Animal testingFrom Wikipedia, the free encyclopedia (Redirected from Lab animal)Jump to: navigation, search          Anima...
breeding, and defense research. The practice is regulated to various degrees in differentcountries.Supporters of the use o...
DefinitionsThe terms animal testing, animal experimentation, animal research, in vivo testing, andvivisection have similar...
Toxicology testing became important in the 20th century. In the 19th century, laws regulatingdrugs were more relaxed. For ...
folly, which is the handmaiden of crime.‘ ‖[34] These divisions between pro- and anti- animaltesting groups first came to ...
raises what he calls a "red flag of special concern."[40] A study published in Science magazinein July 2001 confirmed the ...
down 240 from 2006.[53] A "procedure" refers to an experiment that might last minutes,several months, or years. Most anima...
This rat is being deprived of restful REM sleep by a researcher using a single platform("flower pot") technique. The water...
Around 65,000 primates are used each year in the U.S. and Europe.Non-human primates (NHPs) are used in toxicology tests, s...
A laboratory mouse cage. Mice are either bred commercially, or raised in the laboratory.In the U.S., Class A breeders are ...
Prior to vivisection for educational purposes, chloroform was administered to this commonsand frog to induce terminal anes...
The defining text on animal welfare regulation, "Guide for the Care and Use of LaboratoryAnimals" defines the parameters t...
Research classificationPure researchBasic or pure research investigates how organisms behave, develop, and function. Those...
Genetic modification of animals to study disease. Transgenic animals have specific       genes inserted, modified or remov...
and Huntingdon Life Sciences, to be used in experiments that involved grafting pig tissues,suffered serious and sometimes ...
the animal killed if it shows "continuing signs of severe pain or distress".[138] The HumaneSociety of the United States w...
Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland,Belgium, France, Germany and Italy.[148...
There are efforts in many countries to find alternatives to using animals in education.[152]Horst Spielmann, German direct...
Although these arguments have not been widely accepted, governments such as theNetherlands and New Zealand have responded ...
In 1997, People for the Ethical Treatment of Animals filmed staff inside Huntingdon LifeSciences (HLS) in the UK, Europes ...
BUAVs application for a judicial review rejected the allegation that the Home Secretary hadbeen negligent in granting the ...
In 2006, a primate researcher at the University of California, Los Angeles (UCLA) shut downthe experiments in his lab afte...
Animal testingFrom Wikipedia, the free encyclopediaEnos the space chimp before insertion into the Mercury-Atlas 5 capsule ...
1History2Modern Regulation     2.1Europe     2.2Japan     2.3United States3Animals used     3.1Species4Types of experiment...
One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in hismuzzle. Pavlov Museum, 2005       M...
EuropeExperiments on vertebrate animals in the European Union are subject toDirective 86/609/EEC on the protection of Anim...
deciding whether to grant a licence, the Home Office refers to the Acts cost-benefit analysis, which is defined as "the li...
captured mice, rats, and birds) from regulations.[31] Thus, relatively fewanimals used in research in the U.S. are covered...
Animal Research,[32] which includes all vertebrate species in its careprotocols, including rodents and birds[33] (Introduc...
around 60 million.[45] In 2004, the Department of Agriculture listed 64,932dogs, 23,640 cats, 54,998 non-human primates, 2...
Drosophila are one of the most widely used animals for experimentationListed in descending order of numbers of individual ...
In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodentswere used (84.5% of the total animals used that ye...
In 1957, Laika became the first animal to be launched into space, paving the wayfor human spaceflight.Beagles are used, be...
Most of the NHPs used are macaques, accounting for 79% of all primatesused in research in the UK, and 63% of all primate r...
electrodes to record from or stimulate the brain, and temporary or permanentinactivation of areas of tissue.In 1996, the B...
Experiments can be split into three broad,                     AMPAAAS                                                    ...
and rats are all widely used in research into mechanisms of vision, [51]   taste, [52] hearing, [53] touch, [54] and smell...
smaller numbers of other animals such as rats, sheep and pigs [65]. Pharmaceutical companies [66], medical research instit...
the fact that the demand for human organs for clinical transplantation farexceeds the supply. Currently ten patients die e...
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  1. 1. Animal testingFrom Wikipedia, the free encyclopedia (Redirected from Lab animal)Jump to: navigation, search Animal testing A white Wistar lab rat Description Around 50–100 million vertebrate animals are used in experiments annually. Subjects Animal testing, science, medicine, animal welfare, animal rights, ethics.Animal testing, also known as animal experimentation, animal research, and in vivotesting, is the use of non-human animals in experiments. Worldwide it is estimated that thenumber of vertebrate animals—from zebrafish to non-human primates—ranges from the tensof millions to more than 100 million used annually.[1]Invertebrates, mice, rats, birds, fish,frogs, and animals not yet weaned are not included in the figures; one estimate of mice andrats used in the United States alone in 2001 was 80 million.[2] Most animals are euthanizedafter being used in an experiment.[3]Sources of laboratory animals vary between countries andspecies; most animals are purpose-bred, while others are caught in the wild or supplied bydealers who obtain them from auctions and pounds.[4]The research is conducted inside universities, medical schools, pharmaceutical companies,farms, defense establishments, and commercial facilities that provide animal-testing servicesto industry.[5] It includes pure research such as genetics, developmental biology, behavioralstudies, as well as applied research such as biomedical research, xenotransplantation, drugtesting and toxicology tests, including cosmetics testing. Animals are also used for education,
  2. 2. breeding, and defense research. The practice is regulated to various degrees in differentcountries.Supporters of the use of animals in experiments, such as the British Royal Society, argue thatvirtually every medical achievement in the 20th century relied on the use of animals in someway,[6] with the Institute for Laboratory Animal Research of the U.S. National Academy ofSciences arguing that even sophisticated computers are unable to model interactions betweenmolecules, cells, tissues, organs, organisms, and the environment, making animal researchnecessary in many areas.[7] A number of scientists, animal welfare, and animal rightsorganizations—such as PETA and BUAV—question the legitimacy of it, arguing that it iscruel, poor scientific practice, poorly regulated, that medical progress is being held back bymisleading animal models, that some of the tests are outdated, that it cannot reliably predicteffects in humans, that the costs outweigh the benefits, or that animals have an intrinsic rightnot to be used for experimentation.[8]Contents[hide] 1 Definitions 2 History o 2.1 Historical debate 3 Care and use of animals o 3.1 Regulations o 3.2 Numbers o 3.3 Species  3.3.1 Invertebrates  3.3.2 Vertebrates o 3.4 Sources o 3.5 Pain and suffering o 3.6 Euthanasia 4 Research classification o 4.1 Pure research o 4.2 Applied research  4.2.1 Xenotransplantation o 4.3 Toxicology testing  4.3.1 Cosmetics testing o 4.4 Drug testing o 4.5 Education, breeding, and defense 5 Ethics o 5.1 Background o 5.2 Prominent cases o 5.3 Threats to researchers 6 Alternatives to animal testing 7 See also 8 Notes 9 Further reading and external links
  3. 3. DefinitionsThe terms animal testing, animal experimentation, animal research, in vivo testing, andvivisection have similar denotations but different connotations. Literally, "vivisection" meansthe "cutting up" of a living animal, and historically referred only to experiments that involvedthe dissection of live animals. The term is occasionally used to refer pejoratively to anyexperiment using living animals; for example, the Encyclopædia Britannica defines"vivisection" as: "Operation on a living animal for experimental rather than healing purposes;more broadly, all experimentation on live animals",[9] although dictionaries point out that thebroader definition is "used only by people who are opposed to such work".[10] The word has anegative connotation, implying torture, suffering, and death.[11] The word "vivisection" ispreferred by those opposed to this research, whereas scientists typically use the term "animalexperimentation".[12][13]HistoryMain article: History of animal testingAn Experiment on a Bird in an Air Pump, from 1768, by Joseph WrightThe earliest references to animal testing are found in the writings of the Greeks in the 2ndand 4th centuries BCE. Aristotle (Αριστοτέλης) (384–322 BCE) and Erasistratus (304–258BCE) were among the first to perform experiments on living animals.[14]Galen, a physician in2nd-century Rome, dissected pigs and goats, and is known as the "father ofvivisection."[15]Avenzoar, an Arabic physician in 12th-century Moorish Spain who alsopracticed dissection, introduced animal testing as an experimental method of testing surgicalprocedures before applying them to human patients.[16][17]Animals have been used repeatedly through the history of biomedical research. In the 1880s,Louis Pasteur convincingly demonstrated the germ theory of medicine by inducing anthrax insheep.[18] In the 1890s, Ivan Pavlov famously used dogs to describe classicalconditioning.[19]Insulin was first isolated from dogs in 1922, and revolutionized the treatmentof diabetes.[20] On November 3, 1957, a Russian dog, Laika, became the first of many animalsto orbit the earth. In the 1970s, antibiotic treatments and vaccines for leprosy were developedusing armadillos,[21] then given to humans.[22] The ability of humans to change the genetics ofanimals took a large step forwards in 1974 when Rudolf Jaenisch was able to produce thefirst transgenic mammal, by integrating DNA from the SV40 virus into the genome ofmice.[23] This genetic research progressed rapidly and, in 1996, Dolly the sheep was born, thefirst mammal to be cloned from an adult cell.[24]
  4. 4. Toxicology testing became important in the 20th century. In the 19th century, laws regulatingdrugs were more relaxed. For example, in the U.S., the government could only ban a drugafter a company had been prosecuted for selling products that harmed customers. However,in response to the Elixir Sulfanilamide disaster of 1937 in which the eponymous drug killedmore than 100 users, the U.S. congress passed laws that required safety testing of drugs onanimals before they could be marketed. Other countries enacted similar legislation.[25] In the1960s, in reaction to the Thalidomide tragedy, further laws were passed requiring safetytesting on pregnant animals before a drug can be sold.[26]Historical debateClaude Bernard, regarded as the "prince of vivisectors"[27] argued that experiments onanimals are "entirely conclusive for the toxicology and hygiene of man".[28]As the experimentation on animals increased, especially the practice of vivisection, so didcriticism and controversy. In 1655, the advocate of Galenic physiology Edmund OMearasaid that "the miserable torture of vivisection places the body in an unnatural state."[29][30]OMeara and others argued that animal physiology could be affected by pain duringvivisection, rendering results unreliable. There were also objections on an ethical basis,contending that the benefit to humans did not justify the harm to animals.[30] Early objectionsto animal testing also came from another angle — many people believed that animals wereinferior to humans and so different that results from animals could not be applied tohumans.[30]On the other side of the debate, those in favor of animal testing held that experiments onanimals were necessary to advance medical and biological knowledge. Claude Bernard,known as the "prince of vivisectors"[27] and the father of physiology—whose wife, MarieFrançoise Martin, founded the first anti-vivisection society in France in 1883[31]—famouslywrote in 1865 that "the science of life is a superb and dazzlingly lighted hall which may bereached only by passing through a long and ghastly kitchen".[32] Arguing that "experimentson animals ... are entirely conclusive for the toxicology and hygiene of man...the effects ofthese substances are the same on man as on animals, save for differences in degree,"[28]Bernard established animal experimentation as part of the standard scientific method.[33]In 1896, the physiologist and physician Dr. Walter B. Cannon said ―The antivivisectionistsare the second of the two types Theodore Roosevelt described when he said, ‗Common sensewithout conscience may lead to crime, but conscience without common sense may lead to
  5. 5. folly, which is the handmaiden of crime.‘ ‖[34] These divisions between pro- and anti- animaltesting groups first came to public attention during the brown dog affair in the early 1900s,when hundreds of medical students clashed with anti-vivisectionists and police over amemorial to a vivisected dog.[35]One of Pavlov‘s dogs with a saliva-catch container and tube surgically implanted in hismuzzle, Pavlov Museum, 2005In 1822, the first animal protection law was enacted in the British parliament, followed by theCruelty 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 March1871: "You ask about my opinion on vivisection. I quite agree that it is justifiable for realinvestigations on physiology; but not for mere damnable and detestable curiosity. It is asubject which makes me sick with horror, so I will not say another word about it, else I shallnot sleep to-night."[36][37] Opposition to the use of animals in medical research first arose inthe United States during the 1860s, when Henry Bergh founded the American Society for thePrevention of Cruelty to Animals (ASPCA), with Americas first specifically anti-vivisectionorganization being the American AntiVivisection Society (AAVS), founded in 1883.Antivivisectionists of the era generally believed the spread of mercy was the great cause ofcivilization, and vivisection was cruel. However, in the USA the antivivisectionists effortswere defeated in every legislature, overwhelmed by the superior organization and influenceof the medical community. Overall, this movement had little legislative success until thepassing of the Laboratory Animal Welfare Act, in 1966.[38]Care and use of animalsSee also: Animal testing regulations, Institutional Animal Care and Use Committee, andAnimals (Scientific Procedures) Act 1986RegulationsThe regulations that apply to animals in laboratories vary across species. In the U.S., underthe provisions of the Animal Welfare Act and the Guide for the Care and Use of LaboratoryAnimals (the Guide), published by the National Academy of Sciences, any procedure can beperformed on an animal if it can be successfully argued that it is scientifically justified. Ingeneral, researchers are required to consult with the institutions veterinarian and itsInstitutional Animal Care and Use Committee (IACUC), which every research facility isobliged to maintain.[39] The IACUC must ensure that alternatives, including non-animalalternatives, have been considered, that the experiments are not unnecessarily duplicative,and that pain relief is given unless it would interfere with the study. Larry Carbone, alaboratory animal veterinarian, writes that, in his experience, IACUCs take their work veryseriously regardless of the species involved, though the use of non-human primates always
  6. 6. raises what he calls a "red flag of special concern."[40] A study published in Science magazinein July 2001 confirmed the low reliability of IACUC reviews of animal experiments. Fundedby the National Science Foundation, the three-year study found that animal-use committeesthat do not know the specifics of the university and personnel do not make the same approvaldecisions as those made by animal-use committees that do know the university and personnel.Specifically, blinded committees more often ask for more information rather than approvingstudies.[41]The IACUCs regulate all vertebrates in testing at institutions receiving federal funds in theUSA. Although the provisions of the Animal Welfare Act do not include purpose-bredrodents and birds, these species are equally regulated under Public Health Service policiesthat govern the IACUCs.[42][43] Animal Welfare Act regulations are enforced by the USDA,whereas Public Health Service regulations are enforced by OLAW and in many cases byAAALAC.NumbersTypes of vertebrates used in animal testing in Europe in 2005: a total of 12.1 million animalswere used.[44]Accurate global figures for animal testing are difficult to obtain. The British Union for theAbolition of Vivisection (BUAV) estimates that 100 million vertebrates are experimented onaround the world every year, 10–11 million of them in the European Union.[45] The NuffieldCouncil on Bioethics reports that global annual estimates range from 50 to 100 millionanimals. None of the figures include invertebrates such as shrimp and fruit flies.[46] Animalsbred for research then killed as surplus, animals used for breeding purposes, and animals notyet weaned are also not included in the figures.[47]According to the U.S. Department of Agriculture (USDA), the total number of animals usedin that country in 2005 was almost 1.2 million,[48] but this does not include rats and mice,which make up about 90% of research animals.[49][50] In 1995, researchers at Tufts UniversityCenter for Animals and Public Policy estimated that 14–21 million animals were used inAmerican laboratories in 1992, a reduction from a high of 50 million used in 1970.[51] In1986, the U.S. Congress Office of Technology Assessment reported that estimates of theanimals used in the U.S. range from 10 million to upwards of 100 million each year, and thattheir own best estimate was at least 17 million to 22 million.[52]In the UK, Home Office figures show that 3.2 million procedures were carried out in 2007, arise of 189,500 since the previous year. Four thousand procedures used non-human primates,
  7. 7. down 240 from 2006.[53] A "procedure" refers to an experiment that might last minutes,several months, or years. Most animals are used in only one procedure: animals either diebecause of the experiment or are euthanized afterwards.[46]SpeciesInvertebratesFruit flies are commonly used.Main article: Animal testing on invertebratesAlthough many more invertebrates than vertebrates are used, these experiments are largelyunregulated by law. The most used invertebrate species are Drosophila melanogaster, a fruitfly, and Caenorhabditiselegans, a nematode worm. In the case of C. elegans, the wormsbody is completely transparent and the precise lineage of all the organisms cells is known,[54]while studies in the fly D. melanogaster can use an amazing array of genetic tools.[55] Theseanimals offer great advantages over vertebrates, including their short life cycle and the easewith which large numbers may be studied, with thousands of flies or nematodes fitting into asingle room. However, the lack of an adaptive immune system and their simple organsprevent worms from being used in medical research such as vaccine development.[56]Similarly, flies are not widely used in applied medical research, as their immune systemdiffers greatly from that of humans,[57] and diseases in insects can be very different fromdiseases in vertebrates.[58]VertebratesEnos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961Further information: Animal testing on frogs, Animal testing on rabbits, Animal testing onrodents, Draize test, and Median lethal dose
  8. 8. This rat is being deprived of restful REM sleep by a researcher using a single platform("flower pot") technique. The water is within 1 cm of the small flower pot bottom platformwhere the rat sits. At the onset of REM sleep, the rat would either fall into the water only toclamber back to its pot to avoid drowning, or its nose would become submerged into thewater shocking it back to an awakened state.In the U.S., the numbers of rats and mice used is estimated at 20 million a year.[50] Otherrodents commonly used are guinea pigs, hamsters, and gerbils. Mice are the most commonlyused vertebrate species because of their size, low cost, ease of handling, and fast reproductionrate.[59] Mice are widely considered to be the best model of inherited human disease and share99% of their genes with humans.[59] With the advent of genetic engineering technology,genetically modified mice can be generated to order and can provide models for a range ofhuman diseases.[59] Rats are also widely used for physiology, toxicology and cancer research,but genetic manipulation is much harder in rats than in mice, which limits the use of theserodents in basic science.[60]Nearly 200,000 fish and 20,000 amphibians were used in the UK in 2004.[61] The mainspecies used is the zebrafish, Daniorerio, which are translucent during their embryonic stage,and the African clawed frog, Xenopuslaevis. Over 20,000 rabbits were used for animal testingin the UK in 2004.[61]Albino rabbits are used in eye irritancy tests because rabbits have lesstear flow than other animals, and the lack of eye pigment in albinos make the effects easier tovisualize.[61] Rabbits are also frequently used for the production of polyclonal antibodies.Cats and dogsSee also: Laika and Russian space dogsCats are most commonly used in neurological research. Over 25,500 cats were used in theU.S. in 2000, around half of whom were used in experiments which, according to theAmerican Anti-Vivisection Society, had the potential to cause "pain and/or distress".[62]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 humandiseases in cardiology, endocrinology, and bone and joint studies, research that tends to behighly invasive, according to the Humane Society of the United States.[63] The U.S.Department of Agricultures Animal Welfare Report for 2005 shows that 66,000 dogs wereused in USDA-registered facilities in that year.[48] 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 buyanimals from auctions, shelters, newspaper ads, and who are sometimes accused of stealingpets.[64]Non-human primatesMain article: Animal testing on non-human primates
  9. 9. Around 65,000 primates are used each year in the U.S. and Europe.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 or purpose-bred. In the U.S. and China, most primates aredomestically purpose-bred, whereas in Europe the majority are imported purpose-bred.[65]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.[66] In total, around70,000 NHPs are used each year in the United States and European Union.[44][48] Most of theNHPs used are macaques;[67] but marmosets, spider monkeys, and squirrel monkeys are alsoused, and baboons and chimpanzees are used in the U.S; in 2006 there were 1133chimpanzees in U.S. primate centers.[68] The first transgenic primate was produced in 2001,with the development of a method that could introduce new genes into a rhesus macaque.[69]This transgenic technology is now being applied in the search for a treatment for the geneticdisorderHuntingtons disease.[70] Notable studies on non-human primates have been part ofthe polio vaccine development, and development of Deep Brain Stimulation, and their currentheaviest non-toxicological use occurs in the monkey AIDS model, SIV.[6][67][71] In 2008 aproposal to ban all primates experiments in the EU has sparked a vigorous debate.[72]SourcesMain articles: Laboratory animal sources and International trade in primatesAnimals used by laboratories are largely supplied by specialist dealers. Sources differ forvertebrate and invertebrate animals. Most laboratories breed and raise flies and wormsthemselves, using strains and mutants supplied from a few main stock centers.[73] Forvertebrates, sources include breeders who supply purpose-bred animals; businesses that tradein wild animals; and dealers who supply animals sourced from pounds, auctions, andnewspaper ads. Animal shelters also supply the laboratories directly.[74] Large centers alsoexist to distribute strains of genetically-modified animals; the National Institutes ofHealthKnockout Mouse Project, for example, aims to provide knockout mice for every genein the mouse genome.[75]
  10. 10. A laboratory mouse cage. Mice are either bred commercially, or raised in the laboratory.In the U.S., Class A breeders are licensed by the U.S. Department of Agriculture (USDA) tosell 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 dealershave been accused of kidnapping pets and illegally trapping strays, a practice known asbunching.[76] It was in part out of public concern over the sale of pets to research facilitiesthat the 1966 Laboratory Animal Welfare Act was ushered in — the Senate Committee onCommerce reported in 1966 that stolen pets had been retrieved from Veterans Administrationfacilities, the Mayo Institute, the University of Pennsylvania, Stanford University, andHarvard and Yale Medical Schools.[77] The USDA recovered at least a dozen stolen petsduring a raid on a Class B dealer in Arkansas in 2003.[78]Four states in the U.S. — Minnesota, Utah, Oklahoma, and Iowa — require their shelters toprovide animals to research facilities. Fourteen states explicitly prohibit the practice, whilethe remainder either allow it or have no relevant legislation.[79]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 importedand is not a wild animal or a stray. The latter requirement may also be exempted by specialarrangement.[80] In the UK, most animals used in experiments are bred for the purpose underthe 1988 Animal Protection Act, but wild-caught primates may be used if exceptional andspecific justification can be established.[81][82] 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 RiverLaboratories, Inc., or by Covance, which is the single largest importer of primates into theU.S.[83]Pain and sufferingFurther information: Animal cognition and Pain in animals
  11. 11. Prior to vivisection for educational purposes, chloroform was administered to this commonsand frog to induce terminal anesthesia.The extent to which animal testing causes pain and suffering, and the capacity of animals toexperience and comprehend them, is the subject of much debate.[84][85]According to the U.S. Department of Agriculture, in 2006 about 670,000 animals (57%) (notincluding rats, mice, birds, or invertebrates) were used in procedures that did not includemore than momentary pain or distress. About 420,000 (36%) were used in procedures inwhich pain or distress was relieved by anesthesia, while 84,000 (7%) were used in studiesthat would cause pain or distress that would not be relieved.[48]In the UK, research projects are classified as mild, moderate, and substantial in terms of thesuffering the researchers conducting the study say they may cause; a fourth category of"unclassified" means the animal was anesthetized and killed without recoveringconsciousness, according to the researchers. In December 2001, 1,296 (39%) of projectlicenses in force were classified as mild, 1,811 (55%) as moderate, 63 (2%) as substantial,and 139 (4%) as unclassified.[86] There have, however, been suggestions of systemicunderestimation of procedure severity.[87]The idea that animals might not feel pain as human beings feel it traces back to the 17th-century French philosopher, René Descartes, who argued that animals do not experience painand suffering because they lack consciousness.[46][88]Bernard Rollin of Colorado StateUniversity, the principal author of two U.S. federal laws regulating pain relief for animals,[89]writes that researchers remained unsure into the 1980s as to whether animals experience pain,and that veterinarians trained in the U.S. before 1989 were simply taught to ignore animalpain.[90] In his interactions with scientists and other veterinarians, he was regularly asked to"prove" that animals are conscious, and to provide "scientifically acceptable" grounds forclaiming that they feel pain.[90] Carbone writes that the view that animals feel pain differentlyis now a minority view. Academic reviews of the topic are more equivocal, noting thatalthough the argument that animals have at least simple conscious thoughts and feelings hasstrong support,[91] some critics continue to question how reliably animal mental states can bedetermined.[46][92] The ability of invertebrate species of animals, such as insects, to feel painand suffering is also unclear.[93][94]
  12. 12. The defining text on animal welfare regulation, "Guide for the Care and Use of LaboratoryAnimals" defines the parameters that govern animal testing in the USA. It states "The abilityto experience and respond to pain is widespread in the animal kingdom...Pain is a stressorand, if not relieved, can lead to unacceptable levels of stress and distress in animals."[95] TheGuide states that the ability to recognize the symptoms of pain in different species is vital inefficiently applying pain relief and that it is essential for the people caring for and usinganimals to be entirely familiar with these symptoms. On the subject of analgesics used torelieve pain, the Guide states "The selection of the most appropriate analgesic or anestheticshould reflect professional judgment as to which best meets clinical and humanerequirements without compromising the scientific aspects of the research protocol".Accordingly, all issues of animal pain and distress, and their potential treatment withanalgesia and anesthesia, are required regulatory issues in receiving animal protocolapproval.EuthanasiaFurther information: Euthanasia and Animal euthanasiaThere is general agreement that animal life should not be taken wantonly, and regulationsrequire that scientists use as few animals as possible.[96] However, while policy makersconsider suffering to be the central issue and see animal euthanasia as a way to reducesuffering, others, such as the RSPCA, argue that the lives of laboratory animals have intrinsicvalue.[97] Regulations focus on whether particular methods cause pain and suffering, notwhether their death is undesirable in itself.[98] The animals are euthanized at the end of studiesfor sample collection or post-mortem examination; during studies if their pain or sufferingfalls into certain categories regarded as unacceptable, such as depression, infection that isunresponsive to treatment, or the failure of large animals to eat for five days;[99] or when theyare unsuitable for breeding or unwanted for some other reason.[100]Methods of euthanizing laboratory animals are chosen to induce rapid unconsciousness anddeath without pain or distress.[101]The methods that are preferred are those published bycouncils of veterinarians. The animal can be made to inhale a gas, such as carbon monoxideand carbon dioxide, by being placed in a chamber, or by use of a face mask, with or withoutprior sedation or anesthesia. Sedatives or anesthetics such as barbiturates can be givenintravenously, or inhalant anesthetics may be used. Amphibians and fish may be immersed inwater containing an anesthetic such as tricaine. Physical methods are also used, with orwithout sedation or anesthesia depending on the method. Recommended methods includedecapitation (beheading) for small rodents or rabbits. Cervical dislocation (breaking the neckor spine) may be used for birds, mice, and immature rats and rabbits. Maceration (grindinginto small pieces) is used on 1 day old chicks. High-intensity microwave irradiation of thebrain can preserve brain tissue and induce death in less than 1 second, but this is currentlyonly used on rodents. Captive bolts may be used, typically on dogs, ruminants, horses, pigsand rabbits. It causes death by a concussion to the brain. Gunshot may be used, but only incases where a penetrating captive bolt may not be used. Some physical methods are onlyacceptable after the animal is unconscious. Electrocution may be used for cattle, sheep,swine, foxes, and mink after the animals are unconscious, often by a prior electrical stun.Pithing (inserting a tool into the base of the brain) is usable on animals already unconscious.Slow or rapid freezing, or inducing air embolism are acceptable only with prior anesthesia toinduce unconsciousness.[102]
  13. 13. Research classificationPure researchBasic or pure research investigates how organisms behave, develop, and function. Thoseopposed 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 distinctionbetween pure and applied research—research that has a specific practical aim—unclear.[103]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, thoughsmall numbers of other species are used, ranging from sea slugs through to armadillos.[104]Examples of the types of animals and experiments used in basic research include: Studies on embryogenesis and developmental biology. Mutants are created by adding transposons into their genomes, or specific genes are deleted by gene targeting.[105][106] By studying the changes in development these changes produce, scientists aim to understand both how organisms normally develop, and what can go wrong in this process. These studies are particularly powerful since the basic controls of development, such as the homeobox genes, have similar functions in organisms as diverse as fruit flies and man.[107][108] Experiments into behavior, to understand how organisms detect and interact with each other and their environment, in which fruit flies, worms, mice, and rats are all widely used.[109][110] Studies of brain function, such as memory and social behavior, often use rats and birds.[111][112] For some species, behavioral research is combined with enrichment strategies for animals in captivity because it allows them to engage in a wider range of activities.[113] Breeding experiments to study evolution and genetics. Laboratory mice, flies, fish, and worms are inbred through many generations to create strains with defined characteristics.[114]These provide animals of a known genetic background, an important tool for genetic analyses. Larger mammals are rarely bred specifically for such studies due to their slow rate of reproduction, though some scientists take advantage of inbred domesticated animals, such as dog or cattle breeds, for comparative purposes. Scientists studying how animals evolve use many animal species to see how variations in where and how an organism lives (their niche) produce adaptations in their physiology and morphology. As an example, sticklebacks are now being used to study how many and which types of mutations are selected to produce adaptations in animals morphology during the evolution of new species.[115][116]Applied researchApplied research aims to solve specific and practical problems. Compared to pure research,which is largely academic in origin, applied research is usually carried out in thepharmaceutical industry, or by universities in commercial partnerships. These may involvethe use of animal models of diseases or conditions, which are often discovered or generatedby pure research programmes. In turn, such applied studies may be an early stage in the drugdiscovery process. Examples include:
  14. 14. Genetic modification of animals to study disease. Transgenic animals have specific genes inserted, modified or removed, to mimic specific conditions such as single gene disorders, such as Huntingtons disease.[117] Other models mimic complex, multifactorial diseases with genetic components, such as diabetes,[118] or even transgenic mice that carry the same mutations that occur during the development of cancer.[119] These models allow investigations on how and why the disease develops, as well as providing ways to develop and test new treatments.[120]The vast majority of these transgenic models of human disease are lines of mice, the mammalian species in which genetic modification is most efficient.[59] Smaller numbers of other animals are also used, including rats, pigs, sheep, fish, birds, and amphibians.[82] 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 are used as a model to develop immunodeficiency virus vaccines and to study leukemia because their natural predisposition to FIV and Feline leukemia virus.[121][122] Certain breeds of dog suffer from narcolepsy 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; as the bacteria responsible for this disease cannot yet be grown in culture, armadillos are the primary source of bacilli used in leprosy vaccines.[104] Studies on induced animal models of human diseases. Here, an animal is treated so that it develops pathology and symptoms that resemble a human disease. Examples include restricting blood flow to the brain to induce stroke, or giving neurotoxins that cause damage similar to that seen in Parkinsons disease.[123]Such studies can be difficult to interpret, and it is argued that they are not always comparable to human diseases.[124] For example, although such models are now widely used to study Parkinsons 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.[125] In contrast, scientists assessing the usefulness of animal models of Parkinsons disease, as well as the medical research charity The Parkinsons Appeal, state that these models were invaluable and that they led to improved surgical treatments such as pallidotomy, new drug treatments such as levodopa, and later deep brain stimulation.[71][123][126]XenotransplantationMain article: XenotransplantationXenotransplantation research involves transplanting tissues or organs from one species toanother, as a way to overcome the shortage of human organs for use in organ transplants.[127]Current research involves using primates as the recipients of organs from pigs that have beengenetically-modified to reduce the primates immune response against the pig tissue.[128]Although transplant rejection remains a problem,[128] recent clinical trials that involvedimplanting pig insulin-secreting cells into diabetics did reduce these peoples need forinsulin.[129][130]Documents released to the news media by the animal rights organization Uncaged Campaignsshowed that, between 1994 and 2000, wild baboons imported to the UK from Africa byImutran Ltd, a subsidiary of NovartisPharma AG, in conjunction with Cambridge University
  15. 15. and Huntingdon Life Sciences, to be used in experiments that involved grafting pig tissues,suffered serious and sometimes fatal injuries. A scandal occurred when it was revealed thatthe company had communicated with the British government in an attempt to avoidregulation.[87][131]Toxicology testingMain article: Toxicology testingFurther information: Draize test, LD50, Acute toxicity, and Chronic toxicityToxicology testing, also known as safety testing, is conducted by pharmaceutical companiestesting drugs, or by contract animal testing facilities, such as Huntingdon Life Sciences, onbehalf of a wide variety of customers.[132] According to 2005 EU figures, around one millionanimals are used every year in Europe in toxicology tests; which are about 10% of allprocedures.[44] According to Nature, 5,000 animals are used for each chemical being tested,with 12,000 needed to test pesticides.[133]The tests are conducted without anesthesia, becauseinteractions between drugs can affect how animals detoxify chemicals, and may interferewith the results.[134][135]A rabbit during a Draize testToxicology tests are used to examine finished products such as pesticides, medications, foodadditives, packing materials, and air freshener, or their chemical ingredients. Most testsinvolve testing ingredients rather than finished products, but according to BUAV,manufacturers believe these tests overestimate the toxic effects of substances; they thereforerepeat the tests using their finished products to obtain a less toxic label.[132]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 andrestraining them, or by placing them in an inhalation chamber; or administered orally,through a tube into the stomach, or simply in the animals food. Doses may be given once,repeated regularly for many months, or for the lifespan of the animal.[citation needed]There are several different types of acute toxicity tests. The LD50 ("Lethal Dose 50%") test isused to evaluate the toxicity of a substance by determining the dose required to kill 50% ofthe test animal population. This test was removed from OECD international guidelines in2002, replaced by methods such as the fixed dose procedure, which use fewer animals andcause less suffering.[136][137]Nature writes that, as of 2005, "the LD50 acute toxicity test ...still accounts for one-third of all animal [toxicity] tests worldwide."[133] Irritancy can bemeasured using the Draize test, where a test substance is applied to an animals eyes or skin,usually an albino rabbit. For Draize eye testing, the test involves observing the effects of thesubstance at intervals and grading any damage or irritation, but the test should be halted and
  16. 16. the animal killed if it shows "continuing signs of severe pain or distress".[138] The HumaneSociety of the United States writes that the procedure can cause redness, ulceration,hemorrhaging, cloudiness, or even blindness.[139]This test has also been criticized byscientists for being cruel and inaccurate, subjective, over-sensitive, and failing to reflecthuman exposures in the real world.[140] Although no accepted in vitro alternatives exist, amodified form of the Draize test called the low volume eye test may reduce suffering andprovide more realistic results and this was adopted as the new standard in September2009.[141][142] However, the Draize test will still be used for substances that are not severeirritants.[142]The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests areperformed, lasting less than a month (acute), one to three months (subchronic), and more thanthree months (chronic) to test general toxicity (damage to organs), eye and skin irritancy,mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the fullcomplement of tests is several million dollars per substance and it may take three or fouryears to complete.These toxicity tests provide, in the words of a 2006 United States National Academy ofSciences report, "critical information for assessing hazard and risk potential".[143]Naturereported that most animal tests either over- or underestimate risk, or do not reflect toxicity inhumans particularly well,[133] with false positive results being a particular problem.[144]Thisvariability stems from using the effects of high doses of chemicals in small numbers oflaboratory animals to try to predict the effects of low doses in large numbers ofhumans.[145]Although relationships do exist, opinion is divided on how to use data on onespecies to predict the exact level of risk in another.[146]Cosmetics testingProducts in Europe not tested on animals carry this symbol.Main article: Testing cosmetics on animalsCosmetics testing on animals is particularly controversial. Such tests, which are stillconducted in the U.S., involve general toxicity, eye and skin irritancy, phototoxicity (toxicitytriggered by ultraviolet light) and mutagenicity.[147]Cosmetics testing is banned in the Netherlands, Belgium, and the UK, and in 2002, after 13years of discussion, the European Union (EU) agreed to phase in a near-total ban on the saleof animal-tested cosmetics throughout the EU from 2009, and to ban all cosmetics-relatedanimal testing. France, which is home to the worlds largest cosmetics company, LOreal, hasprotested the proposed ban by lodging a case at the European Court of Justice inLuxembourg, asking that the ban be quashed.[148] The ban is also opposed by the European
  17. 17. Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland,Belgium, France, Germany and Italy.[148]Drug testingBeagles used for safety testing of pharmaceuticals in a British facilityBefore the early 20th century, laws regulating drugs were lax. Currently, all newpharmaceuticals undergo rigorous animal testing before being licensed for human use. Testson pharmaceutical products involve: metabolic tests, investigating pharmacokinetics – how drugs are absorbed, metabolized and excreted by the body when introduced orally, intravenously, intraperitoneally, intramuscularly, or transdermally. 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 demands that "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration".[149] Sub-acute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it causes rapid poisoning, in order to discover if any toxic drug metabolites build up over time. Testing for chronic toxicity can last up to two years and, in the European Union, is required to involve two species of mammals, one of which must be non-rodent.[150] efficacy studies, which test whether experimental drugs work by inducing the appropriate illness in animals. The drug is then administered in a double-blind controlled trial, which allows researchers 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, depending on the result of other studies and the type of drug being tested.Education, breeding, and defenseAnimals are also used for education and training; are bred for use in laboratories; and areused by the military to develop weapons, vaccines, battlefield surgical techniques, anddefensive clothing.[103] For example, in 2008 the United States Defense Advanced ResearchProjects Agency used live pigs to study the effects of improvised explosive device explosionson internal organs, especially the brain.[151]
  18. 18. There are efforts in many countries to find alternatives to using animals in education.[152]Horst Spielmann, German director of the Central Office for Collecting and AssessingAlternatives to Animal Experimentation, while describing Germanys progress in this area,told German broadcaster ARD in 2005: "Using animals in teaching curricula is alreadysuperfluous. In many countries, one can become a doctor, vet or biologist without everhaving performed an experiment on an animal."[153]EthicsBackgroundFurther information: Animal welfare and Animal rightsMonument for animals used in testing at Keio UniversityThe ethical questions raised by performing experiments on animals are subject to muchdebate, and viewpoints have shifted significantly over the 20th century.[154]There remaindisagreements about which procedures are useful for which purposes, as well asdisagreements over which ethical principles apply to which species. The dominant ethicalposition worldwide is that achievement of scientific and medical goals using animal testing isdesirable, so long as animal suffering and use is minimized.[155] The British government hasadditionally required that the cost to animals in an experiment be weighed against the gain inknowledge.[156]Some medical schools and agencies in China, Japan, and South Korea havebuilt cenotaphs for killed animals.[157] In Japan there are also annual memorial services(Ireisai慰霊祭) for animals sacrificed at medical school.A wide range of minority viewpoints exist. The view that animals have moral rights (animalrights) is a philosophical position proposed by Tom Regan, among others, who argues thatanimals are beings with beliefs and desires, and as such are the "subjects of a life" with moralvalue and therefore moral rights.[158] Regan still sees ethical differences between killinghuman and non-human animals, and argues that to save the former it is permissible to kill thelatter. Others, such as Bernard Rollin, argue that benefits to human beings cannot outweighanimal suffering, and that human beings have no moral right to use an animal in ways that donot benefit that individual. Another prominent position is that of philosopher Peter Singer,who argues that there are no grounds to include a beings species in considerations of whethertheir suffering is important in utilitarian moral considerations.[159]
  19. 19. Although these arguments have not been widely accepted, governments such as theNetherlands and New Zealand have responded to the concerns by outlawing invasiveexperiments on certain classes of non-human primates, particularly the great apes.[160][161]Prominent casesVarious specific cases of animal testing have drawn attention, including both instances ofbeneficial scientific research, and instances of alleged ethical violations by those performingthe tests.Muscle physiology This section requires expansion with: more examples of applications to research on other medical applications, besides muscle physiology.The fundamental properties of muscle physiology were determined with on work done usingfrog muscles (including the force generating mechanism of all muscle,[162] the length-tensionrelationship,[163] and the force-velocity curve[164]), and frogs are still the preferred modelorganism due to the long survival of muscles in vitro and the possibility of isolating intactsingle-fiber preparations (not possible in other organisms).[165] Modern physical therapy andthe understanding and treatment of muscular disorders is based on this work and subsequentwork in mice (often engineered to express disease states such as muscular dystrophy).[166]University of California, RiversideMain article: Britches (monkey)1985 was a pivotal year in the debate about animal research in the United States, with theenactment of amendments to the Animal Welfare Act.[167]Britches, a macaque monkey, wasborn that year inside the University of California, Riverside, removed from his mother atbirth, and left alone with his eyelids sewn shut, and a sonar sensor on his head, as part of anexperiment to test sensory substitution devices for blind people. The Animal Liberation Frontraided the laboratory on April 20, 1985, removing Britches and 466 other animals, andreportedly inflicting $700,000-worth of damage to equipment.[168]A spokesman for theuniversity said the allegations of mistreatment were false, and that the raid caused long-termdamage to its research projects.[169] The National Institutes of Health conducted an eight-month investigation and concluded that no corrective action was necessary.[170]Huntingdon Life SciencesFootage filmed by PeTA inside Huntingdon Life Sciences showed staff mistreating beagles.Main article: Stop Huntingdon Animal Cruelty
  20. 20. In 1997, People for the Ethical Treatment of Animals filmed staff inside Huntingdon LifeSciences (HLS) in the UK, Europes largest animal-testing facility, hitting puppies, shoutingat them, and simulating sex acts while taking blood samples.[171] The company said theemployees were dismissed.[172] Two pleaded guilty to "cruelly terrifying dogs," and weregiven community service orders and ordered to pay £250 costs, the first lab technicians tohave been prosecuted for animal cruelty in the UK.[173] The broadcast of the video onBritains Channel 4 Television in March 1997 triggered the formation of Stop HuntingdonAnimal Cruelty (SHAC), an international leaderless resistance campaign to close HLS, whichhas been criticized for its sometimes violent tactics.[174] In January 2009, several BritishSHAC activists were jailed for blackmailing companies linked to HLS.[175]Roslin InstituteMain article: Dolly (sheep)Dolly the sheep: the first clone produced from an adult animalIn February 1997 a team at the Roslin Institute in Scotland announced the birth of Dolly thesheep, a ewe that had been cloned from tissue taken from another adult sheep.[24] Dolly wasproduced through nuclear transfer to an unfertilisedoocyte, and was the only lamb thatsurvived from 277 attempts at this technique.[176] Dolly appeared to be a normal sheep, livingfor six years and giving birth to several lambs, but was euthanized in 2003 after contracting aprogressive lung disease.[177] Although the production of Dolly was a scientific breakthrough,it was controversial, since it showed that not only could cloned animals be produced for usein farming,[178] but also that it would now be, in principle, possible to clone a humanbeing.[179]University of CambridgeA marmoset after being brain damaged, filmed at Cambridge by the BUAVMain article: Primate experiments at Cambridge UniversityThe British Union for the Abolition of Vivisection (BUAV) raised concerns about primateexperiments at the University of Cambridge in 2002. In a series of court cases, the BUAValleged that monkeys had undergone surgery to induce a stroke, and were left alone after theprocedure for 15 hours overnight. Researchers had trained the monkeys to perform certaintasks before inflicting brain damage and re-testing them. The monkeys were only given foodand water for two hours a day, to encourage them to perform the tasks. The judge hearing
  21. 21. BUAVs application for a judicial review rejected the allegation that the Home Secretary hadbeen negligent in granting the university a license.[180] The British governments chiefinspector of animals conducted a review of the facilities and experiments. It concluded theveterinary input at Cambridge was "exemplary"; the facility "seems adequately staffed"; andthe animals afforded "appropriate standards of accommodation and care."[181]Columbia UniversityMain article: Primate experiments at Columbia UniversityCNN reported in October 2003 that Catherine DellOrto, a veterinarian at ColumbiaUniversity, had approached the universitys Institute of Comparative Medicine about thetreatment of baboons who were undergoing surgery as part of an experiment into stroketreatment. She said the baboons, who were in some cases having an eyeball removed, wereleft to suffer in their cages after the surgery. She alleged there was systemic maltreatment,poor record-keeping, and other violations of regulations, according to CNN. She presentedher evidence in October 2002 and, dissatisfied with the response, contacted People for theEthical Treatment of Animals two months later.[182]In March 2003, a lab technician shot video inside the lab, which according to The New YorkDaily News showed primates in cages without pain medication; the video included onebaboon with a metal cylinder screwed into its head, according to the newspaper. DellOrtotold the newspaper that primates were often not euthanized or given painkillers after surgery;she said other primates had torn their fingers off out of fear.[183] The U.S. Department ofAgriculture upheld DellOrtos complaint that there was shoddy record-keeping, and that 11animals had been provided with "inadequate or questionable care." They found no evidencethat the experiments violated federal guidelines or that there had been retaliation againstDellOrto. CNN reported that Columbia responded by ordering better record-keeping, areview of the veterinary care program, and tighter criteria for euthanasia of laboratoryanimals.[184]CovanceMain article: CovanceIn 2004, German journalist Friedrich Mülln shot undercover footage of staff in Covance,Münster, Europes largest primate-testing center, making monkeys dance in time to blaringpop music, handling them roughly, and screaming at them. The monkeys were kept isolatedin small wire cages with little or no natural light, no environmental enrichment, and highnoise levels from staff shouting and playing the radio[185] (video). PrimatologistJane Goodalldescribed the living conditions of the monkeys as horrendous. Another primatologist,Stephen Brend, told BUAV that using monkeys in such a stressed state is bad science, andtrying to extrapolate useful data in such circumstances is what he called an untenableproposition.[185]In 2004 and 2005, PETA shot footage inside the company in the UnitedStates. According to The Washington Post, PETA said an employee of the group filmedprimates being choked, hit, and denied medical attention when badly injured.[186] The U.S.Department of Agriculture fined Covance $8,720 for 16 citations, three of which involved labmonkeys; the other citations involved administrative issues and equipment.[187]Threats to researchers
  22. 22. In 2006, a primate researcher at the University of California, Los Angeles (UCLA) shut downthe experiments in his lab after threats from animal rights activists. The researcher hadreceived a grant to use 30 macaque monkeys for vision experiments; each monkey wasanesthetized for a single physiological experiment lasting up to 120 hours, and theneuthanized.[188]The researchers name, phone number, and address were posted on the websiteof the Primate Freedom Project. Demonstrations were held in front of his home. A Molotovcocktail was placed on the porch of what was believed to be the home of another UCLAprimate researcher; instead, it was accidentally left on the porch of an elderly womanunrelated to the university. The Animal Liberation Front claimed responsibility for theattack.[189] As a result of the campaign, the researcher sent an email to the Primate FreedomProject stating "you win," and "please don‘t bother my family anymore."[190] In anotherincident at UCLA in June 2007, the Animal Liberation Brigade placed a bomb under the carof a UCLA childrens ophthalmologist who experiments on cats and rhesus monkeys; thebomb had a faulty fuse and did not detonate.[191] UCLA is now refusing Freedom ofInformation Act requests for animal medical records.These attacks, as well as similar incidents that caused the Southern Poverty Law Center todeclare in 2002 that the animal rights movement had "clearly taken a turn toward the moreextreme," this prompted the US government to pass the Animal Enterprise Terrorism Act andthe UK government to add the offense of "Intimidation of persons connected with animalresearch organisation" to the Serious Organised Crime and Police Act 2005.[192]Suchlegislation, and the arrest and imprisonment of extremists may have decreased the incidenceof attacks.[193]Alternatives to animal testingMain article: Alternatives to animal testingScientists and governments state that animal testing should cause as little suffering to animalsas possible, and that animal tests should only be performed where necessary. The "threeRs"[96] are guiding principles for the use of animals in research in most countries: 1. Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim. 2. 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. 3. Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.[194]Although such principles have been welcomed as a step forwards by some animal welfaregroups,[195] they have also been criticized as both outdated by current research,[196] and oflittle practical effect in improving animal welfare.[197]
  23. 23. Animal testingFrom Wikipedia, the free encyclopediaEnos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961. Non-human primates make up 0.3% of research animals, with 50,000 used each year in theU.S.[1] and 10,000 in Europe. [2][3]Animal testing, or animal research, refers to the use of animals in experiments.It is estimated that 50 to 100 million animals worldwide [4][5][6] — from fruit flies andmice to non-human primates — are used annually and may either be killed duringthe experiments or subsequently euthanised. The research is carried out insideuniversities, medical schools, pharmaceutical companies, farms, defense-research establishments, and commercial facilities that provide animal-testingservices to industry. [7] Most laboratory animals are bred for research purposes,while a smaller number are caught in the wild or supplied by pounds. [8]The Foundation for Biomedical Research, an American interest group supportinganimal research, writes, "Animal research has played a vital role in virtually everymajor medical advance of the last century." [9] Many major developments that ledto Nobel Prizes involved animal research, including the development of penicillin(mice), organ transplant (dogs), and work on poliomyelitis that led to a vaccine(mice, monkeys). [10][11][12]The topic is controversial. Opponents argue that animal testing is unnecessary,poor scientific practice, poorly regulated, that the costs outweigh the benefits, orthat animals have an intrinsic right not to be used for experimentation. [13][14] Contents [hide]
  24. 24. 1History2Modern Regulation 2.1Europe 2.2Japan 2.3United States3Animals used 3.1Species4Types of experiment 4.1Pure research 4.2Applied research 4.3Toxicology testing  4.3.1Drug testing  4.3.2Cosmetics testing5Controversy 5.1Huntingdon Life Sciences 5.2Covance 5.3University of Cambridge 5.4University of California, Riverside 5.5Columbia University 5.6University of California, Los Angeles6Sampling public opinions on animal testing7Alternatives to animal testing8The arguments in brief 8.1Official statements from representative bodies 8.2Advocates of animal testing 8.3Opponents of animal testing9See also10Links11References 11.1Numbered references 11.2Other References12Further readingHistory
  25. 25. One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in hismuzzle. Pavlov Museum, 2005 Main article: History of animal testing The earliest references to animal testing are found in the writings of the Greeks in the third and fourth centuries BC. Aristotle (Αριστοτέλης) (384-380 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."[15] An Experiment on a Bird in an Air Pump, from 1768, by Joseph Wright. 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. Modern Regulation
  26. 26. EuropeExperiments on vertebrate animals in the European Union are subject toDirective 86/609/EEC on the protection of Animals used for Experimentaland other Scientific purposes, adopted in 1986. [16] There is considerablevariation in the manner member countries choose to exercise the directive:compare, for example, legislation from Sweden, [17]The Netherlands, [18] andGermany. [19] FranceIn France, legislation (principally the decree of October 19, 1987) requires aninstitutional and project licence before testing on vertebrates may be carriedout. An institution must submit details of their facilities and the reason for theuse of animals they house, after which a five-year licence may be grantedfollowing an inspection of the premises. The project licensee must be trainedand educated to an appropriate level. Personal licences are not required forindividuals working under the supervision of a project licence holder. [20][21] United KingdomTechnician assessing the health status of transgenic mice in a UK laboratory, 2000.Provided by RDS/Wellcome Trust Photographic Library [22]The types of institutions conducting animal research in the UK in 2004 were:universities (42.1%); commercial organizations (33.3%); non-profitorganizations (4.9%); government departments (2.4%); National HealthService hospitals (0.9%); public health laboratories (0.6%); other publicbodies (15.8%). [23]The Animals (Scientific Procedures) Act 1986[24] requires experiments to beregulated by three licences: a project licence for the scientist in charge of theproject, which details the numbers and types of animals to be used, theexperiments to be performed, and the purpose of them; a certificate for theinstitution to ensure it has adequate facilities and staff; and a personallicence for each scientist or technician who carries out any procedure. In
  27. 27. deciding whether to grant a licence, the Home Office refers to the Acts cost-benefit analysis, which is defined as "the likely adverse effects on theanimals concerned against the benefit likely to accrue as a result of theprogramme to be specified in the licence" (Section 5(4)). A licence should notbe granted if there is a "reasonably practicable method not entailing the useof protected animals" (Section 5(5) (a)). The experiments must use "theminimum number of animals, involve animals with the lowest degree ofneurophysiological sensitivity, cause the least pain, suffering distress orlasting harm, and [be the] most likely to produce satisfactory results" (Section5(5) (b)). [25]During a 2002 House of Lords select committee inquiry into animal testing inthe UK, witnesses stated that the UK has the tightest regulatory system inthe world, and is the only country to require a cost-benefit assessment ofevery licence application. [26] There are 29 qualified inspectors covering 230establishments, which are visited on average 11-12 times a year. [27](Seealso Animal Procedures Committee.) A report by Animal Aid alleges that thelaw governing animal research in the UK, The Animals (ScientificProcedures) Act 1986, is a "vivisectors charter," allowing researchers to doas they please and making them practically immune from prosecution. Thereport says that licences to perform experiments are obtained on the basis ofa "nod of approval" from the Home Office Inspectorate, and that the HomeOffice relies on the researchers own opinions of the cost-benefit assessmentregarding the value of the experiment versus the amount of suffering it willcause.[25]JapanThe system in Japan is one of self-regulation. Animal experiments areregulated by one clause in the 2000 Law for the Humane Treatment andManagement of Animals [28]PDF, which requires those using animals tocause minimal distress and suffering. There are no inspections, and there isno reporting requirement for the numbers of animals used. [29] A 1988survey published by the Japanese Association for Laboratory AnimalScience reported that eight million had been used that year. [26]United StatesIn the United States, animal testing is primarily regulated by the 1966 AnimalWelfare Act (AWA),[27] which is enforced by the Animal Care division[28] of theAnimal and Plant Health Inspection Service (APHIS) of the United StatesDepartment of Agriculture (USDA). The AWA contains provisions to ensurethat individuals of covered species used in research receive a certainstandard of care and treatment, provided that the standard of care andtreatment does not interfere with "the design, outlines, or guidelines of actualresearch or experimentation."[29][30] 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-
  28. 28. captured mice, rats, and birds) from regulations.[31] Thus, relatively fewanimals used in research in the U.S. are covered by this legislation.[30] TheAWA requires each institution conducting animal testing using coveredspecies to maintain an Institutional Animal Care and Use Committee(IACUC), which is responsible for enforcing the act. Institutions are subject tounannounced annual inspections. There are over 100 inspectors[32]monitoring around 1100 research institutions.[33] The inspectors also conductpre-licensing checks for sites that do not engage in animal research ortransportation, of which more than 4000 exist (e.g. dog kennels).[34]APHIS has been criticized by its own inspectors and the USDA InspectorGenerals office (OIG). Marshall Smith, an APHIS inspector for twelve years,resigned in 1997 recounting a litany of problems at the agency that impededhis duties. In a prepared statement, Smith made note of a 1992 OIG reportciting the agencys inability to ensure the humane care of animals atdealers.[35] In 2000, Isis Johnson-Brown D.V.M. - another APHIS inspector -quit because of problems she documented at the Oregon National PrimateResearch Center, in Beaverton, Oregon. In a prepared statement Dr.Johnson said, "More than once, I was instructed by a supervisor to make apersonal list of violations of the law, cut that list in half, and then cut that listin half again before writing up my inspection reports. My willingness touphold the law during my site visits at the Primate Center led to me beingretrained several times by higher-ups in the USDA.[36] In 2005, the USDAOIG issued another report on APHIS:Of particular concern, AC management in the Eastern Region is not aggressivelypursuing enforcement actions against violators of the AWA. The Eastern Regionsignificantly reduced its referrals of suspected violators to the Investigative andEnforcement 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 (27percent).When violators are assessed stipulated fines, the fines are usually minimal and notalways effective in preventing subsequent violations. Under current APHIS policy,AC gives an automatic 75-percent discount to almost all violators as a means ofamicably reaching an agreement on the amount of the fines and avoiding court.Finally, we noted that some VMOs when inspecting research facilities do not verifythe number of animals used in medical research or adequately review the facilities’protocols and other records.[37]Another regulatory instrument is the Public Health Service (PHS) Policy onHumane Care and Use of Laboratory Animals, which became statutory withthe Health Research Extension Act 1985, and which is enforced by the Officeof Laboratory Animal Welfare (OLAW). This Act applies to any individualscientist or institution in receipt of federal funds and requires each institutionto have an IACUC. OLAW enforces the standards of the Guide for the Careand Use of Laboratory Animals[31] published by the Institute for Laboratory
  29. 29. Animal Research,[32] which includes all vertebrate species in its careprotocols, including rodents and birds[33] (Introduction, p.1). In 2004, theNational Institutes of Health provided funds to 3,180 different researchinstitutions and universities.[34] This means that IACUCs oversee the use ofall vertebrate species in research at facilities receiving federal funds, even ifthe species are not covered by the AWA. OLAW does not carry outscheduled inspections, but requires that "As a condition of receipt of PHSsupport for research involving laboratory animals, awardee institutions mustprovide a written Animal Welfare Assurance of Compliance (Assurance) toOLAW describing the means they will employ to comply with the PHSPolicy."[38] OLAW conducts inspections only when there is a suspected oralleged violation that cannot be resolved through written correspondence.Accreditation from the Association for Assessment and Accreditation ofLaboratory Animal Care International (AAALAC),[39] a non-governmental,nonprofit association, is regarded by the industry as the "gold standard" ofaccreditation.[40] Accreditation is maintained through a prearranged AAALACsite visit and program evaluation hosted by the member institution onceevery three years.[41] Accreditation is intended to ensure compliance with thestandards in the Guide for the Care and Use of Laboratory Animals, as wellas any other national or local laws on animal welfare.Animals usedAccurate global figures for animal testing are difficult to collect. The BritishUnion for the Abolition of Vivisection (BUAV) estimates that 100 millionanimals are experimented on around the world every year, 10–11 million ofthem in the European Union [35]PDF (100 KiB) and 1,101,958 mammals (notincluding rats and mice) in the United States in 2004 [36]PDF (136 KiB) p.3).The Nuffield Council on Bioethics reports that "[e]stimates of the total numberof animals used annually in research around the world are difficult to obtainand range from between 50 to 100 million animals."[6] Animals bred forresearch then killed as surplus, or used for breeding purposes, are notincluded in the figures.According to the U.S. Department of Agriculture, the total number of animalsused in that country in 2002 was 1,137,718, not counting birds, mice, andrats, which make up around 85% of research animals excludinginvertebrates. Other sources estimate the percentage of all lab animals thatare rats, mice, or birds at 85-90%,[42] or 95%[43] The Laboratory PrimateAdvocacy Group has used these figures to estimate that 23-25 millionanimals are used in research each year in America. [37] In 1986, a reportproduced by the U.S. Congress Office of Technology Assessment reportedthat "estimates of the animals used in the United States each year rangefrom 10 million to upwards of 100 million," and that their own best estimatewas "at least 17 million to 22 million."[44] In 1966, the Laboratory AnimalBreeders Association estimated in testimony before Congress that thenumber of mice, rats, guinea pigs, hamsters, and rabbits used in 1965 was
  30. 30. around 60 million.[45] In 2004, the Department of Agriculture listed 64,932dogs, 23,640 cats, 54,998 non-human primates, 244,104 guinea pigs,175,721 hamsters, 261,573 rabbits, 105,678 farm animals, and 171,312other mammals, a total of 1,101,958, a figure that includes all mammalsexcept purpose-bred mice and rats. Of that total, 615,000 were listed onexperiments that did not include more than momentary pain or distress,399,000 were associated with experiments in which pain or distress wasrelieved by drugs, and over 86,000 were listed on experiments that plannedto cause pain and distress that could not be relieved.[46] The use of dogs andcats in research in the USA decreased from 1973 to 2004 from 195,157 to64,932, and from 66,165 to 23,640, respectively[46][47]Figures released by the British Home Office show that, in 2004, 2,854,944procedures were carried out on 2,778,692 animals[48], an increase of 63,000from 2003,[48] the third consecutive annual rise and the highest figure since1992.[49] In 2005, the BBC reported that the UK figures continued to "creepup...mainly due to the growing use of genetically modified mice"[50] with2,896,198 procedures carried out on 2,812,850 animals in that year.[51]The term "procedure" refers to an experiment, which might last severalmonths or even years. The figures show that most animals are used in onlyone procedure: animals either die because of the experiment or are killedand dissected afterwards.[52]Over half the experiments in Britain in 2004 — 1,710,760 — either did notrequire anesthetic (e.g. behavioral tests, breeding stock, controlled dietaryintake) or anesthesia was not used because this would interfere with theexperimental results; 880,897 experiments were conducted in connectionwith pure research; 114,081 were toxicology tests, 982,640 were forbreeding, 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
  31. 31. Drosophila are one of the most widely used animals for experimentationListed in descending order of numbers of individual animals used: InvertebratesMost of the animals used in animal testing are invertebrates, especiallyDrosophila melanogaster, a fruit fly, and Caenorhabditiselegans, anematode. In the case of C. elegans, the precise lineage of all the organismscells is known, and D. melanogaster has various characteristics making itwell suited to genetic studies. These animals offer scientists a number ofadvantages over vertebrates, including their short life cycle and the ease withwhich large numbers of individuals may be studied. Invertebrates are oftenextremely cost-effective, as thousands of flies or nematodes can be housedin a single room, but this is not true for all species of invertebrates.With the exception of some cephalopods, invertebrate species are notprotected under most animal research legislation, and therefore the totalnumber of invertebrates used remains unknown. RodentsRodents commonly used include guinea pigs, hamsters, gerbils, rats andmice. Mice are the most commonly utilized vertebrate species, popularbecause of their availability, size, low cost, ease of handling, and fastreproduction rate. Mice are widely considered to be the prime model ofinherited human disease and share 99% of their genes with humans.[53] Withthe advent of genetic engineering technology, genetically modified mice canbe generated to order. The Mouse Genetics Core at Washington Universityin St. Louis[54] explains what is required to produce todays widely usedtransgenic and chimeric mice:Production of Transgenic MiceThe Transgenic Animal Production serviceconsists of injecting each construct into 300-350 eggs, typically representing threedays work. Twenty to fifty mice will normally be born from this number of injectedeggs. These animals are screened for the presence of the transgene by apolymerase chain reaction genotyping assay. The number of transgenic animalstypically varies from two to eight.Production of Chimeric Mice The chimeric mouse production service consists ofinjecting embryonic stem cells provided by the investigator into 150-175 blastocysts,representing three days of work. Thirty to fifty live mice are normally born from thisnumber of injected blastocysts. Normally, the skin color of the mice from which thehost blastocysts are derived is different from that of the strain used to produce theembryonic stem cells. Typically two to six mice will have skin and hair with greaterthan seventy percent ES cell contribution, indicating a good chance for embryonicstem cell contribution to the germline.
  32. 32. In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodentswere used (84.5% of the total animals used that year). In 2005 the totalnumber of rodents used was similar to the previous year: 1,955,035 mice,414,335 rats and 40,856 other rodents.[51]In the U.S., the numbers of rats and mice used are not reported, but havebeen estimated at 15-20 million. [38] In 2000, the Federal Research Division,Library of Congress, published the results of an analysis of its Rats/Mice/andBirds Database: Researchers, Breeders, Transporters, and Exhibitors. [39]Over 2,000 research organizations are listed in the database, of whichapproximately 500 were researched and of these, 100 were contacted directly byFRD staff. These organizations include hospitals, government organizations, privatecompanies (pharmaceutical companies, etc.), universities/colleges, a fewsecondary schools, and research institutes. Of these 2,000, approximately 960 areregulated by USDA; 349 by NIH; and 560 accredited by AALAC. Approximately 50percent of the organizations contacted revealed a specific or approximated numberof animals in their laboratories. The total number of animals for those organizationsis: 250,000-1,000,000 rats; 400,000-2,000,000 mice; and 130,000-900,000 birds. Fish and amphibiansIn the UK, 194,562 fish and 18,195 amphibians were used in 2004[40]PDF (1.19 MiB). In 2005, the number of fish used increased to 230,315while the number of amphibians used decreased to 13,318.[51] The majorspecies utilized are the zebrafish, Daniorerio, which are translucent duringtheir embryonic stage, and the African clawed frog, Xenopuslaevis. RabbitsOver 20,000 rabbits were used for animal testing in the UK in 2004. Thisnumber decreased, in 2005, to 15,348.[51]Albino rabbits are used in eyeirritancy tests because rabbits have less tear flow than other animals and thelack of eye pigment make the effects easier to visualize. They are also usedin skin irritancy tests (see Draize test). In 2004 less than 12% of the rabbitswere used for safety testing of non-medical products [41]. Dogs
  33. 33. In 1957, Laika became the first animal to be launched into space, paving the wayfor human spaceflight.Beagles are used, because they are friendly and gentle, in toxicity tests,surgery, and dental experiments. Toxicology tests are required to last sixmonths in the UK, although British laboratories carry out tests lasting ninemonths on behalf of Japanese and American customers. Of the 8,018 dogsused in the UK in 2004, 7,799 were beagles (97.3%). [42]PDF (1.19 MiB) In2005 the number of dogs used in the UK decreased to 5,373.[51] Most dogsare bred specifically for the purpose, for example by Harlan in Leicestershire. Non-human primatesIn the United States, 54,998 non-human primates (NHPs) were used in 2004,according to the U.S. Department of Agriculture (USDA), an annual figurethat has been more or less steady since 1973 [43]PDF (136 KiB) (p. 10). Inthe European Union, 10,000 are used each year, with 4,208 used in Britain in2004, a decrease of 591 from the previous year. [44] This decreasing trendcontinued in 2005, with 3,115 primates used in the UK.[51] (p. 20-21)Primates are the species most likely to be re-used in experiments. Re-use isallowed if the animals have been used in mild procedures with no lastingside-effects, according to the Research Defence Society.[55] BUAV report thatit is because of re-use that there has been a fall in the number of individualprimates used in the UK.[56]Filmed by PETA, Covance primate-testing lab, Vienna, Virginia, 2004-5.[57]
  34. 34. Most of the NHPs used are macaques, accounting for 79% of all primatesused in research in the UK, and 63% of all primate research grants in theUSA[58]. Lesser numbers of the New World primates marmosets, spidermonkeys, and squirrel monkeys are used in the UK, and baboons, NewWorld monkeys, and the Great Apechimpanzee used in the USA. Licensesapproving the use of apes, such as gorillas, chimpanzees, and orangutans,are not currently being issued in Britain, though their use has not beenoutlawed,[59] but chimpanzees are used in the U.S., with an estimated 1,500-1600 still remaining in research laboratories, according to The HumaneSociety of the United States.[60] NHPs are used in research into HIV,neurology, behavior, cognition, reproduction, Parkinsons disease, stroke,malaria, respiratory viruses, infectious disease, genetics,xenotransplantation, drug abuse, and also in vaccine and drug testing.According to The Humane Society of the United States, chimpanzees aremost often used in hepatitis research, and monkeys in HIV research, and areoften housed alone because of the nature of the conditions being studied. [60]There are indications that NHP use is on the rise,[60] in part becausebiomedical research funds in the USA have more than doubled since the1990s.[61] In the U.S., the Oregon and California National Primate ResearchCenters and New Iberia Research Center have expanded theirfacilities;[62][63][64] in 2000 the National Institutes of Health (NIH) invitedapplications for the establishment of new breeding specific pathogen freecolonies;[65] and a new breeding colony projected to house 3,000 NHPs hasbeen set up in Florida.[66] The NIHs National Center for Research Resourcesidentified a need to increase the number of breeding colonies in its 2004-2008 strategic plan, as well as to set up a database, using informationprovided through a network of National Primate Research Centers, to allowresearchers to locate NHPs with particular characteristics.[67]China is alsoincreasing its NHP use, and is regarded as attractive to Western companiesbecause of the low cost of research, the relatively lax regulations and theincrease in animal-rights activism in the West.[60]In 2004, the British government reported "a definite long-term downwardtrend" in the use of new world primates (for example, marmosets, tamarins,squirrel, owl, spider and capuchin monkeys), but stated that the use of oldworld primates (for example, baboons and macaques) fluctuates and is moredifficult to determine.[68]Crab-eating macaques and rhesus macaques are themost commonly used species.[56] Home Office figures show the number ofprimates used in the UK rose by 11 per cent in 2005 to 4,650 procedures,440 more than in 2004.[69]Most primate use in the UK is in applied studies, which the Home Officedefines as research conducted for the purpose of developing or testingcommercial products. Toxicology testing is the largest use.[70] The secondlargest category of research using primates is "fundamental biologicalresearch." This includes neuroscientific study of the visual system, cognition,and diseases such as Parkinsons,[71] involving techniques such as inserting
  35. 35. electrodes to record from or stimulate the brain, and temporary or permanentinactivation of areas of tissue.In 1996, the British Animal Procedures Committee recommended newmeasures for dealing with NHPs. The use of wild-caught primates wasbanned, except where "exceptional and specific justification can beestablished"; specific justification must be made for the use of old worldprimates (but not for the use of new world primates); approval for theacquisition of primates from overseas is conditional upon their breeding orsupply center being acceptable to the Home Office; and each batch ofprimates acquired from overseas must be separately authorized. [72] CatsFelines 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[45].[51] According to the USDA, over 25,500 felines were used in the USA in2000, of these around half were reported to have been used in experimentsthat caused "pain and/or distress". The number of cats used in research inthe US has followed a downward trend, from a peak of 74,259 in 1973. [46]Types of experiment Animal testing advocacy Advocates Tipu Aziz Colin Blakemore Michael E. DeBakey Alan Duncan Simon Festing Evan Harris Maurice Hilleman Donald Kennedy John Edward Porter Beverly Sills Frankie Trull Robert Winston Groups/campaigns RDSFBR
  36. 36. Experiments can be split into three broad, AMPAAAS Pro-TestNIHoverlapping categories: pure research, in AVMAAALASwhich experiments are conducted that haveno direct commercial application, with a view Issuesto advancing knowledge, most often insideuniversities; applied research, conducted in Animal rights Animal testingorder to solve specific biological problems or Animal welfareto develop commercial products, either formedical or non-medical use; and toxicology Writersor safety testing, in which commercial Carl Cohenproducts are tested on animals to measure Roger Scrutonpotential adverse biological reactions to the Richard Posneringredients. TiborMachan This box: view • talk • editPure researchBasic or pure research aims to increaseknowledge about the way organisms behave, develop, and functionbiologically.Both the largest number and greatest variety of laboratory animals are usedin this type of research. Drosophila melanogaster, Caenorhabditiselegans,mice and rats together account for the vast majority, though small numbersof other species are used, ranging from sea slugs through blind cavefish[47].In the UK in 2005, 89 macaques, 114 marmosets, 133 dogs and 237 catswere used in basic research to investigate topics such as social behaviour,vision, nutrition and suckling.[51]Examples of the types of animals and experiments used in basic researchinclude: 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 [48]. The 1995 and 2002 Nobel Prizes in Physiology or Medicine were awarded for research into developmental processes in animals using forward genetic screens[49][50]. Embryos used in experiments are often not covered by legislation and therefore not always required to be reported. Consequently, those that believe embryos are defacto 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
  37. 37. and rats are all widely used in research into mechanisms of vision, [51] taste, [52] hearing, [53] touch, [54] and smell. [55] In addition studies of brain function, such as memory and social behaviour, often use rats and birds. [56] 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 [57][58]. 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 [59]. Scientists studying mechanisms of evolution use a number of animal species, including mosquitos[60], sticklebacks[61], cichlids[62] and lampreys[63], due to their nichephysiology, morphology, ecology or phylogeny.Applied researchApplied research aims to solve specific and practical problems, often relatingto the treatment or cure of disease and disorder in humans and animals.Compared to pure research, which is largely academic in origin, appliedresearch programmes are more likely to be carried out in the pharmaceuticalindustry, or in universities in commercial partnership. These may involve theuse of animal models of disease or condition, which are often discovered orgenerated by pure research programmes. In turn, such applied studies maybe an early stage in the modern drug discovery process. Examples of animaluse 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 Alzheimers disease, then investigate how and why the disease develops. The vast majority of transgenic models of disease are mice [64], the mammalian species in which genetic modification is most efficient, though there are
  38. 38. smaller numbers of other animals such as rats, sheep and pigs [65]. Pharmaceutical companies [66], medical research institutes [67], politicians [68], scientists [69] and professional research bodies widely endorse these techniques, describing an "explosion of research on such disease models" [70] resulting in "an increasingly important role in the discovery and development of new medicines" [71]. However, animal rights and welfare groups regularly question the value and effectiveness of transgenic techniques, [72][73] as animals do not always model human diseases accurately [74] or in their entirety. [75][76] 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." [77]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 [78]. Their infection with a related feline virus, FeLV, makes cats a common model for leukemia research also. [79] Certain breeds of dog suffer from narcolepsy[80] 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[81]. As it cannot yet be grown in culture, armadillos are the primary source of bacilli used in leprosy vaccines. [82]Non human primates, being closely related to humans, are applied in the study of a number of human conditions, including visual disorders [83][84] and dental disease [85]. Primates are also used extensively in immunology [86] and reproductive studies [87][88], a synthesis of which resulted in the discovery of the Rhesus factor and its importance in hemolytic disease of the newborn.Xenotransplantation research, primarily using primates as the recipient of pig hearts. 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.According to licensing agencies, the increased experimentation onxenotransplation is motivated by the desire to save human lives. The USFDA says "The development of xenotransplantation is, in part, driven by
  39. 39. the fact that the demand for human organs for clinical transplantation farexceeds the supply. Currently ten patients die each day in the UnitedStates while on the waiting list to receive life-saving vital organ transplants.Moreover, recent evidence has suggested that transplantation of cells andtissues may be therapeutic for certain diseases such as neurodegenerativedisorders and diabetes, where, again human materials are not usuallyavailable.".[73] In Great Britain, the government agency UKXIRA states"There is currently, and will continue to be, a shortage of human organsand tissue for transplantation....Xenotransplantation is a potential solutionto this shortage."[74] Author G. Wayne Miller, in The Xeno Chronicles,suggests another motivation: Assuming xeno could be perfected, the group that brought xeno to the clinic first would claim not only scientific accolades but also a good share of the market that a Saloman Brothers study had predicted would reach $6 billion by 2010. The estimate did not seem unreasonable. No one could state what a working pig organ would cost, but with so many desperate patients and with waiting lists for all organs growing, the seller could all but command his price.[75]Medical journalists Jenny Bryan and John Clare have calledxenotransplatation experiments "some of the most grisly procedurescarried out anywhere in the name of science." They write that: "They dosometimes involve a full transplant of a genetically modified pig heart into amonkey. In some cases, however, the doctors will graft the transgenichearts onto a baboons neck arteries, as this allows them to observe theway the pig heart behaves in another species, and monitor the rejectionprocess. The operation is carried out under general anaesthetic and thebaboon is humanely killed afterwards. These measures, however, do notpacify animal rights campaigners, who say the experiments are cruel andunnecessary."[76] Details of the effects of these experimental procedurescame to light when thousands of documents were leaked to a UK-basedanimal rights organization. After a legal battle, the documents werepublished in a report titled Diaries of Despair.[89] Toxicology testing Drug testing

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