Animal testing

File:NASAchimp.jpg

Enos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961. Non-human primates make up 0.3 percent of research animals, with 55,000 used each year in the U.S. and 10,000 in the European Union.

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Animal testing or animal research refers to the use of 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 the experiments or subsequently euthanized. 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. The vast majority of laboratory animals are bred for research purposes, while a small number are caught in the wild or supplied by pounds.

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 unnecessary, poor scientific practice, poorly regulated, that the costs outweigh the benefits, or that animals have an intrinsic right not to be used for experimentation.

History

Main article: History of animal testing

One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in his muzzle. Pavlov Museum, 2005

File:An Experiment on a Bird in an Air Pump by Joseph Wright of Derby, 1768.jpg

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 Greeks in the second and fourth centuries BC. Aristotle (Αριστοτέλης) (384-322 BC) and Erasistratus (304-258 BC) 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.

Regulation

Europe

Experiments on vertebrate animals in the European Union are subject to Directive 86/609/EEC on the protection of Animals used for Experimental and other Scientific purposes, adopted in 1986. There is considerable variation in the manner member countries choose to exercise the directive: compare, for example, legislation from Sweden, The Netherlands, and Germany.

• France

In France, legislation (principally the decree of October 19, 1987) requires an institutional and project licence before testing on vertebrates may be carried out. An institution must submit details of their facilities and the reason for the use of animals 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 license holder. These regulations do not apply to research using invertebrates.

• United Kingdom

See also: Animal Procedures Committee and Animals (Scientific Procedures) Act 1986

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Technician assessing the health status of transgenic mice in a UK laboratory, 2000. Provided by RDS/Wellcome Trust Photographic Library

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%).

The Animals (Scientific Procedures) Act 1986 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 certificate for the institution to ensure it has adequate facilities and staff; 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)). [12]

During a 2002 House of Lords select committee inquiry into animal testing in the UK, witnesses stated 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. [13] There are 29 qualified inspectors covering 230 establishments, which are visited on average 11-12 times a year. [14]

A report by Animal Aid alleges that the Animals (Scientific Procedures) Act 1986 is a "vivisectors' charter," allowing researchers to do as they please and making them practically immune from prosecution. The report says that licences to perform experiments are obtained on the basis of a "nod of approval" from the Home Office Inspectorate, and that the Home Office relies on the researchers' own opinions of the cost-benefit assessment regarding the value of the experiment versus the amount of suffering it will cause.

Japan

The system in Japan is one of self-regulation. Animal experiments are regulated by the 2000 Law for the Humane Treatment and Management of Animals, which was amended in 2006. This law requires those using animals to use as few animals as possible, and cause minimal distress and suffering. Regulation is at a local level based on national guidelines, but there are no governmental inspections of institutions and no reporting requirement for the numbers of animals used. A 1988 survey published by the Japanese Association for Laboratory Animal Science reported that eight million had been used that year.

United States

In the United States, animal testing on vertebrates is primarily regulated by the 1966 Animal Welfare Act (AWA), which is enforced by the Animal Care division of the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA). The AWA contains provisions to ensure that individuals of covered species used in research receive a certain standard of care and treatment, provided that the standard of care and treatment does not interfere with "the design, outlines, or guidelines of actual research or experimentation." Currently, AWA only protects mammals. In 2002, the Farm Security Act of 2002, the fifth amendment to the AWA, specifically excluded purpose-bred birds, rats, and mice (as opposed to wild-captured mice, rats, and birds) from regulations. Thus, relatively few animals used in research in the U.S. are covered by this legislation.[15] The AWA requires each institution using covered species to maintain an Institutional Animal Care and Use Committee (IACUC), which is responsible for local compliance with the Act.

Institutional Animal Care and Use Committees are of central importance to the application of laws concerning animal care and use in research in the United States. Research suggests that the IACUC system is unreliable. In 2001, the results of a study that evaluated the reliability of IACUCs found little consistency between decisions made by IACUCs at different institutions. A Wesleyan University press release summarized part of the findings:

The investigation, which took three years to complete, compared judgments made by 50 randomly selected animal care and use committees drawn from U.S. colleges and universities. To assess the consistency of approval decisions, 150 recent research proposals from these institutions were each independently evaluated by two different animal care and use committees.

The results showed that approval decisions were statistically unrelated. In most cases, proposals that were disapproved by one committee were approved by the second committee.

The study also explored whether reviews were more reliable when the experiment involved certain types of animals or procedures. For example, reliability was assessed for proposals that involved dogs, cats, and primates, or for experiments involving drugs, surgery, animal pain, or death. Even in these cases, independent reviews did not agree beyond chance levels.

In response to the Plous article, a rebuttal letter to Science written by animal researchers, animal care staff, and members of professional research societies wrote:

That the masked protocols would be rated more negatively was predictable for the following reasons. First, IACUCs rely on knowing the experience of the investigators and staff, information that was not included for the unofficial IACUCs. Not surprisingly, most of the negative shifts (84 of 118) were to categories calling for more information. Second, withholding approval had no practical consequence. Third, participants might have felt scrutinized by researchers with an "animal rights" agenda, and erred on the side of deferral or rejection. Fourth, navigating another institution's forms can be difficult. And fifth, IACUCs unfamiliar with particular species or procedures are less likely to understand a protocol. These factors make it almost impossible to compare the actions of the original and unofficial IACUCs and thus call into question the major premises and conclusions of this study.

Institutions are also subject to unannounced annual inspections from USDA APHIS Veterinarian inspectors. There are about 70 inspectors monitoring around 1100 research institutions. The inspectors also conduct pre-licensing checks for sites that do not engage in animal research or transportation, of which more than 4000 exist (e.g. dog kennels).

APHIS has been criticized by its own inspectors and the USDA Inspector General's office (OIG). Marshall Smith, an APHIS inspector for twelve years, resigned in 1997 recounting a litany of problems at the agency that impeded his duties. In a prepared statement, Smith made note of a 1992 OIG report citing the agency's inability to ensure the humane care of animals at dealers. In 2000, Isis Johnson-Brown D.V.M. - another APHIS inspector - quit because of problems she documented at the Oregon National Primate Research Center, in Beaverton, Oregon. In a prepared statement Dr. Johnson said, "More than once, I was instructed by a supervisor to make a personal list of violations of the law, cut that list in half, and then cut that list in half again before writing up my inspection reports. My willingness to uphold the law during my site visits at the Primate Center led to me being 'retrained' several times by higher-ups in the USDA. In 2005, the USDA OIG issued another report on APHIS:

Of particular concern, AC management in the Eastern Region is not aggressively pursuing enforcement actions against violators of the AWA. The Eastern Region significantly reduced its referrals of suspected violators to the Investigative and Enforcement Services (IES) unit—from an average of 209 cases in fiscal years (FYs) 2002-2003 to 82 cases in FY 2004. When the region did refer cases to IES, management declined to take enforcement action against 126 of 475 violators (27 percent).

When violators are assessed stipulated fines, the fines are usually minimal and not always effective in preventing subsequent violations. Under current APHIS policy, AC gives an automatic 75-percent discount to almost all violators as a means of amicably reaching an agreement on the amount of the fines and avoiding court.

Finally, we noted that some VMOs when inspecting research facilities do not verify the number of animals used in medical research or adequately review the facilities’ protocols and other records.

Another regulatory instrument is the Public Health Service (PHS) 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[16] published by the Institute for Laboratory Animal Research,[17] which includes all vertebrate species in its care protocols, including rodents and birds[18] (Introduction, p.1). In 2004, the National Institutes of Health provided funds to 3,180 different research institutions and universities.[19] This means that IACUCs oversee the use of all vertebrate species in research at facilities receiving federal funds, even if the species are not covered by the AWA. OLAW does not carry out scheduled inspections, but requires that "As a condition of receipt of PHS support for research involving laboratory animals, awardee institutions must provide a written Animal Welfare Assurance of Compliance (Assurance) to OLAW describing the means they will employ to comply with the PHS Policy." OLAW conducts inspections only when there is a suspected or alleged violation that cannot be resolved through written correspondence. Accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), a non-governmental, nonprofit association, is regarded by the industry as the "gold standard" of accreditation. Accreditation is maintained through a prearranged AAALAC site visit and program evaluation hosted by the member institution once every three years. Accreditation is intended to ensure compliance with the standards in the Guide for the Care and Use of Laboratory Animals, as well as any other national or local laws on animal welfare.

Animals used

Accurate global figures for animal testing are difficult to obtain. 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 The Nuffield Council on Bioethics reports that estimates range from 50 to 100 million vertebrate animals used annually worldwide. 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 2005 was 1,177,566. The USDA's animal usage reporting has been challenged by Stop Animal Exploitation Now, an animal rights group. For example, 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 animals are used in research each year in America. [20] In 1986, a report produced by the U.S. Congress Office of Technology Assessment reported that "estimates of the animals used in the United States each year range from 10 million to upwards of 100 million," and that their own best estimate was "at least 17 million to 22 million."

In the UK, Home Office figures show that 2,854,944 procedures were carried out in 2004 on 2,778,692 vertebrate animals.

As the figures show, 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 less than a day, several months, or years.

Pain, distress, and anesthesia

In the U.S. in 2004, 615,000 vertebrate animals (not including rats and mice) were used in procedures that did not include more than momentary pain or distress, according to their Animal Care Committees. Around 399,000 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.

Over half the procedures in Britain in 2004 — 1,710,760 — either did not require anesthetic (e.g. behavioral tests, breeding stock, controlled dietary intake) or anesthesia was not used because the researchers said it would interfere with the results. Of the procedures for which no anesthetic was used in the UK, 880,897 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 procedures involved the use of psychological stress.

Species

Listed in descending order of numbers of individual animals used:

• Invertebrates

File:Drosophila melanogaster - front (aka).jpg

Drosophila are one of the most widely used species for experimentation.

Main article: Animal testing on invertebrates

Although much larger numbers of invertebrates than vertebrates are used, these experiments are largely unregulated in law and are not included in yearly 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 scientists great advantages over using vertebrates, including their short life cycle and the ease with which large numbers of individuals may be studied. Invertebrates are often extremely cost-effective, as thousands of flies or nematodes can be housed in a single room.

• Rodents

Main article: Animal testing on rodents

A white Wistar lab rat.

Rodents commonly used include guinea pigs, hamsters, gerbils, rats and mice. Mice are the most commonly used vertebrate species and are popular because of their small 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. In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents were used (84.5% of the total animals used that year). In 2005, the total number of rodents used was similar to the previous year: 1,955,035 mice, 414,335 rats and 40,856 other rodents. In the U.S., the numbers of rats and mice used are not reported, but have been estimated at 15-20 million.

• Fish and amphibians

In the UK, 194,562 fish and 18,195 amphibians were used in 2004. In 2005, the number of fish used increased to 230,315 while the number of amphibians used decreased to 13,318. The major species utilized are the zebrafish, Danio rerio, which are translucent during their embryonic stage, and the African clawed frog, Xenopus laevis.

• Rabbits

See also: Draize test

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. They are also used in skin irritancy tests called the Draize test.

• Dogs

See also: Laika and Russian space dogs

Beagles are used, largely 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. Of the 8,018 dogs used in the UK in 2004, 7,799 were beagles (97.3%). Most dogs are bred specifically for the purpose, for example by Harlan in Leicestershire.

• Non-human primates

File:AnimaltestingMonkeyCovance2.jpg

Covance primate-testing lab, Vienna, Virginia, 2004-5.

Main article: Animal testing on non-human primates

Non-human primates (NHPs) are used in toxicology tests, 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. 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 around 1,500 chimpanzees in U.S. research laboratories.

• Cats

Felines are most commonly used in neurological research. In the UK in 2005, 308 cats were used. This is a decrease from 819 cats recorded in 2004 [21]. According to the USDA, over 25,500 felines were used in the USA in 2000, of these around half were reported to have been used in experiments that caused "pain and/or distress". [22]

Types of experiment

Experiments can be split into three broad, overlapping categories: pure research, in which experiments are conducted that have no direct commercial application, with a view to advancing knowledge, most often inside universities; applied research, conducted in order to solve specific biological problems or to develop commercial products, either for medical or non-medical use; and toxicology or safety testing, in which commercial products are tested on animals to measure potential adverse biological reactions to the ingredients.

Pure research

Basic or pure research aims to increase knowledge about the way organisms behave, develop, and function biologically.

Both the largest number and greatest variety of laboratory animals are used 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 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 behaviour, vision, nutrition and suckling.

Examples of the types of animals and experiments used in basic research include:

• Mutagenesis to study mechanisms in embryogenesis and developmental biology. Mutants are usually created by treatment with radiation, or transposons are inserted into their genomes. By studying the changes in development that occur in these mutants, scientists aim to understand both how organisms develop normally and what can go wrong in this process. The 1995 and 2002 Nobel Prizes in Physiology or Medicine were awarded for research into developmental processes in flies and worms using forward genetic screens. [23] [24] Embryos used in experiments are often not covered by legislation and are not always required to be reported.

• 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, [25] taste, [26] hearing, [27] touch, [28] and smell. [29] In addition studies of brain function, such as memory and social behaviour, often use rats and birds. [30] Less common is the use of larger mammals in these types of studies. Not all behavioral studies require invasive methods or even laboratories: some behavioural research is conducted in wildlife sanctuaries, zoos and other free-range situations. For some intelligent species, behavioural research is seen as enrichment for animals in captivity because it allows them to engage in a wider range of activities.

• Breeding experiments to study evolution and genetics. Laboratory mice, flies, fish and worms are inbred through many generations to create strains with defined characteristics. [31] [32] 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. [33] Scientists studying mechanisms of evolution use a number of animal species, including mosquitos, [34] sticklebacks, [35] cichlids, [36] and lampreys, [37] due to their niche physiology, morphology, ecology, or phylogeny.

Applied research

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 programmes are more likely to be carried out in the pharmaceutical industry, or in universities in commercial partnership. These may involve the use of animal models of disease or condition, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the modern drug discovery process. Examples of animal use in this type of research include:

• Genetic modification of animals to study disease. Transgenic animals have specific genes inserted, modified or removed, with the aim of modelling a specific condition. The aim of these models may be to exactly mimic a known single gene disorder, such as Duchenne muscular dystrophy or albinism, then use the model to investigate novel ways it may be treated. Other models are generated to approximate complex, multifactorial disease with a genetic component, such as cancer or Alzheimer's disease, then investigate how and why the disease develops. The vast majority of transgenic models of disease are mice [38], the mammalian species in which genetic modification is most efficient, though there are smaller numbers of other animals such as rats, sheep and pigs [39]. Pharmaceutical companies [40], medical research institutes [41], politicians [42], scientists [43] and professional research bodies widely endorse these techniques, describing an "explosion of research on such disease models" [44] resulting in "an increasingly important role in the discovery and development of new medicines" [45]. However, animal rights and welfare groups regularly question the value and effectiveness of transgenic techniques, [46] [47] as animals do not always model human diseases accurately [48] or in their entirety. [49] [50] Genetic engineering pressure group, GeneWatch UK, call genetic modification "highly inefficient, wasteful of animal lives" and calls for "balancing the needs of people for drugs with the welfare and integrity of animal species." [51]

• Studies on models of naturally occurring disease and condition. Certain domestic and wild animals have a natural propensity or predisposition for certain conditions that are also found in humans. Cats, for example are used as a model to develop immunodeficiency virus vaccines due to their natural predisposition to FIV infection [52]. Their infection with a related feline virus, FeLV, makes cats a common model for leukemia research also. [53] Certain breeds of dog suffer from narcolepsy [54] making them the major model used to study the human condition. Armadillos and humans are among only a few animal species that naturally suffer from leprosy [55]. As it cannot yet be grown in culture, armadillos are the primary source of bacilli used in leprosy vaccines. [56] Non human primates, being closely related to humans, are applied in the study of a number of human conditions, including visual disorders [57] [58] and dental disease [59]. Primates are also used extensively in immunology [60] and reproductive studies [61] [62], a synthesis of which resulted in the discovery of the Rhesus factor and its importance in hemolytic disease of the newborn.

Xenotransplantation

Main article: Xenotransplantation

Xenotransplantation involves transplanting living cells, tissues, or organs from one species to another. Current research involves primarily using primates as the recipient of pig hearts. The U.S. FDA has written that the research is "driven by the fact that the demand for human organs for clinical transplantation far exceeds the supply." [63] 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. In 1999, three baboons and 79 cynomolgus monkeys were used.

Medical journalists Jenny Bryan and John Clare have called xenotransplatation experiments "some of the most grisly procedures carried out anywhere in the name of science." They write that: "They do sometimes involve a full transplant of a genetically modified pig heart into a monkey. In some cases, however, the doctors will graft the transgenic hearts onto a baboon's neck arteries, as this allows them to observe the way the pig heart behaves in another species, and monitor the rejection process. The operation is carried out under general anaesthetic and the baboon is humanely killed afterwards. These measures, however, do not pacify animal rights campaigners, who say the experiments are cruel and unnecessary."

Drug testing

File:Dogs6CCcopy.jpg

Dogs used for safety testing of pharmaceuticals in a UK facility, 2000. Provided by RDS/Wellcome Trust Photographic Library [11]

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 Template:PDFlink (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" Template:PDFlink (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.

Cosmetics testing

File:NoAnimalTesting.gif

Products in Europe not tested on animals carry this symbol.

Main article: Testing cosmetics on animals

Cosmetics testing is particularly controversial. It 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. [64] 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.

Controversy

File:It'sADog'sLife.gif

Clip from undercover footage filmed in 1997 by PETA inside Huntingdon Life Sciences in the UK. The footage showed staff punching and screaming at beagles.

Huntingdon Life Sciences

Main article: Stop Huntingdon Animal Cruelty

In 1997, People for the Ethical Treatment of Animals (PETA) filmed staff inside a British laboratory owned by Huntingdon Life Sciences (HLS), 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) HLS obtained a restraining order that prohibited PETA from distributing the footage, although other sources are free to publish it. 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.

Covance

Main article: Covance

File:Covance Undercover 1.jpeg

Image by Friedrich Mülln

In 2004, German journalist Friedrich Mülln was hired as a BUAV operative to shoot 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). A lawsuit by Covance placed an injunction on Mülln from distributing the footage he shot; the same material remains accessible on the web at sites outside jurisdiction of the court. [65]

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." PETA stated they found similar conditions in Covance's Vienna, Virginia lab during an undercover investigation in 2004-5. [66] Covance sued PETA and their undercover operative as a result of the Vienna operation, and obtained a restraining order preventing the operative from performing any further undercover work for three years, and forced PETA and their operative to turn over all materials they obtained documenting conditions at Covance. PETA is further prevented from attempting to infiltrate Covance for five years. [67]

University of Cambridge

Main article: Primate experiments at Cambridge University

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 undergone surgery to induce a stroke, and were then left alone after the procedure for 15 hours overnight, with no veterinary care, because staff only worked from nine to five. [68] 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: "The whole system is very secretive and the public does not get to see what is really going on." [69]

The experiments involved the use of hundreds of macaque monkeys, who were deliberately brain damaged for the purpose of research into strokes and Parkinson's disease. The macaques were first 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. The monkeys were then re-tested to determine how the damage had affected their skills. They were deprived of food and water to encourage them to perform the tasks, with water being withheld for 22 out of every 24 hours. [70] [71] (video)

The Home Office investigated the BUAV report and 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. [72] [73] The Research Defence Society, a lobby group representing 5,000 medical researchers and institutions in the UK, wrote in a summary of the case: "[F]or 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." [74]

University of California, Riverside

File:Eyesewn.jpg

Britches, as the Animal Liberation Front say they found him.

Main article: Britches (monkey)

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.

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, [75] 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.

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 PETA. The university said that the monitoring device attached to the monkey's head had been tampered with by activists before the photograph was taken.

Columbia University

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. [76] 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.'" [77]

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" Template:PDFlink.

A USDA investigation of the Columbia baboons found "no indication that the experiments...violated federal guidelines." Further, the Dean of Research at Columbia's School of Medicine noted that Connolly stopped the experiments because of threats from animal rights activists, despite the fact that Connolly "remained convinced that his experiments were humane and potentially valuable."

University of California, Los Angeles

In 2006, animal rights activists forced a primate researcher at UCLA to shut down the experiments in his lab. The researcher's name, phone number, and address were posted on the website of the UCLA Primate Freedom Project, along with a description of his research, which stated that he had "received a grant to kill 30 macaque monkeys for vision experiments. Each monkey is first paralyzed, then used for a single session that lasts up to 120 hours, and finally killed." [78] Demonstrations were held in front of the professor's 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. [79][80] 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." [81] 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

Main article: 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" [82] are guiding principles for the use of animals in research in many countries:

• Reduction 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.
• Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
• Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.

The arguments in brief

Advocates of animal testing

Testing advocates argue that:

• It would be unethical to test substances or drugs with potentially adverse side-effects on human beings. [83]
• Controlled experiments involve introducing only one variable at a time, which is why animals used for experiments are housed in laboratory settings. In contrast, human environments and genetic backgrounds vary widely, which makes it difficult to control important variables. [84]
• 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. [85]
• There is no substitute for psychiatric studies (e.g., antidepressant clinical trials) that require behavioral data.
• There is no substitute for studies of the infection of a host. For example, infection with hepatitis, malaria or treatment with monoclonal antibodies all have unique advantages in chimpanzees.
• Some animals (e.g. Drosophila) have shorter life and reproductive spans than humans, meaning that several generations can be studied in a relatively shorter time.
• Animals can be bred especially for animal-testing purposes, meaning they arrive at the laboratory free from disease.
• Drugs and vaccines produced through animal testing are vital to modern medicine. [86]
• Animals receive more sophisticated medical care because of animal tests that have led to advances in veterinary medicine. [87]
• There have been several examples of substances causing death or injury to human beings because of inadequate animal testing. [88]
• Activists manipulate and fabricate facts, therefore their claims are not reliable.
• Alternatives to certain kinds of animal testing are unknown.
• Over 10 times more animals are used by humans for other purposes (agriculture, hunting, pest control) than are used in animal testing. 100 million animals are killed by hunting each year. [89] 150 million large mammals are used in agriculture each year. [90] Hundreds of millions of rats are involved in pest control. [91] [92] Over seven million dogs and cats are euthanized by animal shelters each year, and a million animals are killed each day by automobiles. [93]

Governmental and medical group statements

The U.S. Congress held a series of hearings in 1985 on animal research. In it, they heard testimony from veterinarians, doctors, scientists, and animal rights activists including Alex Pacheco. They wrote a summary of their findings on animal research into the law commonly called the Animal Welfare Act. They wrote

(1) the use of animals is instrumental in certain research and education for advancing knowledge of cures and treatment for diseases and injuries which afflict both humans and animals;

(2) methods of testing that do not use animals are being and continue to be developed which are faster, less expensive, and more accurate than traditional animal experiments for some purposes and further opportunities exist for the development of these methods of testing;

(3) measures which eliminate or minimize the unnecessary duplication of experiments on animals can result in more productive use of Federal funds; and

(4) measures which help meet the public concern for laboratory animal care and treatment are important in assuring that research will continue to progress.

The American Medical Association, the largest US group composed exclusively of physicians and medical students, has an official policy statement on the use of animals in research, HR-460.932 that states

Our AMA: (1) supports providing educational materials on the appropriate and compassionate use of animals in biomedical research to students of all grades from kindergarten through grade 12; (2) encourages physicians to work actively in their communities to introduce educational materials on the appropriate and compassionate use of animals in biomedical research into the curricula of all grades from kindergarten through grade 12; and (3) continues to oppose the use of violence, intimidation, and distortion by the opponents of the appropriate and compassionate use of animals in biomedical research.

The American Veterinary Medical Association is authorized voice for the US veterinary profession in presenting its views to concerned publics. It has an official policy statement on the use of animals in research.

The AVMA recognizes that animals play a central and essential role in research, testing, and education for continued improvement in the health and welfare of human beings and animals. The AVMA also recognizes that humane care of animals used in research, testing, and education is an integral part of those activities. In keeping with these concerns, the AVMA endorses the principles embodied in the "Three R" tenet of Russell and Burch (1959). These principles are: refinement of experimental methods to eliminate or reduce animal pain and distress; reduction of the number of animals consistent with sound experimental design; and replacement of animals with non-animal methods wherever feasible.

The AVMA condemns all acts of vandalism against researchers and research facilities. Such acts make it more difficult for responsible individuals and groups to work for continued improvement in research animal care and treatment.

The use of animals is a privilege carrying with it unique professional, scientific, and moral obligations. The AVMA encourages proper stewardship of animals, but defends and promotes the use of animals in meaningful research, testing, and education programs.

One moral basis for animal testing was summarized by a British House of Lords report in 2002: "the whole institution of morality, society and law is founded on the belief that human beings are unique amongst animals. Humans are therefore morally entitled to use animals, whether in the laboratory, the farmyard or the house, for their own purposes." Some researchers also believe animals may suffer less throughout the testing process than human beings would because they have a reduced capacity to remember and anticipate pain. The House of Lords report further made the following statement about research experiments using animals "There is at present a continued need for animal experiments both in applied research, and in research aimed purely at extending knowledge."

Opponents of animal testing

Opponents argue that:

• The suffering of the animals is excessive in relation to whatever benefits may be reaped. Some opponents, particularly supporters of animal rights, argue further that any benefits to human beings cannot 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.
• In practice, there is widespread abuse of animals.
• Animals do not consent to being tested upon.
• Animal testing is bad science because:
  1. Many animal models of disease are induced and cannot be compared to the human disease. For example, although genetic [94] and toxin-mediated animal models are now widely used to model Parkinson's disease, the British anti-vivisection interest group BUAV argues that these models only superficially resemble the disease symptoms, without the same time course or cellular pathology.
  2. Some drugs have dangerous side-effects that were not predicted by animal models. Thalidomide is often used as an example of this, although the harmful effects of this drug are also seen in animals.
  3. Some drugs appear to have different effects on human and other species.
  4. The conditions in which the tests are carried out may undermine the results, because of the stress the environment produces in the animals. BUAV argue 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." [95]
  5. The most vocal proponents of animal testing have vested interests in maintaining the practice. [96]

See also

• Americans For Medical Advancement
• Animal liberation movement
• Boyd Group
• Human experimentation
• Nafovanny
• Non-human primate experiments
• The People's Petition
• Vivisection
• Earthlings (documentary)
• Rat Park

External links

• 1940 American/Soviet Film of Dog Resurrection Experiments

Further reading

• Anderson, R.C. & Anderson, J.H. "Toxic effects of air freshener emissions," Arch Environ Health, Volume 52, Issue 6:433-41, 1997. PMID 9541364
• Bryan, Jenny & Clare, John. Organ Farm. Carlton, 2001.
• Cohen BJ and Loew FM (1984). Laboratory Animal Medicine: Historical Perspectives in Laboratory Animal Medicine. Edited by J.G. Fox, B.J. Cohen and F.M. Loew. Academic Press, Inc., Orlando, Florida.
• Croce, Pietro (2000). Vivisection Or Science? : An Investigation into Testing Drugs and Safeguarding Health, Zed Books, ISBN 1-85649-733-X
• Jha, Alok. "RSPCA outrage as experiments on animals rise to 2.85m", The Guardian, December 9, 2005.
• Laville, Sandra. "Lab monkeys 'scream with fear' in tests", The Guardian, February 8, 2005
• Newkirk, Ingrid (2000). Free the Animals: The Story of the Animal Liberation Front. Lantern Books, ISBN 1-930051-22-0
• Regan, Tom. "Empty cages: Animal rights and vivisection", retrieved October 22, 2005
• Ruesch, Hans (1989) 1000 Doctors (and many more) Against Vivisection Civis: London
• Sharpe, Robert. Extracts from Science of Trial: The Human Cost of Animal Experiments, 1994, retrieved October 22, 2005
• Stephens, Martin & Rowan, Andrew. Template:PDFlink, Humane Society of the United States, retrieved October 29, 2005

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• "Select Committee on Animals In Scientific Procedures Report", Select Committee on Animals in Scientific Procedures, British House of Lords, July 16, 2002, retrieved October 27, 2005.
• "UK Animal Experiments Statistics 2003", British Union for the Abolition of Vivisection factsheet, retrieved October 28, 2005; based on figures from "2003 Home Office Statistics of Scientific Procedures on Living Animals," The Stationery Office, London.
• Template:PDFlink, British Union for the Abolition of Vivisection.
• "Covance Uncovered", 2004
• Template:PDFlink Great Britain, 2004.
• "Medical Milestones" Americans for Medical Progress, retrieved October 25, 2005.
• "Why use animals?" and other FAQ, North Carolina Association for Biomedical Research, retrieved October 23, 2005
• "Benefits to animals", Americans for Medical Progress, retrieved October 23, 2005.
• "The benefits of animal research", Seriously Ill for Medical Research], retrieved October 23, 2005.
• "Basic statement", Aërzte gegen Tierversuche (Doctors against Animal Experiments], retrieved October 23, 2005.
• Template:PDFlink.
• "Biomed for the layperson", Laboratory Primate Advocacy Group, retrieved February 24, 2006.
• "Testing on apes 'might be needed'", BBC News, June 3, 2006.
• "An introduction to primate issues", Humane Society of the United States.
• "Unhappy Anniversary: Twenty years of the Animals (Scientific Procedures) Act 1986", Animal Aid, retrieved July 15, 2006.

Organizations

• National Anti-Vivisection Society
• Perspectives on Medical Research
• In Focus "Animal Experiments in Research" (German Reference Centre for Ethics in the Life Sciences)
• Dr Hadwen Trust for Humane Research
• New test procedure replaces skin provoking tests with rabbits
• Brute Ethics: animal ethics encyclopedia
• Europeans for Medical Progress
• BUAV (British Union for the Abolition of Vivisection)
• American Association for Laboratory Animal Science
• Encyclopedia of Earth: Animal testing alternatives
• Carter-Long, Lawrence. "Life Without Mother," Mainstream, Volume 28, No. 4, Winter 1997
• Slater, Lauren. "Monkey love", The Boston Globe, March 21, 2004
• "Research Defence Society", a website that argues that animal experiments are humane and essential to human health
• Foundation for Biomedical Research, information about animals in research
• "Vivisection - Absurd", a website that argues that animal experiments are cruel and unscientific
• Open Directory Project - Animal Experiments directory category
• Yahoo! - Animal Experimentation directory category
• Americans for Medical Progress
• "Planet of Covance", a German film opposing animal testing
• "Tod im Labor" a film made by Animal Aid and Ärzte gegen Tierversuche (Doctors against Animal Experiments)
• "Survey of NIH-funded investigators who use nonhuman primates: Report of survey findings". National Center for Research Resources (NCRR), Bethesda, Maryland, 2002.
• Barry Yeoman, Can We Trust Research Done with Lab Mice? Discover magazine.
• 3rd World Congress on Alternatives and Animal Use in the Life Sciences
• Animal Welfare Gateway, a collection of international links related to laboratory animals
• Convention on International Trade in Endangered Species (CITES)
• European College of Laboratory Animal Medicine
• European Society of Laboratory Animal Veterinarians
• International Council for Laboratory Animal Science (ICLAS)
• International Foundation for Science
• International Primatological Society
• International Society for Animal Genetics
• International Veterinary Information Service
• International Veterinary Students Association
• World Veterinary Association
• Animal Liberation Through Trade Unions?
• Pro-test UK
• Patients Voice for Medical Advance
• Biomedical Research Education Trust
• European Biomedical Research Association
• Incurably Ill for Animal Research
• The American Physiological Society
• Patient Advocates Against PETA
• States United for Biomedical Research
• American Psychological Society
• Society of Toxicology
• FASEB
• Massachusetts Society for Medical Research
• California Biomedical Research Association
• Michigan Society for Medical Research
• National Science Teacher Association
• Ohio Scientific Education & Research Association
• Defending Our Relationship With Animals

Further Reading

Conn, P. Michael and Parker, James V (2007). The Animal Research War, Palgrave Macmillan, ISBN 978-0230600140