Animal testing

This is a good article. Click here for more information.
Page protected with pending changes
Source: Wikipedia, the free encyclopedia.

Wistar laboratory rat
DescriptionAround 50–100 million vertebrate animals are used in experiments annually.
SubjectsAnimal testing, science, medicine, animal welfare, animal rights, ethics

Animal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals 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.[1] The focus of animal testing varies on a continuum from 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. Examples of applied research include testing disease treatments, breeding, defense research, and toxicology, including cosmetics testing. In education, animal testing is sometimes a component of biology or psychology courses.[2] The practice is regulated to varying degrees in different countries.[3]

It was estimated in 2010 that the annual use of

FDA requirement that all drugs be tested on animals.[9]


The terms animal testing, animal experimentation, animal research, in vivo testing, and vivisection have similar denotations but different connotations. 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",[10][11][12] although dictionaries point out that the broader definition is "used only by people who are opposed to such work".[13] The word has a negative connotation, implying torture, suffering, and death.[14] The word "vivisection" is preferred by those opposed to this research, whereas scientists typically use the term "animal experimentation".[15][16]

The following text excludes as much as possible practices related to in vivo veterinary surgery, which is left to the discussion of vivisection.


An Experiment on a Bird in an Air Pump, from 1768, by Joseph Wright

The earliest references to animal testing are found in the writings of the

Arabic physician in Moorish Spain introduced an experimental method of testing surgical procedures before applying them to human patients.[19][20]

Animals have repeatedly been used throughout the history of biomedical research. In 1831, the founders of the

cloned from an adult cell.[29][30]

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.[31] 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.[32]

Historical debate

Claude Bernard, regarded as the "prince of vivisectors",[33] argued that experiments on animals are "entirely conclusive for the toxicology and hygiene of man".[34]

As the experimentation on animals increased, especially the practice of vivisection, so did criticism and controversy. In 1655, the advocate of Galenic physiology Edmund O'Meara said that "the miserable torture of vivisection places the body in an unnatural state".[35][36] 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.[36] 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.[36]

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"[33] and the father of physiology, and whose wife, Marie Françoise Martin, founded the first anti-vivisection society in France in 1883[37]—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".[38] Arguing that "experiments on animals [. . .] are entirely conclusive for the toxicology and hygiene of man [. . . T]he effects of these substances are the same on man as on animals, save for differences in degree",[34] Bernard established animal experimentation as part of the standard scientific method.[39]

In 1896, the physiologist and physician

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.'"[40] 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.[41]

In 1822, the first

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."[42][43] 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",[44] 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".[45]

Opposition to the use of animals in medical research first arose in the United States during the 1860s, when

Care and use of animals

Regulations and laws

The regulations that apply to animals in laboratories vary across species. In the U.S., under the 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.[47] The IACUC must ensure that alternatives, including non-animal alternatives, have been considered, that the experiments are not unnecessarily duplicative, and 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.[48][49] The Public Health Service policy oversees the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). The CDC conducts infectious disease research on nonhuman primates, rabbits, mice, and other animals, while FDA requirements cover use of animals in pharmaceutical research.[50] 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.[51] The USDA OIG made similar findings in a 2005 report.[52] With only a broad number of 120 inspectors, the United States Department of Agriculture (USDA) oversees more than 12,000 facilities involved in research, exhibition, breeding, or dealing of animals.[50] 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.[53]

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".[54] 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.[55]

Scientists in India are protesting a recent guideline issued by the University Grants Commission to ban the use of live animals in universities and laboratories.[56]


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,[57] 10–11 million of them in the EU.[58] 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.[59]

The USDA/APHIS has published the 2016 animal research statistics. Overall, the number of animals (covered by the Animal Welfare Act) used in research in the US rose 6.9% from 767,622 (2015) to 820,812 (2016).[60] 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.[61] 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.[62]

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.[63] 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.[64] 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.[61]

In the UK, Home Office figures show that 3.79 million procedures were carried out in 2017.[65] 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.[59] The procedures conducted on animals in the UK in 2017 were categorised as –

  • 43% (1.61 million) were assessed as sub-threshold
  • 4% (0.14 million) were assessed as non-recovery
  • 36% (1.35 million) were assessed as mild
  • 15% (0.55 million) were assessed as moderate
  • 4% (0.14 million) were assessed as severe[66]

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.[65]

The Three Rs

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.[67] The 3Rs state:

  1. 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.
  2. 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.
  3. 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.[68]

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.[69]

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, China has also escalated its use of GM animals, resulting in an increase in overall animal use.[70][71][72][73][74][75][excessive citations]


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

waxworms can be useful in studies to identify novel virulence factors or pharmacologically active compounds.[81][82][83]

Several invertebrate systems are considered acceptable alternatives to vertebrates in early-stage discovery screens.[84] 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 virulence traits of mammalian pathogens.[81][82] Waxworms and other insects have also proven valuable for the identification of pharmaceutical compounds with favorable bioavailability.[83] The decision to adopt such models generally involves accepting a lower degree of biological similarity with mammals for significant gains in experimental throughput.


Enos, the third primate to orbit the Earth, before insertion into the Mercury-Atlas 5
capsule in 1961
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[61] to between 20 and 100 million a year.[85] 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.[86][87] Mice are widely considered to be the best model of inherited human disease and share 95% of their genes with humans.[86] 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.[86] 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.[88]

Over 500,000 fish and 9,000 amphibians were used in the UK in 2016.

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,[91] and in 2017 this number was just 63.[89]
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,[61] around a third of which were used in experiments which have the potential to cause "pain and/or distress"[92] 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.[89]


Dogs are widely used in biomedical research, testing, and education—particularly

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.[96]
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.

The U.S. Department of Agriculture's Animal Welfare Report shows that 60,979 dogs were used in USDA-registered facilities in 2016.[61] In the UK, according to the UK Home Office, there were 3,847 procedures on dogs in 2017.[89] Of the other large EU users of dogs, Germany conducted 3,976 procedures on dogs in 2016[97] and France conducted 4,204 procedures in 2016.[98] In both cases this represents under 0.2% of the total number of procedures conducted on animals in the respective countries.


Zebrafish are commonly used for the basic study and development of various cancers. 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.[99][100]

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.[101]

Non-human primates

77-cm primate cage.jpg

Non-human primates (NHPs) are used in toxicology tests, studies of AIDS and hepatitis, studies of

chimpanzees are used in the US. As of 2015, there are approximately 730 chimpanzees in U.S. laboratories.[106]

In a survey in 2003, it was found that 89% of singly-housed primates exhibited self-injurious or abnormal stereotypyical behaviors including pacing, rocking, hair pulling, and biting among others.[107]

The first transgenic primate was produced in 2001, with the development of a method that could introduce new genes into a

Deep Brain Stimulation, and their current heaviest non-toxicological use occurs in the monkey AIDS model, SIV.[110][105][111] In 2008 a proposal to ban all primates experiments in the EU has sparked a vigorous debate.[112]


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.

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 shelters also supply the laboratories directly.[114] Large centers also exist to distribute strains of genetically modified animals; the International Knockout Mouse Consortium, for example, aims to provide knockout mice for every gene in the mouse genome.[115]

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.[116][117][118][119][120][121] 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.[122] The USDA recovered at least a dozen stolen pets during a raid on a Class B dealer in Arkansas in 2003.[123]

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.[124]

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.

Covance, which is the single largest importer of primates into the U.S.[129]

Pain and suffering

common sand frog to induce anesthesia
and death.