Animal testing

Animal testing (also referred to as animal research) refers to the use of non-human animals in experiments. It is estimated that 50 million–100 million animals worldwide   are used annually and subsequently killed in scientific procedures, mostly inside universities, medical schools, pharmaceutical companies, and commercial facilities that provide animal-testing services to industry. Testing is also carried out on farms, in defense-research establishments, and by public-health authorities, on a variety of species from fruit flies and mice to non-human primates. 

Animal experiments fall into three broad and overlapping categories: basic or pure research; studying diseases and developing medicines, also known as applied research; and toxicology testing of chemicals, also known as safety testing. See types of experiment below.

The topic is controversial, with supporters and opponents arguing about ethical issues and whether using animal models is good or bad science. According to the U.S. Foundation for Biomedical Research, "[a]nimal research has played a vital role in virtually every major medical advance of the last century &mdash; for both human and animal health." Many major developments that led to Nobel Prizes used animal research, including the development of penicillin (mice), organ transplant (dogs), and work on poliomyelitis that led to a vaccine (mice, monkeys). Whether animal research was necessary to achieve some of these breakthroughs has been questioned. 

The moral basis of the pro-testing position was summarized by a British House of Lords inquiry in 2001–2: "The institution of morality, society, and law is founded on the belief that human beings are unique amongst animals," and are therefore morally entitled to use them for their own purposes. This belief is "combined with a further belief that there is a moral imperative ... to develop medical and veterinary science for the relief of suffering ..." Some people also believe that animals may suffer less during experiments than human beings would, arguing that although all mammals have similar pain receptors and central nervous system pathways and may feel physical pain in the same way, non-human mammals suffer less because they have a reduced capacity to remember and to anticipate pain.  Opponents of animal testing strongly contest these views.

History
The earliest references to animal testing are in the writing of the Greeks in the third and fourth centuries BCE, with Aristotle (384-322 BCE) and Erasistratus (304-258 BCE) among the first to perform experiments on living animals (Cohen and Loew 1984). Galen, a physician in second-century Rome, dissected pigs and goats, and is known as the "father of vivisection." 

Although the term "vivisection" means literally the "cutting up" of a living animal, and originally referred only to experiments that involved dissection of, or surgery on, live animals, it is now commonly used to refer to any experiment on a living animal, which is also known as in vivo testing (Croce 2000). 

Animals have played a role in numerous historic experiments. In 1796, Edward Jenner extracted pus from pox infected cows to innoculate James Phipps against smallpox. In the 1890s Ivan Pavlov famously used dogs to describe classical conditioning. On November 3, 1957 a Russian dog named Laika became the first of many animals to orbit the earth and in 1996 "Dolly the sheep", the first mammal cloned from an adult cell, was born.

United States
In the United States, animal testing is primarily regulated by the 1985 Animal Welfare Act, which is enforced by the Animal and Plant Health Inspection Service of the United States Department of Agriculture (USDA). It contains provisions to ensure animals used in research receive a certain standard of care and treatment. However mice, rats and birds are exempt, meaning over 95% of research animals in the USA are not covered by this legislation. The Act requires each institution conducting animal testing to set up an Institutional Animal Care and Use Committee (IACUC), which is responsible for enforcing the Act. Institutions are subject to unannounced bi-annual inspections. There are 96 inspectors to monitor around 8,800 institutions, including research universities and industry (compared to the UK's 29 inspectors for 230 institutions).

Another regulatory instrument is the Public Health Service Policy on Humane Care and Use of Laboratory Animals, which became statutory with the Health Research Extension Act 1985, and which is enforced by the Office of Laboratory Animal Welfare (OLAW). This Act applies to any individual scientist or institution in receipt of federal funds, and requires each institution to have an IACUC. OLAW enforces the standards of the Guide for the Care and Use of Laboratory Animals published by the Institute for Laboratory Animal Research, which includes all vertebrate species in its care protocols, including rodents and birds  (Introduction, p1). In 2004, the National Institutes of Health provided funds to 3,180 different research institutions and universities. This means that most IACUC committees effectively regulate the use of all vertebrate species in research, even if they are not covered by federal legislation. OLAW does not carry out scheduled inspections, instead only visiting when there is a suspected or alleged violation.

Some companies and universities also receive accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), a non-governmental, nonprofit association, which accredits 680 institutions in 27 countries. Inspections occur once every three years without prior notice. 

Europe
Experiments on vertebrate animals in Europe are subject to the European Union's Directive 86/609/EEC on the protection of Animals used for Experimental and other Scientific purposes. However, there is considerable variation in the manner member countries choose to exercise the directive (compare, for example, legislation from Sweden, The Netherlands and Germany .)

United Kingdom
The types of institutions conducting animal research in the UK in 2004 were: universities (42.1 %); commercial organizations (33.3 %); non-profit organizations (4.9 %); government departments (2.4 %); National Health Service hospitals (0.9 %); public health laboratories (0.6 %); other public bodies (15.8 %) (pdf).

The 1986 Animals (Scientific Procedures) Act requires experiments to be regulated by three licences: a project licence for the scientist in charge of the project, which details the numbers and types of animals to be used, the experiments to be performed, and the purpose of them; a licence for the institution to ensure it has the facilities and staff to provide proper care; and a personal licence for each scientist or technician who carries out any procedure. In deciding whether to grant a licence, the Home Office refers to the Act's cost-benefit analysis, which is defined as "the likely adverse effects on the animals concerned against the benefit likely to accrue as a result of the programme to be specified in the licence" (Section 5(4)). A licence should not be granted if there is a "reasonably practicable method not entailing the use of protected animals" (Section 5(5)(a)). The experiments must use "the minimum number of animals, involve animals with the lowest degree of neurophysiological sensitivity, cause the least pain, suffering distress or lasting harm, and [be the] most likely to produce satisfactory results" (Section 5(5)(b)). 

During a 2002 House of Lords select committee inquiry into animal testing in the UK, witnesses agreed that the UK has the tightest regulatory system in the world, and is the only country to require a cost-benefit assessment of every licence application. There are 29 qualified inspectors covering 230 establishments, which are visited on average 11-12 times a year. (See also Animal Procedures Committee.)

France
In France, present legislation (principally the decree of 19th October 1987) requires an institutional and project licence before vertebrate experimentation may be carried out. An institution must submit details of their facilities, the reason for the use of animals and the species they house, after which a five-year licence may be granted following an inspection of the premises. The project licensee must be trained and educated to an appropriate level; personal licences are not required for individuals working under the supervision of a project licence holder. 

Japan
The system in Japan is one of self-regulation. Animal experiments are regulated by one clause in the 2000 Law for the Humane Treatment and Management of Animals (pdf), which requires those using animals to cause minimal distress and suffering. There are no inspections, and there is no reporting requirement for the numbers of animals used. 

Numbers
Accurate global figures for animal testing are difficult to collect. The British Union for the Abolition of Vivisection (BUAV) estimates that 100 million animals are experimented on around the world every year, 10–11 million of them in the European Union (pdf) and 1,101,958 in the United States in 2004 (pdf p.3). The Nuffield Council on Bioethics reports that "[e]stimates of the total number of animals used annually in research around the world are difficult to obtain and range from between 50 to 100 million animals" (pdf). Animals bred for research then killed as surplus, or used for breeding purposes, are not included in the figures.

According to the U.S. Department of Agriculture, the total number of animals used in that country in 2002 was 1,137,718, not counting birds, mice, and rats, which make up around 85 per cent of research animals. The Laboratory Primate Advocacy Group has used these figures to estimate that 23-25 million animals are used in research each year in America. 

Figures released by the British Home Office show that, in 2004, 2,854,944 procedures were carried out on 2,778,692 animals, an increase of 63,000 from 2003. The term "procedure" refers to an experiment, which might last several months or even years. The figures show that most animals are used in only one procedure: animals either die because of the experiment or are killed and dissected afterwards (pdf).

Over half the experiments in Britain in 2004 &mdash; 1,710,760 &mdash; were conducted without anesthetic; 880,897 experiments were conducted in connection with pure research; 114,081 were toxicology tests, 982,640 were for breeding, and most of the rest were for applied studies in human medicine, veterinary medicine or dentistry. 9,035 involved the deliberate infliction of "psychological stress".

Species
Listed in descending order of numbers of individal animals used:

Invertebrates
The greatest number of animals used for animal testing are the invertebrates, Drosophila melanogaster and Caenorhabditis elegans. This is due in part to a very short generation time of under a week and in the case of C. elegans details being known about the precise lineage of all of the organisms cells. However, with the exeption of some cephalopods, invertebrate species are not protected under most animal research legislation, therefore the total number of invertebrates used remains unknown.

Rodents
Rats and mice, the most commonly utilized vertebrate species, are used in large proportion because they are small, cheap, easy to handle and care for and can produce up to 100 babies in a year. Moreover, mice are considered the prime model of inhereted human disease, are genetically tractable and share 99% of their genes with humans. In the UK, 1,910,110 mice were used in 2004. In the U.S., the numbers of rats and mice used are not reported, but are estimated to exceed 20 million.

Fish and amphibia
In the UK, 194,562 fish and 18,195 amphibia were used in 2004 (pdf). The major species utilized are the zebrafish, Danio rerio, which are translucent during their embryonic stage, and the African clawed frog, Xenopus laevis.

Rabbits
Over 20,000 rabbits were used for animal testing the UK in 2004. Albino rabbits are notoriously used in eye irritancy tests because they have less tear flow than other animals, and in skin irritancy tests. See Draize test. In 2004 less than 12% of the rabbits were used for safety testing of non-medical products (pdf).

Dogs
Beagles are used, because they are friendly and gentle, in toxicity tests, surgery, and dental experiments. Toxicology tests are required to last six months in the UK, although British laboratories carry out tests lasting nine months on behalf of Japanese and American customers. In the UK, most dogs are bred for the purpose, for example by Harlan in Leicestershire. Of the 5,570 dogs used in the UK in 2004, 5,476 were purpose-bred.

Non-human primates
In the United States, 54,998 non-human primates were used in 2004, according to the United States Department of Agriculture|U.S. Department of Agriculture, an annual figure that has been more or less steady since 1973 (pdf, p. 10). In the European Union, 10,000 are used each year, with 4,208 used in Britain in 2004, a decrease of 591 from the previous year. 

Most of the NHPs used are baboons, macaques, marmosets, and chimpanzees. The use of great apes, also known as Hominidae &mdash; humans, gorillas, chimpanzees, and orangutans &mdash; is prohibited in Britain, but chimpanzees are still used in the U.S., with an estimated 1,300 in use at any given time, according to the Humane Society of the United States. 

Some believe there are indications that NHP use is on the rise, although in 2004 the British government reported, "there is a definate long-term downward trend" (pdf, p16). Oxford University in the UK is building a new animal-research center that protesters say may house a new primate facility,  though Oxford has said that 98% of the animals housed will be rodents and fish, and "there may also be some amphibia, ferrets, rabbits and primates." In the U.S., the Oregon and California National Primate Research Centers and New Iberia Research Center have expanded their facilities, the National Institutes of Health is inviting applications for the establishment of new breeding colonies, and a new breeding colony expected to house 3,000 NHPs is being set up in Florida. China is also increasing its NHP use, and is regarded as attractive to Western companies because of the low cost of research, the relatively lax regulations and the increase in violent animal rights activism in the West. 

Cats
Despite being a focal point for animal activists over many years (see Colin Blakemore), just 819 cats were used in UK research in 2004. This accounts for 0.03% of all animals (pdf).

Types of experiment
There are a range of scientific uses of animals, which can be split into three broad and at times overlapping categories.

Pure research
Basic or pure research aims to increase scientific knowledge about the way organisms behave, develop, and function biologically. Although it is not necessarily intended to lead directly to applications for humans, understanding fundamental biological mechanisms is considered essential for medical advances.

Both the largest number and greatest variety of laboratory animals are utilized in this type of research. Drosophila melanogaster, Caenorhabditis elegans, mice and rats together account for the vast majority, though small numbers of other species are used, ranging from sea slugs, through blind cavefish and armadillos. In the UK in 2004, 76 macaques, 141 dogs and 204 cats were used in basic research to investigate topics such as social behaviour, vision, nutrition and suckling. (pdf).

Examples of the types of animals and experiments used in basic research include:
 * Mutagenesis to study mechanisms in embryogenesis and developmental biology. Animals are often treated with mutagenic chemicals or radiation to generate defective embryos. By studying disrupted development, scientists aim to understand both how organisms develop normally and abnormally . The 1995 and 2002 Nobel Prizes in Physiology or Medicine were awarded for research into developmental processes in animals using forward genetic screens . Embryos used in experiments are often not covered by legislation and therefore not always required to be reported. Consequently, those that believe embryos are de facto animals claim the published number of experimental animals used is an under-representation.


 * Experiments into behaviour, to understand how organisms detect and interact with each other and their environment. Fruit flies, worms, mice and rats are all widely used in research into mechanisms of vision, taste,  hearing,  touch,  and smell.  In addition studies of brain function, such as memory and social behaviour, often use rats and birds.  Less common is the use of larger mammals in these types of studies.


 * Breeding experiments to study evolution and genetics. Laboratory mice, flies, fish and worms are inbred through many generations to create strains with defined characteristics . These provide scientists with animals of a known genetic background, an important tool for genetic analysis that is currently not available when studying outbred subjects (such as most human populations). Larger mammals are rarely bred specifically for such studies due to their longer gestation periods, though some scientists take advantage of inbred domesticated animals, such as dog or cattle breeds, for comparative purposes . Scientists studying mechanisms of evolution use a number of animal species, including mosquitos, sticklebacks , cichlids  and lampreys , due to their niche physiology, morphology, ecology or phylogeny.

Drug testing
In response to the teratogenic effects of Thalidomide in the 1960s, many countries passed new laws to ensure all new pharmaceuticals underwent rigorous animal testing before being licensed for human use. Tests on pharmaceutical products involve:


 * metabolic tests, which are performed to find out how the drugs are absorbed, metabolized and excreted by the body when introduced orally, intravenously, intraperitoneally, or intramuscularly.
 * toxicology tests, which gauge acute, sub-acute, and chronic toxicity. Acute toxicity is studied by using a rising dose until signs of toxicity become apparent. Current European legislation, Directive 2001/83/EC (pdf, p44), demands "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration".  Subacute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it becomes toxic, in order to discover the effects of the build up of toxic metabolites. Testing for chronic toxicity can last up to two years and, in the European Union, is required to utilize "two species of mammals, one of which must be non-rodent"  (pdf, p45).  The data gained from this period can be used to calculate the maximum tolerable dose; that is, the dose where signs of toxicity begin to occur.
 * efficacy studies, which test whether experimental drugs work by inducing the appropriate illness in animals using an animal model of the disease. The drug is then administered in a double-blind controlled trial. This is intended to allow scientists to determine the effect of the drug and the dose-response curve.
 * Specific tests on reproductive function, embryonic toxicity or carcinogenic potential can all be required by law, dependent of the result of other studies and type of drug being tested.

Toxicology tests
Animals are used in toxicological studies to help test the safety of a range of substances that could be harmful to animals, humans or the environment. These include household and industrial chemicals, herbicides, fertilisers, and food additives.

Toxicology tests are conducted by pharmaceutical companies testing drugs, or by animal-testing facilities like Huntingdon Life Sciences and Inveresk Research International on behalf of a wide variety of customers, including manufacturers such as Procter & Gamble, Unilever, Reckitt Benckiser, Colgate-Palmolive, SC Johnson, Union Carbide, and Ciba-Geigy. 

During these tests, which are often conducted without pain relief in part to ensure no interference with the test results, finished products such as pesticides, medications, food additives such as artificial sweetners, cosmetics, packing materials, and household products such as air freshener &mdash; or the chemical ingredients of any of these products &mdash; are applied to the skin or eyes; injected intravenously, intramuscularly, or subcutaneously; inhaled either by placing a mask over the animals and restraining them, or by placing them in an inhalation chamber; or administered orally, whereby the substance is introduced into the animals' stomach by means of a nasal-gastric tube, or added to the animal's food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal.

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, mutagenicity, carcinogenicity, teratogenicity, 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. Tests for cosmetics, which are still conducted in the U.S., involve general toxicity, eye and skin irritancy, phototoxicity (toxicity triggered by ultraviolet light) and mutagenicity. (pdf) Signs of toxicity may include vomiting, diarrhea, dizziness, tremor, lethargy, loss of appetite, convulsions, paralysis, and death.

Most toxicity tests involve testing ingredients rather than finished products. However, according to BUAV, manufacturers regard these tests as crude and believe they overestimate the toxic effects of the substances. They therefore repeat the tests using their finished products in order to obtain a less toxic label. (pdf)

Specific toxicology tests
The LD50 test involves giving the substance to two species to find out what dose kills half the test population: this dose is referred to as the LD50, or Lethal Dose, 50%. The oral LD50, where animals are force fed a substance, was phased out of the Organization for Economic Cooperation and Development's guidelines (test guideline 401) in December 2002. The inhaled and skin-application LD50 tests remain in the guideline. The UK banned the oral LD50 in 1999, but the inhaled and skin-application tests are still used, and the oral LD50 is still used by the Ministry of Defence. The oral LD50 is still widely used in the U.S.

The Draize test involves dropping the test substances into rabbits' eyes or rubbing it onto their shaved or abraded skin. In the eye test, the animal is observed for at least three days for signs of redness, swelling, discharge, ulceration, hemorrhaging, cloudiness or blindness, and is then killed.

Other tests include the:
 * 90-day repeat-dose test, administered by mouth, inhalation, or skin to 30-80 rats, rabbits, or guinea pigs;
 * 90-day-repeat-dose test by mouth in non-rodents, in which dogs are used;
 * teratogenicity test, which tests for the effects of a substance on a foetus, and involves at least 80 mice, rats, hamsters, or rabbits;
 * chronic toxicity test, which involves at least 160 rats, who are given daily doses of the substance for most of their lifespan;
 * carcinogenicity test, another lifetime study testing for cancer in 400-500 rodents;
 * one- and two-generation reproduction toxicity test, which involves more than 100 rats or mice;
 * test for embryonic genetic damage, which involves 10-60 rats, hamsters, mice and their offspring;
 * toxicokinetic study, which involves eight to ten animals to study the absorption, metabolism, distribution, and excretion of a substance. (pdf)

Testing cosmetics on animals
Cosmetics testing is particularly controversial. It is banned in the Netherlands, Belgium, and the UK (pdf), and in 2002, after 13 years of negotiations, the European Union agreed to ban cosmetic testing on animals in 2009, with a ban on products still tested on animals being introduced by 2014. News reports say France is the main reason behind the delays, with the French cosmetics industry allegedly exerting pressure on the government. 

Cosmetic testing on animals includes:


 * testing a finished product such as lipstick;
 * testing individual ingredients, or a combination of them;
 * Contracting a third-party company to perform any of the above;
 * Using a subsidiary or third-party company to perform the tests in countries where animal testing is not banned.

Some cosmetics companies claim that their products are not tested on animals, despite using one or more of the aforementioned practices.

Re-using existing test data obtained from previous animal testing is generally not considered to be cosmetic testing on animals; however, the acceptability of this to opponents of testing is inversely proportional to how recent the data is.

Due to the strong public backlash against cosmetic testing on animals, most cosmetic manufacturers say their products are not tested on animals. However, they are still required by trading standards and consumer protection laws in most countries to show their products are not toxic and dangerous to public health, and that the ingredients are not dangerous in large quantities, such as when in transport or in the manufacturing plant. In some countries, it is possible to meet these requirements without any further tests on animals. In other countries, it may require animal testing to meet legal requirements. The United States and Japan are frequently criticised for their insistence on stringent safety measures, which often requires animal testing, although the U.S. has also been a leader in developing cell culture alternatives.

Some retailers distinguish themselves in the marketplace by their stance on animal testing. The British Co-op maintains a cosmetic-testing website, which includes statements from all their suppliers about the extent of their animal testing. The Body Shop is also well-known for its campaigns against animal testing. 

Although the British Home Office stopped giving licences to test finished cosmetic products in 1998, compounds that have both cosmetic and medical uses, such as those in the "anti-wrinkle" preparations Zyderm, Restylane and Botox, are still bound by the regulations requiring animal testing. A raid on a laboratory in 2004 revealed that the LD50 test is still used on every batch of Botox (a toxin that, when administered intravenously, is lethal to humans) to establish potency.

While some cosmetics manufacturers have genuinely stopped all animal testing of their products, others continue to test. Companies that continue to perform cosmetic testing on animals may falsely claim that they do not do this in their advertising and on their products &mdash; or choose not to state either way.

Cosmetics manufacturers who genuinely do not test on animals generally use the following for safety testing of their products:
 * reliance on existing natural or synthetic ingredients, compounds and substances, which have already been extensively tested on animals;
 * avoiding novel ingredients or combinations of ingredients that have not been fully tested and may not be safe;
 * testing on human volunteers/clinical trials.

This presumes that cosmetics companies are already using computer modeling and cell cultures to simulate human tissue, two techniques that have had ambiguous utility in discovering problems early. Supporters of animal testing say that neither can fully replace live human or non-human animal tests.

Advocates of animal testing
Testing advocates argue that:
 * It would be unethical to test substances or drug with potentially adverse side-effects on human beings.
 * Controlled experiments involve introducing only one variable at a time, which is why animals are experimented on while confined inside a laboratory. Human beings could not be confined in this way.
 * There is no substitute for the living systems necessary to study interaction among cells, tissue, and organs. Animals are good surrogates because of their similarities to humans.
 * There is no substitute for psychiatric studies (e.g., antidepressant clinical trials) that require behavioral data.
 * Animals have shorter life and reproductive spans, meaning that several generations can be studied in a relatively short time.
 * Animals can be bred especially for animal-testing purposes, meaning they arrive at the laboratory free from disease.
 * Humans in some parts of the world are healthier in large part due to advances in medical research derived from animal testing.
 * Animals receive more sophisticated medical care because of animal tests that have led to advances in veterinary medicine.
 * There have been several examples of substances causing death or injury to human beings because of inadequate animal testing.

Opponents of animal testing
Opponents argue that:
 * The animal-testing industry is a multi-million dollar concern. Advocates of testing may argue that their interests are scientific, but they are just as often commercial.
 * Even with medical and non-commercial research, tests are often conducted to produce academic papers in order to acquire a Ph.D., academic tenure, or more funding, and not because the research is beneficial.
 * The suffering of the animals is excessive in relation to whatever benefits may be reaped. (pdf)
 * Animal-testing facilities are not properly regulated or inspected, and several undercover investigations by activist groups have uncovered evidence of animal abuse.
 * Animal testing is regarded by opponents as bad science because they believe:
 * Some animal models of disease are induced, and should not be compared to the same disease in humans. Activists claim Parkinson's disease in humans cannot be reproduced by causing brain damage in an animal, though genetic and toxin-mediated animal models are now widely used.
 * Some drugs have dangerous side-effects that were not predicted by animal models. Opponents often claim Thalidomide as an example of this is, although when tested on pregnant animals, birth defects are seen in mice, rats, hamsters, rabbits, macaques, marmosets, dogs, cats, fish, baboons and rhesus monkeys.
 * Some drugs appear to have different effects on human and non-human animals. Aspirin, for example, is a teratogen when given to animals in high doses, but there is conflicting evidence regarding its effect on human embryos.
 * The conditions in which the tests are carried out may undermine the results, because of the stress the environment produces in the animals. BUAV argues that the laboratory environment and the experiments themselves are capable of affecting every organ and biochemical function in the body. "Noise, restraint, isolation, pain, psychological distress, overcrowding, regrouping, separation from mothers, sleeplessness, hypersexuality, surgery and anaesthesia can all increase mortality, contact sensitivity, tumour susceptibility and metastatic spread, as well as decrease viral resistance and immune response."
 * Some opponents, particularly supporters of animal rights, argue further that, even if animal testing did reap benefits to human beings, these could not outweigh the suffering of the animals, and that human beings have no moral right to use individual animals in ways that do not benefit that individual.

Allegations of abuse


Undercover investigations by the British Union for the Abolition of Vivisection and People for the Ethical Treatment of Animals (PETA) have documented and filmed what appear to be examples of animal abuse in laboratories.

Huntingdon Life Sciences
PETA filmed staff inside a British laboratory owned by Huntingdon Life Sciences (HLS), Europe's largest animal-testing facility, punching puppies in the face, screaming at them, and simulating sex acts while taking blood samples. (video) The film was subsequently shown as "It's a Dog's Life" on Channel 4 television in the UK in 1997, as a result of which Stop Huntingdon Animal Cruelty was formed, an international campaign to close HLS. In the United States, HLS technicians were filmed screaming and laughing at monkeys, and appearing to dissect one that was still alive. (video)

Covance
BUAV filmed staff in Covance, Münster, Europe's largest primate-testing center, making monkeys dance in time to blaring pop music, handling them roughly, and screaming at them. The monkeys are kept isolated in small wire cages with little or no natural light, no environmental enrichment, and high noise levels from staff shouting and playing the radio.

Primatologist Dr. Jane Goodall described the living conditions of the monkeys as "horrendous," and told BUAV that to see them "crazed with boredom, and sadness probably, is deeply, deeply disturbing." Primatologist Stephen Brend told BUAV that using monkeys in such a stressed state is "bad science" and trying to extrapolate useful data in such circumstances is an "untenable proposition." (video) PETA found similar conditions in Covance's Vienna, Virginia lab during an undercover investigation in 2004-5. 

University of Cambridge
In February 2005, while applying for a judicial review of laboratory practices in the United Kingdom, BUAV told the High Court in London that internal documents from the University of Cambridge's primate-testing labs showed that monkeys had had the tops of their heads sawn off to induce a stroke, and were then left alone after the procedure for 15 hours overnight, with their brains exposed and no veterinary care, because staff only worked from nine to five.

The BUAV judicial challenge followed a 10-month undercover investigation by BUAV into three research programmes at Cambridge in 1998. BUAV's lawyer, David Thomas, told the court: "Cambridge staff work 9-5pm, so animals who had just been brain damaged were left overnight without veterinary attention. Some were found to be dead in the morning, some were found to be in a worse condition. Yet there is an obligation of licence holders to keep suffering to a minimum. The whole system is very secretive and the public does not get to see what is really going on." 

The Cambridge experiments involved the use of hundreds of macaque monkeys, who were deliberately brain damaged for pure- and applied-research purposes, in the interests of research into strokes and Parkinson's disease. The macaques were first of all trained to perform behavioral and cognitive tasks. Researchers then caused brain damage either by removing parts of the macaque's brains, or by injecting toxins. After this, the monkeys were re-tested to determine whether the damage had affected their skills. The macaques were deprived of food and water to encourage them to perform the tasks, both before and after the surgery, with water being withheld for 22 out of every 24 hours for the duration of the experiment, with intermittent respite. (video)

The Home Office investigated the BUAV report and the judge hearing BUAV's application for a judical review rejected the allegation that the Home Secretary had been negligent in granting the university a licence. 

The Research Defence Society, a lobby group representing 5,000 medical researchers and institutions in the UK, wrote a summmary of the case, including a description of the macaque research criticized by BUAV. It says: "In fact, for this research into stroke monkeys were fully anaesthetised, a piece of the skull bone was removed (in the same way as for human neurosurgery), one blood vessel was permanently blocked, the skull bone was replaced, the muscle and skin resewn and appropriate pain killers given. On recovery from anaesthesia, monkeys were kept in an incubator, offered food and water and monitored at regular intervals until the early evening. They were then allowed to sleep in the incubators until the next morning. No monkeys died unattended during the night after stroke surgery." 

University of California, Riverside


One of the best-known cases of alleged abuse involved Britches, a macaque monkey born in 1985 into a breeding colony at the University of California, Riverside, removed from his mother at birth, and left alone and tethered, with his eyelids sewn shut, as part of a sight-deprivation experiment. (video)

Britches was removed from the laboratory when he was five weeks old during a raid by the Animal Liberation Front, along with 700 other animals. The university criticized the ALF, claiming that damage to the monkey's eyelids, allegedly caused by the sutures, had in fact been caused by an ALF veterinarian who examined the monkey after the raid and wrote a report. The experiment was condemned by the American Council for the Blind (Newkirk 2000).

The photograph of Britches on the right is taken from a video made by the ALF during the raid, and later released as a short film by People for the Ethical Treatment of Animals. The university said that the monitoring device attached to the monkey's head had been tampered with by activists before the photograph was taken (ibid).

Columbia University
In 2003, according to CNN, a post-doctoral "whistleblowing" veterinarian at Columbia University approached the university's Institutional Animal Care and Use Committee about experiments being carried out by an assistant professor of neurosurgery, E. Sander Connolly. Connolly was allegedly causing an approximation of strokes in baboons by removing their left eyeballs and using the empty eye sockets to reach a critical blood vessel to their brains. A clamp was placed on this blood vessel until the stroke was induced, after which Connolly would attempt to treat the condition with an experimental drug. In a letter to the National Institutes of Health, PETA described one experiment: "On September 19, 2001, baboon B777's left eye was removed, and a stroke was induced. The next morning, it was noted that the animal could not sit up, that he was leaning over, and that he could not eat. That evening, the baboon was still slouched over and was offered food but couldn't chew. On September 21, 2001, the record shows that the baboon was 'awake, but no movement, can't eat (chew), vomited in the a.m.' With no further notation about consulting with a veterinarian, the record reads, 'At 1:30 p.m. the animal died in the cage.'"

In a letter to PETA, neurologist Robert S. Hoffman stated that he regards such experiments to be a "blind alley," and that the baboons are "kept alive for either three or ten days after experiencing a major stroke and in a condition of profound disability. This is obviously as terrifying for animals as it is for humans unless one believes that animals are incapable of terror or other emotional distress" (pdf).

Alternatives to animal testing
Most scientists and governments say they agree 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" are guiding principles for the use of animals in research in many countries:


 * Reduction refers to methods which enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
 * Replacement refers to the use of non-animal methods instead of animals to achieve a scientific aim.
 * Refinement refers to methods which alleviate or minimise potential pain, suffering or distress, and which enhance animal welfare, for those animals which still have to be used.

Animal welfare groups are divided in their position on the 'three Rs'; some support the principles while others accept replacement as the only valid action. There are a number of scientific studies and institutes  researching alternatives to animal tests. However, critics say these facilities perpetuate the myth that animal experiments are necessary for human health, and to reassure the public that steps are being taken to find alternatives. It is further stated these studies are funded with trivial amounts of money, but this view is contested by the UK pharmaceutical industry, which estimates more than £300 million (of a total UK R&D budget of £3285 million) is spent on 'three R' development and implementation annually (pdf).

The two major, widely accepted alternatives to animal testing under development are computer simulations and in vitro cell culture techniques. However, some claim they are not true alternatives since simulations use data from prior animal experiments and cultured cells often require animal derived products, such as serum. Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems. Examples of computer simulations available include models of diabetes, asthma , and drug absorption , though though potential new medicines identified using these techniques are currently still required to be verified in animal tests before licensing.

Cell culture is currently the most successful, and promising, alternative to animal use. For example, cultured cells have also been developed to create monoclonal antibodies, prior to this production required animals to undergo a procedure likely to cause pain and distress.

A third alternative now attracting considerable interest is so-called microdosing, in which the basic behaviour of drugs is assessed using human volunteers receiving doses well below those expected to produce whole-body effects (pdf).

Institutes researching (and organizations funding) alternatives to animal testing include:
 * The Johns Hopkins Center for Alternatives to Animal Testing
 * The University of California Center for Animal Alternatives
 * Dr Hadwen Trust
 * The Fund for the Replacement of Animals in Medical Experiments
 * The National Centre for Replacement, Refinement and Reduction of Animals in Research
 * The 3R Research Foundation