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Animal testing or animal research refers to the use of non-human animals in experiments. It is estimated that 50 to 100 million vertebrate animals worldwide — from zebrafish to non-human primates — are used annually and either killed during or after the experiments. Although much larger numbers of invertebrates are used, these experiments are largely unregulated in law and not included in yearly statistics. The research is carried out inside universities, medical schools, pharmaceutical companies, farms, defense-research establishments, and commercial facilities that provide animal-testing services to industry. Sources of laboratory animals vary between countries and species. While some species are purpose-bred, such as worms, flies, mice and rats, other animals may be caught in the wild or supplied by dealers who obtain them from auctions, pounds and other sources.
The Foundation for Biomedical Research, an American interest group supporting animal research, writes, "Animal research has played a vital role in virtually every major medical advance of the last century." Many major developments that led to Nobel Prizes involved research on vertebrates, including the development of penicillin (mice), organ transplant (dogs), and work on poliomyelitis that led to a vaccine (mice, monkeys).
The topic is controversial. Opponents argue that animal testing is cruel and unnecessary, poor scientific practice, never reliably predictive of human metabolic and physiological specificities, poorly regulated, that the costs outweigh the alleged benefits, or that animals have an intrinsic right not to be used for experimentation.
Additional recommended knowledge
The terms animal testing, animal experimentation, animal research, in vivo testing, and vivisection have similar denotations but different connotations. Literally, "vivisection" means the "cutting up" of a living animal, and historically referred only to experiments that involved the dissection of live animals. The term is now used by some to refer to any experiment using living animals; for example, the Encyclopaedia Britannica defines "vivisection" as: "Operation on a living animal for experimental rather than healing purposes; more broadly, all experimentation on live animals." For others, the word has a pejorative connotation, implying torture and suffering. The word "vivisection" is preferred by those who oppose scientific animal testing, whereas scientists typically use the term "animal experimentation."
The earliest references to animal testing are found in the writings of the Greeks in the second and fourth centuries BCE. Aristotle (Αριστοτέλης) (384-322 BCE) and Erasistratus (304-258 BCE) were 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."
Animals have played a role in numerous well-known experiments. In the 1880s, Louis Pasteur convincingly demonstrated the germ theory of medicine by giving anthrax to sheep. In the 1890s, Ivan Pavlov famously used dogs to describe classical conditioning. Insulin was first isolated from dogs in 1922, and revolutionized the treatment of diabetes. On November 3, 1957 a Russian dog, Laika, became the first of many animals to orbit the earth. In the 1970s, leprosy multi-drug antibiotic treatments were developed first in armadillos, then in humans. In 1996 Dolly the sheep was born, the first mammal to be cloned from an adult cell.
As the experimentation on animals increased, especially the practice of vivisection, so did criticism and controversy. In 1655, physiologist Edmund O'Meara is recorded as saying that "the miserable torture of vivisection places the body in an unnatural state." O'Meara and others argued that animal physiology could be affected by the pain and suffering of vivisection, rendering the results unreliable. There were also objections on an ethical basis, contending that the benefit to humans did not justify the harm to animals. Early objections to animal testing also came from another angle — many people believed that animals are inferior to humans and thus so different that any results obtained from animals would be inapplicable to humans.
On the other side of the debate, those in favor of animal testing held that experiments on living animals were necessary to advance medical and biological knowledge. Claude Bernard, known as the "prince of vivisectors" and the father of physiology, 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". Arguing that "experiments on animals ... are entirely conclusive for the toxicology and hygiene of man ... for as I have shown, the effects of these substances are the same on man as on animals, save for differences in degree," Bernard established the paradigm of animal experimentation in scientific method that is largely followed by the scientific community today. Bernard's wife, Marie Françoise Martin, was a fervent anti-vivisectionist, and in 1883 founded the first anti-vivisection society in France.
In 1822, the first animal protection law was enacted in the British parliament, followed by the 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 real 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."
The growing division between the pro- and anti- animal testing factions first came to dramatic public attention during the Brown Dog riots that raged in the early 1900s in the streets of London, when hundreds of medical students clashed with anti-vivisectionists and police over a memorial to a vivisected dog.
Accurate global figures for animal testing are difficult to obtain. The British Union for the Abolition of Vivisection (BUAV) estimates that 100 million vertebrates are experimented on around the world every year, 10–11 million of them in the European Union. The Nuffield Council on Bioethics reports that estimates range from 50 to 100 million animals used annually worldwide, not counting invertebrates. 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 (USDA), the total number of animals used in that country in 2005 was almost 1.2 million, not including rats, mice, and birds, which jointly make up 85% of research animals, and not including invertebrates. Animals are not counted if they live at breeder sites that do not perform research. The Laboratory Primate Advocacy Group has used the USDA's figures to estimate that 23-25 million vertebrate animals are used in research each year in America.  In 1986, a report produced by 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.
In the UK, Home Office figures show that nearly three million procedures were carried out in 2004 on just under the same number of animals. It is the third consecutive annual rise and the highest figure since 1992. Most animals are used in only one procedure: animals either die because of the experiment or are euthanized afterwards. A "procedure" refers to an experiment that might last minutes, several months, or years.
Although much larger numbers of invertebrates than vertebrates are used, these experiments are largely unregulated in law and are not included in statistics. The most used invertebrate species are Drosophila melanogaster, a fruit fly, and Caenorhabditis elegans, a nematode. In the case of C. elegans, the precise lineage of all the organism's cells is known, and D. melanogaster is well-suited to genetic studies. These animals offer great advantages over vertebrates, including their short life cycle and the ease with which large numbers may be studied, with thousands of flies or nematodes fitting into a single room. However, the lack of an adaptive immune system and their simple organs prevents worms from being used in medical research, such as vaccine development. Similarly, flies are not widely used in applied medical research, as their immune system differs greatly from that of humans, and diseases in insects can be very different from diseases in more complex animals.
In the U.S., the numbers of rats and mice used is estimated at 15-20 million a year. 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. Mice are widely considered to be the best model of inherited human disease and share 99% of their genes with humans. With the advent of genetic engineering technology, genetically modified mice can be generated to order and can cost hundreds of dollars each.
Nearly 200,000 fish and 20,000 amphibians were used in the UK in 2004. The main species used is the zebrafish, Danio rerio, which are translucent during their embryonic stage, and the African clawed frog, Xenopus laevis. Over 20,000 rabbits were used for animal testing in the UK in 2004. Albino rabbits are used in eye irritancy tests because rabbits have less tear flow than other animals, and the lack of eye pigment make the effects easier to visualize.
Cats are most commonly used in neurological research. Over 25,500 cats were used in the U.S. in 2000, around half of whom were used in experiments that caused "pain and/or distress".
Dogs are widely used in biomedical research, testing, and education — particularly beagles, because they are gentle and easy to handle. They are commonly used as models for human diseases in cardiology, endocrinology, and bone and joint studies, research that tends to be highly invasive, according to the Humane Society of the United States. The U.S. Department of Agriculture's Animal Welfare Report for 2004 shows that nearly 65,000 dogs were used in USDA-registered facilities in that year. In the U.S., some of the dogs are purpose-bred, while most are supplied by so-called Class B dealers licensed by the USDA to buy animals from auctions, shelters, newspaper ads, and who are sometimes accused of stealing pets.
Non-human primates (NHPs) are used in toxicology tests, studies of AIDS and hepatitis, studies of neurology, behavior and cognition, reproduction, genetics, and xenotransplantation. They are caught in the wild, taken from zoos, circuses and animal trainers, or purpose-bred. The primates used in the USA, China, and Europe are mostly purpose-bred. In the U.S. and China, most primates are domestically purpose-bred, whereas in Europe the majority are imported purpose-bred. Rhesus monkeys, cynomolgus monkeys, squirrel monkeys, and owl monkeys are imported; around 12,000 to 15,000 monkeys are imported into the U.S. annually. Around 65,000 NHPs are used each year in the United States and European Union. Most of the NHPs used are macaques; but marmosets, spider monkeys, and squirrel monkeys are also used, and baboons and chimpanzees are used in the U.S; there are currently 1133 chimpanzees in U.S. research laboratories. Notable studies on non-human primates have been part of the polio vaccine development, and development of Deep Brain Stimulation, and their current heaviest non-toxicological use occurs in the monkey AIDS model, SIV. 
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. For vertebrates, sources include breeders who supply purpose-bred animals; businesses that trade in wild animals; and dealers who supply animals sourced from pounds, auctions, and newspaper ads. Animal shelters also supply the laboratories directly. Large centers also exist to distribute strains of genetically-modified animals; particularly important is the National Institutes of Health Knockout Mouse Project that aims to provide knockout mice for every gene in the mouse genome.
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. 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. The USDA recovered at least a dozen stolen pets during a raid on a Class B dealer in Arkansas in 2003.
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.
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. In the UK, most animals used in experiments are bred for the purpose under the 1988 Animal Protection Act, but wild-caught primates may be used if exceptional and specific justification can be established. The United States also allows the use of wild-caught primates; between 1995 and 1999, 1,580 wild baboons were imported into the U.S. Over half the primates imported between 1995 and 2000 were handled by Charles River Laboratories, Inc. — former owners of Shamrock Farm in the UK — and Covance, the single largest importer of primates in the U.S. and the world's largest breeder of laboratory dogs.
Basic or pure research investigates how organisms behave, develop, and function. Those opposed to animal testing object that pure research may have little or no practical purpose, but researchers argue that it may produce unforeseen benefits, rendering the distinction between pure and applied research — research that has a specific practical aim — unclear.
Pure research uses larger numbers and a greater variety of animals than applied research. Fruit flies, nematode worms, mice and rats together account for the vast majority, though small numbers of other species are used, ranging from sea slugs through to armadillos. In the UK in 2005, 89 macaques, 114 marmosets, 133 dogs and 237 cats were used in basic research to investigate topics such as social behavior, vision, nutrition and suckling.
Examples of the types of animals and experiments used in basic research include:
Applied research aims to solve specific and practical problems, often relating to the treatment or cure of disease and disorder in humans and animals.
Compared to pure research, which is largely academic in origin, applied research is usually carried out in the pharmaceutical industry, or by universities in commercial partnerships. These may involve the use of animal models of diseases or conditions, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the drug discovery process. Examples include:
Xenotransplantation involves transplanting living cells, tissues, or organs from one species to another. Current research involves using primates as the recipients of pig's organs. The British Home Office released figures in 1999 showing that 270 monkeys had been used in xeno research in the UK during the previous four years. Documents leaked from Huntingdon Life Sciences to The Observer in 2003 showed, between 1994 and 2000, wild baboons were imported to the UK from Africa to be used in experiments that involved grafting pigs' hearts and kidneys onto the primates' necks, abdomens, and chests. The Observer reports that some baboons died after suffering strokes, vomiting, diarrhea, and paralysis, while others died en route to the UK. The experiments were conducted by Imutran Ltd, a subsidiary of Novartis Pharma AG in conjunction with Cambridge University and Huntingdon Life Sciences.
The newspaper also wrote that researchers were deliberately underestimating the suffering in order to obtain licences. A report from Imutran said: "The Home Office will attempt to get the kidney transplants classified as 'moderate,' ensuring that it is easier for Imutran to receive a licence and ignoring the 'severe' nature of these programmes." In its defense, Novartis told the newspaper that developing new cures for humans invariably means experimenting on live animals. 
Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities, such as Huntingdon Life Sciences, on behalf of a wide variety of customers.  Nature reports that around one million animals are used every year in Europe in toxicology tests; 5,000 animals are used for each chemical, with 12,000 needed to test pesticides. The tests are conducted without anesthesia, because interactions between drugs can affect how animals detoxify chemicals, interfering with the results.
Toxicology tests examine finished products such as pesticides, medications, food additives, packing materials, and air freshener, or their chemical ingredients. Most tests involve testing ingredients rather than finished products, but according to BUAV, manufacturers believe these tests overestimate the toxic effects of substances; they therefore repeat the tests using their finished products to obtain a less toxic label.  (pdf)
The substances are applied to the skin or dripped into the 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, through a tube into the stomach, or simply in the animal's food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal. Examples of toxicology tests include the LD50 test (Lethal Dose 50%), which involves administering a chemical to an animal population to determine what dose will kill 50 percent of the test subjects, and the Draize test, in which small amounts of a substance are applied to an animal's eye or skin.
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.
These toxicity tests provide, in the words of a 2006 United States National Academy of Sciences report, "critical information for assessing hazard and risk potential". However, as Nature reported, most animal tests either over- or underestimate risk, or or do not reflect toxicity in humans particularly well. This variability stems from using the effects of high doses of chemicals in small numbers of laboratory animals to try to predict the effects of low doses in large numbers of humans. Although relationships do exist, opinion is divided on how to use data on one species to predict the exact level of risk in another.
Cosmetics testing on animals is particularly controversial. Such tests, which are still conducted in the U.S., involve general toxicity, eye and skin irritancy, phototoxicity (toxicity triggered by ultraviolet light) and mutagenicity.  (pdf)
Cosmetics testing is banned in the Netherlands, Belgium, and the UK, and in 2002, after 13 years of discussion, the European Union (EU) agreed to phase in a near-total ban on the sale of animal-tested cosmetics throughout the EU from 2009, and to ban all cosmetics-related animal testing. France, which is home to the world's largest cosmetics company, L'Oreal, has protested the proposed ban by lodging a case at the European Court of Justice in Luxembourg, asking that the ban be quashed. The ban is also opposed by the European Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland, Belgium, France, Germany and Italy.
Before the early 20th century, laws regulating drugs were lax. For example, in the US the government could only ban a drug after a company had been prosecuted for selling products that harmed customers. However, in response to a tragedy where a drug labeled “Elixir of Sulfanilamide” killed 73 people, the US congress passed laws that required safety testing of drugs, before they could be marketed. Nowadays all new pharmaceuticals undergo rigorous animal testing before being licensed for human use. Tests on pharmaceutical products involve:
Education and breeding
Animals are also used for education and training, and are bred for use in laboratories.
Animals are used by the military to develop weapons, vaccines, battlefield surgical techniques, and defensive clothing.
Levels of suffering
The extent to which animal testing causes suffering, and the capacity of animals to experience and comprehend it, is the subject of much debate. The International Association for the Study of Pain calls pain "an unpleasant sensory and emotional experience associated with actual or potential tissue damage". Suffering is harder to define. Marian Stamp Dawkins defines it as broadly "experiencing one of a wide range of extremely unpleasant subjective (mental) states."
The USDA defines a "painful procedure" as one that would "reasonably be expected to cause more than slight or momentary pain or distress in a human being to which that procedure was applied." Alicia Karas of Tufts University School of Veterinary Medicine writes that pain is unnecessary in most experiments, but there is evidence that unalleviated pain is a problem for some laboratory animals.
The 1990 Assessment and Control of the Severity of Scientific Procedures on Laboratory Animals, to "aid communication between all those concerned with the use and welfare of laboratory animals", presents a detailed severity index metric for the operational assessing and controlling of pain and distress in laboratory animal procedures based on numerically assigned evaluations of the following considerations: consciousness, anesthesia, preparation, restraint, duration, tissue sensitivity, organ risk, mortality, pain, distress, deprivation, and frequency. Operational control of severity considerations include: management practices, psychosocial influences, disease, objective measurement and record keeping, training, procedure design practices, basic husbandry considerations, and planning for emergency and humane end-points for each procedure.
In the U.S. in 2004, over 600,000 animals (not including rats, mice, bird, or invertebrates) were used in procedures that did not include more than momentary pain or distress, according to their Animal Care Committees. Nearly 400,000 were used in procedures in which pain or distress was relieved by anesthesia, while 87,000 were used in studies in which researchers planned to cause pain or distress that would not be relieved.
In the UK, research projects are classified as mild, moderate, and substantial in terms of the suffering they may cause. The fourth category of "unclassified" is for experiments where the animal is anaesthetized and killed without recovering consciousness. In December 2001, 39 percent (1,296) of project licences in force were classified as mild, 55 percent (1,811) as moderate, two percent (63) as substantial, and 4 percent (139) as unclassified.
Allegations of abuse
In 1997, People for the Ethical Treatment of Animals (PETA) filmed staff inside Huntingdon Life Sciences (HLS) in the UK, Europe's largest animal-testing facility, hitting puppies, shouting at them, and simulating sex acts while taking blood samples. The employees were dismissed and prosecuted, and HLS's licence to perform animal experiments was revoked for six months. Footage shot inside HLS in the U.S. appeared to show technicians dissecting a live monkey. (video) The broadcast of the undercover footage on British television in 1997 triggered the formation of Stop Huntingdon Animal Cruelty, an international campaign to close HLS, which has been criticized for its sometimes violent tactics.
In 2004, German journalist Friedrich Mülln shot undercover footage of 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 were 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 (video). Primatologist Dr. Jane Goodall described the living conditions of the monkeys as "horrendous." 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 an "untenable proposition." Covance obtained a restraining order preventing Mülln from performing any further undercover research against the company for three years, and required him and PETA to turn over the material they obtained from Covance. PETA is further prevented from attempting to infiltrate Covance for five years. 
In February 2005, the British Union for the Abolition of Vivisection (BUAV) told the High Court in London that internal documents from the University of Cambridge's primate-testing labs showed that monkeys had undergone surgery to induce a stroke, and were left alone after the procedure for 15 hours overnight.   Researchers had trained the monkeys to perform certain tasks before inflicting brain damage and re-testing them. The monkeys were deprived of food and water to encourage them to perform the tasks.   (video) The judge hearing BUAV's application for a judicial review rejected the allegation that the Home Secretary had been negligent in granting the university a license.  
One of the best-known cases of alleged abuse involved Britches, a macaque monkey born in 1985 at the University of California, Riverside, removed from his mother at birth, and left alone with his eyelids sewn shut, and a sonar device on his head, as part of a sight-deprivation experiment. He was removed from the laboratory during a raid by the Animal Liberation Front. The university criticized the ALF, alleging that damage to the monkey's eyelids, image caused by the sutures according to the ALF, had in fact been caused by an ALF veterinarian, and that the sutures and sonar device had been tampered with by the activists.
CNN reported in October 2003 that 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 strokes in baboons by removing their left eyeballs and using the eye sockets to reach a critical blood vessel to their brains. A clamp was placed on the blood vessel until the stroke was induced, after which Connolly would try to treat the condition with an experimental drug. In a letter to the National Institute of Health, PETA cited the case of one baboon left for two days unable to sit up or eat, who was slouched over in his cage and vomiting before dying. An investigation by the United States Department of Agriculture found the experiments did not violate federal guidelines. Connolly abandoned the research saying he felt under attack after receiving a threatening e-mail, but continued to believe his experiments were humane and potentially valuable.
Threats to researchers
In 2006, a primate researcher at the University of California, Los Angeles (UCLA) shut down the experiments in his lab after threats from animal rights activists. The researcher had received a grant to used 30 macaque monkeys for vision experiments; each monkey was paralyzed, then used for a single session that lasted up to 120 hours, and finally killed. The researcher's name, phone number, and address were posted on the website of the Primate Freedom Project. Demonstrations were held in front of his home. A Molotov cocktail was placed on the porch of what was believed to be the home of another UCLA primate researcher; instead, it was accidentally left on the porch of an elderly woman unrelated to the university. The Animal Liberation Front claimed responsibility for the attack.   As a result of the campaign, the researcher sent an email to the Primate Freedom Project stating "you win," and "please don’t bother my family anymore."  In another incident at UCLA in June 2007, the Animal Liberation Brigade placed a bomb under the car of a UCLA children's ophthalmologist who experiments on cats and rhesus monkeys; the bomb had a faulty fuse and did not detonate.  UCLA is now refusing Freedom of Information Act requests for animal medical records.
Alternatives to animal testing
Most scientists and governments 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 most countries:
Although such principles have been welcomed as a step forwards by some animal welfare groups, they have also been criticized as both outdated by current research, and of little practical effect in improving animal welfare.
While historically many animals were used for medical education, there are efforts in many countries to find suitable alternatives. Horst Spielmann, German director of the Central Office for Collecting and Assessing Altrnatives to Animal Experimentation (ZEBET), while describing Germany's progress in this area, told German broadcaster ARD in 2005: "Using animals in teaching curricula is already superfluous. In many countries, one can become a doctor, vet or biologist without ever having performed an experiment on an animal."
Further reading and external links
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Animal_testing". A list of authors is available in Wikipedia.|