Editing Animal testing (section)

==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=14 August 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=30 September 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>{{Citation |last=Ironside |first=Wallace |title=John Frederick Joseph Cade (1912–1980) |work=Australian Dictionary of Biography |url=https://adb.anu.edu.au/biography/cade-john-frederick-joseph-9657 |access-date=2025-05-13 |place=Canberra |publisher=National Centre of Biography, Australian National University |language=en}}</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>{{Cite web |date= |title=NMAH {{!}} Polio: Two Vaccines |url=http://americanhistory.si.edu/polio/virusvaccine/vacraces2.htm |archive-url=https://web.archive.org/web/20110604021151/http://americanhistory.si.edu/polio/virusvaccine/vacraces2.htm |archive-date=2011-06-04 |access-date=2025-05-13 |website=americanhistory.si.edu}}</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">{{Cite web |title=Horton Corwin Hinshaw |url=http://www.rawbw.com/~hinshaw/cgi-bin/id?1375 |access-date=2025-05-13 |website=www.rawbw.com}}</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=17 December 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 |archive-url=https://web.archive.org/web/20090604111832/http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SulfanilamideDisaster/default.htm |url-status=dead |archive-date=4 June 2009 |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 | archive-url =https://web.archive.org/web/19990421055745/http://www.fda.gov/fdac/features/1997/697_thal.html | url-status =dead | archive-date =21 April 1999 | work =FDA Consumer | publisher =US [[Food and Drug Administration]] | date =1 September 1997}}</ref>