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Animal testing
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          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 vivo
testing, is the use of non-human animals in experiments. Worldwide it is estimated that the
number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens
of 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 and
rats used in the United States alone in 2001 was 80 million.[2] Most animals are euthanized
after being used in an experiment.[3]Sources of laboratory animals vary between countries and
species; most animals are purpose-bred, while others are caught in the wild or supplied by
dealers 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 services
to industry.[5] It includes pure research such as genetics, developmental biology, behavioral
studies, as well as applied research such as biomedical research, xenotransplantation, drug
testing and toxicology tests, including cosmetics testing. Animals are also used for education,
breeding, and defense research. The practice is regulated to various degrees in different
countries.

Supporters of the use of animals in experiments, such as the British Royal Society, argue that
virtually every medical achievement in the 20th century relied on the use of animals in some
way,[6] with the Institute for Laboratory Animal Research of the U.S. National Academy of
Sciences arguing that even sophisticated computers are unable to model interactions between
molecules, cells, tissues, organs, organisms, and the environment, making animal research
necessary in many areas.[7] A number of scientists, animal welfare, and animal rights
organizations—such as PETA and BUAV—question the legitimacy of it, arguing that it is
cruel, poor scientific practice, poorly regulated, that medical progress is being held back by
misleading animal models, that some of the tests are outdated, that it cannot reliably predict
effects in humans, that the costs outweigh the benefits, or that animals have an intrinsic right
not 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
Definitions
The terms animal testing, animal experimentation, animal research, in vivo testing, and
vivisection have similar denotations but different connotations. Literally, "vivisection" means
the "cutting up" of a living animal, and historically referred only to experiments that involved
the dissection of live animals. The term is occasionally used to refer pejoratively to any
experiment using living animals; for example, the Encyclopædia Britannica defines
"vivisection" as: "Operation on a living animal for experimental rather than healing purposes;
more broadly, all experimentation on live animals",[9] although dictionaries point out that the
broader definition is "used only by people who are opposed to such work".[10] The word has a
negative connotation, implying torture, suffering, and death.[11] The word "vivisection" is
preferred by those opposed to this research, whereas scientists typically use the term "animal
experimentation".[12][13]

History
Main article: History of animal testing




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

The earliest references to animal testing are found in the writings of the Greeks in the 2nd
and 4th centuries BCE. Aristotle (Αριστοτέλης) (384–322 BCE) and Erasistratus (304–258
BCE) were among the first to perform experiments on living animals.[14]Galen, a physician in
2nd-century Rome, dissected pigs and goats, and is known as the "father of
vivisection."[15]Avenzoar, an Arabic physician in 12th-century Moorish Spain who also
practiced dissection, introduced animal testing as an experimental method of testing surgical
procedures 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 in
sheep.[18] In the 1890s, Ivan Pavlov famously used dogs to describe classical
conditioning.[19]Insulin was first isolated from dogs in 1922, and revolutionized the treatment
of diabetes.[20] On November 3, 1957, a Russian dog, Laika, became the first of many animals
to orbit the earth. In the 1970s, antibiotic treatments and vaccines for leprosy were developed
using armadillos,[21] then given to humans.[22] The ability of humans to change the genetics of
animals took a large step forwards in 1974 when Rudolf Jaenisch was able to produce the
first transgenic mammal, by integrating DNA from the SV40 virus into the genome of
mice.[23] This genetic research progressed rapidly and, in 1996, Dolly the sheep was born, the
first mammal to be cloned from an adult cell.[24]
Toxicology testing became important in the 20th century. In the 19th century, laws regulating
drugs were more relaxed. For example, in the U.S., the government could only ban a drug
after 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 killed
more than 100 users, the U.S. congress passed laws that required safety testing of drugs on
animals before they could be marketed. Other countries enacted similar legislation.[25] In the
1960s, in reaction to the Thalidomide tragedy, further laws were passed requiring safety
testing on pregnant animals before a drug can be sold.[26]

Historical debate




Claude Bernard, regarded as the "prince of vivisectors"[27] argued that experiments on
animals are "entirely conclusive for the toxicology and hygiene of man".[28]

As the experimentation on animals increased, especially the practice of vivisection, so did
criticism and controversy. In 1655, the advocate of Galenic physiology Edmund O'Meara
said that "the miserable torture of vivisection places the body in an unnatural state."[29][30]
O'Meara and others argued that animal physiology could be affected by pain during
vivisection, 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 objections
to animal testing also came from another angle — many people believed that animals were
inferior to humans and so different that results from animals could not be applied to
humans.[30]

On the other side of the debate, those in favor of animal testing held that experiments on
animals were necessary to advance medical and biological knowledge. Claude Bernard,
known as the "prince of vivisectors"[27] and the father of physiology—whose wife, Marie
Françoise Martin, founded the first anti-vivisection society in France in 1883[31]—famously
wrote in 1865 that "the science of life is a superb and dazzlingly lighted hall which may be
reached only by passing through a long and ghastly kitchen".[32] Arguing that "experiments
on animals ... are entirely conclusive for the toxicology and hygiene of man...the effects of
these 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 antivivisectionists
are the second of the two types Theodore Roosevelt described when he said, ‗Common sense
without conscience may lead to crime, but conscience without common sense may lead to
folly, which is the handmaiden of crime.‘ ‖[34] These divisions between pro- and anti- animal
testing groups first came to public attention during the brown dog affair in the early 1900s,
when hundreds of medical students clashed with anti-vivisectionists and police over a
memorial to a vivisected dog.[35]




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

In 1822, the first animal protection law was enacted in the British parliament, followed by the
Cruelty to Animals Act (1876), the first law specifically aimed at regulating animal testing.
The legislation was promoted by Charles Darwin, who wrote to Ray Lankester in March
1871: "You ask about my opinion on vivisection. I quite agree that it is justifiable for real
investigations on physiology; but not for mere damnable and detestable curiosity. It is a
subject which makes me sick with horror, so I will not say another word about it, else I shall
not sleep to-night."[36][37] Opposition to the use of animals in medical research first arose in
the United States during the 1860s, when Henry Bergh founded the American Society for the
Prevention of Cruelty to Animals (ASPCA), with America's first specifically anti-vivisection
organization being the American AntiVivisection Society (AAVS), founded in 1883.
Antivivisectionists of the era generally believed the spread of mercy was the great cause of
civilization, and vivisection was cruel. However, in the USA the antivivisectionists' efforts
were defeated in every legislature, overwhelmed by the superior organization and influence
of the medical community. Overall, this movement had little legislative success until the
passing of the Laboratory Animal Welfare Act, in 1966.[38]

Care and use of animals
See also: Animal testing regulations, Institutional Animal Care and Use Committee, and
Animals (Scientific Procedures) Act 1986

Regulations

The regulations that apply to animals in laboratories vary across species. In the U.S., under
the provisions of the Animal Welfare Act and the Guide for the Care and Use of Laboratory
Animals (the Guide), published by the National Academy of Sciences, any procedure can be
performed on an animal if it can be successfully argued that it is scientifically justified. In
general, researchers are required to consult with the institution's veterinarian and its
Institutional Animal Care and Use Committee (IACUC), which every research facility is
obliged to maintain.[39] The IACUC must ensure that alternatives, including non-animal
alternatives, have been considered, that the experiments are not unnecessarily duplicative,
and that pain relief is given unless it would interfere with the study. Larry Carbone, a
laboratory animal veterinarian, writes that, in his experience, IACUCs take their work very
seriously regardless of the species involved, though the use of non-human primates always
raises what he calls a "red flag of special concern."[40] A study published in Science magazine
in July 2001 confirmed the low reliability of IACUC reviews of animal experiments. Funded
by the National Science Foundation, the three-year study found that animal-use committees
that do not know the specifics of the university and personnel do not make the same approval
decisions as those made by animal-use committees that do know the university and personnel.
Specifically, blinded committees more often ask for more information rather than approving
studies.[41]

The IACUCs regulate all vertebrates in testing at institutions receiving federal funds in the
USA. Although the provisions of the Animal Welfare Act do not include purpose-bred
rodents and birds, these species are equally regulated under Public Health Service policies
that 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 by
AAALAC.

Numbers




Types of vertebrates used in animal testing in Europe in 2005: a total of 12.1 million animals
were used.[44]

Accurate global figures for animal testing are difficult to obtain. The British Union for the
Abolition of Vivisection (BUAV) estimates that 100 million vertebrates are experimented on
around the world every year, 10–11 million of them in the European Union.[45] The Nuffield
Council on Bioethics reports that global annual estimates range from 50 to 100 million
animals. None of the figures include invertebrates such as shrimp and fruit flies.[46] Animals
bred for research then killed as surplus, animals used for breeding purposes, and animals not
yet weaned are also not included in the figures.[47]

According to the U.S. Department of Agriculture (USDA), the total number of animals used
in that country in 2005 was almost 1.2 million,[48] but this does not include rats and mice,
which make up about 90% of research animals.[49][50] In 1995, researchers at Tufts University
Center for Animals and Public Policy estimated that 14–21 million animals were used in
American laboratories in 1992, a reduction from a high of 50 million used in 1970.[51] In
1986, the U.S. Congress Office of Technology Assessment reported that estimates of the
animals used in the U.S. range from 10 million to upwards of 100 million each year, and that
their own best estimate was at least 17 million to 22 million.[52]

In the UK, Home Office figures show that 3.2 million procedures were carried out in 2007, a
rise of 189,500 since the previous year. Four thousand procedures used non-human primates,
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 die
because of the experiment or are euthanized afterwards.[46]

Species

Invertebrates




Fruit flies are commonly used.
Main article: Animal testing on invertebrates

Although many more invertebrates than vertebrates are used, these experiments are largely
unregulated by law. The most used invertebrate species are Drosophila melanogaster, a fruit
fly, and Caenorhabditiselegans, a nematode worm. In the case of C. elegans, the worm's
body is completely transparent and the precise lineage of all the organism's cells is known,[54]
while studies in the fly D. melanogaster can use an amazing array of genetic tools.[55] These
animals offer great advantages over vertebrates, including their short life cycle and the ease
with which large numbers may be studied, with thousands of flies or nematodes fitting into a
single room. However, the lack of an adaptive immune system and their simple organs
prevent 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 system
differs greatly from that of humans,[57] and diseases in insects can be very different from
diseases in vertebrates.[58]

Vertebrates




Enos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961
Further information: Animal testing on frogs, Animal testing on rabbits, Animal testing on
rodents, Draize test, and Median lethal dose
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 platform
where the rat sits. At the onset of REM sleep, the rat would either fall into the water only to
clamber back to its pot to avoid drowning, or its nose would become submerged into the
water 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] Other
rodents commonly used are guinea pigs, hamsters, and gerbils. Mice are the most commonly
used vertebrate species because of their size, low cost, ease of handling, and fast reproduction
rate.[59] Mice are widely considered to be the best model of inherited human disease and share
99% 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 of
human 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 these
rodents in basic science.[60]

Nearly 200,000 fish and 20,000 amphibians were used in the UK in 2004.[61] The main
species 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 testing
in the UK in 2004.[61]Albino rabbits are used in eye irritancy tests because rabbits have less
tear flow than other animals, and the lack of eye pigment in albinos make the effects easier to
visualize.[61] Rabbits are also frequently used for the production of polyclonal antibodies.

Cats and dogs
See also: Laika and Russian space dogs

Cats are most commonly used in neurological research. Over 25,500 cats were used in the
U.S. in 2000, around half of whom were used in experiments which, according to the
American 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 human
diseases in cardiology, endocrinology, and bone and joint studies, research that tends to be
highly invasive, according to the Humane Society of the United States.[63] The U.S.
Department of Agriculture's Animal Welfare Report for 2005 shows that 66,000 dogs were
used 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 buy
animals from auctions, shelters, newspaper ads, and who are sometimes accused of stealing
pets.[64]

Non-human primates
Main article: Animal testing on non-human primates
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 are
domestically 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, around
70,000 NHPs are used each year in the United States and European Union.[44][48] Most of the
NHPs used are macaques;[67] but marmosets, spider monkeys, and squirrel monkeys are also
used, and baboons and chimpanzees are used in the U.S; in 2006 there were 1133
chimpanzees 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 genetic
disorderHuntington's disease.[70] Notable studies on non-human primates have been part of
the polio vaccine development, and development of Deep Brain Stimulation, and their current
heaviest non-toxicological use occurs in the monkey AIDS model, SIV.[6][67][71] In 2008 a
proposal to ban all primates experiments in the EU has sparked a vigorous debate.[72]

Sources

Main articles: Laboratory animal sources and International trade in primates

Animals used by laboratories are largely supplied by specialist dealers. Sources differ for
vertebrate and invertebrate animals. Most laboratories breed and raise flies and worms
themselves, using strains and mutants supplied from a few main stock centers.[73] For
vertebrates, sources include breeders who supply purpose-bred animals; businesses that trade
in wild animals; and dealers who supply animals sourced from pounds, auctions, and
newspaper ads. Animal shelters also supply the laboratories directly.[74] Large centers also
exist to distribute strains of genetically-modified animals; the National Institutes of
HealthKnockout Mouse Project, for example, aims to provide knockout mice for every gene
in the mouse genome.[75]
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) to
sell animals for research purposes, while Class B dealers are licensed to buy animals from
"random sources" such as auctions, pound seizure, and newspaper ads. Some Class B dealers
have been accused of kidnapping pets and illegally trapping strays, a practice known as
bunching.[76] It was in part out of public concern over the sale of pets to research facilities
that the 1966 Laboratory Animal Welfare Act was ushered in — the Senate Committee on
Commerce reported in 1966 that stolen pets had been retrieved from Veterans Administration
facilities, the Mayo Institute, the University of Pennsylvania, Stanford University, and
Harvard and Yale Medical Schools.[77] The USDA recovered at least a dozen stolen pets
during 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 to
provide animals to research facilities. Fourteen states explicitly prohibit the practice, while
the 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 imported
and is not a wild animal or a stray. The latter requirement may also be exempted by special
arrangement.[80] In the UK, most animals used in experiments are bred for the purpose under
the 1988 Animal Protection Act, but wild-caught primates may be used if exceptional and
specific justification can be established.[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 River
Laboratories, Inc., or by Covance, which is the single largest importer of primates into the
U.S.[83]

Pain and suffering

Further information: Animal cognition and Pain in animals
Prior to vivisection for educational purposes, chloroform was administered to this common
sand frog to induce terminal anesthesia.

The extent to which animal testing causes pain and suffering, and the capacity of animals to
experience 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%) (not
including rats, mice, birds, or invertebrates) were used in procedures that did not include
more than momentary pain or distress. About 420,000 (36%) were used in procedures in
which pain or distress was relieved by anesthesia, while 84,000 (7%) were used in studies
that 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 the
suffering the researchers conducting the study say they may cause; a fourth category of
"unclassified" means the animal was anesthetized and killed without recovering
consciousness, according to the researchers. In December 2001, 1,296 (39%) of project
licenses 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 systemic
underestimation 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 pain
and suffering because they lack consciousness.[46][88]Bernard Rollin of Colorado State
University, 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 animal
pain.[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 for
claiming that they feel pain.[90] Carbone writes that the view that animals feel pain differently
is now a minority view. Academic reviews of the topic are more equivocal, noting that
although the argument that animals have at least simple conscious thoughts and feelings has
strong support,[91] some critics continue to question how reliably animal mental states can be
determined.[46][92] The ability of invertebrate species of animals, such as insects, to feel pain
and suffering is also unclear.[93][94]
The defining text on animal welfare regulation, "Guide for the Care and Use of Laboratory
Animals" defines the parameters that govern animal testing in the USA. It states "The ability
to experience and respond to pain is widespread in the animal kingdom...Pain is a stressor
and, if not relieved, can lead to unacceptable levels of stress and distress in animals."[95] The
Guide states that the ability to recognize the symptoms of pain in different species is vital in
efficiently applying pain relief and that it is essential for the people caring for and using
animals to be entirely familiar with these symptoms. On the subject of analgesics used to
relieve pain, the Guide states "The selection of the most appropriate analgesic or anesthetic
should reflect professional judgment as to which best meets clinical and humane
requirements without compromising the scientific aspects of the research protocol".
Accordingly, all issues of animal pain and distress, and their potential treatment with
analgesia and anesthesia, are required regulatory issues in receiving animal protocol
approval.

Euthanasia

Further information: Euthanasia and Animal euthanasia

There is general agreement that animal life should not be taken wantonly, and regulations
require that scientists use as few animals as possible.[96] However, while policy makers
consider suffering to be the central issue and see animal euthanasia as a way to reduce
suffering, others, such as the RSPCA, argue that the lives of laboratory animals have intrinsic
value.[97] Regulations focus on whether particular methods cause pain and suffering, not
whether their death is undesirable in itself.[98] The animals are euthanized at the end of studies
for sample collection or post-mortem examination; during studies if their pain or suffering
falls into certain categories regarded as unacceptable, such as depression, infection that is
unresponsive to treatment, or the failure of large animals to eat for five days;[99] or when they
are unsuitable for breeding or unwanted for some other reason.[100]

Methods of euthanizing laboratory animals are chosen to induce rapid unconsciousness and
death without pain or distress.[101]The methods that are preferred are those published by
councils of veterinarians. The animal can be made to inhale a gas, such as carbon monoxide
and carbon dioxide, by being placed in a chamber, or by use of a face mask, with or without
prior sedation or anesthesia. Sedatives or anesthetics such as barbiturates can be given
intravenously, or inhalant anesthetics may be used. Amphibians and fish may be immersed in
water containing an anesthetic such as tricaine. Physical methods are also used, with or
without sedation or anesthesia depending on the method. Recommended methods include
decapitation (beheading) for small rodents or rabbits. Cervical dislocation (breaking the neck
or spine) may be used for birds, mice, and immature rats and rabbits. Maceration (grinding
into small pieces) is used on 1 day old chicks. High-intensity microwave irradiation of the
brain can preserve brain tissue and induce death in less than 1 second, but this is currently
only used on rodents. Captive bolts may be used, typically on dogs, ruminants, horses, pigs
and rabbits. It causes death by a concussion to the brain. Gunshot may be used, but only in
cases where a penetrating captive bolt may not be used. Some physical methods are only
acceptable 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 to
induce unconsciousness.[102]
Research classification
Pure research

Basic or pure research investigates how organisms behave, develop, and function. Those
opposed to animal testing object that pure research may have little or no practical purpose,
but researchers argue that it may produce unforeseen benefits, rendering the distinction
between pure and applied research—research that has a specific practical aim—unclear.[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, though
small 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 research

Applied 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 the
pharmaceutical industry, or by universities in commercial partnerships. These may involve
the use of animal models of diseases or conditions, which are often discovered or generated
by pure research programmes. In turn, such applied studies may be an early stage in the drug
discovery process. Examples include:
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 Huntington's 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 Parkinson's 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
       Parkinson's disease, the British anti-vivisection interest group BUAV argues that
       these models only superficially resemble the disease symptoms, without the same
       time course or cellular pathology.[125] In contrast, scientists assessing the usefulness of
       animal models of Parkinson's disease, as well as the medical research charity The
       Parkinson's 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]

Xenotransplantation

Main article: Xenotransplantation

Xenotransplantation research involves transplanting tissues or organs from one species to
another, 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 been
genetically-modified to reduce the primates' immune response against the pig tissue.[128]
Although transplant rejection remains a problem,[128] recent clinical trials that involved
implanting pig insulin-secreting cells into diabetics did reduce these people's need for
insulin.[129][130]

Documents released to the news media by the animal rights organization Uncaged Campaigns
showed that, between 1994 and 2000, wild baboons imported to the UK from Africa by
Imutran Ltd, a subsidiary of NovartisPharma AG, in conjunction with Cambridge University
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 that
the company had communicated with the British government in an attempt to avoid
regulation.[87][131]

Toxicology testing

Main article: Toxicology testing
Further information: Draize test, LD50, Acute toxicity, and Chronic toxicity

Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies
testing drugs, or by contract animal testing facilities, such as Huntingdon Life Sciences, on
behalf of a wide variety of customers.[132] According to 2005 EU figures, around one million
animals are used every year in Europe in toxicology tests; which are about 10% of all
procedures.[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, because
interactions between drugs can affect how animals detoxify chemicals, and may interfere
with the results.[134][135]




A rabbit during a Draize test

Toxicology tests are used to examine finished products such as pesticides, medications, food
additives, packing materials, and air freshener, or their chemical ingredients. Most tests
involve testing ingredients rather than finished products, but according to BUAV,
manufacturers believe these tests overestimate the toxic effects of substances; they therefore
repeat the tests using their finished products to obtain a less toxic label.[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 and
restraining them, or by placing them in an inhalation chamber; or administered orally,
through a tube into the stomach, or simply in the animal's food. Doses may be given once,
repeated regularly for many months, or for the lifespan of the animal.[citation needed]

There are several different types of acute toxicity tests. The LD50 ("Lethal Dose 50%") test is
used to evaluate the toxicity of a substance by determining the dose required to kill 50% of
the test animal population. This test was removed from OECD international guidelines in
2002, replaced by methods such as the fixed dose procedure, which use fewer animals and
cause 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 be
measured using the Draize test, where a test substance is applied to an animal's eyes or skin,
usually an albino rabbit. For Draize eye testing, the test involves observing the effects of the
substance at intervals and grading any damage or irritation, but the test should be halted and
the animal killed if it shows "continuing signs of severe pain or distress".[138] The Humane
Society of the United States writes that the procedure can cause redness, ulceration,
hemorrhaging, cloudiness, or even blindness.[139]This test has also been criticized by
scientists for being cruel and inaccurate, subjective, over-sensitive, and failing to reflect
human exposures in the real world.[140] Although no accepted in vitro alternatives exist, a
modified form of the Draize test called the low volume eye test may reduce suffering and
provide more realistic results and this was adopted as the new standard in September
2009.[141][142] However, the Draize test will still be used for substances that are not severe
irritants.[142]

The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are
performed, lasting less than a month (acute), one to three months (subchronic), and more than
three months (chronic) to test general toxicity (damage to organs), eye and skin irritancy,
mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the full
complement of tests is several million dollars per substance and it may take three or four
years to complete.

These toxicity tests provide, in the words of a 2006 United States National Academy of
Sciences report, "critical information for assessing hazard and risk potential".[143]Nature
reported that most animal tests either over- or underestimate risk, or do not reflect toxicity in
humans particularly well,[133] with false positive results being a particular problem.[144]This
variability stems from using the effects of high doses of chemicals in small numbers of
laboratory animals to try to predict the effects of low doses in large numbers of
humans.[145]Although relationships do exist, opinion is divided on how to use data on one
species to predict the exact level of risk in another.[146]

Cosmetics testing




Products in Europe not tested on animals carry this symbol.
Main article: Testing cosmetics on animals

Cosmetics testing on animals is particularly controversial. Such tests, which are still
conducted in the U.S., involve general toxicity, eye and skin irritancy, phototoxicity (toxicity
triggered by ultraviolet light) and mutagenicity.[147]

Cosmetics testing is banned in the Netherlands, Belgium, and the UK, and in 2002, after 13
years of discussion, the European Union (EU) agreed to phase in a near-total ban on the sale
of animal-tested cosmetics throughout the EU from 2009, and to ban all cosmetics-related
animal testing. France, which is home to the world's largest cosmetics company, L'Oreal, has
protested the proposed ban by lodging a case at the European Court of Justice in
Luxembourg, asking that the ban be quashed.[148] The ban is also opposed by the European
Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland,
Belgium, France, Germany and Italy.[148]

Drug testing




Beagles used for safety testing of pharmaceuticals in a British facility

Before the early 20th century, laws regulating drugs were lax. Currently, all new
pharmaceuticals undergo rigorous animal testing before being licensed for human use. Tests
on 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 defense

Animals are also used for education and training; are bred for use in laboratories; and are
used by the military to develop weapons, vaccines, battlefield surgical techniques, and
defensive clothing.[103] For example, in 2008 the United States Defense Advanced Research
Projects Agency used live pigs to study the effects of improvised explosive device explosions
on internal organs, especially the brain.[151]
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 Assessing
Alternatives to Animal Experimentation, while describing Germany's progress in this area,
told German broadcaster ARD in 2005: "Using animals in teaching curricula is already
superfluous. In many countries, one can become a doctor, vet or biologist without ever
having performed an experiment on an animal."[153]

Ethics
Background

Further information: Animal welfare and Animal rights




Monument for animals used in testing at Keio University

The ethical questions raised by performing experiments on animals are subject to much
debate, and viewpoints have shifted significantly over the 20th century.[154]There remain
disagreements about which procedures are useful for which purposes, as well as
disagreements over which ethical principles apply to which species. The dominant ethical
position worldwide is that achievement of scientific and medical goals using animal testing is
desirable, so long as animal suffering and use is minimized.[155] The British government has
additionally required that the cost to animals in an experiment be weighed against the gain in
knowledge.[156]Some medical schools and agencies in China, Japan, and South Korea have
built 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 (animal
rights) is a philosophical position proposed by Tom Regan, among others, who argues that
animals are beings with beliefs and desires, and as such are the "subjects of a life" with moral
value and therefore moral rights.[158] Regan still sees ethical differences between killing
human and non-human animals, and argues that to save the former it is permissible to kill the
latter. Others, such as Bernard Rollin, argue that benefits to human beings cannot outweigh
animal suffering, and that human beings have no moral right to use an animal in ways that do
not benefit that individual. Another prominent position is that of philosopher Peter Singer,
who argues that there are no grounds to include a being's species in considerations of whether
their suffering is important in utilitarian moral considerations.[159]
Although these arguments have not been widely accepted, governments such as the
Netherlands and New Zealand have responded to the concerns by outlawing invasive
experiments on certain classes of non-human primates, particularly the great apes.[160][161]

Prominent cases

Various specific cases of animal testing have drawn attention, including both instances of
beneficial scientific research, and instances of alleged ethical violations by those performing
the 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 using
frog muscles (including the force generating mechanism of all muscle,[162] the length-tension
relationship,[163] and the force-velocity curve[164]), and frogs are still the preferred model
organism due to the long survival of muscles in vitro and the possibility of isolating intact
single-fiber preparations (not possible in other organisms).[165] Modern physical therapy and
the understanding and treatment of muscular disorders is based on this work and subsequent
work in mice (often engineered to express disease states such as muscular dystrophy).[166]

University of California, Riverside
Main article: Britches (monkey)

1985 was a pivotal year in the debate about animal research in the United States, with the
enactment of amendments to the Animal Welfare Act.[167]Britches, a macaque monkey, was
born that year inside the University of California, Riverside, removed from his mother at
birth, and left alone with his eyelids sewn shut, and a sonar sensor on his head, as part of an
experiment to test sensory substitution devices for blind people. The Animal Liberation Front
raided the laboratory on April 20, 1985, removing Britches and 466 other animals, and
reportedly inflicting $700,000-worth of damage to equipment.[168]A spokesman for the
university said the allegations of mistreatment were false, and that the raid caused long-term
damage 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 Sciences




Footage filmed by PeTA inside Huntingdon Life Sciences showed staff mistreating beagles.
Main article: Stop Huntingdon Animal Cruelty
In 1997, People for the Ethical Treatment of Animals filmed staff inside Huntingdon Life
Sciences (HLS) in the UK, Europe's largest animal-testing facility, hitting puppies, shouting
at them, and simulating sex acts while taking blood samples.[171] The company said the
employees were dismissed.[172] Two pleaded guilty to "cruelly terrifying dogs," and were
given community service orders and ordered to pay £250 costs, the first lab technicians to
have been prosecuted for animal cruelty in the UK.[173] The broadcast of the video on
Britain's Channel 4 Television in March 1997 triggered the formation of Stop Huntingdon
Animal Cruelty (SHAC), an international leaderless resistance campaign to close HLS, which
has been criticized for its sometimes violent tactics.[174] In January 2009, several British
SHAC activists were jailed for blackmailing companies linked to HLS.[175]

Roslin Institute
Main article: Dolly (sheep)




Dolly the sheep: the first clone produced from an adult animal

In February 1997 a team at the Roslin Institute in Scotland announced the birth of Dolly the
sheep, a ewe that had been cloned from tissue taken from another adult sheep.[24] Dolly was
produced through nuclear transfer to an unfertilisedoocyte, and was the only lamb that
survived from 277 attempts at this technique.[176] Dolly appeared to be a normal sheep, living
for six years and giving birth to several lambs, but was euthanized in 2003 after contracting a
progressive 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 use
in farming,[178] but also that it would now be, in principle, possible to clone a human
being.[179]

University of Cambridge




A marmoset after being brain damaged, filmed at Cambridge by the BUAV
Main article: Primate experiments at Cambridge University

The British Union for the Abolition of Vivisection (BUAV) raised concerns about primate
experiments at the University of Cambridge in 2002. In a series of court cases, the BUAV
alleged that monkeys had undergone surgery to induce a stroke, and were left alone after the
procedure for 15 hours overnight. Researchers had trained the monkeys to perform certain
tasks before inflicting brain damage and re-testing them. The monkeys were only given food
and water for two hours a day, to encourage them to perform the tasks. The judge hearing
BUAV's application for a judicial review rejected the allegation that the Home Secretary had
been negligent in granting the university a license.[180] The British government's chief
inspector of animals conducted a review of the facilities and experiments. It concluded the
veterinary input at Cambridge was "exemplary"; the facility "seems adequately staffed"; and
the animals afforded "appropriate standards of accommodation and care."[181]

Columbia University
Main article: Primate experiments at Columbia University

CNN reported in October 2003 that Catherine Dell'Orto, a veterinarian at Columbia
University, had approached the university's Institute of Comparative Medicine about the
treatment of baboons who were undergoing surgery as part of an experiment into stroke
treatment. She said the baboons, who were in some cases having an eyeball removed, were
left 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 presented
her evidence in October 2002 and, dissatisfied with the response, contacted People for the
Ethical Treatment of Animals two months later.[182]

In March 2003, a lab technician shot video inside the lab, which according to The New York
Daily News showed primates in cages without pain medication; the video included one
baboon with a metal cylinder screwed into its head, according to the newspaper. Dell'Orto
told 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 of
Agriculture upheld Dell'Orto's complaint that there was shoddy record-keeping, and that 11
animals had been provided with "inadequate or questionable care." They found no evidence
that the experiments violated federal guidelines or that there had been retaliation against
Dell'Orto. CNN reported that Columbia responded by ordering better record-keeping, a
review of the veterinary care program, and tighter criteria for euthanasia of laboratory
animals.[184]

Covance
Main article: Covance

In 2004, German journalist Friedrich Mülln shot undercover footage of staff in Covance,
Münster, Europe's largest primate-testing center, making monkeys dance in time to blaring
pop music, handling them roughly, and screaming at them. The monkeys were kept isolated
in small wire cages with little or no natural light, no environmental enrichment, and high
noise levels from staff shouting and playing the radio[185] (video). PrimatologistJane Goodall
described 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, and
trying to extrapolate useful data in such circumstances is what he called an untenable
proposition.[185]In 2004 and 2005, PETA shot footage inside the company in the United
States. According to The Washington Post, PETA said an employee of the group filmed
primates 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 lab
monkeys; the other citations involved administrative issues and equipment.[187]

Threats to researchers
In 2006, a primate researcher at the University of California, Los Angeles (UCLA) shut down
the experiments in his lab after threats from animal rights activists. The researcher had
received a grant to use 30 macaque monkeys for vision experiments; each monkey was
anesthetized for a single physiological experiment lasting up to 120 hours, and then
euthanized.[188]The researcher's name, phone number, and address were posted on the website
of the Primate Freedom Project. Demonstrations were held in front of his home. A Molotov
cocktail was placed on the porch of what was believed to be the home of another UCLA
primate researcher; instead, it was accidentally left on the porch of an elderly woman
unrelated to the university. The Animal Liberation Front claimed responsibility for the
attack.[189] As a result of the campaign, the researcher sent an email to the Primate Freedom
Project stating "you win," and "please don‘t bother my family anymore."[190] In another
incident at UCLA in June 2007, the Animal Liberation Brigade placed a bomb under the car
of a UCLA children's ophthalmologist who experiments on cats and rhesus monkeys; the
bomb had a faulty fuse and did not detonate.[191] UCLA is now refusing Freedom of
Information Act requests for animal medical records.

These attacks, as well as similar incidents that caused the Southern Poverty Law Center to
declare in 2002 that the animal rights movement had "clearly taken a turn toward the more
extreme," this prompted the US government to pass the Animal Enterprise Terrorism Act and
the UK government to add the offense of "Intimidation of persons connected with animal
research organisation" to the Serious Organised Crime and Police Act 2005.[192]Such
legislation, and the arrest and imprisonment of extremists may have decreased the incidence
of attacks.[193]

Alternatives to animal testing
Main article: Alternatives to animal testing

Scientists and governments state that animal testing should cause as little suffering to animals
as possible, and that animal tests should only be performed where necessary. The "three
Rs"[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 welfare
groups,[195] they have also been criticized as both outdated by current research,[196] and of
little practical effect in improving animal welfare.[197]
Animal testing
From Wikipedia, the free encyclopedia




Enos 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 the
U.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 and
mice to non-human primates — are used annually and may either be killed during
the experiments or subsequently euthanised. The research is carried out inside
universities, medical schools, pharmaceutical companies, farms, defense-
research establishments, and commercial facilities that provide animal-testing
services to industry. [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 supporting
animal research, writes, "Animal research has played a vital role in virtually every
major medical advance of the last century." [9] Many major developments that led
to 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, or
that animals have an intrinsic right not to be used for experimentation. [13][14]

                   Contents

                     [hide]
1History

2Modern Regulation

     2.1Europe

     2.2Japan

     2.3United States

3Animals used

     3.1Species

4Types of experiment

     4.1Pure research

     4.2Applied research

     4.3Toxicology testing

           4.3.1Drug testing

           4.3.2Cosmetics testing

5Controversy

     5.1Huntingdon Life Sciences

     5.2Covance

     5.3University of Cambridge

     5.4University of California, Riverside

     5.5Columbia University

     5.6University of California, Los Angeles

6Sampling public opinions on animal testing

7Alternatives to animal testing

8The arguments in brief

     8.1Official statements from representative bodies

     8.2Advocates of animal testing

     8.3Opponents of animal testing

9See also

10Links

11References

     11.1Numbered references

     11.2Other References

12Further reading

History
One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in his
muzzle. 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
Europe
Experiments on vertebrate animals in the European Union are subject to
Directive 86/609/EEC on the protection of Animals used for Experimental
and other Scientific purposes, adopted in 1986. [16] There is considerable
variation in the manner member countries choose to exercise the directive:
compare, for example, legislation from Sweden, [17]The Netherlands, [18] and
Germany. [19]

  France

In France, legislation (principally the decree of October 19, 1987) requires an
institutional and project licence before testing on vertebrates may be carried
out. An institution must submit details of their facilities and the reason for the
use of animals they house, after which a five-year licence may be granted
following an inspection of the premises. The project licensee must be trained
and educated to an appropriate level. Personal licences are not required for
individuals working under the supervision of a project licence holder. [20][21]

  United Kingdom




Technician 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-profit
organizations (4.9%); government departments (2.4%); National Health
Service hospitals (0.9%); public health laboratories (0.6%); other public
bodies (15.8%). [23]

The Animals (Scientific Procedures) Act 1986[24] requires experiments to be
regulated by three licences: a project licence for the scientist in charge of the
project, which details the numbers and types of animals to be used, the
experiments to be performed, and the purpose of them; a certificate for the
institution to ensure it has adequate facilities and staff; and a personal
licence for each scientist or technician who carries out any procedure. In
deciding whether to grant a licence, the Home Office refers to the Act's cost-
benefit analysis, which is defined as "the likely adverse effects on the
animals concerned against the benefit likely to accrue as a result of the
programme to be specified in the licence" (Section 5(4)). A licence should not
be granted if there is a "reasonably practicable method not entailing the use
of protected animals" (Section 5(5) (a)). The experiments must use "the
minimum number of animals, involve animals with the lowest degree of
neurophysiological sensitivity, cause the least pain, suffering distress or
lasting harm, and [be the] most likely to produce satisfactory results" (Section
5(5) (b)). [25]

During a 2002 House of Lords select committee inquiry into animal testing in
the UK, witnesses stated that the UK has the tightest regulatory system in
the world, and is the only country to require a cost-benefit assessment of
every licence application. [26] There are 29 qualified inspectors covering 230
establishments, which are visited on average 11-12 times a year. [27](See
also Animal Procedures Committee.) A report by Animal Aid alleges that the
law governing animal research in the UK, The Animals (Scientific
Procedures) Act 1986, is a "vivisectors' charter," allowing researchers to do
as they please and making them practically immune from prosecution. The
report says that licences to perform experiments are obtained on the basis of
a "nod of approval" from the Home Office Inspectorate, and that the Home
Office relies on the researchers' own opinions of the cost-benefit assessment
regarding the value of the experiment versus the amount of suffering it will
cause.[25]

Japan
The system in Japan is one of self-regulation. Animal experiments are
regulated by one clause in the 2000 Law for the Humane Treatment and
Management of Animals [28]PDF, which requires those using animals to
cause minimal distress and suffering. There are no inspections, and there is
no reporting requirement for the numbers of animals used. [29] A 1988
survey published by the Japanese Association for Laboratory Animal
Science reported that eight million had been used that year. [26]

United States
In the United States, animal testing is primarily regulated by the 1966 Animal
Welfare Act (AWA),[27] which is enforced by the Animal Care division[28] of the
Animal and Plant Health Inspection Service (APHIS) of the United States
Department of Agriculture (USDA). The AWA contains provisions to ensure
that individuals of covered species used in research receive a certain
standard of care and treatment, provided that the standard of care and
treatment does not interfere with "the design, outlines, or guidelines of actual
research or experimentation."[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-
captured mice, rats, and birds) from regulations.[31] Thus, relatively few
animals used in research in the U.S. are covered by this legislation.[30] The
AWA requires each institution conducting animal testing using covered
species to maintain an Institutional Animal Care and Use Committee
(IACUC), which is responsible for enforcing the act. Institutions are subject to
unannounced annual inspections. There are over 100 inspectors[32]
monitoring around 1100 research institutions.[33] The inspectors also conduct
pre-licensing checks for sites that do not engage in animal research or
transportation, of which more than 4000 exist (e.g. dog kennels).[34]



APHIS has been criticized by its own inspectors and the USDA Inspector
General's office (OIG). Marshall Smith, an APHIS inspector for twelve years,
resigned in 1997 recounting a litany of problems at the agency that impeded
his duties. In a prepared statement, Smith made note of a 1992 OIG report
citing the agency's inability to ensure the humane care of animals at
dealers.[35] In 2000, Isis Johnson-Brown D.V.M. - another APHIS inspector -
quit because of problems she documented at the Oregon National Primate
Research Center, in Beaverton, Oregon. In a prepared statement Dr.
Johnson said, "More than once, I was instructed by a supervisor to make a
personal list of violations of the law, cut that list in half, and then cut that list
in half again before writing up my inspection reports. My willingness to
uphold the law during my site visits at the Primate Center led to me being
'retrained' several times by higher-ups in the USDA.[36] In 2005, the USDA
OIG issued another report on APHIS:

Of particular concern, AC management in the Eastern Region is not aggressively
pursuing enforcement actions against violators of the AWA. The Eastern Region
significantly reduced its referrals of suspected violators to the Investigative and
Enforcement Services (IES) unit—from an average of 209 cases in fiscal years
(FYs) 2002-2003 to 82 cases in FY 2004. When the region did refer cases to IES,
management declined to take enforcement action against 126 of 475 violators (27
percent).
When violators are assessed stipulated fines, the fines are usually minimal and not
always effective in preventing subsequent violations. Under current APHIS policy,
AC gives an automatic 75-percent discount to almost all violators as a means of
amicably reaching an agreement on the amount of the fines and avoiding court.
Finally, we noted that some VMOs when inspecting research facilities do not verify
the number of animals used in medical research or adequately review the facilities’
protocols and other records.[37]

Another regulatory instrument is the Public Health Service (PHS) Policy on
Humane Care and Use of Laboratory Animals, which became statutory with
the Health Research Extension Act 1985, and which is enforced by the Office
of Laboratory Animal Welfare (OLAW). This Act applies to any individual
scientist or institution in receipt of federal funds and requires each institution
to have an IACUC. OLAW enforces the standards of the Guide for the Care
and Use of Laboratory Animals[31] published by the Institute for Laboratory
Animal Research,[32] which includes all vertebrate species in its care
protocols, including rodents and birds[33] (Introduction, p.1). In 2004, the
National Institutes of Health provided funds to 3,180 different research
institutions and universities.[34] This means that IACUCs oversee the use of
all vertebrate species in research at facilities receiving federal funds, even if
the species are not covered by the AWA. OLAW does not carry out
scheduled inspections, but requires that "As a condition of receipt of PHS
support for research involving laboratory animals, awardee institutions must
provide a written Animal Welfare Assurance of Compliance (Assurance) to
OLAW describing the means they will employ to comply with the PHS
Policy."[38] OLAW conducts inspections only when there is a suspected or
alleged violation that cannot be resolved through written correspondence.
Accreditation from the Association for Assessment and Accreditation of
Laboratory Animal Care International (AAALAC),[39] a non-governmental,
nonprofit association, is regarded by the industry as the "gold standard" of
accreditation.[40] Accreditation is maintained through a prearranged AAALAC
site visit and program evaluation hosted by the member institution once
every three years.[41] Accreditation is intended to ensure compliance with the
standards in the Guide for the Care and Use of Laboratory Animals, as well
as any other national or local laws on animal welfare.

Animals used
Accurate global figures for animal testing are difficult to collect. The British
Union for the Abolition of Vivisection (BUAV) estimates that 100 million
animals are experimented on around the world every year, 10–11 million of
them in the European Union [35]PDF (100 KiB) and 1,101,958 mammals (not
including 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 number
of animals used annually in research around the world are difficult to obtain
and range from between 50 to 100 million animals."[6] Animals bred for
research then killed as surplus, or used for breeding purposes, are not
included in the figures.

According to the U.S. Department of Agriculture, the total number of animals
used in that country in 2002 was 1,137,718, not counting birds, mice, and
rats, which make up around 85% of research animals excluding
invertebrates. Other sources estimate the percentage of all lab animals that
are rats, mice, or birds at 85-90%,[42] or 95%[43] The Laboratory Primate
Advocacy Group has used these figures to estimate that 23-25 million
animals are used in research each year in America. [37] In 1986, a report
produced by the U.S. Congress Office of Technology Assessment reported
that "estimates of the animals used in the United States each year range
from 10 million to upwards of 100 million," and that their own best estimate
was "at least 17 million to 22 million."[44] In 1966, the Laboratory Animal
Breeders Association estimated in testimony before Congress that the
number of mice, rats, guinea pigs, hamsters, and rabbits used in 1965 was
around 60 million.[45] In 2004, the Department of Agriculture listed 64,932
dogs, 23,640 cats, 54,998 non-human primates, 244,104 guinea pigs,
175,721 hamsters, 261,573 rabbits, 105,678 farm animals, and 171,312
other mammals, a total of 1,101,958, a figure that includes all mammals
except purpose-bred mice and rats. Of that total, 615,000 were listed on
experiments that did not include more than momentary pain or distress,
399,000 were associated with experiments in which pain or distress was
relieved by drugs, and over 86,000 were listed on experiments that planned
to cause pain and distress that could not be relieved.[46] The use of dogs and
cats in research in the USA decreased from 1973 to 2004 from 195,157 to
64,932, and from 66,165 to 23,640, respectively[46][47]

Figures released by the British Home Office show that, in 2004, 2,854,944
procedures were carried out on 2,778,692 animals[48], an increase of 63,000
from 2003,[48] the third consecutive annual rise and the highest figure since
1992.[49] In 2005, the BBC reported that the UK figures continued to "creep
up...mainly due to the growing use of genetically modified mice"[50] with
2,896,198 procedures carried out on 2,812,850 animals in that year.[51]

The term "procedure" refers to an experiment, which might last several
months or even years. The figures show that most animals are used in only
one procedure: animals either die because of the experiment or are killed
and dissected afterwards.[52]

Over half the experiments in Britain in 2004 — 1,710,760 — either did not
require anesthetic (e.g. behavioral tests, breeding stock, controlled dietary
intake) or anesthesia was not used because this would interfere with the
experimental results; 880,897 experiments were conducted in connection
with pure research; 114,081 were toxicology tests, 982,640 were for
breeding, and most of the rest were for applied studies in human medicine,
veterinary medicine or dentistry. 9,035 involved the deliberate infliction of
"psychological stress".

Species
Drosophila are one of the most widely used animals for experimentation

Listed in descending order of numbers of individual animals used:

  Invertebrates

Most of the animals used in animal testing are invertebrates, especially
Drosophila melanogaster, a fruit fly, and Caenorhabditiselegans, a
nematode. In the case of C. elegans, the precise lineage of all the organism's
cells is known, and D. melanogaster has various characteristics making it
well suited to genetic studies. These animals offer scientists a number of
advantages over vertebrates, including their short life cycle and the ease with
which large numbers of individuals may be studied. Invertebrates are often
extremely cost-effective, as thousands of flies or nematodes can be housed
in a single room, but this is not true for all species of invertebrates.

With the exception of some cephalopods, invertebrate species are not
protected under most animal research legislation, and therefore the total
number of invertebrates used remains unknown.

  Rodents

Rodents commonly used include guinea pigs, hamsters, gerbils, rats and
mice. Mice are the most commonly utilized vertebrate species, popular
because of their availability, size, low cost, ease of handling, and fast
reproduction rate. Mice are widely considered to be the prime model of
inherited human disease and share 99% of their genes with humans.[53] With
the advent of genetic engineering technology, genetically modified mice can
be generated to order. The Mouse Genetics Core at Washington University
in St. Louis[54] explains what is required to produce today's widely used
transgenic and chimeric mice:

Production of Transgenic MiceThe Transgenic Animal Production service
consists of injecting each construct into 300-350 eggs, typically representing three
days work. Twenty to fifty mice will normally be born from this number of injected
eggs. These animals are screened for the presence of the transgene by a
polymerase chain reaction genotyping assay. The number of transgenic animals
typically varies from two to eight.

Production of Chimeric Mice The chimeric mouse production service consists of
injecting 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 this
number of injected blastocysts. Normally, the skin color of the mice from which the
host blastocysts are derived is different from that of the strain used to produce the
embryonic stem cells. Typically two to six mice will have skin and hair with greater
than seventy percent ES cell contribution, indicating a good chance for embryonic
stem cell contribution to the germline.
In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents
were used (84.5% of the total animals used that year). In 2005 the total
number of rodents used was similar to the previous year: 1,955,035 mice,
414,335 rats and 40,856 other rodents.[51]

In the U.S., the numbers of rats and mice used are not reported, but have
been 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/and
Birds Database: Researchers, Breeders, Transporters, and Exhibitors. [39]

Over 2,000 research organizations are listed in the database, of which
approximately 500 were researched and of these, 100 were contacted directly by
FRD staff. These organizations include hospitals, government organizations, private
companies (pharmaceutical companies, etc.), universities/colleges, a few
secondary schools, and research institutes. Of these 2,000, approximately 960 are
regulated by USDA; 349 by NIH; and 560 accredited by AALAC. Approximately 50
percent of the organizations contacted revealed a specific or approximated number
of animals in their laboratories. The total number of animals for those organizations
is: 250,000-1,000,000 rats; 400,000-2,000,000 mice; and 130,000-900,000 birds.

  Fish and amphibians

In 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 230,315
while the number of amphibians used decreased to 13,318.[51] The major
species utilized are the zebrafish, Daniorerio, which are translucent during
their embryonic stage, and the African clawed frog, Xenopuslaevis.

  Rabbits

Over 20,000 rabbits were used for animal testing in the UK in 2004. This
number decreased, in 2005, to 15,348.[51]Albino rabbits are used in eye
irritancy tests because rabbits have less tear flow than other animals and the
lack of eye pigment make the effects easier to visualize. They are also used
in skin irritancy tests (see Draize test). In 2004 less than 12% of the rabbits
were used for safety testing of non-medical products [41].

  Dogs
In 1957, Laika became the first animal to be launched into space, paving the way
for human spaceflight.

Beagles are used, because they are friendly and gentle, in toxicity tests,
surgery, and dental experiments. Toxicology tests are required to last six
months in the UK, although British laboratories carry out tests lasting nine
months on behalf of Japanese and American customers. Of the 8,018 dogs
used in the UK in 2004, 7,799 were beagles (97.3%). [42]PDF (1.19 MiB) In
2005 the number of dogs used in the UK decreased to 5,373.[51] Most dogs
are bred specifically for the purpose, for example by Harlan in Leicestershire.

  Non-human primates

In the United States, 54,998 non-human primates (NHPs) were used in 2004,
according to the U.S. Department of Agriculture (USDA), an annual figure
that has been more or less steady since 1973 [43]PDF (136 KiB) (p. 10). In
the European Union, 10,000 are used each year, with 4,208 used in Britain in
2004, a decrease of 591 from the previous year. [44] This decreasing trend
continued 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 is
allowed if the animals have been used in mild procedures with no lasting
side-effects, according to the Research Defence Society.[55] BUAV report that
it is because of re-use that there has been a fall in the number of individual
primates used in the UK.[56]




Filmed by PETA, Covance primate-testing lab, Vienna, Virginia, 2004-5.[57]
Most of the NHPs used are macaques, accounting for 79% of all primates
used in research in the UK, and 63% of all primate research grants in the
USA[58]. Lesser numbers of the New World primates marmosets, spider
monkeys, and squirrel monkeys are used in the UK, and baboons, New
World monkeys, and the Great Apechimpanzee used in the USA. Licenses
approving the use of apes, such as gorillas, chimpanzees, and orangutans,
are not currently being issued in Britain, though their use has not been
outlawed,[59] but chimpanzees are used in the U.S., with an estimated 1,500-
1600 still remaining in research laboratories, according to The Humane
Society of the United States.[60] NHPs are used in research into HIV,
neurology, behavior, cognition, reproduction, Parkinson's 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 are
most often used in hepatitis research, and monkeys in HIV research, and are
often 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 because
biomedical research funds in the USA have more than doubled since the
1990s.[61] In the U.S., the Oregon and California National Primate Research
Centers and New Iberia Research Center have expanded their
facilities;[62][63][64] in 2000 the National Institutes of Health (NIH) invited
applications for the establishment of new breeding specific pathogen free
colonies;[65] and a new breeding colony projected to house 3,000 NHPs has
been set up in Florida.[66] The NIH's National Center for Research Resources
identified a need to increase the number of breeding colonies in its 2004-
2008 strategic plan, as well as to set up a database, using information
provided through a network of National Primate Research Centers, to allow
researchers to locate NHPs with particular characteristics.[67]China is also
increasing its NHP use, and is regarded as attractive to Western companies
because of the low cost of research, the relatively lax regulations and the
increase in animal-rights activism in the West.[60]

In 2004, the British government reported "a definite long-term downward
trend" in the use of new world primates (for example, marmosets, tamarins,
squirrel, owl, spider and capuchin monkeys), but stated that the use of old
world primates (for example, baboons and macaques) fluctuates and is more
difficult to determine.[68]Crab-eating macaques and rhesus macaques are the
most commonly used species.[56] Home Office figures show the number of
primates 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 Office
defines as research conducted for the purpose of developing or testing
commercial products. Toxicology testing is the largest use.[70] The second
largest category of research using primates is "fundamental biological
research." This includes neuroscientific study of the visual system, cognition,
and diseases such as Parkinson's,[71] involving techniques such as inserting
electrodes to record from or stimulate the brain, and temporary or permanent
inactivation of areas of tissue.

In 1996, the British Animal Procedures Committee recommended new
measures for dealing with NHPs. The use of wild-caught primates was
banned, except where "exceptional and specific justification can be
established"; specific justification must be made for the use of old world
primates (but not for the use of new world primates); approval for the
acquisition of primates from overseas is conditional upon their breeding or
supply center being acceptable to the Home Office; and each batch of
primates acquired from overseas must be separately authorized. [72]

  Cats

Felines are most commonly used in neurological research. In the UK in 2005,
308 cats were used. This is a decrease from 819 cats recorded in 2004
[45].[51] According to the USDA, over 25,500 felines were used in the USA in
2000, of these around half were reported to have been used in experiments
that caused "pain and/or distress". The number of cats used in research in
the 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
Experiments can be split into three broad,                     AMPAAAS
                                                              Pro-TestNIH
overlapping categories: pure research, in
                                                              AVMAAALAS
which experiments are conducted that have
no direct commercial application, with a view                     Issues
to advancing knowledge, most often inside
universities; applied research, conducted in                  Animal rights
                                                             Animal testing
order to solve specific biological problems or               Animal welfare
to develop commercial products, either for
medical or non-medical use; and toxicology                        Writers
or safety testing, in which commercial
                                                               Carl Cohen
products are tested on animals to measure                    Roger Scruton
potential adverse biological reactions to the                Richard Posner
ingredients.                                                  TiborMachan

                                                          This box: view • talk • edit
Pure research
Basic or pure research aims to increase
knowledge about the way organisms behave, develop, and function
biologically.

Both the largest number and greatest variety of laboratory animals are used
in this type of research. Drosophila melanogaster, Caenorhabditiselegans,
mice and rats together account for the vast majority, though small numbers
of 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 cats
were 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 research
include:

  Mutagenesis to study mechanisms in embryogenesis and developmental
   biology. Animals are often treated with mutagenic chemicals or radiation
   to generate defective embryos. By studying disrupted development,
   scientists aim to understand both how organisms develop normally and
   abnormally [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
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 research
Applied research aims to solve specific and practical problems, often relating
to the treatment or cure of disease and disorder in humans and animals.

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

  Genetic modification of animals to study disease. Transgenic animals have
   specific genes inserted, modified or removed, with the aim of modelling a
   specific condition. The aim of these models may be to exactly mimic a
   known single gene disorder, such as Duchenne muscular dystrophy or
   albinism, then use the model to investigate novel ways it may be treated.
   Other models are generated to approximate complex, multifactorial
   disease with a genetic component, such as cancer or Alzheimer's
   disease, then investigate how and why the disease develops. The vast
   majority of transgenic models of disease are mice [64], the mammalian
   species in which genetic modification is most efficient, though there are
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 on
xenotransplation is motivated by the desire to save human lives. The US
FDA says "The development of xenotransplantation is, in part, driven by
the fact that the demand for human organs for clinical transplantation far
exceeds the supply. Currently ten patients die each day in the United
States while on the waiting list to receive life-saving vital organ transplants.
Moreover, recent evidence has suggested that transplantation of cells and
tissues may be therapeutic for certain diseases such as neurodegenerative
disorders and diabetes, where, again human materials are not usually
available.".[73] In Great Britain, the government agency UKXIRA states
"There is currently, and will continue to be, a shortage of human organs
and tissue for transplantation....Xenotransplantation is a potential solution
to 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 called
xenotransplatation experiments "some of the most grisly procedures
carried out anywhere in the name of science." They write that: "They do
sometimes involve a full transplant of a genetically modified pig heart into a
monkey. In some cases, however, the doctors will graft the transgenic
hearts onto a baboon's neck arteries, as this allows them to observe the
way the pig heart behaves in another species, and monitor the rejection
process. The operation is carried out under general anaesthetic and the
baboon is humanely killed afterwards. These measures, however, do not
pacify animal rights campaigners, who say the experiments are cruel and
unnecessary."[76] Details of the effects of these experimental procedures
came to light when thousands of documents were leaked to a UK-based
animal rights organization. After a legal battle, the documents were
published in a report titled Diaries of Despair.[89]
      Toxicology testing
      Drug testing
Dogs used for safety testing of pharmaceuticals in a UK facility, 2000.
Provided by RDS/Wellcome Trust Photographic Library [23]

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

   metabolic tests, which are performed to find out how the drugs
   are absorbed, metabolized and excreted by the body when
   introduced orally, intravenously, intraperitoneally, or
   intramuscularly.
   toxicology tests, which gauge acute, sub-acute, and chronic
   toxicity. Acute toxicity is studied by using a rising dose until signs
   of toxicity become apparent. Current European legislation,
   Directive 2001/83/EC [90]PDF (371 KiB) (p44), demands "acute
   toxicity tests must be carried out in two or more mammalian
   species" covering "at least two different routes of administration".
   Subacute toxicity is where the drug is given to the animals for
   four to six weeks in doses below the level at which it becomes
   toxic, in order to discover the effects of the build up of toxic
   metabolites. Testing for chronic toxicity can last up to two years
   and, in the European Union, is required to utilize "two species of
   mammals, one of which must be non-rodent" [91]PDF (371 KiB)
   (p45). The data gained from this period can be used to calculate
   the maximum tolerable dose; that is, the dose where signs of
   toxicity begin to occur.
   efficacy studies, which test whether experimental drugs work by
   inducing the appropriate illness in animals using an animal model
   of the disease. The drug is then administered in a double-blind
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Animal testing

  • 1. Animal testing From 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 vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of 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 and rats used in the United States alone in 2001 was 80 million.[2] Most animals are euthanized after being used in an experiment.[3]Sources of laboratory animals vary between countries and species; most animals are purpose-bred, while others are caught in the wild or supplied by dealers 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 services to industry.[5] It includes pure research such as genetics, developmental biology, behavioral studies, as well as applied research such as biomedical research, xenotransplantation, drug testing and toxicology tests, including cosmetics testing. Animals are also used for education,
  • 2. breeding, and defense research. The practice is regulated to various degrees in different countries. Supporters of the use of animals in experiments, such as the British Royal Society, argue that virtually every medical achievement in the 20th century relied on the use of animals in some way,[6] with the Institute for Laboratory Animal Research of the U.S. National Academy of Sciences arguing that even sophisticated computers are unable to model interactions between molecules, cells, tissues, organs, organisms, and the environment, making animal research necessary in many areas.[7] A number of scientists, animal welfare, and animal rights organizations—such as PETA and BUAV—question the legitimacy of it, arguing that it is cruel, poor scientific practice, poorly regulated, that medical progress is being held back by misleading animal models, that some of the tests are outdated, that it cannot reliably predict effects in humans, that the costs outweigh the benefits, or that animals have an intrinsic right not 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. Definitions The terms animal testing, animal experimentation, animal research, in vivo testing, and vivisection have similar denotations but different connotations. Literally, "vivisection" means the "cutting up" of a living animal, and historically referred only to experiments that involved the dissection of live animals. The term is occasionally used to refer pejoratively to any experiment using living animals; for example, the Encyclopædia Britannica defines "vivisection" as: "Operation on a living animal for experimental rather than healing purposes; more broadly, all experimentation on live animals",[9] although dictionaries point out that the broader definition is "used only by people who are opposed to such work".[10] The word has a negative connotation, implying torture, suffering, and death.[11] The word "vivisection" is preferred by those opposed to this research, whereas scientists typically use the term "animal experimentation".[12][13] History Main article: History of animal testing An Experiment on a Bird in an Air Pump, from 1768, by Joseph Wright The earliest references to animal testing are found in the writings of the Greeks in the 2nd and 4th centuries BCE. Aristotle (Αριστοτέλης) (384–322 BCE) and Erasistratus (304–258 BCE) were among the first to perform experiments on living animals.[14]Galen, a physician in 2nd-century Rome, dissected pigs and goats, and is known as the "father of vivisection."[15]Avenzoar, an Arabic physician in 12th-century Moorish Spain who also practiced dissection, introduced animal testing as an experimental method of testing surgical procedures 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 in sheep.[18] In the 1890s, Ivan Pavlov famously used dogs to describe classical conditioning.[19]Insulin was first isolated from dogs in 1922, and revolutionized the treatment of diabetes.[20] On November 3, 1957, a Russian dog, Laika, became the first of many animals to orbit the earth. In the 1970s, antibiotic treatments and vaccines for leprosy were developed using armadillos,[21] then given to humans.[22] The ability of humans to change the genetics of animals took a large step forwards in 1974 when Rudolf Jaenisch was able to produce the first transgenic mammal, by integrating DNA from the SV40 virus into the genome of mice.[23] This genetic research progressed rapidly and, in 1996, Dolly the sheep was born, the first mammal to be cloned from an adult cell.[24]
  • 4. Toxicology testing became important in the 20th century. In the 19th century, laws regulating drugs were more relaxed. For example, in the U.S., the government could only ban a drug after 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 killed more than 100 users, the U.S. congress passed laws that required safety testing of drugs on animals before they could be marketed. Other countries enacted similar legislation.[25] In the 1960s, in reaction to the Thalidomide tragedy, further laws were passed requiring safety testing on pregnant animals before a drug can be sold.[26] Historical debate Claude Bernard, regarded as the "prince of vivisectors"[27] argued that experiments on animals are "entirely conclusive for the toxicology and hygiene of man".[28] As the experimentation on animals increased, especially the practice of vivisection, so did criticism and controversy. In 1655, the advocate of Galenic physiology Edmund O'Meara said that "the miserable torture of vivisection places the body in an unnatural state."[29][30] O'Meara and others argued that animal physiology could be affected by pain during vivisection, 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 objections to animal testing also came from another angle — many people believed that animals were inferior to humans and so different that results from animals could not be applied to humans.[30] On the other side of the debate, those in favor of animal testing held that experiments on animals were necessary to advance medical and biological knowledge. Claude Bernard, known as the "prince of vivisectors"[27] and the father of physiology—whose wife, Marie Françoise Martin, founded the first anti-vivisection society in France in 1883[31]—famously wrote in 1865 that "the science of life is a superb and dazzlingly lighted hall which may be reached only by passing through a long and ghastly kitchen".[32] Arguing that "experiments on animals ... are entirely conclusive for the toxicology and hygiene of man...the effects of these 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 antivivisectionists are the second of the two types Theodore Roosevelt described when he said, ‗Common sense without conscience may lead to crime, but conscience without common sense may lead to
  • 5. folly, which is the handmaiden of crime.‘ ‖[34] These divisions between pro- and anti- animal testing groups first came to public attention during the brown dog affair in the early 1900s, when hundreds of medical students clashed with anti-vivisectionists and police over a memorial to a vivisected dog.[35] One of Pavlov‘s dogs with a saliva-catch container and tube surgically implanted in his muzzle, Pavlov Museum, 2005 In 1822, the first animal protection law was enacted in the British parliament, followed by the Cruelty to Animals Act (1876), the first law specifically aimed at regulating animal testing. The legislation was promoted by Charles Darwin, who wrote to Ray Lankester in March 1871: "You ask about my opinion on vivisection. I quite agree that it is justifiable for real investigations on physiology; but not for mere damnable and detestable curiosity. It is a subject which makes me sick with horror, so I will not say another word about it, else I shall not sleep to-night."[36][37] Opposition to the use of animals in medical research first arose in the United States during the 1860s, when Henry Bergh founded the American Society for the Prevention of Cruelty to Animals (ASPCA), with America's first specifically anti-vivisection organization being the American AntiVivisection Society (AAVS), founded in 1883. Antivivisectionists of the era generally believed the spread of mercy was the great cause of civilization, and vivisection was cruel. However, in the USA the antivivisectionists' efforts were defeated in every legislature, overwhelmed by the superior organization and influence of the medical community. Overall, this movement had little legislative success until the passing of the Laboratory Animal Welfare Act, in 1966.[38] Care and use of animals See also: Animal testing regulations, Institutional Animal Care and Use Committee, and Animals (Scientific Procedures) Act 1986 Regulations The regulations that apply to animals in laboratories vary across species. In the U.S., under the provisions of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals (the Guide), published by the National Academy of Sciences, any procedure can be performed on an animal if it can be successfully argued that it is scientifically justified. In general, researchers are required to consult with the institution's veterinarian and its Institutional Animal Care and Use Committee (IACUC), which every research facility is obliged to maintain.[39] The IACUC must ensure that alternatives, including non-animal alternatives, have been considered, that the experiments are not unnecessarily duplicative, and that pain relief is given unless it would interfere with the study. Larry Carbone, a laboratory animal veterinarian, writes that, in his experience, IACUCs take their work very seriously regardless of the species involved, though the use of non-human primates always
  • 6. raises what he calls a "red flag of special concern."[40] A study published in Science magazine in July 2001 confirmed the low reliability of IACUC reviews of animal experiments. Funded by the National Science Foundation, the three-year study found that animal-use committees that do not know the specifics of the university and personnel do not make the same approval decisions as those made by animal-use committees that do know the university and personnel. Specifically, blinded committees more often ask for more information rather than approving studies.[41] The IACUCs regulate all vertebrates in testing at institutions receiving federal funds in the USA. Although the provisions of the Animal Welfare Act do not include purpose-bred rodents and birds, these species are equally regulated under Public Health Service policies that 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 by AAALAC. Numbers Types of vertebrates used in animal testing in Europe in 2005: a total of 12.1 million animals were used.[44] Accurate global figures for animal testing are difficult to obtain. The British Union for the Abolition of Vivisection (BUAV) estimates that 100 million vertebrates are experimented on around the world every year, 10–11 million of them in the European Union.[45] The Nuffield Council on Bioethics reports that global annual estimates range from 50 to 100 million animals. None of the figures include invertebrates such as shrimp and fruit flies.[46] Animals bred for research then killed as surplus, animals used for breeding purposes, and animals not yet weaned are also not included in the figures.[47] According to the U.S. Department of Agriculture (USDA), the total number of animals used in that country in 2005 was almost 1.2 million,[48] but this does not include rats and mice, which make up about 90% of research animals.[49][50] In 1995, researchers at Tufts University Center for Animals and Public Policy estimated that 14–21 million animals were used in American laboratories in 1992, a reduction from a high of 50 million used in 1970.[51] In 1986, the U.S. Congress Office of Technology Assessment reported that estimates of the animals used in the U.S. range from 10 million to upwards of 100 million each year, and that their own best estimate was at least 17 million to 22 million.[52] In the UK, Home Office figures show that 3.2 million procedures were carried out in 2007, a rise of 189,500 since the previous year. Four thousand procedures used non-human primates,
  • 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 die because of the experiment or are euthanized afterwards.[46] Species Invertebrates Fruit flies are commonly used. Main article: Animal testing on invertebrates Although many more invertebrates than vertebrates are used, these experiments are largely unregulated by law. The most used invertebrate species are Drosophila melanogaster, a fruit fly, and Caenorhabditiselegans, a nematode worm. In the case of C. elegans, the worm's body is completely transparent and the precise lineage of all the organism's cells is known,[54] while studies in the fly D. melanogaster can use an amazing array of genetic tools.[55] These animals offer great advantages over vertebrates, including their short life cycle and the ease with which large numbers may be studied, with thousands of flies or nematodes fitting into a single room. However, the lack of an adaptive immune system and their simple organs prevent 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 system differs greatly from that of humans,[57] and diseases in insects can be very different from diseases in vertebrates.[58] Vertebrates Enos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961 Further information: Animal testing on frogs, Animal testing on rabbits, Animal testing on rodents, Draize test, and Median lethal dose
  • 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 platform where the rat sits. At the onset of REM sleep, the rat would either fall into the water only to clamber back to its pot to avoid drowning, or its nose would become submerged into the water 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] Other rodents commonly used are guinea pigs, hamsters, and gerbils. Mice are the most commonly used vertebrate species because of their size, low cost, ease of handling, and fast reproduction rate.[59] Mice are widely considered to be the best model of inherited human disease and share 99% 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 of human 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 these rodents in basic science.[60] Nearly 200,000 fish and 20,000 amphibians were used in the UK in 2004.[61] The main species 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 testing in the UK in 2004.[61]Albino rabbits are used in eye irritancy tests because rabbits have less tear flow than other animals, and the lack of eye pigment in albinos make the effects easier to visualize.[61] Rabbits are also frequently used for the production of polyclonal antibodies. Cats and dogs See also: Laika and Russian space dogs Cats are most commonly used in neurological research. Over 25,500 cats were used in the U.S. in 2000, around half of whom were used in experiments which, according to the American 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 human diseases in cardiology, endocrinology, and bone and joint studies, research that tends to be highly invasive, according to the Humane Society of the United States.[63] The U.S. Department of Agriculture's Animal Welfare Report for 2005 shows that 66,000 dogs were used 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 buy animals from auctions, shelters, newspaper ads, and who are sometimes accused of stealing pets.[64] Non-human primates Main article: Animal testing on non-human primates
  • 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 are domestically 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, around 70,000 NHPs are used each year in the United States and European Union.[44][48] Most of the NHPs used are macaques;[67] but marmosets, spider monkeys, and squirrel monkeys are also used, and baboons and chimpanzees are used in the U.S; in 2006 there were 1133 chimpanzees 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 genetic disorderHuntington's disease.[70] Notable studies on non-human primates have been part of the polio vaccine development, and development of Deep Brain Stimulation, and their current heaviest non-toxicological use occurs in the monkey AIDS model, SIV.[6][67][71] In 2008 a proposal to ban all primates experiments in the EU has sparked a vigorous debate.[72] Sources Main articles: Laboratory animal sources and International trade in primates Animals used by laboratories are largely supplied by specialist dealers. Sources differ for vertebrate and invertebrate animals. Most laboratories breed and raise flies and worms themselves, using strains and mutants supplied from a few main stock centers.[73] For vertebrates, sources include breeders who supply purpose-bred animals; businesses that trade in wild animals; and dealers who supply animals sourced from pounds, auctions, and newspaper ads. Animal shelters also supply the laboratories directly.[74] Large centers also exist to distribute strains of genetically-modified animals; the National Institutes of HealthKnockout Mouse Project, for example, aims to provide knockout mice for every gene in the mouse genome.[75]
  • 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) to sell animals for research purposes, while Class B dealers are licensed to buy animals from "random sources" such as auctions, pound seizure, and newspaper ads. Some Class B dealers have been accused of kidnapping pets and illegally trapping strays, a practice known as bunching.[76] It was in part out of public concern over the sale of pets to research facilities that the 1966 Laboratory Animal Welfare Act was ushered in — the Senate Committee on Commerce reported in 1966 that stolen pets had been retrieved from Veterans Administration facilities, the Mayo Institute, the University of Pennsylvania, Stanford University, and Harvard and Yale Medical Schools.[77] The USDA recovered at least a dozen stolen pets during 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 to provide animals to research facilities. Fourteen states explicitly prohibit the practice, while the 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 imported and is not a wild animal or a stray. The latter requirement may also be exempted by special arrangement.[80] In the UK, most animals used in experiments are bred for the purpose under the 1988 Animal Protection Act, but wild-caught primates may be used if exceptional and specific justification can be established.[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 River Laboratories, Inc., or by Covance, which is the single largest importer of primates into the U.S.[83] Pain and suffering Further information: Animal cognition and Pain in animals
  • 11. Prior to vivisection for educational purposes, chloroform was administered to this common sand frog to induce terminal anesthesia. The extent to which animal testing causes pain and suffering, and the capacity of animals to experience 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%) (not including rats, mice, birds, or invertebrates) were used in procedures that did not include more than momentary pain or distress. About 420,000 (36%) were used in procedures in which pain or distress was relieved by anesthesia, while 84,000 (7%) were used in studies that 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 the suffering the researchers conducting the study say they may cause; a fourth category of "unclassified" means the animal was anesthetized and killed without recovering consciousness, according to the researchers. In December 2001, 1,296 (39%) of project licenses 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 systemic underestimation 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 pain and suffering because they lack consciousness.[46][88]Bernard Rollin of Colorado State University, 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 animal pain.[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 for claiming that they feel pain.[90] Carbone writes that the view that animals feel pain differently is now a minority view. Academic reviews of the topic are more equivocal, noting that although the argument that animals have at least simple conscious thoughts and feelings has strong support,[91] some critics continue to question how reliably animal mental states can be determined.[46][92] The ability of invertebrate species of animals, such as insects, to feel pain and suffering is also unclear.[93][94]
  • 12. The defining text on animal welfare regulation, "Guide for the Care and Use of Laboratory Animals" defines the parameters that govern animal testing in the USA. It states "The ability to experience and respond to pain is widespread in the animal kingdom...Pain is a stressor and, if not relieved, can lead to unacceptable levels of stress and distress in animals."[95] The Guide states that the ability to recognize the symptoms of pain in different species is vital in efficiently applying pain relief and that it is essential for the people caring for and using animals to be entirely familiar with these symptoms. On the subject of analgesics used to relieve pain, the Guide states "The selection of the most appropriate analgesic or anesthetic should reflect professional judgment as to which best meets clinical and humane requirements without compromising the scientific aspects of the research protocol". Accordingly, all issues of animal pain and distress, and their potential treatment with analgesia and anesthesia, are required regulatory issues in receiving animal protocol approval. Euthanasia Further information: Euthanasia and Animal euthanasia There is general agreement that animal life should not be taken wantonly, and regulations require that scientists use as few animals as possible.[96] However, while policy makers consider suffering to be the central issue and see animal euthanasia as a way to reduce suffering, others, such as the RSPCA, argue that the lives of laboratory animals have intrinsic value.[97] Regulations focus on whether particular methods cause pain and suffering, not whether their death is undesirable in itself.[98] The animals are euthanized at the end of studies for sample collection or post-mortem examination; during studies if their pain or suffering falls into certain categories regarded as unacceptable, such as depression, infection that is unresponsive to treatment, or the failure of large animals to eat for five days;[99] or when they are unsuitable for breeding or unwanted for some other reason.[100] Methods of euthanizing laboratory animals are chosen to induce rapid unconsciousness and death without pain or distress.[101]The methods that are preferred are those published by councils of veterinarians. The animal can be made to inhale a gas, such as carbon monoxide and carbon dioxide, by being placed in a chamber, or by use of a face mask, with or without prior sedation or anesthesia. Sedatives or anesthetics such as barbiturates can be given intravenously, or inhalant anesthetics may be used. Amphibians and fish may be immersed in water containing an anesthetic such as tricaine. Physical methods are also used, with or without sedation or anesthesia depending on the method. Recommended methods include decapitation (beheading) for small rodents or rabbits. Cervical dislocation (breaking the neck or spine) may be used for birds, mice, and immature rats and rabbits. Maceration (grinding into small pieces) is used on 1 day old chicks. High-intensity microwave irradiation of the brain can preserve brain tissue and induce death in less than 1 second, but this is currently only used on rodents. Captive bolts may be used, typically on dogs, ruminants, horses, pigs and rabbits. It causes death by a concussion to the brain. Gunshot may be used, but only in cases where a penetrating captive bolt may not be used. Some physical methods are only acceptable 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 to induce unconsciousness.[102]
  • 13. Research classification Pure research Basic or pure research investigates how organisms behave, develop, and function. Those opposed to animal testing object that pure research may have little or no practical purpose, but researchers argue that it may produce unforeseen benefits, rendering the distinction between pure and applied research—research that has a specific practical aim—unclear.[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, though small 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 research Applied 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 the pharmaceutical industry, or by universities in commercial partnerships. These may involve the use of animal models of diseases or conditions, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the drug discovery process. Examples include:
  • 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 Huntington's 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 Parkinson's 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 Parkinson's disease, the British anti-vivisection interest group BUAV argues that these models only superficially resemble the disease symptoms, without the same time course or cellular pathology.[125] In contrast, scientists assessing the usefulness of animal models of Parkinson's disease, as well as the medical research charity The Parkinson's 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] Xenotransplantation Main article: Xenotransplantation Xenotransplantation research involves transplanting tissues or organs from one species to another, 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 been genetically-modified to reduce the primates' immune response against the pig tissue.[128] Although transplant rejection remains a problem,[128] recent clinical trials that involved implanting pig insulin-secreting cells into diabetics did reduce these people's need for insulin.[129][130] Documents released to the news media by the animal rights organization Uncaged Campaigns showed that, between 1994 and 2000, wild baboons imported to the UK from Africa by Imutran Ltd, a subsidiary of NovartisPharma AG, in conjunction with Cambridge University
  • 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 that the company had communicated with the British government in an attempt to avoid regulation.[87][131] Toxicology testing Main article: Toxicology testing Further information: Draize test, LD50, Acute toxicity, and Chronic toxicity Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities, such as Huntingdon Life Sciences, on behalf of a wide variety of customers.[132] According to 2005 EU figures, around one million animals are used every year in Europe in toxicology tests; which are about 10% of all procedures.[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, because interactions between drugs can affect how animals detoxify chemicals, and may interfere with the results.[134][135] A rabbit during a Draize test Toxicology tests are used to examine finished products such as pesticides, medications, food additives, packing materials, and air freshener, or their chemical ingredients. Most tests involve testing ingredients rather than finished products, but according to BUAV, manufacturers believe these tests overestimate the toxic effects of substances; they therefore repeat the tests using their finished products to obtain a less toxic label.[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 and restraining them, or by placing them in an inhalation chamber; or administered orally, through a tube into the stomach, or simply in the animal's food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal.[citation needed] There are several different types of acute toxicity tests. The LD50 ("Lethal Dose 50%") test is used to evaluate the toxicity of a substance by determining the dose required to kill 50% of the test animal population. This test was removed from OECD international guidelines in 2002, replaced by methods such as the fixed dose procedure, which use fewer animals and cause 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 be measured using the Draize test, where a test substance is applied to an animal's eyes or skin, usually an albino rabbit. For Draize eye testing, the test involves observing the effects of the substance at intervals and grading any damage or irritation, but the test should be halted and
  • 16. the animal killed if it shows "continuing signs of severe pain or distress".[138] The Humane Society of the United States writes that the procedure can cause redness, ulceration, hemorrhaging, cloudiness, or even blindness.[139]This test has also been criticized by scientists for being cruel and inaccurate, subjective, over-sensitive, and failing to reflect human exposures in the real world.[140] Although no accepted in vitro alternatives exist, a modified form of the Draize test called the low volume eye test may reduce suffering and provide more realistic results and this was adopted as the new standard in September 2009.[141][142] However, the Draize test will still be used for substances that are not severe irritants.[142] The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), one to three months (subchronic), and more than three months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take three or four years to complete. These toxicity tests provide, in the words of a 2006 United States National Academy of Sciences report, "critical information for assessing hazard and risk potential".[143]Nature reported that most animal tests either over- or underestimate risk, or do not reflect toxicity in humans particularly well,[133] with false positive results being a particular problem.[144]This variability stems from using the effects of high doses of chemicals in small numbers of laboratory animals to try to predict the effects of low doses in large numbers of humans.[145]Although relationships do exist, opinion is divided on how to use data on one species to predict the exact level of risk in another.[146] Cosmetics testing Products in Europe not tested on animals carry this symbol. Main article: Testing cosmetics on animals Cosmetics testing on animals is particularly controversial. Such tests, which are still conducted in the U.S., involve general toxicity, eye and skin irritancy, phototoxicity (toxicity triggered by ultraviolet light) and mutagenicity.[147] Cosmetics testing is banned in the Netherlands, Belgium, and the UK, and in 2002, after 13 years of discussion, the European Union (EU) agreed to phase in a near-total ban on the sale of animal-tested cosmetics throughout the EU from 2009, and to ban all cosmetics-related animal testing. France, which is home to the world's largest cosmetics company, L'Oreal, has protested the proposed ban by lodging a case at the European Court of Justice in Luxembourg, asking that the ban be quashed.[148] The ban is also opposed by the European
  • 17. Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland, Belgium, France, Germany and Italy.[148] Drug testing Beagles used for safety testing of pharmaceuticals in a British facility Before the early 20th century, laws regulating drugs were lax. Currently, all new pharmaceuticals undergo rigorous animal testing before being licensed for human use. Tests on 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 defense Animals are also used for education and training; are bred for use in laboratories; and are used by the military to develop weapons, vaccines, battlefield surgical techniques, and defensive clothing.[103] For example, in 2008 the United States Defense Advanced Research Projects Agency used live pigs to study the effects of improvised explosive device explosions on internal organs, especially the brain.[151]
  • 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 Assessing Alternatives to Animal Experimentation, while describing Germany's progress in this area, told German broadcaster ARD in 2005: "Using animals in teaching curricula is already superfluous. In many countries, one can become a doctor, vet or biologist without ever having performed an experiment on an animal."[153] Ethics Background Further information: Animal welfare and Animal rights Monument for animals used in testing at Keio University The ethical questions raised by performing experiments on animals are subject to much debate, and viewpoints have shifted significantly over the 20th century.[154]There remain disagreements about which procedures are useful for which purposes, as well as disagreements over which ethical principles apply to which species. The dominant ethical position worldwide is that achievement of scientific and medical goals using animal testing is desirable, so long as animal suffering and use is minimized.[155] The British government has additionally required that the cost to animals in an experiment be weighed against the gain in knowledge.[156]Some medical schools and agencies in China, Japan, and South Korea have built 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 (animal rights) is a philosophical position proposed by Tom Regan, among others, who argues that animals are beings with beliefs and desires, and as such are the "subjects of a life" with moral value and therefore moral rights.[158] Regan still sees ethical differences between killing human and non-human animals, and argues that to save the former it is permissible to kill the latter. Others, such as Bernard Rollin, argue that benefits to human beings cannot outweigh animal suffering, and that human beings have no moral right to use an animal in ways that do not benefit that individual. Another prominent position is that of philosopher Peter Singer, who argues that there are no grounds to include a being's species in considerations of whether their suffering is important in utilitarian moral considerations.[159]
  • 19. Although these arguments have not been widely accepted, governments such as the Netherlands and New Zealand have responded to the concerns by outlawing invasive experiments on certain classes of non-human primates, particularly the great apes.[160][161] Prominent cases Various specific cases of animal testing have drawn attention, including both instances of beneficial scientific research, and instances of alleged ethical violations by those performing the 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 using frog muscles (including the force generating mechanism of all muscle,[162] the length-tension relationship,[163] and the force-velocity curve[164]), and frogs are still the preferred model organism due to the long survival of muscles in vitro and the possibility of isolating intact single-fiber preparations (not possible in other organisms).[165] Modern physical therapy and the understanding and treatment of muscular disorders is based on this work and subsequent work in mice (often engineered to express disease states such as muscular dystrophy).[166] University of California, Riverside Main article: Britches (monkey) 1985 was a pivotal year in the debate about animal research in the United States, with the enactment of amendments to the Animal Welfare Act.[167]Britches, a macaque monkey, was born that year inside the University of California, Riverside, removed from his mother at birth, and left alone with his eyelids sewn shut, and a sonar sensor on his head, as part of an experiment to test sensory substitution devices for blind people. The Animal Liberation Front raided the laboratory on April 20, 1985, removing Britches and 466 other animals, and reportedly inflicting $700,000-worth of damage to equipment.[168]A spokesman for the university said the allegations of mistreatment were false, and that the raid caused long-term damage 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 Sciences Footage filmed by PeTA inside Huntingdon Life Sciences showed staff mistreating beagles. Main article: Stop Huntingdon Animal Cruelty
  • 20. In 1997, People for the Ethical Treatment of Animals filmed staff inside Huntingdon Life Sciences (HLS) in the UK, Europe's largest animal-testing facility, hitting puppies, shouting at them, and simulating sex acts while taking blood samples.[171] The company said the employees were dismissed.[172] Two pleaded guilty to "cruelly terrifying dogs," and were given community service orders and ordered to pay £250 costs, the first lab technicians to have been prosecuted for animal cruelty in the UK.[173] The broadcast of the video on Britain's Channel 4 Television in March 1997 triggered the formation of Stop Huntingdon Animal Cruelty (SHAC), an international leaderless resistance campaign to close HLS, which has been criticized for its sometimes violent tactics.[174] In January 2009, several British SHAC activists were jailed for blackmailing companies linked to HLS.[175] Roslin Institute Main article: Dolly (sheep) Dolly the sheep: the first clone produced from an adult animal In February 1997 a team at the Roslin Institute in Scotland announced the birth of Dolly the sheep, a ewe that had been cloned from tissue taken from another adult sheep.[24] Dolly was produced through nuclear transfer to an unfertilisedoocyte, and was the only lamb that survived from 277 attempts at this technique.[176] Dolly appeared to be a normal sheep, living for six years and giving birth to several lambs, but was euthanized in 2003 after contracting a progressive 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 use in farming,[178] but also that it would now be, in principle, possible to clone a human being.[179] University of Cambridge A marmoset after being brain damaged, filmed at Cambridge by the BUAV Main article: Primate experiments at Cambridge University The British Union for the Abolition of Vivisection (BUAV) raised concerns about primate experiments at the University of Cambridge in 2002. In a series of court cases, the BUAV alleged that monkeys had undergone surgery to induce a stroke, and were left alone after the procedure for 15 hours overnight. Researchers had trained the monkeys to perform certain tasks before inflicting brain damage and re-testing them. The monkeys were only given food and water for two hours a day, to encourage them to perform the tasks. The judge hearing
  • 21. BUAV's application for a judicial review rejected the allegation that the Home Secretary had been negligent in granting the university a license.[180] The British government's chief inspector of animals conducted a review of the facilities and experiments. It concluded the veterinary input at Cambridge was "exemplary"; the facility "seems adequately staffed"; and the animals afforded "appropriate standards of accommodation and care."[181] Columbia University Main article: Primate experiments at Columbia University CNN reported in October 2003 that Catherine Dell'Orto, a veterinarian at Columbia University, had approached the university's Institute of Comparative Medicine about the treatment of baboons who were undergoing surgery as part of an experiment into stroke treatment. She said the baboons, who were in some cases having an eyeball removed, were left 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 presented her evidence in October 2002 and, dissatisfied with the response, contacted People for the Ethical Treatment of Animals two months later.[182] In March 2003, a lab technician shot video inside the lab, which according to The New York Daily News showed primates in cages without pain medication; the video included one baboon with a metal cylinder screwed into its head, according to the newspaper. Dell'Orto told 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 of Agriculture upheld Dell'Orto's complaint that there was shoddy record-keeping, and that 11 animals had been provided with "inadequate or questionable care." They found no evidence that the experiments violated federal guidelines or that there had been retaliation against Dell'Orto. CNN reported that Columbia responded by ordering better record-keeping, a review of the veterinary care program, and tighter criteria for euthanasia of laboratory animals.[184] Covance Main article: Covance In 2004, German journalist Friedrich Mülln shot undercover footage of staff in Covance, Münster, Europe's largest primate-testing center, making monkeys dance in time to blaring pop music, handling them roughly, and screaming at them. The monkeys were kept isolated in small wire cages with little or no natural light, no environmental enrichment, and high noise levels from staff shouting and playing the radio[185] (video). PrimatologistJane Goodall described 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, and trying to extrapolate useful data in such circumstances is what he called an untenable proposition.[185]In 2004 and 2005, PETA shot footage inside the company in the United States. According to The Washington Post, PETA said an employee of the group filmed primates 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 lab monkeys; the other citations involved administrative issues and equipment.[187] Threats to researchers
  • 22. In 2006, a primate researcher at the University of California, Los Angeles (UCLA) shut down the experiments in his lab after threats from animal rights activists. The researcher had received a grant to use 30 macaque monkeys for vision experiments; each monkey was anesthetized for a single physiological experiment lasting up to 120 hours, and then euthanized.[188]The researcher's name, phone number, and address were posted on the website of the Primate Freedom Project. Demonstrations were held in front of his home. A Molotov cocktail was placed on the porch of what was believed to be the home of another UCLA primate researcher; instead, it was accidentally left on the porch of an elderly woman unrelated to the university. The Animal Liberation Front claimed responsibility for the attack.[189] As a result of the campaign, the researcher sent an email to the Primate Freedom Project stating "you win," and "please don‘t bother my family anymore."[190] In another incident at UCLA in June 2007, the Animal Liberation Brigade placed a bomb under the car of a UCLA children's ophthalmologist who experiments on cats and rhesus monkeys; the bomb had a faulty fuse and did not detonate.[191] UCLA is now refusing Freedom of Information Act requests for animal medical records. These attacks, as well as similar incidents that caused the Southern Poverty Law Center to declare in 2002 that the animal rights movement had "clearly taken a turn toward the more extreme," this prompted the US government to pass the Animal Enterprise Terrorism Act and the UK government to add the offense of "Intimidation of persons connected with animal research organisation" to the Serious Organised Crime and Police Act 2005.[192]Such legislation, and the arrest and imprisonment of extremists may have decreased the incidence of attacks.[193] Alternatives to animal testing Main article: Alternatives to animal testing Scientists and governments state that animal testing should cause as little suffering to animals as possible, and that animal tests should only be performed where necessary. The "three Rs"[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 welfare groups,[195] they have also been criticized as both outdated by current research,[196] and of little practical effect in improving animal welfare.[197]
  • 23. Animal testing From Wikipedia, the free encyclopedia Enos 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 the U.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 and mice to non-human primates — are used annually and may either be killed during the experiments or subsequently euthanised. The research is carried out inside universities, medical schools, pharmaceutical companies, farms, defense- research establishments, and commercial facilities that provide animal-testing services to industry. [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 supporting animal research, writes, "Animal research has played a vital role in virtually every major medical advance of the last century." [9] Many major developments that led to 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, or that animals have an intrinsic right not to be used for experimentation. [13][14] Contents [hide]
  • 24. 1History 2Modern Regulation 2.1Europe 2.2Japan 2.3United States 3Animals used 3.1Species 4Types of experiment 4.1Pure research 4.2Applied research 4.3Toxicology testing  4.3.1Drug testing  4.3.2Cosmetics testing 5Controversy 5.1Huntingdon Life Sciences 5.2Covance 5.3University of Cambridge 5.4University of California, Riverside 5.5Columbia University 5.6University of California, Los Angeles 6Sampling public opinions on animal testing 7Alternatives to animal testing 8The arguments in brief 8.1Official statements from representative bodies 8.2Advocates of animal testing 8.3Opponents of animal testing 9See also 10Links 11References 11.1Numbered references 11.2Other References 12Further reading History
  • 25. One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in his muzzle. 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. Europe Experiments on vertebrate animals in the European Union are subject to Directive 86/609/EEC on the protection of Animals used for Experimental and other Scientific purposes, adopted in 1986. [16] There is considerable variation in the manner member countries choose to exercise the directive: compare, for example, legislation from Sweden, [17]The Netherlands, [18] and Germany. [19] France In France, legislation (principally the decree of October 19, 1987) requires an institutional and project licence before testing on vertebrates may be carried out. An institution must submit details of their facilities and the reason for the use of animals they house, after which a five-year licence may be granted following an inspection of the premises. The project licensee must be trained and educated to an appropriate level. Personal licences are not required for individuals working under the supervision of a project licence holder. [20][21] United Kingdom Technician 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-profit organizations (4.9%); government departments (2.4%); National Health Service hospitals (0.9%); public health laboratories (0.6%); other public bodies (15.8%). [23] The Animals (Scientific Procedures) Act 1986[24] requires experiments to be regulated by three licences: a project licence for the scientist in charge of the project, which details the numbers and types of animals to be used, the experiments to be performed, and the purpose of them; a certificate for the institution to ensure it has adequate facilities and staff; and a personal licence for each scientist or technician who carries out any procedure. In
  • 27. deciding whether to grant a licence, the Home Office refers to the Act's cost- benefit analysis, which is defined as "the likely adverse effects on the animals concerned against the benefit likely to accrue as a result of the programme to be specified in the licence" (Section 5(4)). A licence should not be granted if there is a "reasonably practicable method not entailing the use of protected animals" (Section 5(5) (a)). The experiments must use "the minimum number of animals, involve animals with the lowest degree of neurophysiological sensitivity, cause the least pain, suffering distress or lasting harm, and [be the] most likely to produce satisfactory results" (Section 5(5) (b)). [25] During a 2002 House of Lords select committee inquiry into animal testing in the UK, witnesses stated that the UK has the tightest regulatory system in the world, and is the only country to require a cost-benefit assessment of every licence application. [26] There are 29 qualified inspectors covering 230 establishments, which are visited on average 11-12 times a year. [27](See also Animal Procedures Committee.) A report by Animal Aid alleges that the law governing animal research in the UK, The Animals (Scientific Procedures) Act 1986, is a "vivisectors' charter," allowing researchers to do as they please and making them practically immune from prosecution. The report says that licences to perform experiments are obtained on the basis of a "nod of approval" from the Home Office Inspectorate, and that the Home Office relies on the researchers' own opinions of the cost-benefit assessment regarding the value of the experiment versus the amount of suffering it will cause.[25] Japan The system in Japan is one of self-regulation. Animal experiments are regulated by one clause in the 2000 Law for the Humane Treatment and Management of Animals [28]PDF, which requires those using animals to cause minimal distress and suffering. There are no inspections, and there is no reporting requirement for the numbers of animals used. [29] A 1988 survey published by the Japanese Association for Laboratory Animal Science reported that eight million had been used that year. [26] United States In the United States, animal testing is primarily regulated by the 1966 Animal Welfare Act (AWA),[27] which is enforced by the Animal Care division[28] of the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA). The AWA contains provisions to ensure that individuals of covered species used in research receive a certain standard of care and treatment, provided that the standard of care and treatment does not interfere with "the design, outlines, or guidelines of actual research or experimentation."[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. captured mice, rats, and birds) from regulations.[31] Thus, relatively few animals used in research in the U.S. are covered by this legislation.[30] The AWA requires each institution conducting animal testing using covered species to maintain an Institutional Animal Care and Use Committee (IACUC), which is responsible for enforcing the act. Institutions are subject to unannounced annual inspections. There are over 100 inspectors[32] monitoring around 1100 research institutions.[33] The inspectors also conduct pre-licensing checks for sites that do not engage in animal research or transportation, of which more than 4000 exist (e.g. dog kennels).[34] APHIS has been criticized by its own inspectors and the USDA Inspector General's office (OIG). Marshall Smith, an APHIS inspector for twelve years, resigned in 1997 recounting a litany of problems at the agency that impeded his duties. In a prepared statement, Smith made note of a 1992 OIG report citing the agency's inability to ensure the humane care of animals at dealers.[35] In 2000, Isis Johnson-Brown D.V.M. - another APHIS inspector - quit because of problems she documented at the Oregon National Primate Research Center, in Beaverton, Oregon. In a prepared statement Dr. Johnson said, "More than once, I was instructed by a supervisor to make a personal list of violations of the law, cut that list in half, and then cut that list in half again before writing up my inspection reports. My willingness to uphold the law during my site visits at the Primate Center led to me being 'retrained' several times by higher-ups in the USDA.[36] In 2005, the USDA OIG issued another report on APHIS: Of particular concern, AC management in the Eastern Region is not aggressively pursuing enforcement actions against violators of the AWA. The Eastern Region significantly reduced its referrals of suspected violators to the Investigative and Enforcement Services (IES) unit—from an average of 209 cases in fiscal years (FYs) 2002-2003 to 82 cases in FY 2004. When the region did refer cases to IES, management declined to take enforcement action against 126 of 475 violators (27 percent). When violators are assessed stipulated fines, the fines are usually minimal and not always effective in preventing subsequent violations. Under current APHIS policy, AC gives an automatic 75-percent discount to almost all violators as a means of amicably reaching an agreement on the amount of the fines and avoiding court. Finally, we noted that some VMOs when inspecting research facilities do not verify the number of animals used in medical research or adequately review the facilities’ protocols and other records.[37] Another regulatory instrument is the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, which became statutory with the Health Research Extension Act 1985, and which is enforced by the Office of Laboratory Animal Welfare (OLAW). This Act applies to any individual scientist or institution in receipt of federal funds and requires each institution to have an IACUC. OLAW enforces the standards of the Guide for the Care and Use of Laboratory Animals[31] published by the Institute for Laboratory
  • 29. Animal Research,[32] which includes all vertebrate species in its care protocols, including rodents and birds[33] (Introduction, p.1). In 2004, the National Institutes of Health provided funds to 3,180 different research institutions and universities.[34] This means that IACUCs oversee the use of all vertebrate species in research at facilities receiving federal funds, even if the species are not covered by the AWA. OLAW does not carry out scheduled inspections, but requires that "As a condition of receipt of PHS support for research involving laboratory animals, awardee institutions must provide a written Animal Welfare Assurance of Compliance (Assurance) to OLAW describing the means they will employ to comply with the PHS Policy."[38] OLAW conducts inspections only when there is a suspected or alleged violation that cannot be resolved through written correspondence. Accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC),[39] a non-governmental, nonprofit association, is regarded by the industry as the "gold standard" of accreditation.[40] Accreditation is maintained through a prearranged AAALAC site visit and program evaluation hosted by the member institution once every three years.[41] Accreditation is intended to ensure compliance with the standards in the Guide for the Care and Use of Laboratory Animals, as well as any other national or local laws on animal welfare. Animals used Accurate global figures for animal testing are difficult to collect. The British Union for the Abolition of Vivisection (BUAV) estimates that 100 million animals are experimented on around the world every year, 10–11 million of them in the European Union [35]PDF (100 KiB) and 1,101,958 mammals (not including 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 number of animals used annually in research around the world are difficult to obtain and range from between 50 to 100 million animals."[6] Animals bred for research then killed as surplus, or used for breeding purposes, are not included in the figures. According to the U.S. Department of Agriculture, the total number of animals used in that country in 2002 was 1,137,718, not counting birds, mice, and rats, which make up around 85% of research animals excluding invertebrates. Other sources estimate the percentage of all lab animals that are rats, mice, or birds at 85-90%,[42] or 95%[43] The Laboratory Primate Advocacy Group has used these figures to estimate that 23-25 million animals are used in research each year in America. [37] In 1986, a report produced by the U.S. Congress Office of Technology Assessment reported that "estimates of the animals used in the United States each year range from 10 million to upwards of 100 million," and that their own best estimate was "at least 17 million to 22 million."[44] In 1966, the Laboratory Animal Breeders Association estimated in testimony before Congress that the number of mice, rats, guinea pigs, hamsters, and rabbits used in 1965 was
  • 30. around 60 million.[45] In 2004, the Department of Agriculture listed 64,932 dogs, 23,640 cats, 54,998 non-human primates, 244,104 guinea pigs, 175,721 hamsters, 261,573 rabbits, 105,678 farm animals, and 171,312 other mammals, a total of 1,101,958, a figure that includes all mammals except purpose-bred mice and rats. Of that total, 615,000 were listed on experiments that did not include more than momentary pain or distress, 399,000 were associated with experiments in which pain or distress was relieved by drugs, and over 86,000 were listed on experiments that planned to cause pain and distress that could not be relieved.[46] The use of dogs and cats in research in the USA decreased from 1973 to 2004 from 195,157 to 64,932, and from 66,165 to 23,640, respectively[46][47] Figures released by the British Home Office show that, in 2004, 2,854,944 procedures were carried out on 2,778,692 animals[48], an increase of 63,000 from 2003,[48] the third consecutive annual rise and the highest figure since 1992.[49] In 2005, the BBC reported that the UK figures continued to "creep up...mainly due to the growing use of genetically modified mice"[50] with 2,896,198 procedures carried out on 2,812,850 animals in that year.[51] The term "procedure" refers to an experiment, which might last several months or even years. The figures show that most animals are used in only one procedure: animals either die because of the experiment or are killed and dissected afterwards.[52] Over half the experiments in Britain in 2004 — 1,710,760 — either did not require anesthetic (e.g. behavioral tests, breeding stock, controlled dietary intake) or anesthesia was not used because this would interfere with the experimental results; 880,897 experiments were conducted in connection with pure research; 114,081 were toxicology tests, 982,640 were for breeding, and most of the rest were for applied studies in human medicine, veterinary medicine or dentistry. 9,035 involved the deliberate infliction of "psychological stress". Species
  • 31. Drosophila are one of the most widely used animals for experimentation Listed in descending order of numbers of individual animals used: Invertebrates Most of the animals used in animal testing are invertebrates, especially Drosophila melanogaster, a fruit fly, and Caenorhabditiselegans, a nematode. In the case of C. elegans, the precise lineage of all the organism's cells is known, and D. melanogaster has various characteristics making it well suited to genetic studies. These animals offer scientists a number of advantages over vertebrates, including their short life cycle and the ease with which large numbers of individuals may be studied. Invertebrates are often extremely cost-effective, as thousands of flies or nematodes can be housed in a single room, but this is not true for all species of invertebrates. With the exception of some cephalopods, invertebrate species are not protected under most animal research legislation, and therefore the total number of invertebrates used remains unknown. Rodents Rodents commonly used include guinea pigs, hamsters, gerbils, rats and mice. Mice are the most commonly utilized vertebrate species, popular because of their availability, size, low cost, ease of handling, and fast reproduction rate. Mice are widely considered to be the prime model of inherited human disease and share 99% of their genes with humans.[53] With the advent of genetic engineering technology, genetically modified mice can be generated to order. The Mouse Genetics Core at Washington University in St. Louis[54] explains what is required to produce today's widely used transgenic and chimeric mice: Production of Transgenic MiceThe Transgenic Animal Production service consists of injecting each construct into 300-350 eggs, typically representing three days work. Twenty to fifty mice will normally be born from this number of injected eggs. These animals are screened for the presence of the transgene by a polymerase chain reaction genotyping assay. The number of transgenic animals typically varies from two to eight. Production of Chimeric Mice The chimeric mouse production service consists of injecting 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 this number of injected blastocysts. Normally, the skin color of the mice from which the host blastocysts are derived is different from that of the strain used to produce the embryonic stem cells. Typically two to six mice will have skin and hair with greater than seventy percent ES cell contribution, indicating a good chance for embryonic stem cell contribution to the germline.
  • 32. In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents were used (84.5% of the total animals used that year). In 2005 the total number of rodents used was similar to the previous year: 1,955,035 mice, 414,335 rats and 40,856 other rodents.[51] In the U.S., the numbers of rats and mice used are not reported, but have been 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/and Birds Database: Researchers, Breeders, Transporters, and Exhibitors. [39] Over 2,000 research organizations are listed in the database, of which approximately 500 were researched and of these, 100 were contacted directly by FRD staff. These organizations include hospitals, government organizations, private companies (pharmaceutical companies, etc.), universities/colleges, a few secondary schools, and research institutes. Of these 2,000, approximately 960 are regulated by USDA; 349 by NIH; and 560 accredited by AALAC. Approximately 50 percent of the organizations contacted revealed a specific or approximated number of animals in their laboratories. The total number of animals for those organizations is: 250,000-1,000,000 rats; 400,000-2,000,000 mice; and 130,000-900,000 birds. Fish and amphibians In 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 230,315 while the number of amphibians used decreased to 13,318.[51] The major species utilized are the zebrafish, Daniorerio, which are translucent during their embryonic stage, and the African clawed frog, Xenopuslaevis. Rabbits Over 20,000 rabbits were used for animal testing in the UK in 2004. This number decreased, in 2005, to 15,348.[51]Albino rabbits are used in eye irritancy tests because rabbits have less tear flow than other animals and the lack of eye pigment make the effects easier to visualize. They are also used in skin irritancy tests (see Draize test). In 2004 less than 12% of the rabbits were used for safety testing of non-medical products [41]. Dogs
  • 33. In 1957, Laika became the first animal to be launched into space, paving the way for human spaceflight. Beagles are used, because they are friendly and gentle, in toxicity tests, surgery, and dental experiments. Toxicology tests are required to last six months in the UK, although British laboratories carry out tests lasting nine months on behalf of Japanese and American customers. Of the 8,018 dogs used in the UK in 2004, 7,799 were beagles (97.3%). [42]PDF (1.19 MiB) In 2005 the number of dogs used in the UK decreased to 5,373.[51] Most dogs are bred specifically for the purpose, for example by Harlan in Leicestershire. Non-human primates In the United States, 54,998 non-human primates (NHPs) were used in 2004, according to the U.S. Department of Agriculture (USDA), an annual figure that has been more or less steady since 1973 [43]PDF (136 KiB) (p. 10). In the European Union, 10,000 are used each year, with 4,208 used in Britain in 2004, a decrease of 591 from the previous year. [44] This decreasing trend continued 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 is allowed if the animals have been used in mild procedures with no lasting side-effects, according to the Research Defence Society.[55] BUAV report that it is because of re-use that there has been a fall in the number of individual primates used in the UK.[56] Filmed by PETA, Covance primate-testing lab, Vienna, Virginia, 2004-5.[57]
  • 34. Most of the NHPs used are macaques, accounting for 79% of all primates used in research in the UK, and 63% of all primate research grants in the USA[58]. Lesser numbers of the New World primates marmosets, spider monkeys, and squirrel monkeys are used in the UK, and baboons, New World monkeys, and the Great Apechimpanzee used in the USA. Licenses approving the use of apes, such as gorillas, chimpanzees, and orangutans, are not currently being issued in Britain, though their use has not been outlawed,[59] but chimpanzees are used in the U.S., with an estimated 1,500- 1600 still remaining in research laboratories, according to The Humane Society of the United States.[60] NHPs are used in research into HIV, neurology, behavior, cognition, reproduction, Parkinson's 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 are most often used in hepatitis research, and monkeys in HIV research, and are often 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 because biomedical research funds in the USA have more than doubled since the 1990s.[61] In the U.S., the Oregon and California National Primate Research Centers and New Iberia Research Center have expanded their facilities;[62][63][64] in 2000 the National Institutes of Health (NIH) invited applications for the establishment of new breeding specific pathogen free colonies;[65] and a new breeding colony projected to house 3,000 NHPs has been set up in Florida.[66] The NIH's National Center for Research Resources identified a need to increase the number of breeding colonies in its 2004- 2008 strategic plan, as well as to set up a database, using information provided through a network of National Primate Research Centers, to allow researchers to locate NHPs with particular characteristics.[67]China is also increasing its NHP use, and is regarded as attractive to Western companies because of the low cost of research, the relatively lax regulations and the increase in animal-rights activism in the West.[60] In 2004, the British government reported "a definite long-term downward trend" in the use of new world primates (for example, marmosets, tamarins, squirrel, owl, spider and capuchin monkeys), but stated that the use of old world primates (for example, baboons and macaques) fluctuates and is more difficult to determine.[68]Crab-eating macaques and rhesus macaques are the most commonly used species.[56] Home Office figures show the number of primates 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 Office defines as research conducted for the purpose of developing or testing commercial products. Toxicology testing is the largest use.[70] The second largest category of research using primates is "fundamental biological research." This includes neuroscientific study of the visual system, cognition, and diseases such as Parkinson's,[71] involving techniques such as inserting
  • 35. electrodes to record from or stimulate the brain, and temporary or permanent inactivation of areas of tissue. In 1996, the British Animal Procedures Committee recommended new measures for dealing with NHPs. The use of wild-caught primates was banned, except where "exceptional and specific justification can be established"; specific justification must be made for the use of old world primates (but not for the use of new world primates); approval for the acquisition of primates from overseas is conditional upon their breeding or supply center being acceptable to the Home Office; and each batch of primates acquired from overseas must be separately authorized. [72] Cats Felines are most commonly used in neurological research. In the UK in 2005, 308 cats were used. This is a decrease from 819 cats recorded in 2004 [45].[51] According to the USDA, over 25,500 felines were used in the USA in 2000, of these around half were reported to have been used in experiments that caused "pain and/or distress". The number of cats used in research in the 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. Experiments can be split into three broad, AMPAAAS Pro-TestNIH overlapping categories: pure research, in AVMAAALAS which experiments are conducted that have no direct commercial application, with a view Issues to advancing knowledge, most often inside universities; applied research, conducted in Animal rights Animal testing order to solve specific biological problems or Animal welfare to develop commercial products, either for medical or non-medical use; and toxicology Writers or safety testing, in which commercial Carl Cohen products are tested on animals to measure Roger Scruton potential adverse biological reactions to the Richard Posner ingredients. TiborMachan This box: view • talk • edit Pure research Basic or pure research aims to increase knowledge about the way organisms behave, develop, and function biologically. Both the largest number and greatest variety of laboratory animals are used in this type of research. Drosophila melanogaster, Caenorhabditiselegans, mice and rats together account for the vast majority, though small numbers of 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 cats were 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 research include: Mutagenesis to study mechanisms in embryogenesis and developmental biology. Animals are often treated with mutagenic chemicals or radiation to generate defective embryos. By studying disrupted development, scientists aim to understand both how organisms develop normally and abnormally [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. 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 research Applied research aims to solve specific and practical problems, often relating to the treatment or cure of disease and disorder in humans and animals. Compared to pure research, which is largely academic in origin, applied research programmes are more likely to be carried out in the pharmaceutical industry, or in universities in commercial partnership. These may involve the use of animal models of disease or condition, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the modern drug discovery process. Examples of animal use in this type of research include: Genetic modification of animals to study disease. Transgenic animals have specific genes inserted, modified or removed, with the aim of modelling a specific condition. The aim of these models may be to exactly mimic a known single gene disorder, such as Duchenne muscular dystrophy or albinism, then use the model to investigate novel ways it may be treated. Other models are generated to approximate complex, multifactorial disease with a genetic component, such as cancer or Alzheimer's disease, then investigate how and why the disease develops. The vast majority of transgenic models of disease are mice [64], the mammalian species in which genetic modification is most efficient, though there are
  • 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 on xenotransplation is motivated by the desire to save human lives. The US FDA says "The development of xenotransplantation is, in part, driven by
  • 39. the fact that the demand for human organs for clinical transplantation far exceeds the supply. Currently ten patients die each day in the United States while on the waiting list to receive life-saving vital organ transplants. Moreover, recent evidence has suggested that transplantation of cells and tissues may be therapeutic for certain diseases such as neurodegenerative disorders and diabetes, where, again human materials are not usually available.".[73] In Great Britain, the government agency UKXIRA states "There is currently, and will continue to be, a shortage of human organs and tissue for transplantation....Xenotransplantation is a potential solution to 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 called xenotransplatation experiments "some of the most grisly procedures carried out anywhere in the name of science." They write that: "They do sometimes involve a full transplant of a genetically modified pig heart into a monkey. In some cases, however, the doctors will graft the transgenic hearts onto a baboon's neck arteries, as this allows them to observe the way the pig heart behaves in another species, and monitor the rejection process. The operation is carried out under general anaesthetic and the baboon is humanely killed afterwards. These measures, however, do not pacify animal rights campaigners, who say the experiments are cruel and unnecessary."[76] Details of the effects of these experimental procedures came to light when thousands of documents were leaked to a UK-based animal rights organization. After a legal battle, the documents were published in a report titled Diaries of Despair.[89] Toxicology testing Drug testing
  • 40. Dogs used for safety testing of pharmaceuticals in a UK facility, 2000. Provided by RDS/Wellcome Trust Photographic Library [23] In response to the teratogenic effects of Thalidomide in the 1960s, many countries passed new laws to ensure all new pharmaceuticals underwent rigorous animal testing before being licensed for human use. Tests on pharmaceutical products involve: metabolic tests, which are performed to find out how the drugs are absorbed, metabolized and excreted by the body when introduced orally, intravenously, intraperitoneally, or intramuscularly. toxicology tests, which gauge acute, sub-acute, and chronic toxicity. Acute toxicity is studied by using a rising dose until signs of toxicity become apparent. Current European legislation, Directive 2001/83/EC [90]PDF (371 KiB) (p44), demands "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration". Subacute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it becomes toxic, in order to discover the effects of the build up of toxic metabolites. Testing for chronic toxicity can last up to two years and, in the European Union, is required to utilize "two species of mammals, one of which must be non-rodent" [91]PDF (371 KiB) (p45). The data gained from this period can be used to calculate the maximum tolerable dose; that is, the dose where signs of toxicity begin to occur. efficacy studies, which test whether experimental drugs work by inducing the appropriate illness in animals using an animal model of the disease. The drug is then administered in a double-blind