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'{{Short description|Use of animals in experiments}} {{cs1 config|name-list-style=vanc}}151.181.173.10 {{Redirect|Animal research|other uses|Animal studies (disambiguation)|the journal|Animal Research (journal)}} {{See also|Vivisection}} {{Good article}} {{Pp-pc}} {{Use dmy dates|date=November 2020}} {{Infobox| bodystyle = width:10em; font-size:85%; |aboabovestyle = background-color: #99BADD |subheader = |image1 = [[File:Wistar rat.jpg|200px]] |caption1 = A [[Wistar rat|Wistar laboratory rat]] |headerstyle = background-color: #99BADD |label2 = Description |data2 = Around 50–100 million [[vertebrate]] animals are used in experiments annually. |label3 = Early proponents |label4 = Modern proponents |label5 = Key texts |label6 = Subjects |data6 = Animal testing, science, medicine, animal welfare, animal rights, ethics |below = }} '''Animal testing''', also known as '''animal experimentation''', '''animal research''', and '''''in vivo'' testing''', is the use of [[non-human animals]], such as [[model organism]]s, in experiments that seek to control the variables that affect the [[behavior]] or [[biological system]] under study. This approach can be contrasted with field studies in which animals are observed in their natural environments or habitats. Experimental research with animals is usually conducted in universities, medical schools, pharmaceutical companies, defense establishments, and commercial facilities that provide animal-testing services to the industry.<ref name=selectcommintro>{{cite web|url=https://publications.parliament.uk/pa/ld200102/ldselect/ldanimal/150/15004.htm#a7 |title="Introduction", Select Committee on Animals in Scientific Procedures Report|publisher=UK Parliament|access-date=2012-07-13}}</ref> The focus of animal testing varies on a continuum from [[Basic research|pure research]], focusing on developing fundamental knowledge of an organism, to applied research, which may focus on answering some questions of great practical importance, such as finding a cure for a disease.<ref name="Ethical">{{cite journal |author1=Liguori, G.| display-authors=etal| year = 2017 | title = Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, 3Rs Strategies, and Harm-Benefit Analysis| journal = Tissue Engineering Part C: Methods | volume = 23 | issue = 12 | pages= 850–62 | doi=10.1089/ten.TEC.2017.0189| pmid=28756735| s2cid=206268293| url=https://pure.rug.nl/ws/files/51950145/ten.tec.2017.0189.pdf}}</ref> Examples of applied research include testing disease treatments, breeding, defense research, and [[Toxicology testing|toxicology]], including [[Testing cosmetics on animals|cosmetics testing]]. In education, animal testing is sometimes a component of [[biology]] or [[psychology]] courses.<ref>{{cite journal |last=Hajar |first=Rachel |date=2011 |title=Animal Testing and Medicine |journal=Heart Views |volume=12 |issue=1 |pages=42 |doi=10.4103/1995-705X.81548 |issn=1995-705X |pmc=3123518 |pmid=21731811 |doi-access=free }}</ref> Research using animal models has been central to most of the achievements of modern medicine.<ref name=RSM2015/><ref name=NRCIOM/><ref name="Nature2007"/> It has contributed to most of the basic knowledge in fields such as human [[physiology]] and [[biochemistry]], and has played significant roles in fields such as [[neuroscience]] and [[infectious disease]].<ref name=NRCIOMb/><ref name="HLAS2011"/> The results have included the near-[[Poliomyelitis eradication|eradication of polio]] and the development of [[organ transplantation]], and have benefited both humans and animals.<ref name=RSM2015/><ref name="IOM1991"/> From 1910 to 1927, [[Thomas Hunt Morgan]]'s work with the fruit fly ''[[Drosophila melanogaster]]'' identified [[chromosome]]s as the vector of inheritance for genes,<ref name="nobelprize.org"/><ref name="nobel2"/> and [[Eric Kandel]] wrote that Morgan's discoveries "helped transform biology into an experimental science".<ref name="Kandel1999"/> Research in model organisms led to further medical advances, such as the production of the [[diphtheria antitoxin]]<ref name="nobel3"/><ref name="Cannon2009"/> and the 1922 discovery of [[insulin]]<ref name="insulin"/> and its use in treating diabetes, which had previously meant death.<ref name="Thompson2009"/> Modern general anaesthetics such as [[halothane]] were also developed through studies on model organisms, and are necessary for modern, complex surgical operations.<ref name="raventos1956"/> Other 20th-century medical advances and treatments that relied on research performed in animals include [[organ transplant]] techniques,<ref name="carrel1912"/><ref name="williamson1926">Williamson C (1926) ''J. Urol.'' 16: p. 231</ref><ref name="woodruff1986"/><ref name="moore1964"/> the heart-lung machine,<ref name="gibbon1937"/> [[antibiotic]]s,<ref name="rawbw"/><ref name="fleming1929"/> and the [[whooping cough]] vaccine.<ref name="mrc1956"/> Animal testing is widely used to research human [[disease]] when [[human experimentation]] would be unfeasible or [[bioethics|unethical]].<ref>{{cite book|url=https://books.google.com/books?id=yTfNH3cScKAC<!--confirmed ISBN match; full text access-->|title=The Case for Animal Experimention: An Evolutionary and Ethical Perspective|last=Fox|first=Michael Allen|publisher=University of California Press|year=1986|isbn=978-0-520-05501-8|location=Berkeley and Los Angeles, California|oclc=11754940|via=Google Books}}</ref> This strategy is made possible by the [[common descent]] of all living organisms, and the conservation of [[Metabolic pathway|metabolic]] and [[developmental biology|developmental]] pathways and [[genetic material]] over the course of [[evolution]].<ref>{{cite journal |last1=Allmon |first1=Warren D. |last2=Ross |first2=Robert M. |title=Evolutionary remnants as widely accessible evidence for evolution: the structure of the argument for application to evolution education |journal=Evolution: Education and Outreach |date=December 2018 |volume=11 |issue=1 |pages=1 |doi=10.1186/s12052-017-0075-1 |s2cid=29281160 |doi-access=free }}</ref> Performing experiments in model organisms allows for better understanding the disease process without the added risk of harming an actual human. The species of the model organism is usually chosen so that it reacts to disease or its treatment in a way that resembles human [[physiology]] as needed. [[Biological activity]] in a model organism does not ensure an effect in humans, and care must be taken when generalizing from one organism to another.<ref>{{Cite book|title=Essential Developmental Biology|last=Slack|first=Jonathan M. W.|publisher=Wiley-Blackwell|year=2013|location=Oxford|oclc=785558800}}</ref>{{Page needed|date=October 2016}} However, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models.<ref name="zam">{{cite journal |last1=Chakraborty |first1=Chiranjib |last2=Hsu |first2=Chi |last3=Wen |first3=Zhi |last4=Lin |first4=Chang |last5=Agoramoorthy |first5=Govindasamy |title=Zebrafish: A Complete Animal Model for In Vivo Drug Discovery and Development |journal=Current Drug Metabolism |date=2009-02-01 |volume=10 |issue=2 |pages=116–124 |doi=10.2174/138920009787522197 |pmid=19275547 }}</ref><ref name=zrug>{{cite journal |last1=Kari |first1=G |last2=Rodeck |first2=U |last3=Dicker |first3=A P |title=Zebrafish: An Emerging Model System for Human Disease and Drug Discovery |journal=Clinical Pharmacology & Therapeutics |date=July 2007 |volume=82 |issue=1 |pages=70–80 |doi=10.1038/sj.clpt.6100223 |pmid=17495877 |s2cid=41443542 }}</ref> Treatments for animal diseases have also been developed, including for [[rabies]],<ref name="buck1904"/> [[anthrax]],<ref name="buck1904" /> [[glanders]],<ref name="buck1904" /> [[feline immunodeficiency virus]] (FIV),<ref name="pu2005"/> [[tuberculosis]],<ref name="buck1904" /> Texas cattle fever,<ref name="buck1904" /> [[classical swine fever]] (hog cholera),<ref name="buck1904" /> [[heartworm]], and other [[Parasitic disease|parasitic infections]].<ref name="dryden2005"/> Animal experimentation continues to be required for biomedical research,<ref name=bundle/> and is used with the aim of solving medical problems such as Alzheimer's disease,<ref name="geula1998"/> AIDS,<ref name="AIDS2005"/> multiple sclerosis,<ref name="jameson1994"/> spinal cord injury, many headaches,<ref name="lyuksyutova1984"/> and other conditions in which there is no useful ''[[in vitro]]'' model system available. The annual use of [[vertebrate]] animals—from [[zebrafish]] to non-human [[primates]]—was estimated at 192 million as of 2015.<ref name="Taylor Alvarez 2019 pp. 196–213">{{cite journal | last1=Taylor | first1=Katy | last2=Alvarez | first2=Laura Rego | title=An Estimate of the Number of Animals Used for Scientific Purposes Worldwide in 2015 | journal=Alternatives to Laboratory Animals | publisher=SAGE Publications | volume=47 | issue=5–6 | year=2019 | issn=0261-1929 | doi=10.1177/0261192919899853 | pages=196–213| pmid=32090616 | s2cid=211261775 | doi-access=free }}</ref> In the [[European Union]], vertebrate species represent 93% of animals used in research,<ref name="Taylor Alvarez 2019 pp. 196–213">{{cite journal | last1=Taylor | first1=Katy | last2=Alvarez | first2=Laura Rego | title=An Estimate of the Number of Animals Used for Scientific Purposes Worldwide in 2015 | journal=Alternatives to Laboratory Animals | publisher=SAGE Publications | volume=47 | issue=5–6 | year=2019 | issn=0261-1929 | doi=10.1177/0261192919899853 | pages=196–213| pmid=32090616 | s2cid=211261775 | doi-access=free }}</ref> and 11.5 million animals were used there in 2011.<ref name="eurlex13">{{cite news |title=REPORT FROM THE COMMISSION TO THE COUNCIL AND THE EUROPEAN PARLIAMENT Seventh Report on the Statistics on the Number of Animals used for Experimental and other Scientific Purposes in the Member States of the European Union |url=https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52013DC0859 |issue=Document 52013DC0859 |publisher=EUR-Lex |date=12 May 2013}}</ref> The mouse (''[[House mouse|Mus musculus]]'') is associated with many important biological discoveries of the 20th and 21st centuries,<ref name="Hedrich"/> and by one estimate, the number of mice and rats used in the United States alone in 2001 was 80 million.<ref name=Carbone26>Carbone, Larry. (2004). What Animals Want: Expertise and Advocacy in Laboratory Animal Welfare Policy.</ref> In 2013, it was reported that mammals (mice and rats), fish, amphibians, and reptiles together accounted for over 85% of research animals.<ref name="EUstatistics2013">{{cite web|title=EU statistics show decline in animal research numbers|url=http://speakingofresearch.com/2013/12/12/eu-statistics-show-decline-in-animal-research-numbers/|publisher=Speaking of Research|year=2013|access-date=24 January 2016}}</ref> In 2022, a law was passed in the United States that eliminated the [[FDA]] requirement that all drugs be tested on animals.<ref>{{cite web|url=https://reason.com/2023/01/13/u-s-will-no-longer-require-animal-testing-for-new-drugs/|title=U.S. Will No Longer Require Animal Testing for New Drugs|date=January 13, 2022}}</ref> Animal testing is regulated to varying degrees in different countries.<ref>{{cite journal |last1=Festing |first1=Simon |last2=Wilkinson |first2=Robin |date=June 2007 |title=The ethics of animal research. Talking Point on the use of animals in scientific research |journal=EMBO Reports |volume=8 |issue=6 |pages=526–530 |doi=10.1038/sj.embor.7400993 |issn=1469-221X |pmc=2002542 |pmid=17545991}}</ref> Animal testing is regulated differently in different countries: in some cases it is strictly controlled while others have more relaxed regulations. There are ongoing debates about the ethics and necessity of animal testing. Proponents argue that it has led to significant advancements in medicine and other fields while opponents raise concerns about [[Cruelty to animals|cruelty towards animals]] and question its effectiveness and reliability.<ref>{{cite journal |last1=Reddy |first1=Navya |last2=Lynch |first2=Barry |last3=Gujral |first3=Jaspreet |last4=Karnik |first4=Kavita |date=September 2023 |title=Regulatory landscape of alternatives to animal testing in food safety evaluations with a focus on the western world |url=https://pubmed.ncbi.nlm.nih.gov/37591329 |journal=Regulatory Toxicology and Pharmacology |volume=143 |pages=105470 |doi=10.1016/j.yrtph.2023.105470 |issn=1096-0295 |pmid=37591329|s2cid=260938742 }}</ref><ref>{{cite journal |last1=Petetta |first1=Francesca |last2=Ciccocioppo |first2=Roberto |date=November 2021 |title=Public perception of laboratory animal testing: Historical, philosophical, and ethical view |journal=Addiction Biology |volume=26 |issue=6 |pages=e12991 |doi=10.1111/adb.12991 |issn=1369-1600 |pmc=9252265 |pmid=33331099}}</ref> There are efforts underway to find alternatives to animal testing such as [[Computer simulation|computer simulation models]], [[Organ-on-a-chip|organs-on-chips technology]] that mimics human organs for lab tests,<ref>{{cite journal |last1=Low |first1=Lucie A. |last2=Mummery |first2=Christine |last3=Berridge |first3=Brian R. |last4=Austin |first4=Christopher P. |last5=Tagle |first5=Danilo A. |date=May 2021 |title=Organs-on-chips: into the next decade |url=https://pubmed.ncbi.nlm.nih.gov/32913334 |journal=Nature Reviews. Drug Discovery |volume=20 |issue=5 |pages=345–361 |doi=10.1038/s41573-020-0079-3 |issn=1474-1784 |pmid=32913334|hdl=1887/3151779 |s2cid=221621465 |hdl-access=free }}</ref> microdosing techniques which involve administering small doses of test compounds to human volunteers instead of non-human animals for safety tests or drug screenings; [[positron emission tomography]] (PET) scans which allow scanning of the human brain without harming humans; comparative epidemiological studies among human populations; simulators and computer programs for teaching purposes; among others.<ref>{{cite journal |last1=Löwa |first1=Anna |last2=Jevtić |first2=Marijana |last3=Gorreja |first3=Frida |last4=Hedtrich |first4=Sarah |date=May 2018 |title=Alternatives to animal testing in basic and preclinical research of atopic dermatitis |journal=Experimental Dermatology |volume=27 |issue=5 |pages=476–483 |doi=10.1111/exd.13498 |issn=1600-0625 |pmid=29356091|s2cid=3378256 |doi-access=free }}</ref><ref>{{cite journal |last1=Madden |first1=Judith C. |last2=Enoch |first2=Steven J. |last3=Paini |first3=Alicia |last4=Cronin |first4=Mark T. D. |date=July 2020 |title=A Review of In Silico Tools as Alternatives to Animal Testing: Principles, Resources and Applications |journal=Alternatives to Laboratory Animals: ATLA |volume=48 |issue=4 |pages=146–172 |doi=10.1177/0261192920965977 |issn=0261-1929 |pmid=33119417|s2cid=226204296 |doi-access=free }}</ref><ref>{{cite journal |last1=Reddy |first1=Navya |last2=Lynch |first2=Barry |last3=Gujral |first3=Jaspreet |last4=Karnik |first4=Kavita |date=September 2023 |title=Alternatives to animal testing in toxicity testing: Current status and future perspectives in food safety assessments |url=https://pubmed.ncbi.nlm.nih.gov/37453475 |journal=Food and Chemical Toxicology|volume=179 |pages=113944 |doi=10.1016/j.fct.2023.113944 |issn=1873-6351 |pmid=37453475|s2cid=259915886 }}</ref> ==Definitions== The terms ''animal testing, animal experimentation, animal research'', ''[[in vivo]]'' testing, and [[vivisection]] have similar [[denotation]]s but different [[connotation]]s. Literally, "vivisection" means "live sectioning" of an animal, and historically referred only to experiments that involved the [[dissection]] of live animals. The term is occasionally used to refer pejoratively to any experiment using living animals; for example, the ''Encyclopædia Britannica'' defines "vivisection" as: "Operation on a living animal for experimental rather than healing purposes; more broadly, all experimentation on live animals",<ref name=croce>Croce, Pietro (1999). ''Vivisection or Science? An Investigation into Testing Drugs and Safeguarding Health''. Zed Books, {{ISBN|1-85649-732-1}}.</ref><ref>{{cite encyclopedia|url=https://www.britannica.com/ebc/article-9382118?query=Vivisection&ct= |title=Vivisection |archive-url=https://web.archive.org/web/20080101153454/https://www.britannica.com/ebc/article-9382118?query=Vivisection&ct= |archive-date=1 January 2008 |encyclopedia=Encyclopædia Britannica |year=2007}}</ref><ref name=buavfaq>{{cite web |url=http://www.buav.org/pdf/VivisectionFAQs.pdf |title=Vivisection FAQ |publisher=British Union for the Abolition of Vivisection |archive-url=https://web.archive.org/web/20150513021651/http://www.buav.org/pdf/VivisectionFAQs.pdf |archive-date=13 May 2015 }}</ref> although dictionaries point out that the broader definition is "used only by people who are opposed to such work".<ref>{{cite encyclopedia |entry=Vivisection |encyclopedia=Encyclopedia.com |url=https://www.encyclopedia.com/medicine/divisions-diagnostics-and-procedures/medicine/vivisection#vivisection |access-date=2023-05-05}}</ref><ref>{{cite encyclopedia |entry=Vivisection |url=https://www.merriam-webster.com/dictionary/vivisection |access-date=2023-05-05 |dictionary=Merriam-Webster |language=en |title=Definition of VIVISECTION }}</ref> The word has a negative connotation, implying torture, suffering, and death.<ref name=Carbone22/> The word "vivisection" is preferred by those opposed to this research, whereas scientists typically use the term "animal experimentation".<ref>{{cite journal | vauthors = Paixão RL, Schramm FR | title = Ethics and animal experimentation: what is debated? | journal = Cadernos de Saúde Pública | volume = 15 | issue = Suppl 1 | pages = 99–110 | year = 1999 | pmid = 10089552 | doi=10.1590/s0102-311x1999000500011 | doi-access = free }}</ref><ref>Yarri, Donna (2005). ''The Ethics of Animal Experimentation'', Oxford University Press U.S., {{ISBN|0-19-518179-4}}.</ref> The following text excludes as much as possible practices related to ''in vivo'' [[veterinary surgery]], which is left to the discussion of [[vivisection]]. ==History== {{Main|History of animal testing}} [[File:An Experiment on a Bird in an Air Pump by Joseph Wright of Derby, 1768.jpg|thumb|''[[An Experiment on a Bird in an Air Pump]]'', from 1768, by [[Joseph Wright of Derby|Joseph Wright]]]] [[File:One of Pavlov's dogs.jpg|thumb|right|One of [[Ivan Pavlov|Pavlov]]'s dogs with a [[cannula|saliva-catch]] container and tube surgically implanted in his muzzle, Pavlov Museum, 2005]] The earliest references to animal testing are found in the writings of the [[Ancient Greece|Greeks]] in the 2nd and 4th centuries BCE. [[Aristotle]] and [[Erasistratus]] were among the first to perform experiments on living animals.<ref>Cohen and Loew 1984.</ref> [[Galen]], a 2nd-century Roman physician, performed ''[[post-mortem]]'' dissections of pigs and goats.<ref name=lpag>{{cite web|url=http://www.lpag.org/layperson/layperson.html#history |title=History of nonhuman animal research |publisher=Laboratory Primate Advocacy Group |archive-url=https://web.archive.org/web/20061013110949/http://www.lpag.org/layperson/layperson.html |archive-date=13 October 2006 }}</ref> [[Ibn Zuhr|Avenzoar]], a 12th-century [[Medicine in medieval Islam|Arabic physician]] in [[Al-Andalus|Moorish Spain]] introduced an experimental method of testing surgical procedures before applying them to human patients.<ref name=Rabie2005>{{cite journal | author = Abdel-Halim RE | title = Contributions of Ibn Zuhr (Avenzoar) to the progress of surgery: a study and translations from his book Al-Taisir | journal = Saudi Medical Journal | volume = 26 | issue = 9 | pages = 1333–39 | year = 2005 | pmid = 16155644 }}</ref><ref name=Rabie2006>{{cite journal | author = Abdel-Halim RE | title = Contributions of Muhadhdhab Al-Deen Al-Baghdadi to the progress of medicine and urology. A study and translations from his book Al-Mukhtar | journal = Saudi Medical Journal | volume = 27 | issue = 11 | pages = 1631–41 | year = 2006 | pmid = 17106533 }}</ref> Discoveries in the 18th and 19th centuries included [[Antoine Lavoisier]]'s use of a [[guinea pig]] in a [[calorimeter]] to prove that [[Respiration (physiology)|respiration]] was a form of combustion, and [[Louis Pasteur]]'s demonstration of the [[germ theory of disease]] in the 1880s using [[anthrax]] in sheep.<ref name="pmid11544370">{{cite journal | vauthors = Mock M, Fouet A | title = Anthrax | journal = Annu. Rev. Microbiol. | volume = 55 | pages = 647–71 | year = 2001 | pmid = 11544370 | doi = 10.1146/annurev.micro.55.1.647 }}</ref> [[Robert Koch]] used animal testing of mice and guinea pigs to discover the bacteria that cause anthrax and [[tuberculosis]]. In the 1890s, [[Ivan Pavlov]] famously used dogs to describe [[classical conditioning]].<ref name="pmid3309839">{{cite journal | author = Windholz G | title = Pavlov as a psychologist. A reappraisal | journal = Pavlovian J. Biol. Sci. | volume = 22 | issue = 3 | pages = 103–12 | year = 1987 | doi = 10.1007/BF02734662 | pmid = 3309839 | s2cid = 141344843 }}</ref> Research using animal models has been central to most of the achievements of modern medicine.<ref name=RSM2015>{{cite web| title = Statement of the Royal Society's position on the use of animals in research| author = Royal Society of Medicine| date = 13 May 2015| url = https://royalsociety.org/topics-policy/publications/2015/animals-in-research/|quote=From antibiotics and insulin to blood transfusions and treatments for cancer or HIV, virtually every medical achievement in the past century has depended directly or indirectly on research using animals, including veterinary medicine.}}</ref><ref name=NRCIOM>{{cite book|author=[[National Research Council (United States)|National Research Council]] and [[Institute of Medicine]]|title=Use of Laboratory Animals in Biomedical and Behavioral Research|url=https://books.google.com/books?id=EzorAAAAYAAJ|date=1988|publisher=National Academies Press|page=37|isbn=9780309038393|id=NAP:13195|quote=The...methods of scientific inquiry have greatly reduced the incidence of human disease and have substantially increased life expectancy. Those results have come largely through experimental methods based in part on the use of animals.}}</ref><ref name="Nature2007">{{cite journal |last1=Lieschke |first1=Graham J. |last2=Currie |first2=Peter D. |title=Animal models of human disease: zebrafish swim into view |journal=Nature Reviews Genetics |date=May 2007 |volume=8 |issue=5 |pages=353–367 |doi=10.1038/nrg2091 |pmid=17440532 |s2cid=13857842 |quote=Biomedical research depends on the use of animal models to understand the pathogenesis of human disease at a cellular and molecular level and to provide systems for developing and testing new therapies. }}</ref> It has contributed most of the basic knowledge in fields such as human [[physiology]] and [[biochemistry]], and has played significant roles in fields such as [[neuroscience]] and [[infectious disease]].<ref name=NRCIOMb>{{cite book|author=[[National Research Council (United States)|National Research Council]] and [[Institute of Medicine]]|title=Use of Laboratory Animals in Biomedical and Behavioral Research|url=https://books.google.com/books?id=EzorAAAAYAAJ|date=1988|publisher=National Academies Press|page=27|isbn=9780309038393|id=NAP:13195|quote=Animal studies have been an essential component of every field of medical research and have been crucial for the acquisition of basic knowledge in biology.}}</ref><ref name="HLAS2011">Hau and Shapiro 2011: * {{cite book|author1=Jann Hau|author2=Steven J. Schapiro|title=Handbook of Laboratory Animal Science, Volume I, Third Edition: Essential Principles and Practices|url=https://books.google.com/books?id=D-IHAaggi_4C|year=2011|publisher=CRC Press|page=2|isbn=978-1-4200-8456-6|quote=Animal-based research has played a key role in understanding infectious diseases, neuroscience, physiology, and toxicology. Experimental results from animal studies have served as the basis for many key biomedical breakthroughs.}} * {{cite book|author1=Jann Hau|author2=Steven J. Schapiro|title=Handbook of Laboratory Animal Science, Volume II, Third Edition: Animal Models|url=https://books.google.com/books?id=yk7TFvsFCBcC|year=2011|publisher=CRC Press|page=1|isbn=978-1-4200-8458-0|quote=Most of our basic knowledge of human biochemistry, physiology, endocrinology, and pharmacology has been derived from initial studies of mechanisms in animal models.}}</ref> For example, the results have included the near-[[Poliomyelitis eradication|eradication of polio]] and the development of [[organ transplantation]], and have benefited both humans and animals.<ref name=RSM2015/><ref name="IOM1991">{{cite book|author=Institute of Medicine|title=Science, Medicine, and Animals|url=https://archive.org/details/sciencemedicinea00comm|url-access=registration|date=1991|publisher=National Academies Press|isbn=978-0-309-56994-1|page=[https://archive.org/details/sciencemedicinea00comm/page/3 3]|quote=...without this fundamental knowledge, most of the clinical advances described in these pages would not have occurred.}}</ref> From 1910 to 1927, [[Thomas Hunt Morgan]]'s work with the fruit fly ''[[Drosophila melanogaster]]'' identified [[chromosome]]s as the vector of inheritance for genes.<ref name="nobelprize.org">{{cite web|title=The Nobel Prize in Physiology or Medicine 1933|url=http://nobelprize.org/nobel_prizes/medicine/laureates/1933/index.html|access-date=2015-06-20|publisher=Nobel Web AB}}</ref><ref name="nobel2">{{cite web|title=Thomas Hunt Morgan and his Legacy|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1933/morgan-article.html|access-date=2015-06-20|publisher=Nobel Web AB}}</ref> ''Drosophila'' became one of the first, and for some time the most widely used, model organisms,<ref>Kohler, ''Lords of the Fly'', chapter 5</ref> and [[Eric Kandel]] wrote that Morgan's discoveries "helped transform biology into an experimental science".<ref name="Kandel1999">Kandel, Eric. 1999. [http://www.columbia.edu/cu/alumni/Magazine/Legacies/Morgan/ "Genes, Chromosomes, and the Origins of Modern Biology"], ''Columbia Magazine''</ref> ''D. melanogaster'' remains one of the most widely used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of [[William Ernest Castle]] in collaboration with [[Abbie Lathrop]] led to generation of the DBA ("dilute, brown and non-agouti") inbred mouse strain and the systematic generation of other inbred strains.<ref name="Steensma">{{cite journal|last=Steensma|first=David P. |author2=Kyle Robert A. |author3=Shampo Marc A.|date=November 2010|title=Abbie Lathrop, the "Mouse Woman of Granby": Rodent Fancier and Accidental Genetics Pioneer|journal=Mayo Clinic Proceedings|volume=85|issue=11|pmc=2966381|pmid=21061734|doi=10.4065/mcp.2010.0647|pages=e83}}</ref><ref>{{cite web|url=https://immunology.hms.harvard.edu/about-us/history|title=History of Immunology at Harvard|last=Pillai|first=Shiv|work=Harvard Medical School:About us|publisher=Harvard Medical School|access-date=19 December 2013|archive-url=https://web.archive.org/web/20131220022416/https://immunology.hms.harvard.edu/about-us/history|archive-date=20 December 2013|url-status=dead}}</ref> The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries.<ref name="Hedrich">{{cite book|title=The Laboratory Mouse|editor= Hedrich, Hans|publisher=Elsevier Science|chapter=The house mouse as a laboratory model: a historical perspective|isbn=9780080542539|date= 2004-08-21}}</ref> In the late 19th century, [[Emil von Behring]] isolated the [[diphtheria]] toxin and demonstrated its effects in guinea pigs. He went on to develop an antitoxin against diphtheria in animals and then in humans, which resulted in the modern methods of immunization and largely ended diphtheria as a threatening disease.<ref name="nobel3">[http://nobelprize.org/nobel_prizes/medicine/laureates/1901/behring-bio.html Bering Nobel Biography]</ref> The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the [[1925 serum run to Nome]]. The success of animal studies in producing the diphtheria antitoxin has also been attributed as a cause for the decline of the early 20th-century opposition to animal research in the United States.<ref name="Cannon2009">[http://www.amphilsoc.org/library/mole/c/cannon.htm Walter B. Cannon Papers, American Philosophical Society] {{webarchive |url=https://web.archive.org/web/20090814184304/http://www.amphilsoc.org/library/mole/c/cannon.htm |date=August 14, 2009 }}</ref> Subsequent research in model organisms led to further medical advances, such as [[Frederick Banting]]'s research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with [[Diabetes mellitus|diabetes]]. This led to the 1922 discovery of [[insulin]] (with [[John Macleod (physiologist)|John Macleod]])<ref name="insulin">[http://www.mta.ca/faculty/arts/canadian_studies/english/about/study_guide/doctors/insulin.html Discovery of Insulin] {{webarchive |url=https://web.archive.org/web/20090930142937/http://www.mta.ca/faculty/arts/canadian_studies/english/about/study_guide/doctors/insulin.html |date=September 30, 2009 }}</ref> and its use in treating diabetes, which had previously meant death.<ref name="Thompson2009">[http://www.dlife.com/dLife/do/ShowContent/inspiration_expert_advice/famous_people/leonard_thompson.html Thompson bio ref] {{webarchive|url=https://web.archive.org/web/20090210030429/http://www.dlife.com/dLife/do/ShowContent/inspiration_expert_advice/famous_people/leonard_thompson.html |date=2009-02-10 }}</ref><ref name="pmid9285027">{{cite journal | author = Gorden P | title = Non-insulin dependent diabetes – the past, present and future | journal = Ann. Acad. Med. Singap. | volume = 26 | issue = 3 | pages = 326–30 | year = 1997 | pmid = 9285027 }}</ref> [[John Cade]]'s research in guinea pigs discovered the anticonvulsant properties of lithium salts,<ref>[http://www.adb.online.anu.edu.au/biogs/A130374b.htm] John Cade and Lithium</ref> which revolutionized the treatment of [[bipolar disorder]], replacing the previous treatments of lobotomy or electroconvulsive therapy. Modern general anaesthetics, such as [[halothane]] and related compounds, were also developed through studies on model organisms, and are necessary for modern, complex surgical operations.<ref name="raventos1956">Raventos J (1956) ''Br J Pharmacol'' 11, 394</ref><ref name="whalen2005">Whalen FX, Bacon DR & Smith HM (2005) ''Best Pract Res Clin Anaesthesiol'' 19, 323</ref> In the 1940s, [[Jonas Salk]] used rhesus monkey studies to isolate the most virulent forms of the [[polio]] virus,<ref>{{cite web |url=http://www.post-gazette.com/pg/05093/481117.stm |title=Developing a medical milestone: The Salk polio vaccine |access-date=2015-06-20 |url-status=dead |archive-url=https://web.archive.org/web/20100311191427/http://www.post-gazette.com/pg/05093/481117.stm |archive-date=2010-03-11 }} Virus-typing of polio by Salk</ref> which led to his creation of a [[polio vaccine]]. The vaccine, which was made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years.<ref>{{cite web |url=http://www.post-gazette.com/pg/05094/482468.stm |title=Tireless polio research effort bears fruit and indignation |access-date=2008-08-23 |url-status=dead |archive-url=https://web.archive.org/web/20080905022100/http://www.post-gazette.com/pg/05094/482468.stm |archive-date=2008-09-05 }} Salk polio virus</ref> [[Albert Sabin]] improved the vaccine by passing the polio virus through animal hosts, including monkeys; the Sabin vaccine was produced for mass consumption in 1963, and had virtually eradicated polio in the United States by 1965.<ref>[http://americanhistory.si.edu/polio/virusvaccine/vacraces2.htm] {{Webarchive|url=https://web.archive.org/web/20110604021151/http://americanhistory.si.edu/polio/virusvaccine/vacraces2.htm|date=2011-06-04}} History of polio vaccine</ref> It has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but also among animals."<ref>[http://www.animalresearch.info/en/resources/163/-the-work-on-polio-prevention-was-long-dela/ "the work on [polio&#93; prevention was long delayed by... misleading experimental models of the disease in monkeys" | ari.info<!-- Bot generated title -->]</ref> On 3 November 1957, a [[Soviet space dogs|Soviet dog]], [[Laika]], became the first of many [[Animals in space|animals to orbit the Earth]]. In the 1970s, antibiotic treatments and vaccines for [[leprosy]] were developed using armadillos,<ref name="pmid7242665">{{cite journal | author = Walgate R | title = Armadillos fight leprosy | journal = Nature | volume = 291 | issue = 5816 | page = 527 | year = 1981 | pmid = 7242665 | doi = 10.1038/291527a0 | bibcode = 1981Natur.291..527W | doi-access = free }}</ref> then given to humans.<ref>{{cite journal | vauthors = Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL | title = The Continuing Challenges of Leprosy | journal = Clin. Microbiol. Rev. | volume = 19 | issue = 2 | pages = 338–81 | year = 2006 | pmid = 16614253 | pmc = 1471987 | doi = 10.1128/CMR.19.2.338-381.2006 }}</ref> The ability of humans to change the [[genetics]] of animals took an enormous step forward in 1974 when [[Rudolf Jaenisch]] could produce the first [[genetically modified organism|transgenic mammal]], by integrating DNA from [[simians]] into the [[genome]] of mice.<ref>{{cite journal | vauthors = Jaenisch R, Mintz B | title = Simian Virus 40 DNA Sequences in DNA of Healthy Adult Mice Derived from Preimplantation Blastocysts Injected with Viral DNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 71 | issue = 4 | pages = 1250–54 | year = 1974 | pmid = 4364530 | pmc = 388203 | doi = 10.1073/pnas.71.4.1250 | bibcode = 1974PNAS...71.1250J | doi-access = free }}</ref> This genetic research progressed rapidly and, in 1996, [[Dolly the sheep]] was born, the first mammal to be [[Clone (genetics)|cloned]] from an adult cell.<ref name=Wilmut/><ref>{{cite web|url=http://www.understandinganimalresearch.org.uk/resources/animal-research-essay-resources/history-of-animal-research/|title=History of animal research|website=www.understandinganimalresearch.org.uk|access-date=2016-04-08}}</ref> Other 20th-century medical advances and treatments that relied on research performed in animals include [[organ transplant]] techniques,<ref name="carrel1912">Carrel A (1912) ''Surg. Gynec. Obst.'' 14: p. 246</ref><ref name="williamson1926">Williamson C (1926) ''J. Urol.'' 16: p. 231</ref><ref name="woodruff1986">Woodruff H & Burg R (1986) in ''Discoveries in Pharmacology'' vol 3, ed Parnham & Bruinvels, Elsevier, Amsterdam</ref><ref name="moore1964">Moore F (1964) ''Give and Take: the Development of Tissue Transplantation''. Saunders, New York</ref> the heart-lung machine,<ref name="gibbon1937">Gibbon JH (1937) ''Arch. Surg.'' 34, 1105</ref> [[antibiotic]]s,<ref name="rawbw">[http://www.rawbw.com/~hinshaw/cgi-bin/id?1375] Hinshaw obituary</ref><ref name="fleming1929">Fleming A (1929) ''Br J Exp Path'' 10, 226</ref> and the [[whooping cough]] vaccine.<ref name="mrc1956">Medical Research Council (1956) ''Br. Med. J.'' 2: p. 454</ref> Treatments for animal diseases have also been developed, including for [[rabies]],<ref name="buck1904">''A reference handbook of the medical sciences''. William Wood and Co., 1904, Edited by Albert H. Buck.</ref> [[anthrax]],<ref name="buck1904" /> [[glanders]],<ref name="buck1904" /> [[feline immunodeficiency virus]] (FIV),<ref name="pu2005">{{cite journal |last1=Pu |first1=Ruiyu |last2=Coleman |first2=James |last3=Coisman |first3=James |last4=Sato |first4=Eiji |last5=Tanabe |first5=Taishi |last6=Arai |first6=Maki |last7=Yamamoto |first7=Janet K |title=Dual-subtype FIV vaccine (Fel-O-Vax® FIV) protection against a heterologous subtype B FIV isolate |journal=Journal of Feline Medicine and Surgery |date=February 2005 |volume=7 |issue=1 |pages=65–70 |doi=10.1016/j.jfms.2004.08.005 |pmid=15686976 |s2cid=26525327 |pmc=10911555 }}</ref> [[tuberculosis]],<ref name="buck1904" /> Texas cattle fever,<ref name="buck1904" /> [[classical swine fever]] (hog cholera),<ref name="buck1904" /> [[heartworm]], and other [[Parasitic disease|parasitic infections]].<ref name="dryden2005">{{cite journal | last1 = Dryden | first1 = MW | last2 = Payne | first2 = PA | title = Preventing parasites in cats | journal = Veterinary Therapeutics | volume = 6 | issue = 3 | pages = 260–7 | year = 2005 | pmid = 16299672 }}</ref> Animal experimentation continues to be required for biomedical research,<ref name=bundle>Sources: * {{cite book|author=P. Michael Conn|title=Animal Models for the Study of Human Disease|url=https://books.google.com/books?id=dVLVLIV8rD0C|date=29 May 2013|publisher=Academic Press|isbn=978-0-12-415912-9|page=37|quote=...animal models are central to the effective study and discovery of treatments for human diseases.}} * {{cite journal |last1=Lieschke |first1=Graham J. |last2=Currie |first2=Peter D. |title=Animal models of human disease: zebrafish swim into view |journal=Nature Reviews Genetics |date=May 2007 |volume=8 |issue=5 |pages=353–367 |doi=10.1038/nrg2091 |pmid=17440532 |s2cid=13857842 |quote=Biomedical research depends on the use of animal models to understand the pathogenesis of human disease at a cellular and molecular level and to provide systems for developing and testing new therapies.}} * {{cite book|author1=Pierce K. H. Chow|author2=Robert T. H. Ng|author3=Bryan E. Ogden|title=Using Animal Models in Biomedical Research: A Primer for the Investigator|url=https://books.google.com/books?id=NtWM8gD9Z2MC|year=2008|publisher=World Scientific|isbn=978-981-281-202-5|pages=1–2|quote=Arguments regarding whether biomedical science can advance without the use of animals are frequently mooted and make as much sense as questioning if clinical trials are necessary before new medical therapies are allowed to be widely used in the general population [pg. 1] ...animal models are likely to remain necessary until science develops alternative models and systems that are equally sound and robust [pg. 2].}} * {{cite book|author1=Jann Hau|author2=Steven J. Schapiro|title=Handbook of Laboratory Animal Science, Volume I, Third Edition: Essential Principles and Practices|chapter-url=https://books.google.com/books?id=D-IHAaggi_4C|year=2011|publisher=CRC Press|chapter=The contribution of laboratory animals to medical progress|isbn=978-1-4200-8456-6|quote=Animal models are required to connect [modern biological technologies] in order to understand whole organisms, both in healthy and diseased states. In turn, these animal studies are required for understanding and treating human disease [pg. 2] ...In many cases, though, there will be no substitute for whole-animal studies because of the involvement of multiple tissue and organ systems in both normal and aberrant physiological conditions [pg. 15].}} * {{cite web| title = Statement of the Royal Society's position on the use of animals in research| author = Royal Society of Medicine| date = 24 May 2023| url = https://royalsociety.org/about-us/what-we-do/supporting-researchers/animal-testing/|quote=At present the use of animals remains the only way for some areas of research to progress.}}</ref> and is used with the aim of solving medical problems such as Alzheimer's disease,<ref name="geula1998">{{cite journal |last1=Guela |first1=Changiz |last2=Wu |first2=Chuang-Kuo |last3=Saroff |first3=Daniel |last4=Lorenzo |first4=Alfredo |last5=Yuan |first5=Menglan |last6=Yankner |first6=Bruce A. |title=Aging renders the brain vulnerable to amyloid β-protein neurotoxicity |journal=Nature Medicine |date=July 1998 |volume=4 |issue=7 |pages=827–831 |doi=10.1038/nm0798-827 |pmid=9662375 |s2cid=45108486 }}</ref> AIDS,<ref name="AIDS2005">[http://www.aidsreviews.com/files/2005_7_2_67_83.pdf AIDS Reviews 2005;7:67-83 Antiretroviral Drug Studies in Nonhuman Primates: a Valid Animal Model for Innovative Drug Efficacy and Pathogenesis Experiments] {{webarchive |url=https://web.archive.org/web/20081217131711/http://www.aidsreviews.com/files/2005_7_2_67_83.pdf |date=December 17, 2008 }}</ref><ref>[http://www.thebody.com/cdc/tb165.html PMPA blocks SIV in monkeys]</ref><ref>[http://www.thebody.com/bp/dec99/medical.html PMPA is tenofovir]</ref> multiple sclerosis,<ref name="jameson1994">{{cite journal |last1=Jameson |first1=Bradford A. |last2=McDonnell |first2=James M. |last3=Marini |first3=Joseph C. |last4=Korngold |first4=Robert |title=A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis |journal=Nature |date=April 1994 |volume=368 |issue=6473 |pages=744–746 |doi=10.1038/368744a0 |pmid=8152486 |bibcode=1994Natur.368..744J |s2cid=4370797 }}</ref> spinal cord injury, many headaches,<ref name="lyuksyutova1984">{{cite journal | last1 = Lyuksyutova | first1 = AL | last2 = Lu C-C | first2 = Milanesio N | year = 2003 | title = Anterior-posterior guidance of commissural axons by Wnt-Frizzled signaling | journal = Science | volume = 302 | issue = 5652| doi=10.1126/science.1089610 | pmid=14671310 | last3 = Milanesio | first3 = N | last4 = King | first4 = LA | last5 = Guo | first5 = N | last6 = Wang | first6 = Y | last7 = Nathans | first7 = J | last8 = Tessier-Lavigne | first8 = M | last9 = Zou | first9 = Y | display-authors = 8| pages = 1984–8| bibcode = 2003Sci...302.1984L | s2cid = 39309990 }}</ref> and other conditions in which there is no useful ''[[in vitro]]'' model system available. [[Toxicology]] testing became important in the 20th century. In the 19th century, laws regulating drugs were more relaxed. For example, in the US, the government could only ban a drug after they had prosecuted a company for selling products that harmed customers. However, in response to the [[Elixir Sulfanilamide disaster]] of 1937 in which the eponymous drug killed over 100 users, the US Congress passed laws that required safety testing of drugs on animals before they could be marketed. Other countries enacted similar legislation.<ref name=afda>{{cite web|url=https://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SulfanilamideDisaster/default.htm |title=Taste of Raspberries, Taste of Death. The 1937 Elixir Sulfanilamide Incident|work= FDA Consumer magazine |date=June 1981 }}</ref> In the 1960s, in reaction to the [[Thalidomide]] tragedy, further laws were passed requiring safety testing on pregnant animals before a drug can be sold.<ref name =Burkholz>{{cite news| first =Herbert | last =Burkholz | title = Giving Thalidomide a Second Chance | url =https://www.fda.gov/fdac/features/1997/697_thal.html | work =FDA Consumer | publisher =US [[Food and Drug Administration]] | date =1 September 1997}}</ref> ==Model organisms== {{main|Model organism}} ===Invertebrates=== {{Main|Animal testing on invertebrates}} {{See also|Pain in invertebrates}} [[File:Drosophila melanogaster - front (aka).jpg|thumb|[[Drosophila melanogaster|Fruit flies]] are an invertebrate commonly used in animal testing.]] Although many more invertebrates than vertebrates are used in animal testing, these studies are largely unregulated by law. The most frequently used invertebrate species are ''[[Drosophila melanogaster]]'', a fruit fly, and ''[[Caenorhabditis elegans]]'', a [[nematode]] worm. In the case of ''C. elegans'', the worm's body is completely transparent and the precise lineage of all the organism's cells is known,<ref>{{cite journal |vauthors=Antoshechkin I, Sternberg PW | title = The versatile worm: genetic and genomic resources for Caenorhabditis elegans research | journal = Nature Reviews Genetics | volume = 8 | issue = 7 | pages = 518–32 | year = 2007 | pmid = 17549065 | doi = 10.1038/nrg2105 | s2cid = 12923468 }}</ref> while studies in the fly ''D. melanogaster'' can use an amazing array of genetic tools.<ref>{{cite journal |vauthors=Matthews KA, Kaufman TC, Gelbart WM | title = Research resources for Drosophila: the expanding universe | journal = Nature Reviews Genetics | volume = 6 | issue = 3 | pages = 179–93 | year = 2005 | pmid = 15738962 | doi = 10.1038/nrg1554 | s2cid = 31002250 }}</ref> These invertebrates offer some advantages over vertebrates in animal testing, including their short life cycle and the ease with which large numbers may be housed and studied. However, the lack of an adaptive [[immune system]] and their simple organs prevent worms from being used in several aspects of medical research such as vaccine development.<ref name=Schulenburg>{{cite journal |vauthors=Schulenburg H, Kurz CL, Ewbank JJ | title = Evolution of the innate immune system: the worm perspective | journal = Immunological Reviews | volume = 198 | pages = 36–58 | year = 2004 | pmid = 15199953 | doi = 10.1111/j.0105-2896.2004.0125.x | s2cid = 21541043 }}</ref> Similarly, the fruit fly [[immune system]] differs greatly from that of humans,<ref>{{cite journal |vauthors=Leclerc V, Reichhart JM | title = The immune response of Drosophila melanogaster | journal = Immunological Reviews | volume = 198 | pages = 59–71 | year = 2004 | pmid = 15199954 | doi = 10.1111/j.0105-2896.2004.0130.x | s2cid = 7395057 }}</ref> and diseases in insects can be different from diseases in vertebrates;<ref>{{cite journal |vauthors=Mylonakis E, Aballay A | title = Worms and flies as genetically tractable animal models to study host-pathogen interactions | journal = Infection and Immunity | volume = 73 | issue = 7 | pages = 3833–41 | year = 2005 | pmid = 15972468 | pmc = 1168613 | doi = 10.1128/IAI.73.7.3833-3841.2005 }}</ref> however, fruit flies and [[waxworms]] can be useful in studies to identify novel virulence factors or pharmacologically active compounds.<ref name="ncbi.nlm.nih.gov">{{cite journal |vauthors=Kavanagh K, Reeves EP | title = Exploiting the potential of insects for in vivo pathogenicity testing of microbial pathogens | journal = FEMS Microbiology Reviews | volume = 28 | issue = 1 | pages = 101–12 | year = 2004 | pmid = 14975532 | doi = 10.1016/j.femsre.2003.09.002 | doi-access = free }}</ref><ref name="plosone.org">{{cite journal | vauthors = Antunes LC, Imperi F, Carattoli A, Visca P | title = Deciphering the Multifactorial Nature of Acinetobacter baumannii Pathogenicity | journal = PLOS ONE| volume = 6 | issue = 8 | pages = e22674 | year = 2011 | pmid = 21829642 | pmc = 3148234 | doi = 10.1371/journal.pone.0022674 | editor1-last = Adler | editor1-first = Ben |bibcode = 2011PLoSO...622674A | doi-access = free }}</ref><ref name="Aperis G 2011">{{cite journal |vauthors=Aperis G, Fuchs BB, Anderson CA, Warner JE, Calderwood SB, Mylonakis E | title = Galleria mellonella as a model host to study infection by the Francisella tularensis live vaccine strain | journal = Microbes and Infection / Institut Pasteur | volume = 9 | issue = 6 | pages = 729–34 | year = 2007 | pmid = 17400503 | pmc = 1974785 | doi = 10.1016/j.micinf.2007.02.016 }}</ref> Several invertebrate systems are considered acceptable alternatives to vertebrates in early-stage discovery screens.<ref>{{cite journal|vauthors=Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Yang G, Wilkinson P, Parkhill J, Thomson N, Reynolds SE, Bode HB, Dorus S, Ffrench-Constant RH |doi=10.1073/pnas.0711114105|title=Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts|year=2008|journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105|issue=41|pages=15967–72 |bibcode = 2008PNAS..10515967W |pmid=18838673 |pmc=2572985|doi-access=free}}</ref> Because of similarities between the innate immune system of insects and mammals, insects can replace mammals in some types of studies. ''Drosophila melanogaster'' and the ''[[Galleria mellonella]]'' waxworm have been particularly important for analysis of virulent traits of mammalian pathogens.<ref name="ncbi.nlm.nih.gov"/><ref name="plosone.org"/> Waxworms and other insects have also proven valuable for the identification of pharmaceutical compounds with favorable bioavailability.<ref name="Aperis G 2011"/> The decision to adopt such models generally involves accepting a lower degree of biological similarity with mammals for significant gains in experimental throughput. ===Rodents=== {{main|Animal testing on rodents}} {{also|Median lethal dose}} [[Image:Sleep-deprivation-flowerpot-technique-jepoirrier.jpg|thumb|This rat is being deprived of rapid eye-movement (REM) sleep using a [[Flowerpot technique|single platform ("flower pot") technique]]. The water is within 1&nbsp;cm of the small flower pot bottom platform where the rat sits. The rat is able to sleep but at the onset of REM sleep muscle tone is lost and the rat would either fall into the water only to clamber back to the pot to avoid drowning, or its [[nose]] would become submerged into the water [[Acute stress reaction|shocking]] it back to an awakened state.]]In the U.S., the numbers of rats and mice used is estimated to be from 11 million<ref name=USDA2016 /> to between 20 and 100 million a year.<ref name="Trull">{{cite journal|last1=Trull|first1=F. L.|year=1999|title=More Regulation of Rodents|journal=Science|volume=284|issue=5419|page=1463|bibcode=1999Sci...284.1463T|doi=10.1126/science.284.5419.1463|pmid=10383321|s2cid=10122407}}</ref> Other rodents commonly used are guinea pigs, hamsters, and gerbils. Mice are the most commonly used vertebrate species because of their size, low cost, ease of handling, and fast reproduction rate.<ref name=Rosenthal>{{cite journal |vauthors=Rosenthal N, Brown S | title = The mouse ascending: perspectives for human-disease models | journal = Nature Cell Biology | volume = 9 | issue = 9 | pages = 993–99 | year = 2007 | pmid = 17762889 | doi = 10.1038/ncb437 | s2cid = 4472227 }}</ref><ref>{{cite journal|last1=Mukerjee|first1=M|title=Speaking for the Animals|journal=Scientific American|date=August 2004|volume=291|issue=2|pages=96–97|doi=10.1038/scientificamerican0804-96|bibcode=2004SciAm.291b..96M}}</ref> Mice are widely considered to be the best model of [[Genetic disorder|inherited human disease]] and share 95% of their [[gene]]s with humans.<ref name=Rosenthal/> With the advent of [[genetic engineering]] technology, genetically modified mice can be generated to order and can provide models for a range of human diseases.<ref name=Rosenthal/> Rats are also widely used for physiology, toxicology and cancer research, but genetic manipulation is much harder in rats than in mice, which limits the use of these rodents in basic science.<ref>{{cite journal |vauthors=Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, Gauguier D, Geurts AM, Gould M, Harris PC, Holmdahl R, Hubner N, Izsvák Z, Jacob HJ, Kuramoto T, Kwitek AE, Marrone A, Mashimo T, Moreno C, Mullins J, Mullins L, Olsson T, Pravenec M, Riley L, Saar K, Serikawa T, Shull JD, Szpirer C, Twigger SN, Voigt B, Worley K | title = Progress and prospects in rat genetics: a community view | journal = Nature Genetics | volume = 40 | issue = 5 | pages = 516–22 | year = 2008 | pmid = 18443588 | doi = 10.1038/ng.147 | s2cid = 22522876 }}</ref> ===Dogs=== {{See also|Laika|Soviet space dogs}}{{anchor|Cats and dogs}} [[File:Beagle 600.jpg|thumb|Beagles are commonly used for animal testing.]] Dogs are widely used in biomedical research, testing, and education—particularly [[beagle]]s, because they are gentle and easy to handle, and to allow for comparisons with historical data from beagles (a Reduction technique).<ref>{{cite journal |last1=Taylor |first1=Katy |last2=Alvarez |first2=Laura Rego |date=November 2019 |title=An Estimate of the Number of Animals Used for Scientific Purposes Worldwide in 2015 |journal=Alternatives to Laboratory Animals |volume=47 |issue=5–6 |pages=196–213 |doi=10.1177/0261192919899853 |pmid=32090616 |s2cid=211261775 |issn=0261-1929|doi-access=free }}</ref> They are used as models for human and veterinary diseases in cardiology, [[endocrinology]], and bone and joint studies, research that tends to be highly invasive, according to the [[Humane Society of the United States]].<ref name="HSUSDogs">[https://web.archive.org/web/20080226113001/http://www.hsus.org/animals_in_research/species_used_in_research/dog.html Dog profile], The Humane Society of the United States</ref> The most common use of dogs is in the safety assessment of new medicines<ref>{{cite journal|last1=Smith|first1=D|last2=Broadhead|first2=C|last3=Descotes|first3=G|last4=Fosse|first4=R|last5=Hack|first5=R|last6=Krauser|first6=K|last7=Pfister|first7=R|last8=Phillips|first8=B|last9=Rabemampianina|first9=Y|last10=Sanders|first10=J|last11=Sparrow|first11=S|last12=Stephan-Gueldner|first12=M|last13=Jacobsen|first13=SD|date=2002|title=Preclinical Safety Evaluation Using Nonrodent Species: An Industry/ Welfare Project to Minimize Dog Use|journal=ILAR|volume=43 Suppl|pages=S39-42|doi=10.1093/ilar.43.Suppl_1.S39|pmid=12388850|doi-access=free}}</ref> for human or veterinary use as a second species following testing in rodents, in accordance with the regulations set out in the [[International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use]]. One of the most significant advancements in medical science involves the use of dogs in developing the answers to insulin production in the body for diabetics and the role of the pancreas in this process. They found that the pancreas was responsible for producing insulin in the body and that removal of the pancreas, resulted in the development of diabetes in the dog. After re-injecting the pancreatic extract (insulin), the blood glucose levels were significantly lowered.<ref>{{cite journal|last1=Quianzon|first1=Celeste C.|last2=Cheikh|first2=Issam|date=2012-07-16|title=History of insulin|journal=Journal of Community Hospital Internal Medicine Perspectives|volume=2|issue=2|pages=18701|doi=10.3402/jchimp.v2i2.18701|issn=2000-9666|pmc=3714061|pmid=23882369}}</ref> The advancements made in this research involving the use of dogs has resulted in a definite improvement in the quality of life for both humans and animals.{{Citation needed|date=February 2024}} The U.S. Department of Agriculture's Animal Welfare Report shows that 60,979 dogs were used in USDA-registered facilities in 2016.<ref name=USDA2016 /> In the UK, according to the UK Home Office, there were 3,847 procedures on dogs in 2017.<ref name=UK2017/> Of the other large EU users of dogs, Germany conducted 3,976 procedures on dogs in 2016<ref>{{cite web|url=https://speakingofresearch.com/2018/02/06/germany-sees-7-rise-in-animal-research-procedures-in-2016/|title=Germany sees 7% rise in animal research procedures in 2016|date=6 February 2018|publisher=Speaking of Research}}</ref> and France conducted 4,204 procedures in 2016.<ref>{{cite web|url=https://speakingofresearch.com/2018/03/20/france-italy-and-the-netherlands-publish-their-2016-statistics/#France|title=France, Italy and the Netherlands publish their 2016 statistics|date=20 March 2018|publisher=Speaking of Research}}</ref> In both cases this represents under 0.2% of the total number of procedures conducted on animals in the respective countries. === Zebrafish === [[Zebrafish]] are commonly used for the basic study and development of various [[cancer]]s. Used to explore the immune system and genetic strains. They are low in cost, small size, fast reproduction rate, and able to observe cancer cells in real time. Humans and zebrafish share [[neoplasm]] similarities which is why they are used for research. The National Library of Medicine shows many examples of the types of cancer zebrafish are used in. The use of zebrafish have allowed them to find differences between MYC-driven pre-B vs T-ALL and be exploited to discover novel pre-B ALL therapies on acute lymphocytic [[leukemia]].<ref>{{cite journal |last1=Li |first1=Zhitao |last2=Zheng |first2=Wubin |last3=Wang |first3=Hanjin |last4=Cheng |first4=Ye |last5=Fang |first5=Yijiao |last6=Wu |first6=Fan |last7=Sun |first7=Guoqiang |last8=Sun |first8=Guangshun |last9=Lv |first9=Chengyu |last10=Hui |first10=Bingqing |date=2021-03-15 |title=Application of Animal Models in Cancer Research: Recent Progress and Future Prospects |journal=Cancer Management and Research |volume=13 |pages=2455–2475 |doi=10.2147/CMAR.S302565 |issn=1179-1322 |pmc=7979343 |pmid=33758544 |doi-access=free }}</ref><ref>{{cite journal |last1=Workman |first1=P. |last2=Aboagye |first2=E. O. |last3=Balkwill |first3=F. |last4=Balmain |first4=A. |last5=Bruder |first5=G. |last6=Chaplin |first6=D. J. |last7=Double |first7=J. A. |last8=Everitt |first8=J. |last9=Farningham |first9=D. a. H. |last10=Glennie |first10=M. J. |last11=Kelland |first11=L. R. |date=2010-05-25 |title=Guidelines for the welfare and use of animals in cancer research |journal=British Journal of Cancer |volume=102 |issue=11 |pages=1555–1577 |doi=10.1038/sj.bjc.6605642 |issn=1532-1827 |pmc=2883160 |pmid=20502460}}</ref> The National Library of Medicine also explains how a neoplasm is difficult to diagnose at an early stage. Understanding the molecular mechanism of digestive tract tumorigenesis and searching for new treatments is the current research. Zebrafish and humans share similar gastric cancer cells in the gastric cancer xenotransplantation model. This allowed researchers to find that Triphala could inhibit the growth and metastasis of gastric cancer cells. Since zebrafish liver cancer genes are related with humans they have become widely used in liver cancer search, as will as many other cancers.<ref>{{cite journal |last1=Tsering |first1=Jokyab |last2=Hu |first2=Xianda |date=2018 |title=Triphala Suppresses Growth and Migration of Human Gastric Carcinoma Cells In Vitro and in a Zebrafish Xenograft Model |journal=BioMed Research International |volume=2018 |pages=7046927 |doi=10.1155/2018/7046927 |issn=2314-6141 |pmc=6311269 |pmid=30643816|doi-access=free }}</ref> [[File:Danio rerio lab left.JPG|thumb|[[Zebrafish]] are a freshwaterfish and belong to the minnow family. They are commonly used for cancer research.]] ===Non-human primates=== {{Main|Animal testing on non-human primates}} [[File:Chimpanzee Enos before the flight of Mercury-Atlas 5.jpg|thumb|left|[[Enos (chimpanzee)|Enos]], the third primate to orbit the Earth, before insertion into the [[Mercury-Atlas 5]] capsule in 1961]] [[File:77-cm primate cage.jpg|thumb]] Non-human primates (NHPs) are used in toxicology tests, studies of AIDS and hepatitis, studies of [[neurology]], behavior and cognition, reproduction, [[genetics]], and [[xenotransplantation]]. They are caught in the wild or purpose-bred. In the United States and China, most primates are domestically purpose-bred, whereas in Europe the majority are imported purpose-bred.<ref>[http://books.nap.edu/openbook.php?record_id=10774&page=R1 International Perspectives: The Future of Nonhuman Primate Resources], Proceedings of the Workshop Held 17–19 April, pp. 36–45, 46–48, 63–69, 197–200.</ref> The [[European Commission]] reported that in 2011, 6,012 monkeys were experimented on in European laboratories.<ref>{{cite journal|title=Seventh Report on the Statistics on the Number of Animals used for Experimental and other Scientific Purposes in the Member States of the European Union|journal=Report from the Commission to the Council and the European Parliament|date=12 May 2013|url=http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:52013DC0859&from=EN|access-date=9 July 2015}}</ref> According to the [[U.S. Department of Agriculture]], there were 71,188 monkeys in U.S. laboratories in 2016.<ref name=USDA2016 /> 23,465 monkeys were imported into the U.S. in 2014 including 929 who were caught in the wild.<ref>{{cite web|title=U.S. primate import statistics for 2014|url=http://www.ippl.org/gibbon/2015/01/|website=International Primate Protection League|access-date=9 July 2015|archive-date=4 July 2017|archive-url=https://web.archive.org/web/20170704090032/https://www.ippl.org/gibbon/2015/01/}}</ref> Most of the NHPs used in experiments are [[macaque]]s;<ref name="Humaneprimate"/> but [[marmoset]]s, [[spider monkey]]s, and [[squirrel monkey]]s are also used, and [[baboon]]s and [[Common chimpanzee|chimpanzee]]s are used in the US. {{as of|2015}}, there are approximately 730 chimpanzees in U.S. laboratories.<ref>{{cite news|last1=St. Fleur|first1=Nicholas|title=U.S. Will Call All Chimps 'Endangered'|work=The New York Times |url=https://www.nytimes.com/2015/06/13/science/chimpanzees-endangered-fish-and-wildlife-service.html|access-date=9 July 2015|agency=The New York Times|date=12 June 2015}}</ref> In a survey in 2003, it was found that 89% of singly-housed primates exhibited self-injurious or [[List of abnormal behaviours in animals|abnormal]] [[stereotypy]]ical behaviors including pacing, rocking, hair pulling, and biting among others.<ref>{{cite journal|last1=Lutz|first1=C|last2=Well|first2=A|last3=Novak|first3=M|title=Stereotypic and Self-Injurious Behavior in Rhesus Macaques: A Survey and Retrospective Analysis of Environment and Early Experience|journal=American Journal of Primatology|date=2003|volume=60|issue=1|pages=1–15|doi=10.1002/ajp.10075|pmid=12766938|s2cid=19980505}}<!--|access-date=9 July 2015--></ref> The first transgenic primate was produced in 2001, with the development of a method that could introduce new genes into a [[rhesus macaque]].<ref>{{cite journal |vauthors=Chan AW, Chong KY, Martinovich C, Simerly C, Schatten G | title = Transgenic monkeys produced by retroviral gene transfer into mature oocytes | journal = Science | volume = 291 | issue = 5502 | pages = 309–12 | year = 2001 | pmid = 11209082 | doi = 10.1126/science.291.5502.309 | bibcode = 2001Sci...291..309C }}</ref> This transgenic technology is now being applied in the search for a treatment for the [[genetic disorder]] [[Huntington's disease]].<ref>{{cite journal |vauthors=Yang SH, Cheng PH, Banta H, Piotrowska-Nitsche K, Yang JJ, Cheng EC, Snyder B, Larkin K, Liu J, Orkin J, Fang ZH, Smith Y, Bachevalier J, Zola SM, Li SH, Li XJ, Chan AW | title = Towards a transgenic model of Huntington's disease in a non-human primate | journal = Nature | volume = 453 | issue = 7197 | pages = 921–24 | year = 2008 | pmid = 18488016 | pmc = 2652570 | doi = 10.1038/nature06975 | bibcode = 2008Natur.453..921Y }}</ref> Notable studies on non-human primates have been part of the polio vaccine development, and development of [[Deep Brain Stimulation]], and their current heaviest non-toxicological use occurs in the monkey AIDS model, [[Simian immunodeficiency virus|SIV]].<ref name=TheRoyalSociety/><ref name="Humaneprimate">Kathleen M. Conlee, Erika H. Hoffeld and Martin L. Stephens (2004) [https://web.archive.org/web/20080227041442/http://www.worldcongress.net/2002/proceedings/C2%20Conlee.pdf Demographic Analysis of Primate Research in the United States], ''ATLA'' 32, Supplement 1, 315–22</ref><ref name=Emborg/> In 2008, a proposal to ban all primates experiments in the EU has sparked a vigorous debate.<ref>{{cite news|url=https://www.theguardian.com/science/2008/nov/02/primate-monkey-animal-testing-drugs|title=Ban on primate experiments would be devastating, scientists warn|work=[[The Observer]]|date=2 November 2008|first=Robin|last=McKie|location=London}}</ref> ===Other species=== {{Further|Animal testing on frogs|Animal testing on rabbits|Draize test}} Over 500,000 fish and 9,000 amphibians were used in the UK in 2016.<ref name=UK2017>{{cite web|url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/724611/annual-statistics-scientific-procedures-living-animals-2017.pdf |title=Statistics of Scientific Procedures on Living Animals, Great Britain|year= 2017|work= UK Home Office |access-date=2018-07-23}}</ref> The main species used is the zebrafish, ''[[Danio rerio]]'', which are translucent during their embryonic stage, and the African clawed frog, ''[[Xenopus laevis]]''. Over 20,000 rabbits were used for animal testing in the UK in 2004.<ref name=HomeOffice2004>{{cite web|url=http://www.official-documents.gov.uk/document/cm67/6713/6713.pdf |title=Statistics of Scientific Procedures on Living Animals, Great Britain|year= 2004|work= British government |access-date=2012-07-13}}</ref> [[Albino]] rabbits are used in eye irritancy tests ([[Draize test]]) because rabbits have less tear flow than other animals, and the lack of eye pigment in albinos make the effects easier to visualize. The numbers of rabbits used for this purpose has fallen substantially over the past two decades. In 1996, there were 3,693 procedures on rabbits for eye irritation in the UK,<ref>Statistics of Scientific Procedures on Living Animals, Great Britain, 1996 – UK Home Office, Table 13</ref> and in 2017 this number was just 63.<ref name=UK2017 /> Rabbits are also frequently used for the production of polyclonal antibodies. Cats are most commonly used in neurological research. In 2016, 18,898 cats were used in the United States alone,<ref name=USDA2016 /> around a third of which were used in experiments which have the potential to cause "pain and/or distress"<ref>{{cite web|url=https://www.aphis.usda.gov/animal_welfare/downloads/reports/Annual-Report-Animal-Usage-by-FY2016.pdf|title=Annual Report Animals|publisher=Aphis.usda.gov|access-date=2017-08-06|archive-date=23 November 2020|archive-url=https://web.archive.org/web/20201123182104/https://www.aphis.usda.gov/animal_welfare/downloads/reports/Annual-Report-Animal-Usage-by-FY2016.pdf|url-status=dead}}</ref> though only 0.1% of cat experiments involved potential pain which was not relieved by anesthetics/analgesics. In the UK, just 198 procedures were carried out on cats in 2017. The number has been around 200 for most of the last decade.<ref name=UK2017/> ==Care and use of animals== ===Regulations and laws=== {{See also|Animal testing regulations|Institutional Animal Care and Use Committee|Animals (Scientific Procedures) Act 1986|European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes}}{{World laws on cosmetic animal testing}} The regulations that apply to animals in laboratories vary across species. In the U.S., under the [[Animal Welfare Act of 1966|Animal Welfare Act]] and the ''Guide for the Care and Use of Laboratory Animals'' (the ''Guide''), published by the National Academy of Sciences, any procedure can be performed on an animal if it can be successfully argued that it is scientifically justified. Researchers are required to consult with the institution's veterinarian and its [[Institutional Animal Care and Use Committee]] (IACUC), which every research facility is obliged to maintain.<ref name=Carbone68>Carbone, pp. 68–69.</ref> The IACUC must ensure that alternatives, including non-animal alternatives, have been considered, that the experiments are not unnecessarily duplicative, and [[Pain in animals|that pain relief is given]] unless it would interfere with the study. The IACUCs regulate all vertebrates in testing at institutions receiving federal funds in the USA. Although the Animal Welfare Act does not include purpose-bred rodents and birds, these species are equally regulated under Public Health Service policies that govern the IACUCs.<ref>[http://grants.nih.gov/grants/olaw/references/phspol.htm#AnimalWelfareAssurance Office of Laboratory Animal Welfare]. Public Health Service Policy on Humane Care and Use of Laboratory Animals. nih.gov</ref><ref>[http://edocket.access.gpo.gov/cfr_2008/janqtr/9cfr1.1.htm Title 9 – Animals and Animal Products]. Code of Federal Regulations. Vol. 1 (1 January 2008).</ref> The Public Health Service policy oversees the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC).&nbsp;The CDC conducts infectious disease research on nonhuman primates, rabbits, mice, and other animals, while FDA requirements cover use of animals in pharmaceutical research.<ref name="aldf.org">{{cite web|url=http://aldf.org/resources/when-you-witness-animal-cruelty/animal-testing-and-the-law/?gclid=CJmh4vzmvdQCFUWCfgodqA8Hlg|title=Animal Testing and the Law – Animal Legal Defense Fund|website=Animal Legal Defense Fund|access-date=2017-06-14|archive-url=https://web.archive.org/web/20170823020847/http://aldf.org/resources/when-you-witness-animal-cruelty/animal-testing-and-the-law/?gclid=CJmh4vzmvdQCFUWCfgodqA8Hlg|archive-date=23 August 2017}}</ref> Animal Welfare Act (AWA) regulations are enforced by the USDA, whereas Public Health Service regulations are enforced by OLAW and in many cases by AAALAC. According to the 2014 U.S. Department of Agriculture Office of the Inspector General (OIG) report—which looked at the oversight of animal use during a three-year period—"some Institutional Animal Care and Use Committees ...did not adequately approve, monitor, or report on experimental procedures on animals". The OIG found that "as a result, animals are not always receiving basic humane care and treatment and, in some cases, pain and distress are not minimized during and after experimental procedures". According to the report, within a three-year period, nearly half of all American laboratories with regulated species were cited for AWA violations relating to improper IACUC oversight.<ref>{{cite journal|last1=Harden|first1=Gil|title=USDA Inspector General Audit Report of APHIS Animal Care Program Inspection and Enforcement Activities|journal=United States Department of Agriculture Office of Inspector General|issue=Report No. 33601–0001–41|url=http://www.usda.gov/oig/webdocs/33601-0001-41.pdf|access-date=7 July 2015}}</ref> The USDA OIG made similar findings in a 2005 report.<ref>{{cite journal|date=September 2005|title=Audit Report: APHIS Animal Care Program Inspection and Enforcement Activities|url=http://www.usda.gov/oig/webdocs/33002-03-SF.pdf|journal=USDA Office of Inspector General Western Region|issue=Report No. 33002–3–SF|last1=Young|first1=Robert|access-date=7 July 2015}}</ref> With only a broad number of 120 inspectors, the United States Department of Agriculture&nbsp;(USDA) oversees more than 12,000 facilities involved in research, exhibition, breeding, or dealing of animals.<ref name="aldf.org"/> Others have criticized the composition of IACUCs, asserting that the committees are predominantly made up of animal researchers and university representatives who may be biased against animal welfare concerns.<ref>{{cite journal|last1=Hansen|first1=L|last2=Goodman|first2=J|last3=Chandna|first3=A|title=Analysis of animal research ethics committee membership at American institutions|journal=Animals|date=2012|volume=2|issue=1|pages=68–75|doi=10.3390/ani2010068|pmid=26486777|pmc=4494267|doi-access=free}}</ref> Larry Carbone, a laboratory animal veterinarian, writes that, in his experience, IACUCs take their work very seriously regardless of the species involved, though the use of [[non-human primates]] always raises what he calls a "red flag of special concern".<ref>Carbone, p. 94.</ref> A study published in ''Science'' magazine in July 2001 confirmed the low reliability of IACUC reviews of animal experiments. Funded by the National Science Foundation, the three-year study found that animal-use committees that do not know the specifics of the university and personnel do not make the same approval decisions as those made by animal-use committees that do know the university and personnel. Specifically, blinded committees more often ask for more information rather than approving studies.<ref>{{cite journal | vauthors = Plous S, Herzog H | title = Animal Research: Reliability of Protocol Reviews for Animal Research | journal = Science | volume = 293 | issue = 5530 | pages = 608–09 | year = 2001 | pmid = 11474086 | doi = 10.1126/science.1061621 | s2cid = 33314019 }}</ref> Scientists in India are protesting a recent guideline issued by the [[University Grants Commission (India)|University Grants Commission]] to ban the use of live animals in universities and laboratories.<ref>{{cite news|first =Jayashree|last =Nandi|url=http://articles.timesofindia.indiatimes.com/2012-04-27/science/31421085_1_animals-zoology-scientists |archive-url=https://web.archive.org/web/20121027144438/http://articles.timesofindia.indiatimes.com/2012-04-27/science/31421085_1_animals-zoology-scientists |archive-date=27 October 2012 |title=Scientists take on activists, want ban on live testing on animals lifted|date=27 April 2012 |newspaper =[[The Times of India]]|access-date=2012-07-13}}</ref> ===Numbers=== Accurate global figures for animal testing are difficult to obtain; it has been estimated that 100 million vertebrates are experimented on around the world every year,<ref>{{cite journal |last1=Taylor |first1=Katy |last2=Gordon |first2=Nicky |last3=Langley |first3=Gill |last4=Higgins |first4=Wendy |date=2008 |title=Estimates for worldwide laboratory animal use in 2005 |journal=ATLA |volume=36 |issue=3 |pages=327–42 |pmid=18662096|doi=10.1177/026119290803600310 |s2cid=196613886 |url=https://animalstudiesrepository.org/acwp_lab/14 |doi-access=free }}</ref> 10–11 million of them in the EU.<ref name="hunter2014">{{cite news | author=Hunter, Robert G. | title=Alternatives to animal testing drive market | quote=While growth has leveled off and there have been significant reductions in some countries, the number of animals used in research globally still totals almost 100 million a year. | work=[[Gen. Eng. Biotechnol. News]] | date=1 January 2014 | page=11 | issue=1 | volume=34 | url=http://www.genengnews.com/gen-articles/alternatives-to-animal-testing-drive-market/5095/ }}{{open access}}</ref> The [[Nuffield Council on Bioethics]] reports that global annual estimates range from 50 to 100 million animals. None of the figures include invertebrates such as shrimp and fruit flies.<ref name=nuffield45>{{cite web|url=http://www.nuffieldbioethics.org/fileLibrary/pdf/RIA_Report_FINAL-opt.pdf |title=The Ethics of research involving animals |publisher=Nuffield Council on Bioethics |archive-url=https://web.archive.org/web/20080625033250/http://www.nuffieldbioethics.org/fileLibrary/pdf/RIA_Report_FINAL-opt.pdf |archive-date=25 June 2008 }}</ref> The&nbsp;USDA/APHIS&nbsp;has&nbsp;published the 2016 animal research statistics. Overall, the number of animals (covered by the Animal Welfare Act) used in research in the US&nbsp;rose 6.9%&nbsp;from 767,622 (2015) to 820,812 (2016).<ref>{{cite news|url=https://speakingofresearch.com/2017/06/19/usda-publishes-2016-animal-research-statistics-7-rise-in-animal-use/|title=USDA publishes 2016 animal research statistics – 7% rise in animal use|date=2017-06-19|work=Speaking of Research|access-date=2017-12-10}}</ref> This includes both public and private institutions. By comparing with EU data, where all [[vertebrate]] species are counted, [[Speaking of Research]] estimated that around 12 million vertebrates were used in research in the US in 2016.<ref name="USDA2016">{{cite web|url=http://speakingofresearch.com/facts/statistics/|title=USDA Statistics for Animals Used in Research in the US|publisher=Speaking of Research|date=20 March 2008}}</ref> A 2015 article published in the ''[[Journal of Medical Ethics]]'', argued that the use of animals in the US has dramatically increased in recent years. Researchers found this increase is largely the result of an increased reliance on genetically modified mice in animal studies.<ref name="GoodmanChandnaRoe">{{cite journal|last1=Goodman|first1=J.|last2=Chandna|first2=A.|last3=Roe|first3=K.|date=2015|title=Trends in animal use at US research facilities|url=http://jme.bmj.com/content/early/2015/01/27/medethics-2014-102404.abstract|journal=Journal of Medical Ethics|volume=41|issue=7|pages=567–69|doi=10.1136/medethics-2014-102404|pmid=25717142|s2cid=46187262|access-date=7 July 2015}}</ref> In 1995, researchers at Tufts University Center for Animals and Public Policy estimated that 14–21 million animals were used in American laboratories in 1992, a reduction from a high of 50 million used in 1970.<ref>Rowan, A., Loew, F., and Weer, J. (1995) "The Animal Research Controversy. Protest, Process and Public Policy: An Analysis of Strategic Issues." ''Tufts University'', North Grafton. cited in Carbone 2004, p. 26.</ref> In 1986, the U.S. Congress Office of Technology Assessment reported that estimates of the animals used in the U.S. range from 10 million to upwards of 100 million each year, and that their own best estimate was at least 17 million to 22 million.<ref>''Alternatives to Animal Use in Research, Testing and Education'', U.S. Congress Office of Technology Assessment, Washington, D.C.:Government Printing Office, 1986, p. 64. In 1966, the Laboratory Animal Breeders Association estimated in testimony before Congress that the number of mice, rats, guinea pigs, hamsters, and rabbits used in 1965 was around 60 million. (Hearings before the Subcommittee on Livestock and Feed Grains, Committee on Agriculture, U.S. House of Representatives, 1966, p. 63.)</ref> In 2016, the Department of Agriculture listed 60,979 dogs, 18,898 cats, 71,188 non-human primates, 183,237 guinea pigs, 102,633 hamsters, 139,391 rabbits, 83,059 farm animals, and 161,467 other mammals, a total of 820,812, a figure that includes all mammals except purpose-bred mice and rats. The use of dogs and cats in research in the U.S. decreased from 1973 to 2016 from 195,157 to 60,979, and from 66,165 to 18,898, respectively.<ref name=USDA2016 /> In the UK, Home Office figures show that 3.79 million procedures were carried out in 2017.<ref name="UK Home Office 2016">{{cite web|date=2017|url=http://www.understandinganimalresearch.org.uk/news/communications-media/animal-research-numbers-in-2017/ |title=Animal research numbers in 2017 |publisher=Understanding Animal Research}}</ref> 2,960 procedures used non-human primates, down over 50% since 1988. A "procedure" refers here to an experiment that might last minutes, several months, or years. Most animals are used in only one procedure: animals are frequently euthanized after the experiment; however death is the endpoint of some procedures.<ref name=nuffield45/> The procedures conducted on animals in the UK in 2017 were categorised as: 43% (1.61 million) sub-threshold, 4% (0.14 million) non-recovery, 36% (1.35 million) mild, 15% (0.55 million) moderate, and 4% (0.14 million) severe.<ref name=SR2017>{{cite web|url=https://speakingofresearch.com/facts/uk-statistics/ |title=Home Office Statistics for Animals Used in Research in the UK |publisher=Speaking of Research|date=23 October 2012 }}</ref> A 'severe' procedure would be, for instance, any test where death is the end-point or fatalities are expected, whereas a 'mild' procedure would be something like a blood test or an MRI scan.<ref name="UK Home Office 2016" /> ===The Three Rs=== {{Main|Three Rs (animal research)}} The Three Rs (3Rs) are guiding principles for more ethical use of animals in testing. These were first described by W.M.S. Russell and R.L. Burch in 1959.<ref name="altweb.jhsph">{{cite book |url=http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc |title=The principles of humane experimental technique |last1=Russell, W. M. S. (William Moy Stratton) |last2=Health |first2=JH Bloomberg School of Public |date=1992 |publisher=Universities Federation for Animal Welfare |isbn=0-900767-78-2 |edition=Special |location=South Mimms, Potters Bar, Herts, England |oclc=27347928 |access-date=16 August 2013 |archive-date=27 September 2011 |archive-url=https://web.archive.org/web/20110927060555/http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc |url-status=dead }}</ref> The 3Rs state: # Replacement which refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aims. These methods include computer modeling. # Reduction which refers to methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals. # Refinement which refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance [[animal welfare]] for the animals used. These methods include non-invasive techniques.<ref name="Badyal">{{cite journal |author=Badyal D. |author2=Desai C.|year=2014|title=Animal use in pharmacology education and research: The changing scenario|journal=Indian Journal of Pharmacology|volume=46|issue=3|pages=257–65|doi=10.4103/0253-7613.132153|pmc=4071700|pmid=24987170 |doi-access=free }}</ref> The 3Rs have a broader scope than simply encouraging alternatives to animal testing, but aim to improve animal welfare and scientific quality where the use of animals can not be avoided. These 3Rs are now implemented in many testing establishments worldwide and have been adopted by various pieces of legislation and regulations.<ref name="Ethical">{{cite journal |author1=Liguori, G.| display-authors=etal| year = 2017 | title = Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, 3Rs Strategies, and Harm-Benefit Analysis| journal = Tissue Engineering Part C: Methods | volume = 23 | issue = 12 | pages= 850–62 | doi=10.1089/ten.TEC.2017.0189| pmid=28756735| s2cid=206268293| url=https://pure.rug.nl/ws/files/51950145/ten.tec.2017.0189.pdf}}</ref> Despite the widespread acceptance of the 3Rs, many countries—including Canada, Australia, Israel, South Korea, and Germany—have reported rising experimental use of animals in recent years with increased use of mice and, in some cases, fish while reporting declines in the use of cats, dogs, primates, rabbits, guinea pigs, and hamsters. Along with other countries<!-- which specific ''other" countries? -->, China has also escalated its use of [[Genetically modified animal|GM animals]], resulting in an increase in overall animal use.<ref>{{cite web |website=Canadian Council on Animal Care |title=2009 CCAC Survey of Animal Use |date=December 2010 |url=http://www.ccac.ca/Documents/Publications/Statistics/Survey_2009.pdf |access-date=7 July 2015 |archive-url=https://web.archive.org/web/20150607174417/http://www.ccac.ca/Documents/Publications/Statistics/Survey_2009.pdf |archive-date=7 June 2015 }}</ref><ref>{{cite news |last1=Merkes |first1=M. |last2=Buttrose |first2=R. |title=New code, same suffering: animals in the lab |url=http://www.abc.net.au/news/2013-08-01/merkes-and-buttrose-animal-testing/4857604 |access-date=7 July 2015 |agency=The Drum |publisher=ABC}}</ref><ref>{{cite news |last1=Even |first1=Dan |title=Number of animal experiments up for first time since 2008 |url=http://www.haaretz.com/news/national/number-of-animal-experiments-up-for-firsttime-since-2008.premium-1.526516 |access-date=7 July 2015 |agency=Haaretz |date=29 May 2013}}</ref><ref>{{cite web |title=Rise in animal research in South Korea in 2017 |website=Speaking of Research |date=20 April 2018 |url=https://speakingofresearch.com/2018/04/12/rise-in-animal-research-in-south-korea-in-2017/ |access-date=23 July 2017}}</ref><ref>{{cite web |title=Number of laboratory animals in Germany |url=http://www.mpg.de/286584/Numbers |website=Max-Planck-Gesellschaft |access-date=7 July 2015}}</ref><ref>{{cite journal |last1=Kong |first1=Q. |last2=Qin |first2=C. |title=Analysis of current laboratory animal science policies and administration in China |journal=ILAR |date=2009 |volume=51 |issue=1 |pages=e1–e11 |pmid=20075493 |doi=10.1093/ilar.51.1.e1|doi-access=free }}</ref>{{Excessive citations inline | date = July 2020 }} ===Sources=== {{Main|Laboratory animal sources|International primate trade}} Animals used by laboratories are largely supplied by specialist dealers. Sources differ for vertebrate and invertebrate animals. Most laboratories breed and raise flies and worms themselves, using strains and mutants supplied from a few main stock centers.<ref>[http://www.ncrr.nih.gov/comparative_medicine/resource_directory/invertebrates.asp Invertebrate Animal Resources] {{webarchive|url=https://web.archive.org/web/20071025061451/http://www.ncrr.nih.gov/comparative_medicine/resource_directory/invertebrates.asp |date=25 October 2007 }}. National Center for Research Resources. ncrr.nih.gov</ref> For vertebrates, sources include breeders and dealers like [[Covance]] and [[Charles River Laboratories]] who supply purpose-bred and wild-caught animals; businesses that trade in wild animals such as [[Nafovanny]]; and dealers who supply animals sourced from pounds, auctions, and newspaper ads. [[Animal shelter]]s also supply the laboratories directly.<ref>{{cite web|url=http://www.aesop-project.org/Oversight.htm |title=Who's Who of Federal Oversight of Animal Issues |publisher=Aesop-project.org |archive-url=https://web.archive.org/web/20070922123927/http://www.aesop-project.org/Oversight.htm |archive-date=22 September 2007 }}</ref> Large centers also exist to distribute strains of [[genetically modified animal]]s; the [[International Knockout Mouse Consortium]], for example, aims to provide [[knockout mouse|knockout mice]] for every gene in the mouse genome.<ref>{{cite journal |vauthors=Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | year = 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 | s2cid = 18872015 | doi-access = free }}</ref> [[File:Muizenkooi met houten muizen (3).JPG|thumb|left|A laboratory mouse cage. Mice are either bred commercially, or raised in the laboratory.]] In the U.S., Class A breeders are licensed by the U.S. Department of Agriculture (USDA) to sell animals for research purposes, while Class B dealers are licensed to buy animals from "random sources" such as auctions, pound seizure, and newspaper ads. Some Class B dealers have been accused of kidnapping pets and illegally trapping strays, a practice known as ''bunching''.<ref name=Gillham/><ref name="Class B dealers">[http://www.hsus.org/animals_in_research/class_b_dealers/ Class B dealers] {{Webarchive|url=https://web.archive.org/web/20100429102206/http://www.hsus.org/animals_in_research/class_b_dealers/ |date=29 April 2010 }}, Humane Society of the United States.</ref><ref>[http://www.aesop-project.org/Oversight.htm "Who's Who of Federal Oversight of Animal Issues"] {{webarchive |url=https://web.archive.org/web/20070922123927/http://www.aesop-project.org/Oversight.htm |date=22 September 2007 }}, Aesop Project.</ref><ref>Salinger, Lawrence and Teddlie, Patricia. [http://citation.allacademic.com/meta/p_mla_apa_research_citation/0/3/3/8/8/p33882_index.html "Stealing Pets for Research and Profit: The Enforcement (?) of the Animal Welfare Act"] {{Webarchive|url=https://archive.today/20130116184728/http://citation.allacademic.com/meta/p_mla_apa_research_citation/0/3/3/8/8/p33882_index.html |date=16 January 2013 }}, paper presented at the annual meeting of the American Society of Criminology, Royal York, Toronto, 15 October 2006</ref><ref>Reitman, Judith (1995) ''Stolen for Profit'', Zebra, {{ISBN|0-8217-4951-X}}.</ref><ref>Moran, Julio (12 September 1991) [https://www.latimes.com/archives/la-xpm-1991-09-12-me-3212-story.html "Three Sentenced to Prison for Stealing Pets for Research,"] L.A. Times.</ref> It was in part out of public concern over the sale of pets to research facilities that the 1966 Laboratory Animal Welfare Act was ushered in—the Senate Committee on Commerce reported in 1966 that stolen pets had been retrieved from Veterans Administration facilities, the Mayo Institute, the University of Pennsylvania, Stanford University, and Harvard and Yale Medical Schools.<ref>[[Gary L. Francione|Francione, Gary]]. ''Animals, Property, and the Law''. Temple University Press, 1995, p. 192; Magnuson, Warren G., Chairman. "Opening remarks in hearings prior to enactment of Pub. L. 89-544, the Laboratory Animal Welfare Act," U.S. Senate Committee on Commerce, 25 March 1966.</ref> The USDA recovered at least a dozen stolen pets during a raid on a Class B dealer in Arkansas in 2003.<ref name=HSUSBaird>[https://web.archive.org/web/20080325225027/http://www.hsus.org/animals_in_research/animals_in_research_news/animal_dealer_loses_license_and_pays_record_fine.html Notorious Animal Dealer Loses License and Pays Record Fine], The Humane Society of the United States</ref> Four states in the U.S.—[[Minnesota]], [[Utah]], [[Oklahoma]], and [[Iowa]]—require their shelters to provide animals to research facilities. Fourteen states explicitly prohibit the practice, while the remainder either allow it or have no relevant legislation.<ref name=ASPCAdealers>[https://web.archive.org/web/20080627163237/http://www.aspca.org/site/PageServer?pagename=kids_ri_animaltesting_comefrom Animal Testing: Where Do the Animals Come From?]. American Society for the Prevention of Cruelty to Animals. According to the ASPCA, the following states prohibit shelters from providing animals for research: Connecticut, Delaware, Hawaii, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, South Carolina, Vermont, and West Virginia.</ref> In the European Union, animal sources are governed by ''Council Directive 86/609/EEC'', which requires lab animals to be specially bred, unless the animal has been lawfully imported and is not a wild animal or a stray. The latter requirement may also be exempted by special arrangement.<ref name=direct1>{{cite web|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31986L0609:EN:NOT |title=Council Directive 86/609/EEC of 24 November 1986 |date=24 November 1986 |publisher=Eur-lex.europa.eu }}</ref> In 2010 the Directive was revised with [[EU Directive 2010/63/EU]].<ref>{{cite web|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32010L0063:EN:NOT |title=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 Text with EEA relevance |date=22 September 2010 |publisher=Eur-lex.europa.eu }}</ref> In the UK, most animals used in experiments are bred for the purpose under the 1988 Animal Protection Act, but wild-caught primates may be used if exceptional and specific justification can be established.<ref>[http://www.ukcites.gov.uk/pdf_files/Sep05GN9%20Primate%20imports.pdf Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES)] {{webarchive|url=https://web.archive.org/web/20070731082707/http://www.ukcites.gov.uk/pdf_files/Sep05GN9%20Primate%20imports.pdf |date=31 July 2007 }} Department for Environment, Food and Rural Affairs</ref><ref name=HOStats>{{cite web|url=http://www.official-documents.gov.uk/document/cm67/6713/6713.pdf |title="Statistics of Scientific Procedures on Living Animals", Statistics of Scientific Procedures on Living Animals, Home Office|year= 2004| page=87 }}</ref> The United States also allows the use of wild-caught primates; between 1995 and 1999, 1,580 wild baboons were imported into the U.S. Over half the primates imported between 1995 and 2000 were handled by [[Charles River Laboratories]], or by [[Covance]], which is the single largest [[International primate trade|importer of primates]] into the U.S.<ref>[https://web.archive.org/web/20070708204056/http://www.ippl.org/04-25-07c.html U.S. Primate Imports Spike] ''International Primate Protection League'' April 2007</ref> ===Pain and suffering=== {{Further|Animal cognition|Pain in animals|Pain in fish|Pain in amphibians|Pain in invertebrates|Pain in cephalopods}} [[File:Frog vivisection.jpg|thumb|right|Prior to dissection for educational purposes, [[chloroform]] was administered to this [[Common Sand Frog|common sand frog]] to induce [[anesthesia]] and death.]] The extent to which animal testing causes [[pain]] and [[suffering]], and the capacity of animals to experience and comprehend them, is the subject of much debate.<ref>{{cite journal |vauthors=Duncan IJ, Petherick JC | title = The implications of cognitive processes for animal welfare | journal = Journal of Animal Science | volume = 69 | issue = 12 | pages = 5017–22 | year = 1991 | pmid = 1808195 | doi=10.2527/1991.69125017x}}</ref><ref>{{cite journal |vauthors=Curtis SE, Stricklin WR | title = The importance of animal cognition in agricultural animal production systems: an overview | journal = Journal of Animal Science | volume = 69 | issue = 12 | pages = 5001–07 | year = 1991 | pmid = 1808193 | doi=10.2527/1991.69125001x}}</ref> According to the USDA, in 2016 501,560 animals (61%) (not including rats, mice, birds, or invertebrates) were used in procedures that did not include more than momentary pain or distress. 247,882 (31%) animals were used in procedures in which pain or distress was relieved by anesthesia, while 71,370 (9%) were used in studies that would cause pain or distress that would not be relieved.<ref name="USDA2016" /> The idea that animals might not feel pain as human beings feel it traces back to the 17th-century French philosopher, [[René Descartes]], who argued that animals do not experience pain and suffering because they lack [[consciousness]].<ref name=nuffield45/><ref name=Carbone149>Carbone, p. 149.</ref> [[Bernard Rollin]] of [[Colorado State University]], the principal author of two U.S. federal laws regulating pain relief for animals,<ref>Rollin drafted the 1985 Health Research Extension Act and an animal welfare amendment to the 1985 Food Security Act: see Rollin, Bernard. [http://www.nature.com/embor/journal/v8/n6/full/7400996.html "Animal research: a moral science. Talking Point on the use of animals in scientific research"], EMBO Reports 8, 6, 2007, pp. 521–25</ref> writes that researchers remained unsure into the 1980s as to whether animals experience pain, and that veterinarians trained in the U.S. before 1989 were simply taught to ignore animal pain.<ref name=Rollin117>Rollin, Bernard. ''The Unheeded Cry: Animal Consciousness, Animal Pain, and Science''. New York: Oxford University Press, 1989, pp. xii, 117–18, cited in Carbone 2004, p. 150.</ref> In his interactions with scientists and other veterinarians, he was regularly asked to "prove" that animals are conscious, and to provide "scientifically acceptable" grounds for claiming that they feel pain.<ref name=Rollin117/> Carbone writes that ''the view that animals feel pain differently is now a minority view.'' Academic reviews of the topic are more equivocal, noting that although the argument that [[Animal consciousness|animals have at least simple conscious thoughts and feelings]] has strong support,<ref>{{cite journal |vauthors=Griffin DR, Speck GB | title = New evidence of animal consciousness | journal = Animal Cognition | volume = 7 | issue = 1 | pages = 5–18 | year = 2004 | pmid = 14658059 | doi = 10.1007/s10071-003-0203-x | s2cid = 8650837 }}</ref> some critics continue to question how reliably animal mental states can be determined.<ref name=nuffield45/><ref>{{cite journal | author = Allen C | title = Assessing animal cognition: ethological and philosophical perspectives | journal = Journal of Animal Science | volume = 76 | issue = 1 | pages = 42–47 | year = 1998 | pmid = 9464883 | doi = 10.2527/1998.76142x }}</ref> However, some canine experts are stating that, while intelligence does differ animal to animal, dogs have the intelligence of a two to two-and-a-half-year old. This does support the idea that dogs, at the very least, have some form of consciousness.<ref>{{cite web |url=https://www.apa.org/news/press/releases/2009/08/dogs-think |title=Smarter Than You Think: Renowned Canine Researcher Puts Dogs' Intelligence on Par with 2-Year-Old Human |access-date=2023-05-05 |website=www.apa.org}}</ref> The ability of invertebrates to experience pain and suffering is less clear, however, legislation in several countries (e.g. U.K., [[Regulation of animal research in New Zealand|New Zealand]],<ref>{{cite web|url=http://www.legislation.govt.nz/act/public/1999/0142/latest/DLM49664.html|title=Animal Welfare Act 1999|publisher=Parliamentary Counsel Office|year=2015|access-date=23 January 2016}}</ref> Norway<ref name="Norway">{{cite web |title=Norwegian animal welfare act |url=https://www.animallaw.info/statute/noway-cruelty-norwegian-animal-welfare-act-2010#s1|access-date=25 January 2016|website=Animal Legal and Historical Center |year=2011}}</ref>) protects some invertebrate species if they are being used in animal testing. In the U.S., the defining text on animal welfare regulation in animal testing is the ''Guide for the Care and Use of Laboratory Animals''.<ref>[http://www.nap.edu/openbook.php?record_id=5140 "Guide for the Care and Use of Laboratory Animals"], ILAR, National Research Council, National Academies Press, 1996, p. 64, {{ISBN|0-309-05377-3}}.</ref> This defines the parameters that govern animal testing in the U.S. It states "The ability to experience and respond to pain is widespread in the animal kingdom...Pain is a stressor and, if not relieved, can lead to unacceptable levels of stress and distress in animals." The Guide states that the ability to recognize the symptoms of pain in different species is vital in efficiently applying pain relief and that it is essential for the people caring for and using animals to be entirely familiar with these symptoms. On the subject of analgesics used to relieve pain, the Guide states "The selection of the most appropriate analgesic or anesthetic should reflect professional judgment as to which best meets clinical and humane requirements without compromising the scientific aspects of the research protocol". Accordingly, all issues of animal pain and distress, and their potential treatment with analgesia and anesthesia, are required regulatory issues in receiving animal protocol approval.<ref>{{cite web|url=https://ori.hhs.gov/education/products/ncstate/iacuc.htm|title=How to Work With Your Institutional Animal Care and Use Committee (IACUC)|website=ori.hhs.gov}}</ref> Currently, traumatic methods of marking laboratory animals are being replaced with non-invasive alternatives.<ref>{{cite journal |last1=Klabukov |first1=Ilya |last2=Shestakova |first2=Victoria |last3=Krasilnikova |first3=Olga |last4=Smirnova |first4=Anna |last5=Abramova |first5=Olga |last6=Baranovskii |first6=Denis |last7=Atiakshin |first7=Dmitri |last8=Kostin |first8=Andrey A. |last9=Shegay |first9=Peter |last10=Kaprin |first10=Andrey D. |date=2023 |title=Refinement of Animal Experiments: Replacing Traumatic Methods of Laboratory Animal Marking with Non-Invasive Alternatives |journal=Animals |volume=13 |issue=22 |pages=3452 |doi=10.3390/ani13223452 |doi-access=free |issn=2076-2615 |pmc=10668729 |pmid=38003070}}</ref><ref>{{cite journal |last1=Lindner |first1=Elke |last2=Fuelling |first2=Olaf |date=2002 |title=Marking methods in small mammals: ear-tattoo as an alternative to toe-clipping |url=https://zslpublications.onlinelibrary.wiley.com/doi/10.1017/S0952836902000195 |journal=Journal of Zoology |language=en |volume=256 |issue=2 |pages=159–163 |doi=10.1017/S0952836902000195 |issn=0952-8369}}</ref> In 2019, Katrien Devolder and Matthias Eggel proposed [[Genetically modified animal|gene editing research animals]] to [[eradication of suffering|remove the ability to feel pain]]. This would be an intermediate step towards eventually stopping all experimentation on animals and adopting [[alternatives to animal testing|alternatives]].<ref>{{cite journal |last1=Devolder |first1=Katrien |last2=Eggel |first2=Matthias |title=No Pain, No Gain? In Defence of Genetically Disenhancing (Most) Research Animals |journal=Animals |date=2019 |volume=9 |issue=4 |page=154 |doi=10.3390/ani9040154 |pmc=6523187 |pmid=30970545 |doi-access=free }}</ref> Additionally, this would not stop research animals from experiencing psychological harm. ===Euthanasia=== {{Further|Euthanasia|Animal euthanasia}} Regulations require that scientists use as few animals as possible, especially for terminal experiments.<ref name=Flecknell/> However, while policy makers consider suffering to be the central issue and see animal euthanasia as a way to reduce suffering, others, such as the [[RSPCA]], argue that the lives of laboratory animals have intrinsic value.<ref>[http://www.apc.gov.uk/reference/costbenefit.pdf Animal Procedures Committee: review of cost-benefit assessment in the use of animals in research] {{webarchive |url=https://web.archive.org/web/20080227041442/http://www.apc.gov.uk/reference/costbenefit.pdf |date=27 February 2008 }} The Animal Procedures Committee, June 2003 p46-7</ref> Regulations focus on whether particular methods cause [[pain]] and [[suffering]], not whether their death is undesirable in itself.<ref name=Carbone2>Carbone, Larry. "Euthanasia," in Bekoff, M. and Meaney, C. ''Encyclopedia of Animal Rights and Welfare''. Greenwood Publishing Group, pp. 164–66, cited in Carbone 2004, pp. 189–90.</ref> The animals are euthanized at the end of studies for sample collection or [[Autopsy|post-mortem examination]]; during studies if their pain or suffering falls into certain categories regarded as unacceptable, such as depression, infection that is unresponsive to treatment, or the failure of large animals to eat for five days;<ref>{{cite web|first =Dale |last =Cooper |url=http://www.ahc.umn.edu/rar/euthanasia.html |title="Euthanasia Guidelines", Research animal resources|publisher=University of Minnesota|date=11 June 2017 }}</ref> or when they are unsuitable for breeding or unwanted for some other reason.<ref>{{cite journal |vauthors=Close B, Banister K, Baumans V, Bernoth EM, Bromage N, Bunyan J, Erhardt W, Flecknell P, Gregory N, Hackbarth H, Morton D, Warwick C | title = Recommendations for euthanasia of experimental animals: Part 1 | journal = Laboratory Animals | volume = 30 | issue = 4 | pages = 293–316 (295) | year = 1996 | pmid = 8938617 | doi = 10.1258/002367796780739871| doi-access = free }}</ref> Methods of euthanizing laboratory animals are chosen to induce rapid unconsciousness and death without pain or distress.<ref>[http://www.nap.edu/openbook.php?record_id=5140 "Guide for the Care and Use of Laboratory Animals"], ILAR, National Research Council, National Academies Press, 1996, p. 65, {{ISBN|0-309-05377-3}}.</ref> The methods that are preferred are those published by councils of veterinarians. The animal can be made to inhale a gas, such as [[carbon monoxide]] and [[carbon dioxide]], by being placed in a chamber, or by use of a face mask, with or without prior sedation or anesthesia. [[Sedative]]s or [[anesthetic]]s such as [[barbiturate]]s can be given [[Intravenous therapy|intravenously]], or inhalant anesthetics may be used. Amphibians and fish may be immersed in water containing an anesthetic such as [[tricaine]]. Physical methods are also used, with or without sedation or anesthesia depending on the method. Recommended methods include [[decapitation]] (beheading) for small rodents or rabbits. [[Cervical dislocation]] (breaking the neck or spine) may be used for birds, mice, rats, and rabbits depending on the size and weight of the animal.<ref>{{cite journal |last=Diaz |first=Silvina L. |date=2020 |title=Conducting and reporting animal experimentation: Quo vadis? |url=https://onlinelibrary.wiley.com/doi/10.1111/ejn.14091 |journal=European Journal of Neuroscience |language=en |volume=52 |issue=6 |pages=3493–3498 |doi=10.1111/ejn.14091 |pmid=30058230 |s2cid=51865025 |issn=0953-816X|hdl=11336/88084 |hdl-access=free }}</ref> High-intensity microwave [[irradiation]] of the brain can preserve brain tissue and induce death in less than 1 second, but this is currently only used on rodents. [[Captive bolt]]s may be used, typically on dogs, ruminants, horses, pigs and rabbits. It causes death by a concussion to the brain. Gunshot may be used, but only in cases where a penetrating captive bolt may not be used. Some physical methods are only acceptable after the animal is unconscious. [[electric shock|Electrocution]] may be used for cattle, sheep, swine, foxes, and mink after the animals are unconscious, often by a prior electrical stun. [[Pithing]] (inserting a tool into the base of the brain) is usable on animals already unconscious. Slow or rapid freezing, or inducing [[air embolism]] are acceptable only with prior anesthesia to induce unconsciousness.<ref>{{cite web|url=http://www.avma.org/resources/euthanasia.pdf |title=AVMA Guidelines on Euthanasia, June 2007 edition, Report of the AVMA Panel on Euthanasia |publisher=Avma.org |archive-url=https://web.archive.org/web/20110815114956/http://www.avma.org/resources/euthanasia.pdf |archive-date=15 August 2011 }}</ref><!--add subsections on cage sizes; use versus care--> ==Research classification== <!--add subsection on laboratory landscape--> ===Pure research=== Basic or pure research investigates how organisms behave, develop, and function. Those opposed to animal testing object that pure research may have little or no practical purpose, but researchers argue that it forms the necessary basis for the development of applied research, rendering the distinction between pure and applied research—research that has a specific practical aim—unclear.<ref name=Lords3>[https://publications.parliament.uk/pa/ld200102/ldselect/ldanimal/150/15006.htm "Select Committee on Animals in Scientific Procedures Report"], House of Lords, 16 July 2002. See chapter 3: "The purpose and nature of animal experiments." Retrieved 6 July 2010.</ref> Pure research uses larger numbers and a greater variety of animals than applied research. Fruit flies, nematode worms, mice and rats together account for the vast majority, though small numbers of other species are used, ranging from [[California sea slug|sea slugs]] through to [[armadillo]]s.<ref name="ReferenceA">{{cite journal | author = Job CK | title = Nine-banded armadillo and leprosy research | journal = Indian Journal of Pathology & Microbiology | volume = 46 | issue = 4 | pages = 541–50 | year = 2003 | pmid = 15025339 }}</ref> Examples of the types of animals and experiments used in basic research include: * Studies on ''[[embryogenesis]]'' and ''[[developmental biology]]''. Mutants are created by adding [[transposon]]s into their [[genome]]s, or specific genes are deleted by [[gene targeting]].<ref>{{cite journal |vauthors=Venken KJ, Bellen HJ | title = Emerging technologies for gene manipulation in Drosophila melanogaster | journal = Nature Reviews Genetics | volume = 6 | issue = 3 | pages = 167–78 | year = 2005 | pmid = 15738961 | doi = 10.1038/nrg1553 | s2cid = 21184903 }}</ref><ref>{{cite journal |vauthors=Sung YH, Song J, Lee HW | title = Functional genomics approach using mice | journal = Journal of Biochemistry and Molecular Biology | volume = 37 | issue = 1 | pages = 122–32 | year = 2004 | pmid = 14761310 | doi = 10.5483/BMBRep.2004.37.1.122 | doi-access = free }}</ref> By studying the changes in development these changes produce, scientists aim to understand both how organisms normally develop, and what can go wrong in this process. These studies are particularly powerful since the basic controls of development, such as the [[homeobox]] genes, have similar functions in organisms as diverse as fruit flies and man.<ref>{{cite journal |vauthors=Janies D, DeSalle R | title = Development, evolution, and corroboration | journal = The Anatomical Record | volume = 257 | issue = 1 | pages = 6–14 | year = 1999 | pmid = 10333399 | doi = 10.1002/(SICI)1097-0185(19990215)257:1<6::AID-AR4>3.0.CO;2-I | s2cid = 23492348 | doi-access = free }}</ref><ref>{{cite journal | author = Akam M | title = Hox genes and the evolution of diverse body plans | journal = Philosophical Transactions of the Royal Society B | volume = 349 | issue = 1329 | pages = 313–19 | year = 1995 | pmid = 8577843 | doi = 10.1098/rstb.1995.0119 | bibcode = 1995RSPTB.349..313A }}</ref> * Experiments into ''behavior'', to understand how organisms detect and interact with each other and their environment, in which fruit flies, worms, mice, and rats are all widely used.<ref>{{cite journal |vauthors=Prasad BC, Reed RR | title = Chemosensation: Molecular mechanisms in worms and mammals | journal = Trends in Genetics | volume = 15 | issue = 4 | pages = 150–53 | year = 1999 | pmid = 10203825 | doi = 10.1016/S0168-9525(99)01695-9 }}</ref><ref>{{cite journal | author = Schafer WR | title = Neurophysiological methods in C. elegans: an introduction | journal = WormBook | pages = 1–4 | year = 2006 | pmid = 18050439 | pmc = 4780964 | doi = 10.1895/wormbook.1.113.1 }}</ref> Studies of brain function, such as memory and social behavior, often use rats and birds.<ref>{{cite journal |last1=Yamamuro |first1=Yutaka |title=Social behavior in laboratory rats: Applications for psycho-neuroethology studies |journal=Animal Science Journal |volume=77 |pages=386–94 |year=2006 |doi=10.1111/j.1740-0929.2006.00363.x |issue=4}}</ref><ref>Marler P., Slabbekoorn H, ''Nature's Music: The Science of Birdsong'', Academic Press, 2004. {{ISBN|0-12-473070-1}}{{page needed|date=December 2010}}</ref> For some species, behavioral research is combined with [[Behavioral enrichment|enrichment]] strategies for animals in captivity because it allows them to engage in a wider range of activities.<ref>For example "in addition to providing the chimpanzees with enrichment, the termite mound is also the focal point of a tool-use study being conducted", from the web page of the [https://web.archive.org/web/20080701010656/http://lpzoo.com/info/media-center/index.html Lincoln Park Zoo]. Retrieved 25 April 2007.</ref> * Breeding experiments to study ''[[evolution]]'' and ''[[genetics]]''. Laboratory mice, flies, fish, and worms are [[Inbreeding|inbred]] through many generations to create strains with defined characteristics.<ref>[[Michael Festing|Festing, M.]], ''[http://www.informatics.jax.org/external/festing/mouse/INTRO.shtml "Inbred Strains of Mice and their Characteristics"],'' ''[[The Jackson Laboratory]] ''. Retrieved 30 January 2008.</ref> These provide animals of a known genetic background, an important tool for genetic analyses. Larger mammals are rarely bred specifically for such studies due to their slow rate of reproduction, though some scientists take advantage of [[Selective breeding|inbred domesticated animals]], such as dog or cattle breeds, for [[Comparative genomics|comparative]] purposes. Scientists studying how animals evolve use many animal species to see how variations in where and how an organism lives (their [[ecological niche|niche]]) produce [[adaptation]]s in their physiology and [[Comparative anatomy|morphology]]. As an example, [[stickleback]]s are now being used to study how many and which types of mutations are selected to produce adaptations in animals' morphology during the evolution of new species.<ref>{{cite journal | author = Peichel CL | title = Fishing for the secrets of vertebrate evolution in threespine sticklebacks | journal = Developmental Dynamics | volume = 234 | issue = 4 | pages = 815–23 | year = 2005 | pmid = 16252286 | doi = 10.1002/dvdy.20564 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Peichel CL, Nereng KS, Ohgi KA, Cole BL, Colosimo PF, Buerkle CA, Schluter D, Kingsley DM | title = The genetic architecture of divergence between threespine stickleback species | journal = Nature | volume = 414 | issue = 6866 | pages = 901–05 | year = 2001 | pmid = 11780061 | doi = 10.1038/414901a | bibcode = 2001Natur.414..901P | s2cid = 4304296 | url = http://authors.fhcrc.org/42/1/Peichel_et_al_Nature_2001.pdf }}</ref> ===Applied research=== Applied research aims to solve specific and practical problems. These may involve the use of [[animal model]]s of diseases or conditions, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the [[drug discovery]] process. Examples include: * [[Genetic modification]] of animals to study disease. [[Genetically modified animal|Transgenic animals]] have specific genes inserted, modified or removed, to mimic specific conditions such as [[single gene disorders]], such as [[Huntington's disease]].<ref>{{cite journal |vauthors=Ramaswamy S, McBride JL, Kordower JH | title = Animal models of Huntington's disease | journal = ILAR Journal | volume = 48 | issue = 4 | pages = 356–73 | year = 2007 | pmid = 17712222 | doi = 10.1093/ilar.48.4.356 | doi-access = free }}</ref> Other models mimic complex, multifactorial diseases with genetic components, such as [[Diabetes mellitus|diabetes]],<ref>{{cite journal |vauthors=Rees DA, Alcolado JC | title = Animal models of diabetes mellitus | journal = Diabetic Medicine | volume = 22 | issue = 4 | pages = 359–70 | year = 2005 | pmid = 15787657 | doi = 10.1111/j.1464-5491.2005.01499.x | doi-access = free }}</ref> or even transgenic mice that carry the same mutations that occur during the development of [[cancer]].<ref>{{cite journal |vauthors=Iwakuma T, Lozano G | title = Crippling p53 activities via knock-in mutations in mouse models | journal = Oncogene | volume = 26 | issue = 15 | pages = 2177–84 | year = 2007 | pmid = 17401426 | doi = 10.1038/sj.onc.1210278 | doi-access = free }}</ref> These models allow investigations on how and why the disease develops, as well as providing ways to develop and test new treatments.<ref>{{cite journal |vauthors=Frese KK, Tuveson DA | title = Maximizing mouse cancer models | journal = Nature Reviews Cancer | volume = 7 | issue = 9 | pages = 645–58 | year = 2007 | pmid = 17687385 | doi = 10.1038/nrc2192 | s2cid = 6490409 }}</ref> The vast majority of these transgenic models of human disease are lines of mice, the mammalian species in which genetic modification is most efficient.<ref name=Rosenthal/> Smaller numbers of other animals are also used, including rats, pigs, sheep, fish, birds, and amphibians.<ref name=HOStats/> * Studies on models of naturally occurring disease and condition. Certain domestic and wild animals have a natural propensity or predisposition for certain conditions that are also found in humans. Cats are used as a model to develop immunodeficiency virus vaccines and to study [[leukemia]] because their natural predisposition to [[FIV]] and [[Feline leukemia virus]].<ref>{{cite journal | author = Dunham SP | title = Lessons from the cat: development of vaccines against lentiviruses | journal = Veterinary Immunology and Immunopathology | volume = 112 | issue = 1–2 | pages = 67–77 | year = 2006 | pmid = 16678276 | doi = 10.1016/j.vetimm.2006.03.013 }}</ref><ref>{{cite journal |vauthors=Vail DM, MacEwen EG | title = Spontaneously occurring tumors of companion animals as models for human cancer | journal = Cancer Investigation | volume = 18 | issue = 8 | pages = 781–92 | year = 2000 | pmid = 11107448 | doi = 10.3109/07357900009012210 | s2cid = 32489790 }}</ref> Certain breeds of dog experience [[narcolepsy]] making them the major model used to study the human condition. [[Armadillo]]s and humans are among only a few animal species that naturally have [[leprosy]]; as the bacteria responsible for this disease cannot yet be grown in culture, armadillos are the primary source of [[bacilli]] used in leprosy vaccines.<ref name="ReferenceA"/> * Studies on induced animal models of human diseases. Here, an animal is treated so that it develops [[pathology]] and symptoms that resemble a human disease. Examples include restricting blood flow to the brain to induce [[stroke]], or giving [[neurotoxin]]s that cause damage similar to that seen in [[Parkinson's disease]].<ref name=Tolwani/> Much animal research into potential treatments for humans is wasted because it is poorly conducted and not evaluated through systematic reviews.<ref>{{cite journal | vauthors = Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I | title = Where is the evidence that animal research benefits humans? | journal = BMJ | volume = 328 | issue = 7438 | pages = 514–47 | year = 2004 | pmid = 14988196 | pmc = 351856 | doi = 10.1136/bmj.328.7438.514 | others = Reviewing Animal Trials Systematically (RATS) Group }}</ref> For example, although such models are now widely used to study Parkinson's disease, the British anti-vivisection interest group [[British Union for the Abolition of Vivisection|BUAV]] argues that these models only superficially resemble the disease symptoms, without the same time course or cellular pathology.<ref>Langley, Gill (2006) [http://www.buav.org/downloads/pdf/BUAV_Report-Next_of_Kin.pdf ''next of kin...A report on the use of primates in experiments''] {{Webarchive|url=https://web.archive.org/web/20080227041454/http://www.buav.org/downloads/pdf/BUAV_Report-Next_of_Kin.pdf |date=27 February 2008 }}, BUAV.</ref> In contrast, scientists assessing the usefulness of [[animal models of Parkinson's disease]], as well as the medical research charity ''The Parkinson's Appeal'', state that these models were invaluable and that they led to improved surgical treatments such as [[pallidotomy]], new drug treatments such as [[levodopa]], and later [[deep brain stimulation]].<ref name=Emborg>{{cite journal | author = Emborg ME | title = Nonhuman primate models of Parkinson's disease | journal = ILAR Journal | volume = 48 | issue = 4 | pages = 339–55 | year = 2007 | pmid = 17712221 | doi = 10.1093/ilar.48.4.339 | doi-access = free }}</ref><ref name=Tolwani>{{cite journal |vauthors=Tolwani RJ, Jakowec MW, Petzinger GM, Green S, Waggie K | title = Experimental models of Parkinson's disease: insights from many models | journal = Laboratory Animal Science | volume = 49 | issue = 4 | pages = 363–71 | year = 1999 | pmid = 10480640 }}</ref><ref>[http://www.parkinsonsappeal.com/pdfs/The%20History%20of%20Deep%20Brain%20Stimulation.pdf The History of Deep Brain Stimulation] {{Webarchive|url=https://web.archive.org/web/20170331165911/http://www.parkinsonsappeal.com/pdfs/The%20History%20of%20Deep%20Brain%20Stimulation.pdf |date=31 March 2017 }}. parkinsonsappeal.com</ref> * Animal testing has also included the use of [[placebo]] testing. In these cases animals are treated with a substance that produces no pharmacological effect, but is administered in order to determine any biological alterations due to the experience of a substance being administered, and the results are compared with those obtained with an active compound. ====Xenotransplantation==== {{Main|Xenotransplantation}} [[Xenotransplantation]] research involves transplanting tissues or organs from one species to another, as a way to overcome the shortage of human organs for use in [[organ transplant]]s.<ref>{{cite journal |vauthors=Platt JL, Lin SS | title = The future promises of xenotransplantation | journal = Annals of the New York Academy of Sciences | volume = 862 | issue = 1 | pages = 5–18 | year = 1998 | pmid = 9928201 | doi = 10.1111/j.1749-6632.1998.tb09112.x | bibcode = 1998NYASA.862....5P | s2cid = 72941995 }}</ref> Current research involves using primates as the recipients of organs from pigs that have been genetically modified to reduce the primates' [[immune system|immune response]] against the pig tissue.<ref name=Schuurman>{{cite journal |vauthors=Schuurman HJ, Pierson RN | title = Progress towards clinical xenotransplantation | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 204–20 | year = 2008 | pmid = 17981539 | doi = 10.2741/2671 | doi-access = free }}</ref> Although [[transplant rejection]] remains a problem,<ref name=Schuurman/> recent clinical trials that involved implanting pig insulin-secreting cells into diabetics did reduce these people's need for insulin.<ref>{{cite journal |vauthors=Valdés-González RA, Dorantes LM, Garibay GN, Bracho-Blanchet E, Mendez AJ, Dávila-Pérez R, Elliott RB, Terán L, White DJ | title = Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study | journal = European Journal of Endocrinology | volume = 153 | issue = 3 | pages = 419–27 | year = 2005 | pmid = 16131605 | doi = 10.1530/eje.1.01982 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Valdés-González RA, White DJ, Dorantes LM, Terán L, Garibay-Nieto GN, Bracho-Blanchet E, Dávila-Pérez R, Evia-Viscarra L, Ormsby CE, Ayala-Sumuano JT, Silva-Torres ML, Ramírez-González B | title = Three-yr follow-up of a type 1 diabetes mellitus patient with an islet xenotransplant | journal = Clinical Transplantation | volume = 21 | issue = 3 | pages = 352–57 | year = 2007 | pmid = 17488384 | doi = 10.1111/j.1399-0012.2007.00648.x | s2cid = 22668776 }}</ref> Documents released to the news media by the animal rights organization [[Uncaged Campaigns]] showed that, between 1994 and 2000, wild baboons imported to the UK from Africa by Imutran Ltd, a subsidiary of [[Novartis]] Pharma AG, in conjunction with Cambridge University and [[Huntingdon Life Sciences]], to be used in experiments that involved grafting pig tissues, had serious and sometimes fatal injuries. A scandal occurred when it was revealed that the company had communicated with the British government in an attempt to avoid regulation.<ref name=autogenerated2>Townsend, Mark (20 April 2003). [http://observer.guardian.co.uk/uk_news/story/0,6903,940033,00.html "Exposed: secrets of the animal organ lab"] {{webarchive|url=https://web.archive.org/web/20080706041140/http://observer.guardian.co.uk/uk_news/story/0%2C6903%2C940033%2C00.html |date=6 July 2008 }}, ''The Guardian''.</ref><ref>Curtis, Polly (11 July 2003). [https://www.theguardian.com/education/2003/jul/11/research.highereducation "Home Office under renewed fire in animal rights row"], ''The Guardian''.</ref> ===Toxicology testing=== {{Main|Toxicology testing}} {{Further|Draize test|LD50|Acute toxicity|Chronic toxicity|Genetically modified food controversies#Animal feeding studies}} Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities, such as [[Huntingdon Life Sciences]], on behalf of a wide variety of customers.<ref name=BUAVHPT>[http://www.buav.org/pdf/HouseholdProductTests.pdf Household Product Tests] {{Webarchive|url=https://web.archive.org/web/20080227041444/http://www.buav.org/pdf/HouseholdProductTests.pdf |date=27 February 2008 }} [[BUAV]]</ref> According to 2005 EU figures, around one million animals are used every year in Europe in toxicology tests; which are about 10% of all procedures.<ref name=EU2005>[https://web.archive.org/web/20080216072132/http://ec.europa.eu/environment/chemicals/lab_animals/pdf/5th_stat_rep_lab_animals_en.pdf Fifth Report on the Statistics on the Number of Animals used for Experimental and other Scientific Purposes in the Member States of the European Union], ''Commission of the European Communities'', published November 2007</ref> According to ''Nature'', 5,000 animals are used for each chemical being tested, with 12,000 needed to test pesticides.<ref name=Abbott>{{cite journal|author=Abbott A |title=Animal testing: More than a cosmetic change |journal=Nature |volume=438 |issue=7065 |pages=144–46 |year=2005 |pmid=16281001 |doi=10.1038/438144a |url=http://ethics.ucsd.edu/journal/2006/readings/Animal_Testing_More_than_a_cosmetic_change.pdf |bibcode=2005Natur.438..144A |s2cid=4422086 |archive-url=https://web.archive.org/web/20080227041442/http://ethics.ucsd.edu/journal/2006/readings/Animal_Testing_More_than_a_cosmetic_change.pdf |archive-date=27 February 2008 }}</ref> The tests are conducted without [[anesthesia]], because [[drug interaction|interactions between drugs]] can affect how animals [[xenobiotic metabolism|detoxify]] chemicals, and may interfere with the results.<ref>{{cite journal | author = Watkins JB | title = Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 250 | issue = 2 | pages = 421–27 | year = 1989 | pmid = 2760837 }}</ref><ref>{{cite journal |vauthors=Watt JA, Dickinson RG | title = The effect of diethyl ether, pentobarbitone and urethane anaesthesia on diflunisal conjugation and disposition in rats | journal = Xenobiotica | volume = 20 | issue = 3 | pages = 289–301 | year = 1990 | pmid = 2336839 | doi = 10.3109/00498259009046848 }}</ref> Toxicology tests are used to examine finished products such as [[pesticide]]s, [[medication]]s, [[food additives]], packing materials, and [[air freshener]], or their chemical ingredients. Most tests involve testing ingredients rather than finished products, but according to [[BUAV]], manufacturers believe these tests overestimate the toxic effects of substances; they therefore repeat the tests using their finished products to obtain a less toxic label.<ref name=BUAVHPT/> The substances are applied to the skin or dripped into the eyes; injected [[intravenous]]ly, [[intramuscular]]ly, or [[Subcutaneous injection|subcutaneous]]ly; inhaled either by placing a mask over the animals and restraining them, or by placing them in an inhalation chamber; or administered orally, through a tube into the stomach, or simply in the animal's food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal.<ref>{{cite web |title=Testing of chemicals – OECD |url=https://www.oecd.org/chemicalsafety/testing/ |access-date=2022-05-23 |website=www.oecd.org}}</ref> There are several different types of [[acute toxicity]] tests. The {{LD50}} ("Lethal Dose 50%") test is used to evaluate the toxicity of a substance by determining the dose required to kill 50% of the test animal [[Statistical population|population]]. This test was removed from [[Organisation for Economic Co-operation and Development|OECD]] international guidelines in 2002, replaced by methods such as the [[Fixed Dose Procedure|fixed dose procedure]], which use fewer animals and cause less suffering.<ref>{{cite journal | author = Walum E | title = Acute oral toxicity | journal = Environmental Health Perspectives | volume = 106 | issue = Suppl 2 | pages = 497–503 | year = 1998 | pmid = 9599698 | pmc = 1533392 | doi = 10.2307/3433801 | jstor = 3433801 }}</ref><ref>[https://web.archive.org/web/20081119080934/http://hsus.org/animals_in_research/animals_in_research_news/intergovernmental_organization_eliminates_the_ld50_test.html Inter-Governmental Organization Eliminates the LD50 Test], The Humane Society of the United States (2003-02-05)</ref> Abbott writes that, as of 2005, "the LD50 acute toxicity test ... still accounts for one-third of all animal [toxicity] tests worldwide".<ref name=Abbott/> Irritancy can be measured using the [[Draize test]], where a test substance is applied to an animal's eyes or skin, usually an albino rabbit. For Draize eye testing, the test involves observing the effects of the substance at intervals and grading any damage or irritation, but the test should be halted and the animal killed if it shows "continuing signs of severe pain or distress".<ref>{{cite web|url=http://213.253.134.43/oecd/pdfs/browseit/9740501E.PDF |title=OECD guideline 405, Organisation for Economic Co-operation and Development |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20080227041440/http://213.253.134.43/oecd/pdfs/browseit/9740501E.PDF |archive-date=27 February 2008 }}</ref> The [[Humane Society of the United States]] writes that the procedure can cause redness, ulceration, hemorrhaging, cloudiness, or even blindness.<ref>[https://web.archive.org/web/20090203060123/http://hsus.org/animals_in_research/species_used_in_research/rabbit.html Species Used in Research: Rabbit], Humane Society of the United States</ref> [[Cruelty to animals|This test has also been criticized by scientists for being cruel]] and inaccurate, subjective, over-sensitive, and failing to reflect human exposures in the real world.<ref>{{cite journal | author = Wilhelmus KR | title = The Draize eye test | journal = Survey of Ophthalmology | volume = 45 | issue = 6 | pages = 493–515 | year = 2001 | pmid = 11425356 | doi = 10.1016/S0039-6257(01)00211-9 }}</ref> Although no accepted ''in vitro'' alternatives exist, a modified form of the Draize test called the ''low volume eye test'' may reduce suffering and provide more realistic results and this was adopted as the new standard in September 2009.<ref>{{cite journal |vauthors=Secchi A, Deligianni V | title = Ocular toxicology: the Draize eye test | journal = Current Opinion in Allergy and Clinical Immunology | volume = 6 | issue = 5 | pages = 367–72 | year = 2006 | pmid = 16954791 | doi = 10.1097/01.all.0000244798.26110.00 | s2cid = 24972694 }}</ref><ref name=Hadwen>[https://web.archive.org/web/20100327195524/http://www.drhadwentrust.org/news/rabbit-eye-test-replacement Draize rabbit eye test replacement milestone welcomed]. ''Dr Hadwen Trust'' (2009-09-21)</ref> However, the Draize test will still be used for substances that are not severe irritants.<ref name=Hadwen/> The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), one to three months (subchronic), and more than three months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, [[mutagen]]icity, [[carcinogen]]icity, [[teratogen]]icity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take three or four years to complete. These toxicity tests provide, in the words of a 2006 [[United States National Academy of Sciences]] report, "critical information for assessing hazard and risk potential".<ref>[http://books.nap.edu/openbook.php?record_id=11523&page=R1 Toxicity Testing for Assessment of Environmental Agents"] National Academies Press, (2006), p. 21.</ref> Animal tests may overestimate risk, with [[false positive]] results being a particular problem,<ref name=Abbott/><ref>{{cite journal | author = Hartung T | title = Toxicology for the twenty-first century | journal = Nature | volume = 460 | issue = 7252 | pages = 208–12 | year = 2009 | pmid = 19587762 | doi = 10.1038/460208a | bibcode = 2009Natur.460..208H | s2cid = 851143 }}</ref> but false positives appear not to be prohibitively common.<ref>{{cite web |url= http://protestitalia.wordpress.com/2013/12/09/where-is-the-toxicology-for-the-twenty-first-century/ |title= Where is the toxicology for the twenty-first century? |year= 2013 |publisher= Pro-Test Italia |access-date=30 January 2014}}</ref> Variability in results arises from using the effects of high doses of chemicals in small numbers of laboratory animals to try to predict the effects of low doses in large numbers of humans.<ref>{{cite journal | author = Smith LL | title = Key challenges for toxicologists in the 21st century | journal = Trends Pharmacol. Sci. | volume = 22 | issue = 6 | pages = 281–85 | year = 2001 | pmid = 11395155 | doi = 10.1016/S0165-6147(00)01714-4 }}</ref> Although relationships do exist, opinion is divided on how to use data on one species to predict the exact level of risk in another.<ref>{{cite journal |vauthors=Brown SL, Brett SM, Gough M, Rodricks JV, Tardiff RG, Turnbull D | title = Review of interspecies risk comparisons | journal = Regul. Toxicol. Pharmacol. | volume = 8 | issue = 2 | pages = 191–206 | year = 1988 | pmid = 3051142 | doi = 10.1016/0273-2300(88)90028-1 }}</ref> Scientists face growing pressure to move away from using traditional animal toxicity tests to determine whether manufactured chemicals are safe.<ref name="Burden2015">{{cite journal | pmid = 26018957 | pmc = 4446337 | year = 2015 | last1 = Burden | first1 = N | title = Testing Chemical Safety: What Is Needed to Ensure the Widespread Application of Non-animal Approaches? | journal = PLOS Biol | volume = 13 | issue = 5 | pages = e1002156 | last2 = Sewell | first2 = F | last3 = Chapman | first3 = K | doi = 10.1371/journal.pbio.1002156 | doi-access = free }}</ref> Among variety of approaches to toxicity evaluation the ones which have attracted increasing interests are in vitro cell-based sensing methods applying fluorescence.<ref name="Moczko2016">{{cite journal | pmid = 27653274 | pmc = 5031998 | year = 2016 | last1 = Moczko | first1 = E | title = Fluorescence-based assay as a new screening tool for toxic chemicals | journal = Scientific Reports | volume = 6 | pages = 33922 | last2 = Mirkes | first2 = EM | last3 = Cáceres | first3 = C | last4 = Gorban | first4 = AN | last5 = Piletsky | first5 = S | doi = 10.1038/srep33922 | bibcode = 2016NatSR...633922M }}</ref> ====Cosmetics testing==== {{Main|Testing cosmetics on animals}} [[Image:NoAnimalTesting.png|thumb|The "Leaping Bunny" logo: Some products in Europe that are not tested on animals carry this symbol.]] Cosmetics testing on animals is particularly controversial. Such tests, which are still conducted in the U.S., involve general toxicity, eye and skin irritancy, [[phototoxic]]ity (toxicity triggered by [[ultraviolet]] light) and mutagenicity.<ref>Stephens, Martin & Rowan, Andrew. [https://web.archive.org/web/20080308163106/http://www.hsus.org/web-files/PDF/ARI/ARIS_An_Overview_Of_Animal_Testing_Issues.pdf An overview of Animal Testing Issues, Humane Society of the United States]</ref> Cosmetics testing on animals is banned in India, the United Kingdom, the European Union,<ref>{{cite news|url=https://www.ceway.eu/cosmetics-animal-testing-eu/|title=Cosmetics animal testing in the EU|access-date=5 December 2018|archive-date=30 December 2020|archive-url=https://web.archive.org/web/20201230121610/https://www.ceway.eu/cosmetics-animal-testing-eu/|url-status=dead}}</ref> Israel and Norway<ref name="WorldPost">{{cite news|title=India Joins the EU and Israel in Surpassing the US in Cruelty-Free Cosmetics Testing Policy|url=http://www.huffingtonpost.com/monica-engebretson/cruelty-free-cosmetics-testing_b_3605460.html|date=16 March 2014|author =Engebretson, Monica|work=The World Post}}</ref><ref name="US Bill">{{cite press release|title=Cruelty Free International Applauds Congressman Jim Moran for Bill to End Cosmetics Testing on Animals in the United States |url=https://www.reuters.com/article/2014/03/05/bc-cfi-idUSnPnpHM6w1+98+PRN20140305 |date=5 March 2014 |archive-url=https://web.archive.org/web/20140318031816/https://www.reuters.com/article/2014/03/05/bc-cfi-idUSnPnpHM6w1%2B98%2BPRN20140305 |archive-date=18 March 2014 }}</ref> while legislation in the U.S. and Brazil is currently considering similar bans.<ref name="HSUS">{{cite press release|title=Animal Attraction: Federal Bill to End Cosmetics Testing on Animals Introduced in Congress |url=http://www.khou.com/community/blogs/animal-attraction/Animal-Attraction---249254631.html |date=10 March 2014 |author=Fox, Stacy |publisher=Humane Society of the United States |archive-url=https://web.archive.org/web/20140311022116/http://www.khou.com/community/blogs/animal-attraction/Animal-Attraction---249254631.html |archive-date=11 March 2014 }}</ref> In 2002, after 13 years of discussion, the European Union agreed to phase in a near-total ban on the sale of animal-tested cosmetics by 2009, and to ban all cosmetics-related animal testing. France, which is home to the world's largest cosmetics company, [[L'Oreal]], has protested the proposed ban by lodging a case at the [[European Court of Justice]] in [[Luxembourg]], asking that the ban be quashed.<ref name=Osborn/> The ban is also opposed by the European Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland, Belgium, France, Germany, and Italy.<ref name=Osborn>Osborn, Andrew & Gentleman, Amelia.[https://www.theguardian.com/animalrights/story/0,11917,1021527,00.html "Secret French move to block animal-testing ban"], ''The Guardian'' (19 August 2003). Retrieved 27 February 2008.</ref> In October 2014, India passed stricter laws that also ban the importation of any cosmetic products that are tested on animals.<ref>{{cite news|url = http://timesofindia.indiatimes.com/india/India-bans-import-of-cosmetics-tested-on-animals/articleshow/44814398.cms|title = India bans import of cosmetics tested on animals|last = Mohan|first = Vishwa|date = 14 October 2014|work = The Times of India|access-date = 14 October 2014}}</ref> ===Drug testing=== Before the early 20th century, laws regulating drugs were lax. Currently, all new pharmaceuticals undergo rigorous animal testing before being licensed for human use. Tests on pharmaceutical products involve: * ''metabolic tests'', investigating [[pharmacokinetics]]—how drugs are absorbed, [[Drug metabolism|metabolized]] and [[Excretion|excreted]] by the body when introduced [[wikt:oral|orally]], [[intravenous]]ly, intraperitoneally, [[intramuscular]]ly, or [[Transdermal patch|transdermally]]. * ''toxicology tests'', which gauge [[acute toxicity|acute]], sub-acute, and [[chronic toxicity]]. Acute toxicity is studied by using a rising dose until signs of toxicity become apparent. Current European legislation demands that "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration".<ref>{{cite web|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32001L0083:EN:HTML |title=EU Directive 2001/83/EC, p. 44 |publisher=Eur-lex.europa.eu}}</ref> Sub-acute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it causes rapid poisoning, in order to discover if any toxic [[drug metabolism|drug metabolites]] build up over time. Testing for chronic toxicity can last up to two years and, in the European Union, is required to involve two species of mammals, one of which must be non-rodent.<ref>{{cite web|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32001L0083:EN:HTML |title=EU Directive 2001/83/EC, p. 45 |publisher=Eur-lex.europa.eu }}</ref> * ''efficacy studies'', which test whether experimental drugs work by inducing the appropriate illness in animals. The drug is then administered in a [[Randomized controlled trial|double-blind controlled trial]], which allows researchers to determine the effect of the drug and the [[Dose response|dose-response]] curve. * Specific tests on ''reproductive function'', ''embryonic toxicity'', or ''carcinogenic potential'' can all be required by law, depending on the result of other studies and the type of drug being tested. ===Education=== It is estimated that 20 million animals are used annually for educational purposes in the United States including, classroom observational exercises, dissections and live-animal surgeries.<ref>{{cite journal|last1=Patronek|first1=G|last2=Rauch|first2=A|title=Systematic review of comparative studies examining alternatives to the harmful use of animals in biomedical education|journal=Journal of the American Veterinary Medical Association|date=1 January 2007|volume=230|issue=1|pages=37–43|doi=10.2460/javma.230.1.37|pmid=17199490}}</ref><ref>{{cite book|last1=Hart|first1=L|last2=Hart|first2=B|last3=Wood|first3=M|title=Why Dissection: Animal Use in Education|url=https://archive.org/details/whydissectionani0000hart|url-access=registration|date=2008|publisher=Greenwood Press|location=Westport|isbn=978-0-313-32390-4}}</ref> Frogs, [[fetal pigs]], perch, cats, earthworms, grasshoppers, crayfish and starfish are commonly used in classroom dissections.<ref>{{cite book|last1=Orlans|first1=Barbara|last2=Beauchamp|first2=Tom|author3-link=Rebecca Dresser|last3=Dresser|first3=Rebecca|last4=Morton|first4=David|last5=Gluck|first5=John|title=The Human Use of Animals|date=1998|publisher=Oxford University Press|isbn=978-0-19-511908-4|pages=[https://archive.org/details/humanuseofanimal0000unse/page/213 213]|url=https://archive.org/details/humanuseofanimal0000unse/page/213}}</ref> Alternatives to the use of animals in classroom dissections are widely used, with many U.S. States and school districts mandating students be offered the choice to not dissect.<ref>{{cite news|last1=Downey|first1=Maureen|title=Should students dissect animals or should schools move to virtual dissections?|url=http://www.ajc.com/weblogs/get-schooled/2013/jun/25/should-students-dissect-animals-or-should-schools-/|access-date=7 July 2015|work=The Atlanta Journal-Constitution|date=25 June 2013}}</ref> Citing the wide availability of alternatives and the decimation of local frog species, India banned dissections in 2014.<ref>{{cite news|last1=Pulla|first1=Priyanka|title=Dissections banned in Indian universities|url=https://www.science.org/content/article/dissections-banned-indian-universities|access-date=7 July 2015|agency=Science|date=6 August 2014}}</ref><ref>{{cite news|last1=Shine|first1=Nicole|title=The Battle Over High School Animal Dissection|url=https://psmag.com/environment/battle-high-school-animal-dissection-92391|work=Pacific Standard|access-date=7 July 2015}}</ref> The Sonoran Arthropod Institute hosts an annual Invertebrates in Education and Conservation Conference to discuss the use of invertebrates in education.<ref>{{cite web |url=http://neurosci.arizona.edu/iecc |title=Invertebrates in Education and Conservation Conference &#124; Department of Neuroscience |publisher=Neurosci.arizona.edu |access-date=2015-04-06 |archive-date=15 December 2018 |archive-url=https://web.archive.org/web/20181215123040/http://neurosci.arizona.edu/iecc }}</ref> There also are efforts in many countries to find alternatives to using animals in education.<ref>{{cite web |last1=Dalal|first1=Rooshin |last2=Even|first2=Megha |last3=Sandusky|first3=Chad |last4=Barnard|first4=Neal |title=Replacement Alternatives in Education: Animal-Free Teaching |url=http://www.pcrm.org/research/animaltestalt/animaltesting/replacement-alternatives-in-education-animal-free |publisher=The Physicians Committee for Responsible Medicine |access-date=9 April 2015 |url-status=live |archive-url=https://web.archive.org/web/20140722162218/http://pcrm.org/research/animaltestalt/animaltesting/replacement-alternatives-in-education-animal-free |archive-date=22 July 2014 |format=Abstract from Fifth World Congress on Alternatives and Animal Use in the Life Sciences, Berlin |date=August 2005}}</ref> The NORINA database, maintained by Norecopa, lists products that may be used as alternatives or supplements to animal use in education, and in the training of personnel who work with animals.<ref>{{cite web|url=http://oslovet.norecopa.no/NORINA |title=The NORINA database of alternatives |publisher=Oslovet.norecopa.no |access-date=2015-04-06}}</ref> These include alternatives to dissection in schools. [[InterNICHE]] has a similar database and a loans system.<ref>{{cite web|url=http://www.interniche.org |title=Welcome |publisher=Interniche.org |access-date=2015-04-06}}</ref> In November 2013, the U.S.-based company Backyard Brains released for sale to the public what they call the "Roboroach", an "electronic backpack" that can be attached to [[cockroach]]es. The operator is required to amputate a cockroach's [[Antenna (biology)|antennae]], use sandpaper to wear down the shell, insert a wire into the [[thorax]], and then glue the [[electrode]]s and [[Printed circuit board|circuit board]] onto the insect's back. A [[Mobile app|mobile phone app]] can then be used to control it via [[Bluetooth]].<ref name="BBC 09-11-13">{{cite news|url=https://www.bbc.co.uk/news/science-environment-24455141|title=Row over US mobile phone 'cockroach backpack' app|work=BBC News|date=9 November 2013|access-date=9 November 2013}}</ref> It has been suggested that the use of such a device may be a teaching aid that can promote interest in science. The makers of the "Roboroach" have been funded by the [[National Institute of Mental Health]] and state that the device is intended to encourage children to become interested in [[neuroscience]].<ref name="BBC 09-11-13" /><ref name="Time 01-11-13">{{cite magazine|url=http://newsfeed.time.com/2013/11/01/cyborg-cockroaches-are-coming-but-not-if-peta-has-anything-to-say-about-it/|title=Resistance is Futile: PETA Attempts to Halt the Sale of Remote-Controlled Cyborg Cockroaches|magazine=Time|date=1 November 2013|author =Hamilton, Anita|access-date=10 November 2013}}</ref> ===Defense=== Animals are used by the military to develop weapons, vaccines, battlefield surgical techniques, and defensive clothing.<ref name=Lords3/> For example, in 2008 the United States [[DARPA|Defense Advanced Research Projects Agency]] used live pigs to study the effects of [[improvised explosive device]] explosions on internal organs, especially the brain.<ref>Brook, Tom Vanden, "[https://www.usatoday.com/printedition/news/20090407/1apigs07_st.art.htm Brain Study, Animal Rights Collide]", ''[[USA Today]]'' (7 April 2009), p. 1.</ref> In the US military, [[goat]]s are commonly used to train [[combat medic]]s. (Goats have become the main animal species used for this purpose after the Pentagon phased out using dogs for medical training in the 1980s.<ref name=kelly2013>{{cite news |title=Who, What, Why: Does shooting goats save soldiers' lives? |first=Jon|last=Kelly|periodical= BBC News Magazine|date=7 March 2013 |url=https://www.bbc.co.uk/news/magazine-21620521}}</ref>) While modern [[Mannequin#Medical education|mannequins]] used in medical training are quite efficient in simulating the behavior of a human body, some trainees feel that "the goat exercise provide[s] a sense of urgency that only real life trauma can provide".<ref>{{cite news|title=Military is required to justify using animals in medic training after pressure from activists|first=Ernesto|last=Londoño|date=24 February 2013|newspaper=The Washington Post|url=https://articles.washingtonpost.com/2013-02-24/world/37276084_1_animal-activists-human-simulators-civilian-trauma|archive-url=https://web.archive.org/web/20131215065035/http://articles.washingtonpost.com/2013-02-24/world/37276084_1_animal-activists-human-simulators-civilian-trauma|archive-date=15 December 2013}}</ref> Nevertheless, in 2014, the [[U.S. Coast Guard]] announced that it would reduce the number of animals it uses in its training exercises by half after [[PETA]] released video showing Guard members cutting off the limbs of unconscious goats with tree trimmers and inflicting other injuries with a shotgun, pistol, ax and a scalpel.<ref>{{cite news|last1=Vergakis|first1=Brock|title=Coast Guard reduces use of live animals in training|url=http://hamptonroads.com/2014/02/coast-guard-reduces-use-live-animals-training|access-date=7 July 2015|date=14 February 2014|archive-date=9 July 2015|archive-url=https://web.archive.org/web/20150709080350/http://hamptonroads.com/2014/02/coast-guard-reduces-use-live-animals-training|url-status=dead}}</ref> That same year, citing the availability of human simulators and other alternatives, the Department of Defense announced it would begin reducing the number of animals it uses in various training programs.<ref>{{cite news|last1=Bender|first1=Bryan|title=Military to curtail use of live animals in medical training|url=https://www.bostonglobe.com/news/nation/2014/11/11/pentagon-takes-major-steps-phase-out-use-live-animals-medical-training/2XOfgaevD80qsHs1A1SbNJ/story.html|access-date=7 July 2015|agency=Boston Globe|date=12 November 2014}}</ref> In 2013, several [[United States Navy|Navy]] medical centers stopped using ferrets in intubation exercises after complaints from [[PETA]].<ref>{{cite news|last1=Champaco|first1=Brent|title=PETA: Madigan Army Medical Center Has Stopped 'Cruel' Ferret-Testing|url=http://patch.com/washington/lakewood-jblm/peta-madigan-army-medical-center-has-stopped-ferrettesting|access-date=7 July 2015|agency=Patch|date=15 August 2013}}</ref> Besides the United States, six out of 28 NATO countries, including Poland and Denmark, use live animals for combat medic training.<ref name=kelly2013/> ==Ethics== Most animals are [[Animal euthanasia|euthanized]] after being used in an experiment.<ref name=Carbone22>Carbone, p. 22.</ref> [[Laboratory animal sources|Sources of laboratory animals]] vary between countries and species; most animals are purpose-bred, while a minority are caught in the wild or supplied by dealers who obtain them from auctions and [[Animal shelter|pounds]].<ref name=ilar88>"Use of Laboratory Animals in Biomedical and Behavioral Research", Institute for Laboratory Animal Research, The National Academies Press, 1988 {{ISBN|0-309-07878-4}}.</ref><ref>Cooper, Sylvia (1 August 1999). [http://chronicle.augusta.com/stories/1999/08/01/met_266886.shtml "Pets crowd animal shelter"] {{Webarchive|url=https://web.archive.org/web/20140202203913/http://chronicle.augusta.com/stories/1999/08/01/met_266886.shtml |date=2 February 2014 }}, ''The Augusta Chronicle''.</ref><ref name=Gillham>Gillham, Christina (17 February 2006). [http://www.newsweek.com/id/57139 "Bought to be sold"], ''Newsweek''.</ref> Supporters of the use of animals in experiments, such as the British [[Royal Society]], argue that virtually every medical achievement in the 20th century relied on the use of animals in some way.<ref name="TheRoyalSociety">[https://royalsociety.org/topics-policy/publications/2004/non-human-animals/ The use of non-human animals in research: a guide for scientists] [[The Royal Society]], 2004, p. 1</ref> The Institute for Laboratory Animal Research of the United States [[National Academy of Sciences]] has argued that animal testing cannot be replaced by even [[Digital twin|sophisticated computer models]], which are unable to deal with the extremely complex interactions between molecules, cells, tissues, organs, organisms and the environment.<ref>[http://books.nap.edu/openbook.php?record_id=10733 "Science, Medicine, and Animals"], Institute for Laboratory Animal Research, Published by the [[United States National Academy of Sciences|National Research Council of the National Academies]] 2004, p. 2</ref> [[Animal rights]] organizations—such as [[People for the Ethical Treatment of Animals|PETA]] and [[British Union for the Abolition of Vivisection|BUAV]]—question the need for and legitimacy of animal testing, arguing that it is [[cruelty to animals|cruel]] and poorly regulated, that medical progress is actually held back by misleading animal models that cannot reliably predict effects in humans, that some of the tests are outdated, that the costs outweigh the benefits, or that animals have the intrinsic right not to be used or harmed in experimentation.<ref name="croce" /><ref>{{cite web|url=http://www.peta.org/about/faq-viv.asp |title=About |work=Peta.org |access-date=2015-04-06}}</ref><ref>{{cite web|url=http://www.buav.org/pdf/UK-Legislation.pdf |title=UK Legislation: A Criticism |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20080625161126/http://www.buav.org/pdf/UK-Legislation.pdf |archive-date=25 June 2008 }}</ref><ref>{{cite web |url=http://www.buav.org/pdf/VivisectionFAQs.pdf |title=FAQs: Vivisection |publisher=[[British Union for the Abolition of Vivisection]] |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20150513021651/http://www.buav.org/pdf/VivisectionFAQs.pdf |archive-date=13 May 2015 }}</ref><ref>{{cite web |url=http://www.humanesociety.org/issues/biomedical_research/ |title=Biomedical Research: The Humane Society of the United States |work=Humanesociety.org |access-date=2015-04-06 |archive-date=30 September 2020 |archive-url=https://web.archive.org/web/20200930150512/https://www.humanesociety.org/all-our-fights/taking-suffering-out-science |url-status=dead }}</ref><ref>{{cite web|url=http://www.pcrm.org/resch/anexp/index.html |title=Animal Testing and Animal Experimentation Issues &#124; Physicians Committee |work=Pcrm.org |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20110723001342/http://www.pcrm.org/resch/anexp/index.html |archive-date=23 July 2011 }}</ref> ===Viewpoints=== {{Further|Animal welfare|Animal rights|History of animal testing}} [[File:実験動物慰霊碑.jpg|thumb|upright|Monument for animals used in testing at [[Keio University]]]]{{Animal rights sidebar}}The moral and ethical questions raised by performing experiments on animals are subject to debate, and viewpoints have shifted significantly over the 20th century.<ref>{{cite journal | author = Rollin BE | title = The regulation of animal research and the emergence of animal ethics: A conceptual history | journal = Theoretical Medicine and Bioethics | volume = 27 | issue = 4 | pages = 285–304 | year = 2006 | pmid = 16937023 | doi = 10.1007/s11017-006-9007-8 | s2cid = 18620094 | url = https://org.uib.no/dyreavd/handouts/Rollin__B._2006._Animal_Research_Regulation_in_Theoret._Medicin_....PDF | access-date = 4 December 2019 | archive-date = 8 October 2020 | archive-url = https://web.archive.org/web/20201008152801/https://org.uib.no/dyreavd/handouts/Rollin__B._2006._Animal_Research_Regulation_in_Theoret._Medicin_....PDF }}</ref> There remain disagreements about which procedures are useful for which purposes, as well as disagreements over which ethical principles apply to which species. A 2015 Gallup poll found that 67% of Americans were "very concerned" or "somewhat concerned" about animals used in research.<ref>{{cite news|last1=Riffkin|first1=Rebecca|title=In U.S., More Say Animals Should Have Same Rights as People|url=http://www.gallup.com/poll/183275/say-animals-rights-people.aspx|access-date=7 July 2015|agency=Gallup|date=18 May 2015}}</ref> A Pew poll taken the same year found 50% of American adults opposed the use of animals in research.<ref>{{cite news|last1=Funk|first1=Cary|last2=Rainie|first2=Lee|title=Public and Scientists' Views on Science and Society|url=http://www.pewinternet.org/2015/01/29/public-and-scientists-views-on-science-and-society/|access-date=7 July 2015|agency=Pew Research Center|date=29 January 2015}}</ref> Still, a wide range of viewpoints exist. The view that animals have moral rights ([[animal rights]]) is a philosophical position proposed by [[Tom Regan]], among others, who argues that animals are beings with beliefs and desires, and as such are the "subjects of a life" with moral value and therefore moral rights.<ref>Singer, Peter (ed.). "A Companion to Ethics". Blackwell Companions to Philosophy, 1991.</ref> Regan still sees ethical differences between killing human and non-human animals, and argues that to save the former it is permissible to kill the latter. Likewise, a "moral dilemma" view suggests that avoiding potential benefit to humans is unacceptable on similar grounds, and holds the issue to be a dilemma in balancing such harm to humans to the harm done to animals in research.<ref name=Nuffield>[http://www.nuffieldbioethics.org/sites/default/files/files/Animals%20Chapter%2014%20Discussion%20of%20Ethical%20Issues.pdf Chapter 14, Discussion of ethical issues, p . 244] {{webarchive|url=https://web.archive.org/web/20110928072631/http://www.nuffieldbioethics.org/sites/default/files/files/Animals%20Chapter%2014%20Discussion%20of%20Ethical%20Issues.pdf |date=28 September 2011 }} in: [http://www.nuffieldbioethics.org/animal-research The ethics of research involving animals] {{Webarchive|url=https://web.archive.org/web/20110429185538/http://www.nuffieldbioethics.org/animal-research |date=29 April 2011 }} at the Nuffield Council on Bioethics. Published 25 May 2005</ref> In contrast, an [[Abolitionism (animal rights)|abolitionist view in animal rights]] holds that there is no moral justification for any harmful research on animals that is not to the benefit of the individual animal.<ref name=Nuffield/> [[Bernard Rollin]] argues that benefits to human beings cannot outweigh animal suffering, and that human beings have no moral right to use an animal in ways that do not benefit that individual. [[Donald Watson]] has stated that [[vivisection]] and animal experimentation "is probably the cruelest of all Man's attack on the rest of Creation."<ref name=":3">{{cite web|url=https://www.vegansociety.com/sites/default/files/DW_Interview_2002_Unabridged_Transcript.pdf|title=Donald Watson 2002 Unabridged Interview|last=George|first=Roger|url-status=live|archive-url=https://web.archive.org/web/20191027031624/https://www.vegansociety.com/sites/default/files/DW_Interview_2002_Unabridged_Transcript.pdf|archive-date=27 October 2019}}</ref> Another prominent position is that of philosopher [[Peter Singer]], who argues that there are no grounds to include a being's species in considerations of whether their suffering is important in [[utilitarianism|utilitarian]] moral considerations.<ref name=Rollin1998>Rollin, Bernard E. (1998) "The moral status of animals and their use as experimental subjects," in Kuhse, Helga and Singer, Peter (eds.). "A Companion to Bioethics". Blackwell Publishing, {{ISBN|0-631-23019-X}}.</ref> [[Malcolm Macleod]] and collaborators argue that most [[Scientific control|controlled]] animal studies do not employ [[Randomized controlled trial|randomization]], [[Double-blind trials|allocation concealment]], and [[Blind experiment|blinding]] outcome assessment, and that failure to employ these features exaggerates the apparent benefit of drugs tested in animals, leading to a failure to translate much animal research for human benefit.<ref>{{cite journal |vauthors=Bebarta V, Luyten D, Heard K |title=Emergency medicine animal research: does use of randomization and blinding affect the results? |journal=Academic Emergency Medicine | year=2003 | pmid=12782533 |doi=10.1111/j.1553-2712.2003.tb00056.x |volume=10 |issue=6 |pages=684–87|doi-access=free }}</ref><ref>{{cite journal |last1=Macleod |first1=Malcolm R. |last2=van der Worp |first2=H. Bart |last3=Sena |first3=Emily S. |last4=Howells |first4=David W. |last5=Dirnagl |first5=Ulrich |last6=Donnan |first6=Geoffrey A. |title=Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality |journal=Stroke |volume=39 |pages=2824–29 |year=2008 |pmid=18635842 |doi=10.1161/strokeaha.108.515957 |issue=10|doi-access=free }}</ref><ref>{{cite journal |vauthors=Sena E, Wheble P, Sandercock P, Macleod M |title=Systematic review and meta-analysis of the efficacy of tirilazad in experimental stroke |journal=Stroke |volume=38 |pages=388–94 |year=2007 |pmid=17204689|doi=10.1161/01.str.0000254462.75851.22 |issue=2|doi-access=free }}</ref><ref>{{cite journal |vauthors=Hirst JA, Howick J, Aronson J, Roberts N, Perera R, Koshiaris C, Heneghan C |title= The Need for Randomization in Animal Trials: An Overview of Systematic Reviews |journal=PLOS ONE|volume=9 |issue= 6 |page=e98856 |year=2014 |doi=10.1371/journal.pone.0098856 |pmid=24906117 |pmc=4048216|bibcode=2014PLoSO...998856H |doi-access= free }}</ref><ref>{{cite journal |vauthors=Van der Worp B, Sena E, Porritt M, Rewell S, O'Collins V, Macleod MR |title=Can Animal Models of Disease Reliably Inform Human Studies? |journal=PLOS Med |volume=7 |issue=3 |page=e1000245 |year=2010 |pmid=20361020|doi=10.1371/journal.pmed.1000245 |pmc=2846855 |doi-access=free }}</ref> Governments such as the Netherlands and New Zealand have responded to the public's concerns by outlawing invasive experiments on certain classes of non-human primates, particularly the [[great apes]].<ref>{{cite journal |vauthors=Gagneux P, Moore JJ, Varki A | title = The ethics of research on great apes | journal = Nature | volume = 437 | issue = 7055 | pages = 27–29 | year = 2005 | pmid = 16136111 | doi = 10.1038/437027a | bibcode = 2005Natur.437...27G | s2cid = 11500691 }}</ref><ref>{{cite journal | author = Vermij P | title = Europe's last research chimps to retire | journal = Nature Medicine | volume = 9 | issue = 8 | page = 981 | year = 2003 | pmid = 12894144 | doi = 10.1038/nm0803-981b | s2cid = 9892510 | doi-access = free }}</ref> In 2015, captive chimpanzees in the U.S. were added to the [[Endangered Species Act]] adding new road blocks to those wishing to experiment on them.<ref>{{cite news|last1=St Fleur|first1=Nicholas|title=U.S. Will Call All Chimps 'Endangered'|url=https://www.nytimes.com/2015/06/13/science/chimpanzees-endangered-fish-and-wildlife-service.html|access-date=7 July 2015|work=The New York Times|date=12 June 2015}}</ref> Similarly, citing ethical considerations and the availability of alternative research methods, the U.S. [[NIH]] announced in 2013 that it would dramatically reduce and eventually phase out experiments on chimpanzees.<ref>{{cite news|last1=Kaiser|first1=Jocelyn|title=NIH Will Retire Most Research Chimps, End Many Projects|url=https://www.science.org/content/article/nih-will-retire-most-research-chimps-end-many-projects|access-date=7 July 2015|work=sciencemag.org|date=26 June 2013}}</ref> The British government has required that the cost to animals in an experiment be weighed against the gain in knowledge.<ref name=SelectComm>{{cite web|url=https://publications.parliament.uk/pa/ld200102/ldselect/ldanimal/150/15003.htm |title=Summary of House of Lords Select Committee on Animals in Scientific Procedures |publisher=UK Parliament|date=24 July 2002 |access-date=2012-07-13}}</ref> Some medical schools and agencies in China, Japan, and South Korea have built [[cenotaph]]s for killed animals.<ref>[http://rayinfo.koizumiengei.com/anilog/000145.html 韓国・食薬庁で「実験動物慰霊祭」挙行] {{webarchive|url=https://web.archive.org/web/20070829151819/http://rayinfo.koizumiengei.com/anilog/000145.html |date=29 August 2007 }}</ref> In Japan there are also annual memorial services ''Ireisai'' ({{lang-ja|慰霊祭}}) for animals sacrificed at medical school. [[File:Dollyscotland (crop).jpg|thumb|left|[[Dolly (sheep)|Dolly the sheep]]: the first [[cloning|clone]] produced from the somatic cells of an adult mammal]] Various specific cases of animal testing have drawn attention, including both instances of beneficial scientific research, and instances of alleged ethical violations by those performing the tests. The fundamental properties of [[muscle contraction#Force-length and force-velocity relationships|muscle physiology]] were determined with work done using frog muscles (including the force generating mechanism of all muscle,<ref>{{cite journal |vauthors=Huxley AF, Simmons RM | title = Proposed Mechanism of Force Generation in Striated Muscle | journal = Nature | volume = 233 | issue = 5321 | pages = 533–38 | year = 1971 | pmid = 4939977 | doi = 10.1038/233533a0 | bibcode = 1971Natur.233..533H | s2cid = 26159256 }}</ref> the length-tension relationship,<ref>{{cite journal |vauthors=Gordon AM, Huxley AF, Julian FJ | title = The variation in isometric tension with sarcomere length in vertebrate muscle fibres | journal = The Journal of Physiology | volume = 184 | issue = 1 | pages = 170–92 | year = 1966 | pmid = 5921536 | pmc = 1357553 | doi=10.1113/jphysiol.1966.sp007909}}</ref> and the force-velocity curve<ref>{{cite journal |vauthors=Ford LE, Huxley AF, Simmons RM | title = Tension transients during steady shortening of frog muscle fibres | journal = The Journal of Physiology | volume = 361 | issue = 1 | pages = 131–50 | year = 1985 | pmid = 3872938 | pmc = 1192851 | doi=10.1113/jphysiol.1985.sp015637}}</ref>), and frogs are still the preferred model organism due to the long survival of muscles ''in vitro'' and the possibility of isolating intact [[Fast twitch muscle|single-fiber]] preparations (not possible in other organisms).<ref>{{cite journal |vauthors=Lutz GJ, Lieber RL | title = Myosin isoforms in anuran skeletal muscle: Their influence on contractile properties and in vivo muscle function | journal = Microscopy Research and Technique | volume = 50 | issue = 6 | pages = 443–57 | year = 2000 | pmid = 10998635 | doi = 10.1002/1097-0029(20000915)50:6<443::AID-JEMT3>3.0.CO;2-5 | s2cid = 3477585 }}</ref> Modern [[physical therapy]] and the understanding and treatment of muscular disorders is based on this work and subsequent work in mice (often engineered to express disease states such as [[muscular dystrophy]]).<ref>Liber, R. L. (2002). [https://books.google.com/books?id=T0fbq_b89cAC Skeletal Muscle Structure, Function, and Plasticity: The Physiological Basis of Rehabilitation], 2nd ed. Lippincott Williams & Wilkins, {{ISBN|978-0-7817-3061-7}}.</ref> In February 1997 a team at the [[Roslin Institute]] in Scotland announced the birth of [[Dolly (sheep)|Dolly]] the sheep, the first mammal to be [[cloning|cloned]] from an adult [[somatic cell]].<ref name=Wilmut>{{cite journal |vauthors=Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH | title = Viable offspring derived from fetal and adult mammalian cells | journal = Nature | volume = 385 | issue = 6619 | pages = 810–13 | year = 1997 | pmid = 9039911 | doi = 10.1038/385810a0 | bibcode = 1997Natur.385..810W | s2cid = 4260518 }}</ref> Concerns have been raised over the mistreatment of primates undergoing testing. In 1985, the case of [[Britches (monkey)|Britches]], a macaque monkey at the [[University of California, Riverside]], gained public attention. He had his eyelids sewn shut and a sonar sensor on his head as part of an experiment to test [[sensory substitution]] devices for blind people. The laboratory was raided by [[Animal Liberation Front]] in 1985, removing Britches and 466 other animals.<ref>Franklin, Ben A. (30 August 1987) [https://www.nytimes.com/1987/08/30/weekinreview/going-to-extremes-for-animal-rights.html "Going to Extremes for 'Animal Rights'"], ''The New York Times''.</ref> The National Institutes of Health conducted an eight-month investigation and concluded, however, that no corrective action was necessary.<ref>{{cite journal | author = Holden C | title = A pivotal year for lab animal welfare | journal = Science | volume = 232 | issue = 4747 | pages = 147–50 | year = 1986 | pmid = 3952503 | doi = 10.1126/science.3952503 | bibcode = 1986Sci...232..147H | url = https://animalstudiesrepository.org/hensppite/1 }}</ref> During the 2000s other cases have made headlines, including experiments at the [[Cambridge University primates|University of Cambridge]]<ref>Laville, Sandra (8 February 2005). [https://www.theguardian.com/uk_news/story/0,3604,1407818,00.html "Lab monkeys 'scream with fear' in tests"], ''The Guardian''.</ref> and [[Primate experiments at Columbia University|Columbia University]] in 2002.<ref>[https://web.archive.org/web/20080307223434/http://www.cnn.com/2003/US/Northeast/10/12/columbia.animals.ap/ "Columbia in animal cruelty dispute"], CNN (2003-10-12)</ref> In 2004 and 2005, undercover footage of staff of [[Covance]]'s, a [[contract research organization]] that provides animal testing services, [[Vienna, Virginia|Virginia]] lab was shot by [[People for the Ethical Treatment of Animals]] (PETA). Following release of the footage, the U.S. Department of Agriculture fined Covance $8,720 for 16 citations, three of which involved lab monkeys; the other citations involved administrative issues and equipment.<ref>Benz, Kathy and McManus, Michael (17 May 2005). [http://www.cnn.com/2005/US/05/17/peta.lab/index.html PETA accuses lab of animal cruelty], CNN.</ref><ref>Scott, Luci (1 April 2006). [https://www.newspapers.com/newspage/125672411/ "Probe leads to Covance fine"], ''The Arizona Republic''. Retrieved 8 March 2021.</ref> ===Threats to researchers=== Threats of violence to animal researchers are not uncommon.{{Vague|date=November 2019}}<ref name=naturebiotech>{{cite journal | author = Huggett B | title = When animal rights turns ugly | journal = Nature Biotechnology | volume = 26 | issue = 6 | pages = 603–05 | year = 2008 | pmid = 18536673 | doi = 10.1038/nbt0608-603 | s2cid = 8006958 }}</ref> In 2006, a primate researcher at the [[University of California, Los Angeles]] (UCLA) shut down the experiments in his lab after threats from animal rights activists. The researcher had received a grant to use 30 [[macaque]] monkeys for vision experiments; each monkey was anesthetized for a single physiological experiment lasting up to 120 hours, and then euthanized.<ref>{{cite journal |vauthors=Malone BJ, Kumar VR, Ringach DL | title = Dynamics of Receptive Field Size in Primary Visual Cortex | journal = Journal of Neurophysiology | volume = 97 | issue = 1 | pages = 407–14 | year = 2007 | pmid = 17021020 | doi = 10.1152/jn.00830.2006 | citeseerx = 10.1.1.133.3969 }}</ref> The researcher's name, phone number, and address were posted on the website of the [[Primate Freedom Project]]. Demonstrations were held in front of his home. A [[Molotov cocktail]] was placed on the porch of what was believed to be the home of another UCLA primate researcher; instead, it was accidentally left on the porch of an elderly woman unrelated to the university. The [[Animal Liberation Front]] claimed responsibility for the attack.<ref>Epstein, David (22 August 2006). [http://www.insidehighered.com/news/2006/08/22/animal Throwing in the Towel] {{Webarchive|url=https://web.archive.org/web/20201127012451/https://www.insidehighered.com/news/2006/08/22/animal |date=27 November 2020 }}, ''Inside Higher Education''</ref> As a result of the campaign, the researcher sent an email to the Primate Freedom Project stating "you win", and "please don't bother my family anymore".<ref>[https://web.archive.org/web/20080517050122/http://www.investors.com/editorial/editorialcontent.asp?secid=1501&status=article&id=241311597601024 Predators Unleashed], ''Investor's Business Daily'' (2006-08-24)</ref> In another incident at UCLA in June 2007, the [[Revolutionary Cells (RCALB)|Animal Liberation Brigade]] placed a bomb under the car of a UCLA children's [[ophthalmologist]] who [[Animal testing on cats|experiments on cats]] and rhesus monkeys; the bomb had a faulty fuse and did not detonate.<ref>McDonald, Patrick Range (8 August 2007). [https://web.archive.org/web/20080215232132/http://www.laweekly.com/news/news/monkey-madness-at-ucla/16986/ UCLA Monkey Madness], ''LA Weekly''.</ref> In 1997, PETA filmed staff from [[Huntingdon Life Sciences]], showing dogs being mistreated.<ref>"It's a Dog's Life", ''Countryside Undercover'', Channel Four Television, UK (26 March 1997).</ref><ref>[http://www.smallworldtv.co.uk/public/main.cfm?m1=c_75&m2=c_2&m3=c_54&m4=e_0 "It's a dog's life"] {{webarchive |url=https://web.archive.org/web/20120308224555/http://www.smallworldtv.co.uk/public/main.cfm?m1=c_75&m2=c_2&m3=c_54&m4=e_0 |date=8 March 2012 }}, Small World Productions (2005). Retrieved 6 July 2010.</ref> The employees responsible were dismissed,<ref>{{cite news|url=http://news.bbc.co.uk/2/hi/uk_news/1123837.stm |title=A controversial laboratory |work=BBC News |date=18 January 2001 |access-date=2012-07-13}}</ref> with two given community service orders and ordered to pay £250 costs, the first lab technicians to have been prosecuted for animal cruelty in the UK.<ref>Broughton, Zoe (March 2001). [https://archive.today/20120629060332/http://findarticles.com/p/articles/mi_m2465/is_2_31/ai_71634854/ "Seeing Is Believing – cruelty to dogs at Huntingdon Life Sciences"], ''The Ecologist''.</ref> The [[Stop Huntingdon Animal Cruelty]] campaign used tactics ranging from non-violent protest to the alleged firebombing of houses owned by executives associated with HLS's clients and investors. The [[Southern Poverty Law Center]], which monitors US domestic extremism, has described SHAC's ''modus operandi'' as "frankly terroristic tactics similar to those of anti-abortion extremists", and in 2005 an official with the FBI's counter-terrorism division referred to SHAC's activities in the United States as domestic terrorist threats.<ref>[http://www.splcenter.org/intel/intelreport/article.jsp?aid=42 "From push to shove"] {{Webarchive|url=https://web.archive.org/web/20091122190431/http://www.splcenter.org/intel/intelreport/article.jsp?aid=42 |date=22 November 2009 }}, Southern Poverty Law Group ''Intelligence Report'', Fall 2002</ref><ref>Lewis, John E. [https://web.archive.org/web/20080801014736/http://epw.senate.gov/hearing_statements.cfm?id=247787 "Statement of John Lewis"], US Senate Committee on Environment and Public Works, 26 October 2005, accessed 17 January 2011.</ref> 13 members of SHAC were jailed for between 15 months and eleven years on charges of conspiracy to blackmail or harm HLS and its suppliers.<ref name="Evers">Evers, Marco. [http://www.spiegel.de/international/europe/0,1518,517875,00.html "Resisting the Animal Avengers", Part 1], [http://www.spiegel.de/international/europe/0,1518,517875-2,00.html Part 2], ''Der Spiegel'', 19 November 2007.</ref><ref name="Weaver">Weaver, Matthew. [https://www.theguardian.com/science/2010/oct/25/animal-research-animal-welfare "Animal rights activists jailed for terrorising suppliers to Huntingdon Life Sciences"], ''The Guardian'', 25 October 2010.</ref> These attacks—as well as similar incidents that caused the [[Southern Poverty Law Center]] to declare in 2002 that the animal rights movement had "clearly taken a turn toward the more extreme"—prompted the US government to pass the [[Animal Enterprise Terrorism Act]] and the UK government to add the offense of "Intimidation of persons connected with animal research organisation" to the [[Serious Organised Crime and Police Act 2005]]. Such legislation and the arrest and imprisonment of activists may have decreased the incidence of attacks.<ref>Herbert, Ian (27 January 2007). [https://www.independent.co.uk/news/uk/this-britain/collapse-in-support-for-animal-rights-extremist-attacks-433872.html "Collapse in support for animal rights extremist attacks"], ''The Independent''.</ref> === Scientific criticism === [[Systematic review]]s have pointed out that animal testing often fails to accurately mirror outcomes in humans.<ref>{{cite journal|last=Knight|first=Andrew|date=May 2008|title=Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare|journal=Reviews on Recent Clinical Trials|volume=3|issue=2|pages=89–96|doi=10.2174/157488708784223844|issn=1574-8871|pmid=18474018}}</ref><ref name=":0">{{cite journal|last1=Greek|first1=Ray|last2=Menache|first2=Andre|date=2013-01-11|title=Systematic Reviews of Animal Models: Methodology versus Epistemology|journal=International Journal of Medical Sciences|volume=10|issue=3|pages=206–21|doi=10.7150/ijms.5529|issn=1449-1907|pmc=3558708|pmid=23372426}}</ref> For instance, a 2013 review noted that some 100 vaccines have been shown to prevent HIV in animals, yet none of them have worked on humans.<ref name=":0" /> Effects seen in animals may not be replicated in humans, and vice versa. Many [[corticosteroid]]s cause birth defects in animals, but not in humans. Conversely, [[thalidomide]] causes serious birth defects in humans, but not in some animals such as mice (however, it does cause birth defects in rabbits).<ref name=":1">{{cite journal|last=Bracken|first=Michael B|date=2009-03-01|title=Why animal studies are often poor predictors of human reactions to exposure|journal=Journal of the Royal Society of Medicine|volume=102|issue=3|pages=120–22|doi=10.1258/jrsm.2008.08k033|issn=0141-0768|pmc=2746847|pmid=19297654}}</ref> A 2004 paper concluded that much animal research is wasted because systemic reviews are not used, and due to poor methodology.<ref>{{cite journal|last1=Pound|first1=Pandora|last2=Ebrahim|first2=Shah|last3=Sandercock|first3=Peter|last4=Bracken|first4=Michael B|last5=Roberts|first5=Ian|date=2004-02-28|title=Where is the evidence that animal research benefits humans?|journal=BMJ: British Medical Journal|volume=328|issue=7438|pages=514–17|issn=0959-8138|pmid=14988196|pmc=351856|doi=10.1136/bmj.328.7438.514}}</ref> A 2006 review found multiple studies where there were promising results for new drugs in animals, but human clinical studies did not show the same results. The researchers suggested that this might be due to researcher bias, or simply because animal models do not accurately reflect human biology.<ref>{{cite journal|last1=Perel|first1=Pablo|last2=Roberts|first2=Ian|last3=Sena|first3=Emily|last4=Wheble|first4=Philipa|last5=Briscoe|first5=Catherine|last6=Sandercock|first6=Peter|last7=Macleod|first7=Malcolm|last8=Mignini|first8=Luciano E.|last9=Jayaram|first9=Pradeep|last10=Khan|first10=Khalid S.|date=2007-01-25|title=Comparison of treatment effects between animal experiments and clinical trials: systematic review|journal=BMJ|volume=334|issue=7586|pages=197|doi=10.1136/bmj.39048.407928.BE|issn=0959-8138|pmc=1781970|pmid=17175568}}</ref> Lack of meta-reviews may be partially to blame.<ref name=":1"/> Poor methodology is an issue in many studies. A 2009 review noted that many animal experiments did not use [[blinded experiment]]s, a key element of many scientific studies in which researchers are not told about the part of the study they are working on to reduce bias.<ref name=":1" /><ref>{{cite journal|last1=Schulz|first1=Kenneth F.|last2=Chalmers|first2=Iain|last3=Altman|first3=Douglas G.|date=2002-02-05|title=The Landscape and Lexicon of Blinding in Randomized Trials|journal=Annals of Internal Medicine|volume=136|issue=3|pages=254–59|doi=10.7326/0003-4819-136-3-200202050-00022|pmid=11827510|s2cid=34932997|issn=0003-4819}}</ref> A 2021 paper found, in a sample of Open Access Alzheimer Disease studies, that if the authors omit from the title that the experiment was performed in mice, the News Headline follow suit, and that also the Twitter repercussion is higher.<ref>{{cite journal|last1=Triunfol|first1=Marcia|last2=Gouveia|first2=Fabio C.|date=2021-06-15|editor-last=Bero|editor-first=Lisa|title=What's not in the news headlines or titles of Alzheimer disease articles? #InMice|journal=PLOS Biology|language=en|volume=19|issue=6|pages=e3001260|doi=10.1371/journal.pbio.3001260|pmid=34129637|pmc=8205157|issn=1545-7885|doi-access=free}}</ref> ===Activism=== There are various examples of activists utilizing [[Freedom of Information Act (United States)|Freedom of Information Act (FOIA)]] requests to obtain information about taxpayer funding of animal testing. For example, the White Coat Waste Project, a group of activists that hold that taxpayers should not have [[File:Animal Testing Protestors.jpg|thumb|Anti-animal testing activists protesting in the streets of London in 2009]] to pay $20 billion every year for experiments on animals,<ref>{{cite web|url=https://www.whitecoatwaste.org/|title=White Coat Waste Project|access-date=March 8, 2022}}</ref> highlighted that the [[National Institute of Allergy and Infectious Diseases]] provided $400,000 in taxpayer money to fund experiments in which 28 beagles were infected by disease-causing parasites.<ref>{{cite news|url=https://www.washingtonpost.com/news/animalia/wp/2016/11/15/saving-dogs-from-government-research-labs-gets-some-bipartisan-attention/|title=Should dogs be guinea pigs in government research? A bipartisan group says no.|newspaper=[[The Washington Post]]|date=November 15, 2016}}</ref> The White Coat Project found reports that said dogs taking part in the experiments were "vocalizing in pain" after being injected with foreign substances.<ref>{{cite web|url=https://blog.whitecoatwaste.org/2021/07/30/fauci-funding-wasteful-deadly-dog-tests/|title=WCW EXPOSÉ: FAUCI SPENT $424K ON BEAGLE EXPERIMENTS, DOGS BITTEN TO DEATH BY FLIES|date=July 30, 2021}}</ref> Following public outcry, [[People for the Ethical Treatment of Animals|People for the Ethical Treatment of Animals (PETA)]] made a call to action that all members of the [[National Institute of Health]] resign effective immediately<ref>{{cite web|url=https://www.foxnews.com/us/peta-calls-for-dr-fauci-to-resign-our-position-is-clear|title=PETA calls for Dr. Fauci to resign: 'Our position is clear'|website=[[Fox News]] |date=November 5, 2021}}</ref> and that there is a "need to find a new NIH director to replace the outgoing [[Francis Collins]] who will shut down research that violates the dignity of nonhuman animals."<ref>{{cite web|url=https://www.peta.org/blog/fauci-niaid-puppies-animal-testing/|title=Experimenters Fed Puppies' Heads to Infected Flies, but That's Not All Fauci's NIH Funded|date=October 25, 2021}}</ref> ===Historical debate=== [[File:Claude Bernard 5.jpg|right|thumb|[[Claude Bernard]], regarded as the "prince of vivisectors",<ref name=Croce11/> argued that experiments on animals are "entirely conclusive for the [[toxicology]] and hygiene of man".<ref name=Bernard>[[Claude Bernard|Bernard, Claude]] ''An Introduction to the Study of Experimental Medicine'', 1865. First English translation by Henry Copley Greene, published by Macmillan & Co., Ltd., 1927; reprinted in 1949, p. 125.</ref>]] As the experimentation on animals increased, especially the practice of vivisection, so did criticism and controversy. In 1655, the advocate of [[Galen]]ic physiology [[Edmund O'Meara]] said that "the miserable torture of vivisection places the body in an unnatural state".<ref name=Ryder54>[[Richard D. Ryder|Ryder, Richard D.]] (2000). ''Animal Revolution: Changing Attitudes Towards Speciesism''. Berg Publishers, p. 54 {{ISBN|1-85973-330-1}}.</ref><ref name=ANZCCART>[https://web.archive.org/web/20090327033757/http://www.adelaide.edu.au/ANZCCART/resources/AnimalExperimentation.pdf "Animal Experimentation: A Student Guide to Balancing the Issues"], Australian and New Zealand Council for the Care of Animals in Research and Teaching (ANZCCART), accessed 12 December 2007, cites original reference in Maehle, A-H. and Tr6hler, U. ''Animal experimentation from antiquity to the end of the eighteenth century: attitudes and arguments''. In N. A. Rupke (ed.) Vivisection in Historical Perspective. Croom Helm, London, 1987, p. 22.</ref> O'Meara and others argued pain could affect animal physiology during vivisection, rendering results unreliable. There were also objections ethically, contending that the benefit to humans did not justify the harm to animals.<ref name=ANZCCART/> Early objections to animal testing also came from another angle—many people believed animals were inferior to humans and so different that results from animals could not be applied to humans.<ref name="Ethical"/><ref name=ANZCCART/> On the other side of the debate, those in favor of animal testing held that experiments on animals were necessary to advance medical and biological knowledge. [[Claude Bernard]]—who is sometimes known as the "prince of vivisectors"<ref name=Croce11>Croce, Pietro. ''Vivisection or Science? An Investigation into Testing Drugs and Safeguarding Health''. Zed Books, 1999, {{ISBN|1-85649-732-1}} p. 11.</ref> and the father of physiology, and whose wife, [[Marie Françoise Bernard |Marie Françoise Martin]], founded the first anti-vivisection society in France in 1883<ref>Rudacille, Deborah (2000). ''The Scalpel and the Butterfly: The Conflict'', University of California Press, p. 19 {{ISBN|0-520-23154-6}}.</ref>—famously wrote in 1865 that "the science of life is a superb and dazzlingly lighted hall which may be reached only by passing through a long and ghastly kitchen".<ref name=TelegraphNov2003>[https://web.archive.org/web/20080213180427/http://www.telegraph.co.uk/health/main.jhtml?xml=%2Fhealth%2F2003%2F11%2F24%2Fhsick23.xml "In sickness and in health: vivisection's undoing"], ''The Daily Telegraph'', November 2003</ref> Arguing that "experiments on animals {{nowrap|[.{{hsp}}.{{hsp}}.]}} are entirely conclusive for the [[toxicology]] and hygiene of man {{nowrap|[.{{hsp}}.{{hsp}}. T]he}} effects of these substances are the same on man as on animals, save for differences in degree",<ref name=Bernard/> Bernard established animal experimentation as part of the standard [[scientific method]].<ref name=LaFollette>LaFollette, H., Shanks, N., [http://www.hughlafollette.com/papers/BERNARD.HTM Animal Experimentation: the Legacy of Claude Bernard] {{Webarchive|url=https://web.archive.org/web/20200110205729/http://www.hughlafollette.com/papers/BERNARD.HTM |date=10 January 2020 }}, ''International Studies in the Philosophy of Science'' (1994) pp. 195–210.</ref> In 1896, the physiologist and physician [[Walter Cannon|Dr. Walter B. Cannon]] said "The antivivisectionists are the second of the two types Theodore Roosevelt described when he said, 'Common sense without conscience may lead to crime, but conscience without common sense may lead to folly, which is the handmaiden of crime.{{'"}}<ref>{{cite journal | author = Nicoll CS | title = A Physiologist's Views on the Animal Rights/Liberation Movement | journal = The Physiologist | volume = 34 | issue = 6 | pages = 303, 306–08, 315 | year = 1991 | pmid = 1775539 }}</ref> These divisions between pro- and anti-animal testing groups first came to public attention during the [[Brown Dog affair]] in the early 1900s, when hundreds of medical students clashed with anti-vivisectionists and police over a memorial to a vivisected dog.<ref name=Mason>Mason, Peter. [http://www.london-books.co.uk/books/browndog.html ''The Brown Dog Affair''] {{Webarchive|url=https://web.archive.org/web/20201006123454/http://www.london-books.co.uk/books/browndog.html |date=6 October 2020 }}. Two Sevens Publishing, 1997.</ref> In 1822, the first [[Cruel Treatment of Cattle Act 1822|animal protection law]] was enacted in the British parliament, followed by the [[Cruelty to Animals Act 1876|Cruelty to Animals Act (1876)]], the first law specifically aimed at regulating animal testing. The legislation was promoted by [[Charles Darwin]], who wrote to [[Ray Lankester]] in March 1871: "You ask about my opinion on vivisection. I quite agree that it is justifiable for proper investigations on physiology; but not for mere damnable and detestable curiosity. It is a subject which makes me sick with horror, so I will not say another word about it, else I shall not sleep to-night."<ref>{{cite web|url=http://www.fullbooks.com/The-Life-and-Letters-of-Charles-Darwinx29407.html |title=''The Life and Letters of Charles Darwin, Volume II'' |publisher=Fullbooks.com }}</ref><ref>Bowlby, John (1991). ''Charles Darwin: A New Life'', W. W. Norton & Company, p. 420 {{ISBN|0-393-30930-4}}.</ref> In response to the lobbying by anti-vivisectionists, several organizations were set up in Britain to defend animal research: [[The Physiological Society]] was formed in 1876 to give physiologists "mutual benefit and protection",<ref>{{cite book|last=Ilman|first=John|title=Animal Research in Medicine: 100 years of politics, protest and progress. The Story of the Research Defence Society|year=2008|publisher=Research Defence Society|isbn=978-0-9560008-0-4|page=16}}</ref> the Association for the Advancement of Medicine by Research was formed in 1882 and focused on policy-making, and the [[Research Defence Society]] (now [[Understanding Animal Research]]) was formed in 1908 "to make known the facts as to experiments on animals in this country; the immense importance to the welfare of mankind of such experiments and the great saving of human life and health directly attributable to them".<ref>{{cite book|title=Publications of the Research Defence Society: March 1908–1909; Selected by the committee|url=https://archive.org/details/b21509025|year=1909|publisher=Macmillan|location=London|page=xiv}}</ref> Opposition to the use of animals in medical research first arose in the United States during the 1860s, when [[Henry Bergh]] founded the [[American Society for the Prevention of Cruelty to Animals]] (ASPCA), with America's first specifically anti-vivisection organization being the American AntiVivisection Society (AAVS), founded in 1883. Antivivisectionists of the era generally believed the spread of mercy was the great cause of civilization, and vivisection was cruel. However, in the USA the antivivisectionists' efforts were defeated in every legislature, overwhelmed by the superior organization and influence of the medical community. Overall, this movement had little legislative success until the passing of the [[Laboratory Animal Welfare Act]], in 1966.<ref>Buettinger, Craig (1 January 1993) [https://web.archive.org/web/20080215121937/http://www.encyclopedia.com/doc/1G1-13506650.html Antivivisection and the charge of zoophil-psychosis in the early twentieth century.] ''The Historian''.</ref> Real progress in thinking about animal rights build on the "theory of justice" (1971) by the philosopher John Rawls and work on ethics by philosopher Peter Singer.<ref name="Ethical"/> ==Alternatives== {{Main|Alternatives to animal testing}} Most scientists and governments state that animal testing should cause as little suffering to animals as possible, and that animal tests should only be performed where necessary. The "[[Three Rs (animal research)|Three Rs]]" are guiding [[Moral obligation|principles]] for the use of animals in research in most countries.<ref name="altweb.jhsph" /><ref name=Flecknell>{{cite journal | author = Flecknell P | title = Replacement, reduction and refinement | journal = ALTEX | volume = 19 | issue = 2 | pages = 73–78 | year = 2002 | pmid = 12098013 }}</ref> Whilst replacement of animals, i.e. alternatives to animal testing, is one of the principles, their scope is much broader.<ref>{{cite web |url=http://www.nc3rs.org.uk/page.asp?id=7 |title=What are the 3Rs? |publisher=NC3Rs |access-date=16 December 2018 |archive-url=https://web.archive.org/web/20140801110031/http://www.nc3rs.org.uk/page.asp?id=7 |archive-date=1 August 2014 }}</ref> Although such principles have been welcomed as a step forwards by some animal welfare groups,<ref>{{cite journal | author = Kolar R | title = ECVAM: desperately needed or superfluous? An animal welfare perspective | journal = Altern Lab Anim | volume = 30 | issue = Suppl 2 | pages = 169–74 | year = 2002 | pmid = 12513669 | doi = 10.1177/026119290203002S26 | doi-access = free }}</ref> they have also been criticized as both outdated by current research,<ref>{{cite journal |vauthors=Schuppli CA, Fraser D, McDonald M | title = Expanding the three Rs to meet new challenges in humane animal experimentation | journal = Altern Lab Anim | volume = 32 | issue = 5 | pages = 525–32 | year = 2004 | pmid = 15656775 | doi = 10.1177/026119290403200507 | s2cid = 25015151 | doi-access = free }}</ref> and of little practical effect in improving animal welfare.<ref>{{cite journal | author = Rusche B | title = The 3Rs and animal welfare – conflict or the way forward? | journal = ALTEX | volume = 20 | issue = Suppl 1 | pages = 63–76 | year = 2003 | pmid = 14671703 }}</ref> The scientists and engineers at Harvard's [[Wyss Institute for Biologically Inspired Engineering|Wyss Institute]] have created "organs-on-a-chip", including the "lung-on-a-chip" and "gut-on-a-chip". Researchers at cellasys in Germany developed a "skin-on-a-chip".<ref>{{cite journal | vauthors = Alexander FA, Eggert S, Wiest J | title = Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface | journal = Genes | volume = 9 | issue = 2 | pages = 114 | date = February 2018 | pmid = 29466319 | pmc = 5852610 | doi = 10.3390/genes9020114 | doi-access = free }}</ref> These tiny devices contain human cells in a 3-dimensional system that mimics human organs. The chips can be used instead of animals in ''[[in vitro]]'' disease research, drug testing, and toxicity testing.<ref>{{cite web|url=http://www.peta.org/issues/animals-used-for-experimentation/alternatives-to-animal-testing.aspx |title=Alternatives to Animal Testing &#124; Animals Used for Experimentation &#124; The Issues |date=21 June 2010 |publisher=Peta.org |access-date=2015-04-06}}</ref> Researchers have also begun using 3-D bioprinters to create human tissues for ''in vitro'' testing.<ref>{{cite news|last1=Rhodes|first1=Margaret|title=Inside L'Oreal's Plan to 3-D Print Human Skin|url=https://www.wired.com/2015/05/inside-loreals-plan-3-d-print-human-skin/|access-date=7 July 2015|agency=Wired|date=28 May 2015}}</ref> Another non-animal research method is ''[[in silico]]'' or computer simulation and mathematical modeling which seeks to investigate and ultimately predict toxicity and drug effects on humans without using animals. This is done by investigating test compounds on a molecular level using recent advances in technological capabilities with the ultimate goal of creating treatments unique to each patient.<ref>{{cite journal|last1=Watts|first1=Geoff|title=Alternatives to animal experimentation|journal=BMJ|date=27 January 2007|volume=334|issue=7586|pages=182–84|doi=10.1136/bmj.39058.469491.68|pmid=17255608|pmc=1782004}}</ref><ref>{{cite journal|last1=Edelman|first1=L|last2=Eddy|first2=J|last3=Price|first3=N|title=In silico models of cancer|journal=Wiley Interdiscip Rev Syst Biol Med|date=July–August 2010|volume=2|issue=4|doi=10.1002/wsbm.75|pmid=20836040|pmc=3157287|pages=438–59}}</ref> [[Microdosing]] is another alternative to the use of animals in experimentation. Microdosing is a process whereby volunteers are administered a small dose of a test compound allowing researchers to investigate its pharmacological affects without harming the volunteers. Microdosing can replace the use of animals in pre-clinical drug screening and can reduce the number of animals used in safety and toxicity testing.<ref>{{cite web|title=Microdosing|url=http://3rs.ccac.ca/en/research/refinement/microdosing.html|website=3Rs|publisher=Canadian Council on Animal Care in Science|access-date=7 July 2015|archive-date=7 June 2015|archive-url=https://web.archive.org/web/20150607172022/http://3rs.ccac.ca/en/research/refinement/microdosing.html}}</ref> Additional alternative methods include [[positron emission tomography]] (PET), which allows scanning of the [[human brain]] ''in vivo'',<ref>{{cite web|url=http://www.medicalnewstoday.com/articles/154877.php |title=What Is A PET Scan? How Does A PET Scan Work? |date=23 June 2017 |publisher=Medicalnewstoday.com}}</ref> and [[Clinical study design|comparative]] [[Epidemiology|epidemiological]] studies of disease [[Risk factor (epidemiology)|risk factor]]s among human populations.<ref>{{cite journal|vauthors=Jiang J, Liu B, Nasca PC, Han W, Zou X, Zeng X, Tian X, Wu Y, Zhao P, Li J |doi=10.7150/ijms.6.329|pmid=19918375| title=Comparative study of control selection in a national population -based case-control study: Estimating risk of smoking on cancer deaths in Chinese men| year=2009| journal=International Journal of Medical Sciences|volume=6|issue=6|pages=329–37| pmc=2777271}}</ref> Simulators and computer programs have also replaced the use of animals in [[dissection]], teaching and training exercises.<ref>{{cite news|last1=McNeil|first1=Donald|title=PETA's Donation to Help Save Lives, Animal and Human|url=https://www.nytimes.com/2014/01/14/health/petas-donation-to-help-save-lives-animal-and-human.html|access-date=7 July 2015|work=The New York Times|date=13 January 2014}}</ref><ref>{{cite news|last1=Bernstein|first1=Fred|title=An On-Screen Alternative to Hands-On Dissection|url=https://www.nytimes.com/2005/10/04/science/an-onscreen-alternative-to-handson-dissection.html|access-date=7 July 2015|work=The New York Times|date=4 October 2005}}</ref> Official bodies such as the European Centre for the Validation of Alternative Test Methods of the [[European Commission]], the Interagency Coordinating Committee for the Validation of Alternative Methods in the US,<ref>{{cite web |url=http://iccvam.niehs.nih.gov/ |title=NTP Interagency Center for the Evaluation of Alternative Toxicological Methods – NTP |publisher=Iccvam.niehs.nih.gov |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20131209203359/http://iccvam.niehs.nih.gov/ |archive-date=9 December 2013}}</ref> ZEBET in Germany,<ref>[http://www.bfr.bund.de/en/zebet_database_on_alternatives_to_animal_experiments_on_the_internet__animalt_zebet_-1508.html ZEBET database on alternatives to animal experiments on the Internet (AnimAlt-ZEBET)]. BfR (30 September 2004). Retrieved on 2013-01-21.</ref> and the Japanese Center for the Validation of Alternative Methods<ref>[http://jacvam.jp/en_about/en_about03.html About JaCVAM-Organization of JaCVAM] {{webarchive |url=https://web.archive.org/web/20120511183409/http://jacvam.jp/en_about/en_about03.html |date=11 May 2012 }}. Jacvam.jp. Retrieved on 2013-01-21.</ref> (among others) also promote and disseminate the 3Rs. These bodies are mainly driven by responding to regulatory requirements, such as supporting the cosmetics testing ban in the EU by validating alternative methods. The European Partnership for Alternative Approaches to Animal Testing serves as a liaison between the European Commission and industries.<ref>[http://ec.europa.eu/enterprise/epaa/index_en.htm EPAA – Home] {{webarchive |url=https://web.archive.org/web/20131101045330/http://ec.europa.eu/enterprise/epaa/index_en.htm |date=1 November 2013 }}. Ec.europa.eu. Retrieved on 2013-01-21.</ref> The European Consensus Platform for Alternatives coordinates efforts amongst EU member states.<ref>[http://www.ecopa.eu/ ecopa – european consensus-platform for alternatives]. Ecopa.eu. Retrieved on 2013-01-21.</ref> Academic centers also investigate alternatives, including the Center for Alternatives to Animal Testing at the [[Johns Hopkins University]]<ref>[http://caat.jhsph.edu/ Center for Alternatives to Animal Testing – Johns Hopkins Bloomberg School of Public Health]. Caat.jhsph.edu. Retrieved on 2013-01-21.</ref> and the NC3Rs in the UK.<ref>{{cite web|url=http://www.nc3rs.org.uk/ |title=NC3Rs |publisher=NC3Rs.org.uk |access-date=2015-04-06}}</ref> == See also == {{div col|colwidth=20em}} * [[Bateson's cube]] * [[Effect of psychoactive drugs on animals]] * [[Human subject research]] * [[Krogh's principle]] * [[Microphysiometry]] * [[The People's Petition]] * [[Preclinical imaging]] * [[Remote control animal]] * [[Sentinel species]] * [[Sham feeding]] * [[U.S. Meat Animal Research Center]] * [[Women and animal advocacy]] * [[Wuzhishan pig]] {{div col end}} ==References== === Citations === {{Reflist}} === Works cited === * {{cite book |last=Carbone |first=Larry |date=2004 |title=What animals want: expertise and advocacy in laboratory animal welfare policy |location=Oxford, UK |publisher=Oxford University Press |isbn=978-0-19-972188-7 |oclc=57138138}} ==Further reading== {{Library resources box |by=no |onlinebooks=no |others=yes lcheading=Animal experimentation}} {{Refbegin}} * Conn, P. Michael and Parker, James V (2008). The Animal Research War, Palgrave Macmillan, {{ISBN|978-0-230-60014-0}} * {{cite book|author =Guerrini, Anita |title=Experimenting with humans and animals: from Galen to animal rights |publisher=The Johns Hopkins University Press |location=Baltimore |year=2003 |isbn=978-0-8018-7197-9}} * [https://finance.yahoo.com/news/15-companies-still-test-animals-014537588.html 15 Companies That Still Test on Animals in 2022]. [[Yahoo! Finance]]. January 9, 2023. {{Refend}} == External links == * {{Commons category-inline}} * {{Wikiquote-inline}} {{atestingend}} {{Animal rights|state=collapsed}}151.181.173.10 {{Medical research studies}}151.181.173.10 {{Mammals in culture}}151.181.173.10 {{Authority control}}151.181.173.10 [[Category:Animal testing| ]]151.181.173.10 [[Category:Animal test conditions]]151.181.173.10 [[Category:Bioethics]]151.181.173.10 [[Category:Biology experiments]]151.181.173.10 [[Category:Comparative psychology]]151.181.173.10 [[Category:Ethically disputed research practices towards animals]]151.181.173.10 [[Category:Ethics and statistics]]151.181.173.10 [[Category:Laboratory techniques]]151.181.173.10 [[Category:Research methods]]151.181.173.10'