Editing Animal testing (section)

==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}}
{{see also|Median lethal dose}}
[[File: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">{{usurped|1=[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 in size, have a 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 name="eurlex13"/> 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">{{cite web | first1=Kathleen M. | last1=Conlee | first2=Erika H. | last2=Hoffeld | first3=Martin L. | last3=Stephens | year=2004 | archiveurl=https://web.archive.org/web/20080227041442/http://www.worldcongress.net/2002/proceedings/C2%20Conlee.pdf | archivedate=27 February 2008 | url=http://www.worldcongress.net/2002/proceedings/C2%20Conlee.pdf | title=Demographic Analysis of Primate Research in the United States | work=ATLA | volume=32 | issue=Supplement 1 | pages=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/>