author":"Cajavilca","year":"2009","journal-title":"Resuscitation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0166-2236(97)01101-6","article-title":"Luigi Galvani and animal electricity: Two centuries after the foundation of electrophysiology","volume":"20","author":"Piccolino","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_66","unstructured":"Roe, S.A. (1981). Matter, Life, and Generation: Eighteenth-Century Embryology and the Haller-Wolff Debate, Cambridge University Press."},{"key":"ref_67","unstructured":"(2005). The Ethics of Research Involving Animals, Nuffield Council on Bioethics."},{"key":"ref_68","unstructured":"Voltaire, F.M.A. (2004). Philosophical Dictionary, Penguin Books."},{"key":"ref_69","unstructured":"Schopenhauer, A. (1903). On the Basis of Morality, Swan Sonnenschein & Co., Ltd."},{"key":"ref_70","unstructured":"Rousseau, J.-J. (2007). Discourse on the Origin of Inequality, Filiquarian Publishing, LLC."},{"key":"ref_71","unstructured":"Bentham, J. (1823). An Introduction to the Principles of Morals and Legislation, W. Pickering."},{"key":"ref_72","unstructured":"Bowring, J. (1843). The Works of Jeremy Bentham, William Tate."},{"key":"ref_73","unstructured":"Boralevi, L.C. (1984). Bentham and the Oppressed, W. de Gruyter."},{"key":"ref_74","unstructured":"Brunton, D. (2004). Medicine Transformed: Health, Disease and Society in Europe, 1800\u20131930, Manchester University Press."},{"key":"ref_75","first-page":"133","article-title":"Biomedical science and human health","volume":"51","author":"Thomas","year":"1978","journal-title":"Yale J. Biol. Med."},{"key":"ref_76","unstructured":"Duffin, J. (2010). History of Medicine: A Scandalously Short Introduction, University of Toronto Press. [2nd ed.]."},{"key":"ref_77","unstructured":"Bynum, W.F. (1994). Science and the Practice of Medicine in the Nineteenth Century, Cambridge University Press."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Coleman, W., and Holmes, F.L. (1988). The Investigative Enterprise: Experimental Physiology in Nineteenth-Century Medicine, University of California Press.","DOI":"10.1525\/9780520310353"},{"key":"ref_79","unstructured":"Rupke, N.A. (1987). Vivisection in Historical Perspective, Croom Helm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/02698599408573495","article-title":"Animal experimentation: The legacy of Claude Bernard","volume":"8","author":"LaFollette","year":"1994","journal-title":"Int. Stud. Philos. Sci."},{"key":"ref_81","unstructured":"Kuhse, H., and Singer, P. (1998). A Companion to Bioethics, Blackwell Publishing."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.3171\/JNS\/2008\/108\/5\/1038","article-title":"Fran\u00e7ois Magendie (1783\u20131855) and his contributions to the foundations of neuroscience and neurosurgery","volume":"108","author":"Tubbs","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/007327536800700102","article-title":"Physiology\u2019s struggle for independence in the first half of the nineteenth century","volume":"7","author":"Schiller","year":"1968","journal-title":"Hist. Sci."},{"key":"ref_84","unstructured":"Monamy, V. (2000). Animal Experimentation: A Guide to the Issues, Cambridge University Press."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ryder, R.D. (2000). Animal Revolution: Changing Attitudes Toward Speciesism, Berg.","DOI":"10.1017\/S0962728600024003"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1097\/00007611-198910000-00013","article-title":"Francois Magendie, Claude Bernard, and the interrelation of science, history, and philosophy","volume":"82","author":"Bloch","year":"1989","journal-title":"South. Med. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/jhmas\/jrm015","article-title":"Claude Bernard and an introduction to the study of experimental medicine: \u201cPhysical vitalism\u201d, dialectic, and epistemology","volume":"62","author":"Normandin","year":"2007","journal-title":"J. Hist. Med. Allied Sci."},{"key":"ref_88","unstructured":"Rudacille, D. (2001). The Scalpel and the Butterfly: The Conflict between Animal Research and Animal Protection, University of California Press."},{"key":"ref_89","unstructured":"Bernard, C. (1927). An Introduction to the Study of Experimental Medicine, Macmillan."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.endeavour.2006.07.001","article-title":"Disputed discovery: Vivisection and experiment in the 19th century","volume":"30","author":"Berkowitz","year":"2006","journal-title":"Endeavour"},{"key":"ref_91","unstructured":"Bynum, W.F. (1994). Science and the Practice of Medicine in the Nineteenth Century, Press Syndicate of the University of Cambridge."},{"key":"ref_92","first-page":"R9","article-title":"Carl Ludwig: The man, his time, his influence","volume":"432","author":"Zimmer","year":"1996","journal-title":"Pfl\u00fcgers Archiv-Eur. J. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Coleman, W., and Holmes, F.L. (1988). The Investigative Enterprise: Experimental Physiology in Nineteenth-Century Medicine, University of California Press.","DOI":"10.1525\/9780520310353"},{"key":"ref_94","unstructured":"Cahan, D. (1993). Hermann von Helmholtz and the Foundations of Nineteenth-Century Science, University of California Press."},{"key":"ref_95","unstructured":"Otis, L. Johannes Peter M\u00fcller (1801\u20131858). Available online:http:\/\/vlp.mpiwg-berlin.mpg.de\/essays\/data\/enc22."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Coleman, W., and Holmes, F.L. (1988). The Investigative Enterprise: Experimental Physiology in Nineteenth-Century Medicine, University of California Press.","DOI":"10.1525\/9780520310353"},{"key":"ref_97","unstructured":"O\u2019Malley, C.D. (1970). The History of Medical Education, University of California Press."},{"key":"ref_98","unstructured":"Rupke, N.A. (1987). Vivisection in Historical Perspective, Croom Helm."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Blazina, C., Boyra, G., and Shen-Miller, D. (2011). The Psychology of the Human-Animal Bond: A Resource for Clinicians and Researchers, Springer.","DOI":"10.1007\/978-1-4419-9761-6"},{"key":"ref_100","unstructured":"King, C.K., and Goodall, J.R. (2008). Frankenstein\u2019s Science: Experimentation and Discovery in Romantic Culture, 1780\u20131830, Ashgate."},{"key":"ref_101","unstructured":"Olmsted, J.M.D. (1944). Fran\u00e7ois Magendie, Arno Press."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/107385849800400520","article-title":"Claude Bernard and the constancy of the internal environment","volume":"4","author":"Gross","year":"1998","journal-title":"The Neuroscientist"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1213\/00000539-199101000-00030","article-title":"Lectures on anesthetics and on asphyxia (book review)","volume":"72","author":"Broennle","year":"1991","journal-title":"Anesth. Analg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/j.1365-2044.1978.tb08473.x","article-title":"Claude Bernard (1813\u20131878)","volume":"33","author":"Lee","year":"1978","journal-title":"Anaesthesia"},{"key":"ref_105","first-page":"203","article-title":"The moral aspects of vivisection","volume":"140","author":"Davis","year":"1885","journal-title":"North Am. Rev."},{"key":"ref_106","unstructured":"Inoue, T., and Kodama, Y. (2007, January 21\u201325). Future Alternatives in \u201c3Rs\u201d: Learning from History. Proceedings of the 6th World Congress on Alternatives & Animal Use in the Life Sciences, Tokyo, Japan."},{"key":"ref_107","unstructured":"Debr\u00e9, P. (2000). Louis Pasteur, Johns Hopkins University Press."},{"key":"ref_108","unstructured":"Rey, R. (1998). The History of Pain, Harvard University Press."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Snow, S.J. (2008). Blessed Days of Anaesthesia: How Anaesthetics Changed the World, Oxford University Press.","DOI":"10.1093\/oso\/9780192805867.001.0001"},{"key":"ref_110","unstructured":"Cunningham, A., and Williams, P. (1992). The Laboratory Revolution in Medicine, Cambridge University Press."},{"key":"ref_111","first-page":"265","article-title":"Dog fight: Darwin as animal advocate in the antivivisection controversy of 1875","volume":"40","author":"Feller","year":"2009","journal-title":"Stud. Hist. Philos. Sci. Part C: Stud. Hist. Philos. Biol. Biomed. Sci."},{"key":"ref_112","unstructured":"Tait, L. (1882). The Uselessness of Vivisection upon Animals as a Method of Scientific Research, The Herald Press."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1126\/science.3.64.421","article-title":"Vivisection\u2014A statement in behalf of science","volume":"3","author":"Elliot","year":"1896","journal-title":"Science"},{"key":"ref_114","unstructured":"Johnson, E.M. Charles Darwin and the vivisection outrage. The Primate Diaries. Scientific American, 2011. Available online:http:\/\/blogs.scientificamerican.com\/primate-diaries\/2011\/10\/06\/vivisection-outrage\/."},{"key":"ref_115","unstructured":"Darwin, C. (1881). Darwin on vivisection\u2014Experiments on living animals necessary to the progress of physiological study. The New York Times."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Gaw, J.L. (1999). \u201cA Time to Heal\u201d: The Diffusion of Listerism in Victorian Britain, American Philosophical Society.","DOI":"10.2307\/3185883"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/00033798600200111","article-title":"Drawing the life-blood of physiology: Vivisection and the physiologists\u2019 dilemma, 1870\u20131900","volume":"43","author":"Richards","year":"1986","journal-title":"Ann. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Dolan, K. (2007). Laboratory Animal Law: Legal Control of the Use of Animals in Research, Blackwell Publisher. [2nd ed.].","DOI":"10.1002\/9780470753361"},{"key":"ref_119","first-page":"37","article-title":"Cruel knives? Vivisection and biomedical research in Victorian English Canada","volume":"14","author":"Connor","year":"1997","journal-title":"Can. Bull. Med. Hist."},{"key":"ref_120","unstructured":"Semmelweis, I. (1983). Etiology, Concept and Prophylaxis of Childbed Fever, University of Wisconsin Press."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1107\/S0108767309024088","article-title":"Louis Pasteur\u2019s discovery of molecular chirality and spontaneous resolution in 1848, together with a complete review of his crystallographic and chemical work","volume":"65","author":"Flack","year":"2009","journal-title":"Acta Crystallogr. Sec. A"},{"key":"ref_122","unstructured":"Bazin, H. (2011). Vaccination\u2014A History: From Lady Montagu to Genetic Engineering, John Libbey Eurotext Ltd."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2307\/2649773","article-title":"America\u2019s first medical breakthrough: How popular excitement about a french rabies cure in 1885 raised new expectations for medical progress","volume":"103","author":"Hansen","year":"1998","journal-title":"Am. Hist. Rev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1046\/j.1365-2672.2001.01495.x","article-title":"The life and works of Louis Pasteur","volume":"91","author":"Schwartz","year":"2001","journal-title":"J. Appl. Microbiol."},{"key":"ref_125","unstructured":"Hendriksen, C.F.M., and Morton, D.B. (1999). Humane Endpoints in Animals Experiments for Biomedical Research, Royal Society of Medicine Press."},{"key":"ref_126","unstructured":"Rosenau, M.J. (1916). Preventive Medicine and Hygiene, D. Appleton and Co.. [2nd ed.]."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Vallery-Radot, R. (1911). The Life of Pasteur, Doubleday.","DOI":"10.5962\/bhl.title.20935"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Vallery-Radot, R. (1886). Louis Pasteur\u2014His Life and Labours, D. Appleton and Company.","DOI":"10.5962\/bhl.title.29261"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/bmj.288.6414.379","article-title":"Robert Koch and the cholera vibrio: A centenary","volume":"288","year":"1984","journal-title":"Br. Med. J."},{"key":"ref_130","first-page":"383","article-title":"Pasteur\u2013Koch: Distinctive ways of thinking about infectious diseases","volume":"2","author":"Ullmann","year":"2007","journal-title":"Microbe"},{"key":"ref_131","unstructured":"Brock, T.D. (1988). Robert Koch: A Life in Medicine and Bacteriology, ASM Press."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000149583","article-title":"The contributions of Paul Ehrlich to pharmacology: A tribute on the occasion of the centenary of his Nobel Prize","volume":"82","author":"Bosch","year":"2008","journal-title":"Pharmacology"},{"key":"ref_133","unstructured":"Silverstein, A.M. (2001). Paul Ehrlich\u2019s Receptor Immunology: The Magnificent Obsession, Elsevier Science."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2302\/kjm.40.35","article-title":"A centennial review: The 1890 tetanus antitoxin paper of von Behring and Kitasato and the related developments","volume":"40","author":"Kantha","year":"1991","journal-title":"Keio J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Linton, D.S. (2005). Emil von Behring: Infectious Disease, Immunology, Serum Therapy, American Philosophical Society.","DOI":"10.70249\/9780871692863"},{"key":"ref_136","first-page":"548","article-title":"Research in medicine. II. The development of laboratories for the medical sciences","volume":"80","author":"Pearce","year":"1912","journal-title":"Popul. Sci. Month."},{"key":"ref_137","unstructured":"Davis, N. (1903). History of Medicine, Cleveland Press."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ernst, H.C. (1902). Animal Experimentation; A Series of Statements Indicating its Value to Biological and Medical Science, Little, Brown, and Company.","DOI":"10.5962\/bhl.title.1879"},{"key":"ref_139","unstructured":"Romano, T.M. (2002). Making Medicine Scientific: John Burdon Sanderson and the Culture of Victorian Science, Johns Hopkins University Press."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/355837","article-title":"Ideals of science and their discontents in late nineteenth-century American medicine","volume":"82","author":"Warner","year":"1991","journal-title":"Isis"},{"key":"ref_141","unstructured":"Cunningham, A., and Williams, P. (1992). The Laboratory Revolution in Medicine, Cambridge University Press."},{"key":"ref_142","unstructured":"(2007). Medical Advances and Animal Research\u2014The Contribution of Animal Science to the Medical Revolution: Some Case Histories, Understanding Animal Research."},{"key":"ref_143","unstructured":"Available online:http:\/\/www.fbresearch.org\/nobelprize\/."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/451644a","article-title":"A systematic look at an old problem","volume":"451","author":"Kirkwood","year":"2008","journal-title":"Nature"},{"key":"ref_145","unstructured":"Kinsella, K., and He, W. (2009). An Aging World: 2008; U.S. Census Bureau, International Population Reports, P95\/09-1, U.S. Government Printing Office."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1069675","article-title":"Broken limits to life expectancy","volume":"296","author":"Oeppen","year":"2002","journal-title":"Science"},{"key":"ref_147","unstructured":"Rudacille, D. (2001). The Scalpel and the Butterfly: The Conflict between Animal Research and Animal Protection, University of California Press."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Preece, R. (2011). Animal Sensibility and Inclusive Justice in the Age of Bernard Shaw, University of British Columbia Press.","DOI":"10.59962\/9780774821117"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Liddick, D. (2006). Eco-Terrorism: Radical Environmental and Animal Liberation Movements, Praeger.","DOI":"10.5040\/9798400643422"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1086\/356025","article-title":"Political animals. The shaping of biomedical research literature in twentieth-century america","volume":"83","author":"Lederer","year":"1992","journal-title":"Isis"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-1-4020-2271-5_7","article-title":"The welfare of laboratory mice","volume":"Volume 2","author":"Kaliste","year":"2007","journal-title":"The Welfare of Laboratory Animals"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-1-4020-2271-5_8","article-title":"The welfare of laboratory rats","volume":"Volume 2","author":"Kaliste","year":"2007","journal-title":"The Welfare of Laboratory Animals"},{"key":"ref_153","unstructured":"Suckow, M.A., Weisbroth, S.H., and Franklin, C.L. (2006). The Laboratory Rat, Elsevier."},{"key":"ref_154","unstructured":"Krinke, G. (2000). The Laboratory Rat, Academic."},{"key":"ref_155","unstructured":"Henig, R.M. (2001). The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics, Houghton Mifflin."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1126\/science.6272397","article-title":"Integration and stable germ line transmission of genes injected into mouse pronuclei","volume":"214","author":"Gordon","year":"1981","journal-title":"Science"},{"key":"ref_157","unstructured":"Fox, J.G. (2007). The Mouse in Biomedical Research: History, Wild Mice, and Genetics, Academic Press."},{"key":"ref_158","unstructured":"Hedrich, H.J., and Bullock, G.R. (2004). The Laboratory Mouse, Elsevier Academic Press."},{"key":"ref_159","unstructured":"(2010). Sixth Report on the Statistics on the Number of Animals Used for Experimental and Other Scientific Purposes in the Member States of the European Union, European Commission."},{"key":"ref_160","unstructured":"Singer, P. (2003). Animal liberation at 30. The New York Review of Books."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Ryder, R.D. (2000). Animal Revolution: Changing Attitudes toward Speciesism, Berg.","DOI":"10.1017\/S0962728600024003"},{"key":"ref_162","unstructured":"Singer, P. (2001). Animal Liberation, HarperCollins Publishers."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Singer, P. (2011). Practical Ethics, Cambridge University Press.","DOI":"10.1017\/CBO9780511975950"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Singer, P. (2011). Practical Ethics, Cambridge University Press.","DOI":"10.1017\/CBO9780511975950"},{"key":"ref_165","unstructured":"Singer, P. (2006). Setting limits on animal testing. The Sunday Times."},{"key":"ref_166","unstructured":"Regan, T., and Singer, P. (1989). Animal Rights and Human Obligations, Prentice Hall. [2nd ed.]."},{"key":"ref_167","unstructured":"Orlans, F.B. (1996). In the Name of Science: Issues in Responsible Animal Experimentation, Oxford University Press."},{"key":"ref_168","unstructured":"Cohen, C., and Regan, T. (2001). The Animal Rights Debate, Rowman & Littlefield Publishers."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Conn, P.M., and Parker, J.V. (2008). The Animal Research War, Palgrave Macmillan.","DOI":"10.1057\/9780230611993"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Liddick, D. (2006). Eco-Terrorism: Radical Environmental and Animal Liberation Movements, Praeger.","DOI":"10.5040\/9798400643422"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Regan, T., and Masson, J.M. (2005). Empty Cages: Facing the Challenge of Animal Rights, Rowman & Littlefield Publishers.","DOI":"10.5771\/9780742578210"},{"key":"ref_172","first-page":"50","article-title":"Scientists in bunkers: How appeasement of \u201canimal rights\u201d activism has failed","volume":"Volume 1","author":"Donway","year":"1999","journal-title":"Cerebrum: The Dana Forum on Brain Science"},{"key":"ref_173","first-page":"29","article-title":"Views from behind the barricade","volume":"134","author":"Birke","year":"1992","journal-title":"New Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/470452a","article-title":"Battle scars","volume":"470","author":"Cressey","year":"2011","journal-title":"Nature"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/sj.embor.7400996","article-title":"The ethics of animal research. Talking point on the use of animals in scientific research","volume":"8","author":"Rollin","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_176","first-page":"26","article-title":"Animal experiments: Let the people speak","volume":"162","author":"Aldhous","year":"1999","journal-title":"New Sci."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Crettaz von Roten, F. (2012). Public perceptions of animal experimentation across Europe. Public Underst. Sci.","DOI":"10.1177\/0963662511428045"},{"key":"ref_178","unstructured":"Singer, P. (2000). Ethics into Action: Henry Spira and the Animal Rights Movement, Rowman & Littlefield Publishers."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1017\/S0962728600029596","article-title":"The three Rs: Past, present and future","volume":"14","author":"Russell","year":"2005","journal-title":"Anim. Welf."},{"key":"ref_180","unstructured":"Balls, M. (2007, January 21\u201325). Professor W.M.S. Russell (1925\u20132006): Doyen of the three Rs. Proceedings of the 6th World Congress on Alternatives & Animal Use in the Life Sciences, Tokyo, Japan."},{"key":"ref_181","unstructured":"Salem, D.J., and Rowan, A.N. (2001). The STate of the Animals: 2001, Humane Society Press."},{"key":"ref_182","unstructured":"Russell, W.M.S., and Burch, R.L. (1959). The Principles of Humane Experimental Technique, Methuen & Co. Ltd."},{"key":"ref_183","first-page":"4","article-title":"Alternatives to animal experiments: Serving in the middle ground","volume":"11","author":"Balls","year":"2005","journal-title":"AATEX"},{"key":"ref_184","unstructured":"Smyth, D.H. (1978). Alternatives to Animal Experiments, Scolar Press [for] the Research Defence Society."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Hau, J., and Schapiro, S.J. (2011). Handbook of Laboratory Animal Science-Volume I: Essential Principles and Practices, CRC Press. [3rd ed.].","DOI":"10.1201\/b10837"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Beauchamp, T.L., and Frey, R.G. (2011). The Oxford Handbook of Animal Ethics, Oxford University Press.","DOI":"10.1093\/oxfordhb\/9780195371963.001.0001"},{"key":"ref_187","first-page":"1","article-title":"Animal rights law: Fundamentalism versus pragmatism","volume":"5","author":"Sztybel","year":"2007","journal-title":"J. Crit. Anim. Stud."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10677-005-3297-1","article-title":"Reasonable partiality and animal ethics","volume":"8","author":"Rollin","year":"2005","journal-title":"Ethical Theory Moral Pract."},{"key":"ref_189","unstructured":"Francione, G.L. (1996). Rain without Thunder: The Ideology of the Animal Rights Movement, Temple University Press."},{"key":"ref_190","unstructured":"Francione, G.L. Animal rights theory and utilitarianism: Relative normative guidance. Available online:http:\/\/digitalcommons.calpoly.edu\/cgi\/viewcontent.cgi?article=1054&context=bts."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1177\/026119299502300607","article-title":"The progress of humane experimental technique since 1959: A personal view","volume":"23","author":"Burch","year":"1995","journal-title":"Altern. Lab. Anim."},{"key":"ref_192","first-page":"23","article-title":"Pursuing Medawar\u2019s challenge for full replacement","volume":"1","author":"Stephens","year":"2012","journal-title":"ALTEX Proc."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/scientificamerican0297-86","article-title":"Trends in animal research","volume":"276","author":"Mukerjee","year":"1997","journal-title":"Sci. Am."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1136\/vr.154.15.467","article-title":"Implementation of the \u2018three Rs\u2019 in biomedical research","volume":"154","author":"Carlsson","year":"2004","journal-title":"Vet. Record"},{"key":"ref_195","unstructured":"Kulpa-Eddy, J., Snyder, M., and Stokes, W. (2007, January 21\u201325). A review of trends in animal use in the united states (1972\u20132006). Proceedings of the 6th World Congress on Alternatives & Animal Use in the Life Sciences, Tokyo, Japan."},{"key":"ref_196","first-page":"203","article-title":"A brief history of the animal research debate and the place of alternatives","volume":"12","author":"Rowan","year":"2007","journal-title":"AATEX"},{"key":"ref_197","first-page":"327","article-title":"Estimates for worldwide laboratory animal use in 2005","volume":"36","author":"Taylor","year":"2008","journal-title":"ATLA"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/026119290903700109","article-title":"Worldwide trends in the use of animals in research: The contribution of genetically-modified animal models","volume":"37","author":"Ormandy","year":"2009","journal-title":"Altern. Lab. Anim."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.embor.7400993","article-title":"The ethics of animal research\u2014Talking point on the use of animals in scientific research","volume":"8","author":"Festing","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_200","unstructured":"(2009). Background to the three Rs declaration of bologna, as adopted by the 3rd world congress on alternatives and animal use in the life sciences, bologna, italy, on 31 august 1999. Altern. Lab. Anim., 37, 286\u2013289."},{"key":"ref_201","unstructured":"(2010). Directive 2010\/63\/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes."},{"key":"ref_202","unstructured":"Position paper: 3R in research\u2014how can the concept of 3Rs best be implemented in the context of fundamental research? Adopted on 17 October 2011. Available online:http:\/\/www.basel-declaration.org\/basel-declaration\/the-3rs\/."},{"key":"ref_203","unstructured":"Basel declaration: A call for more trust, transparency and communication on animal research. Adopted on 29 November 2010. Available online:http:\/\/www.basel-declaration.org\/basel-declaration\/."},{"key":"ref_204","first-page":"27","article-title":"Eu Directive 2010\/63\/EU: \u201cImplementing the three Rs through policy\u201d","volume":"1","author":"Louhimies","year":"2012","journal-title":"ALTEX Proc."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/3\/1\/238\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:45:39Z","timestamp":1760219139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/3\/1\/238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,19]]},"references-count":204,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,3]]}},"alternative-id":["ani3010238"],"URL":"https:\/\/doi.org\/10.3390\/ani3010238","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,19]]}}}