Animal testing

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. Other sources estimate the percentage of all lab animals that are rats, mice, or birds at 85-90%["National Association of Biomedical Research], or 95%"Science Magazine, Trull and Rich 1999 Vol. 284. no. 5419, p. 1463The Laboratory Primate Advocacy Group has used these figures to estimate that 23-25 million animals are used in research each year in America. [link] 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." Alternatives to Animal Use in Research, Testing and Education, U.S. Congress Office of Technology Assessment, Washington, D.C.:Government Printing Office, 1986, p. 64. 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. Hearings before the Subcommittee on Livestock and Feed Grains, Committee on Agriculture, U.S. House of Representatives, 1966, p. 63 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 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["USDA Animal Welfare Act Report 2004]. 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["USDA Animal Welfare Act Report 2004]http://www.fbresearch.org/Education/quickfacts.htm "Foundation for Biomedical Research, Quick Facts

Figures released by the British Home Office show that, in 2004, 2,854,944 procedures were carried out on 2,778,692 animals ["Statistics of Scientific Procedures on Living Animals"], Great Britain, 2004, p. 14 (pdf), an increase of 63,000 from 2003, the third consective annual rise and the highest figure since 1992. Jha, Alok. ["RSPCA outrage as experiments on animals rise to 2.85m"], The Guardian, December 9, 2005. 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. ["UK Legislation: A Criticism"], British Union for the Abolition of Vivisection.(pdf).

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

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

Fish and amphibia

Rabbits

Dogs

Non-human primates

Most of the NHPs used are baboons, macaques, marmosets, and chimpanzees. Licenses approving the use of non-human great apes, such as gorillas, chimpanzees, and orangutans (also known as Hominidae), are not currently being issued in Britain, though their use has not been outlawed, ["Testing on apes 'might be needed'"], BBC News, June 3, 2006. but chimpanzees are used in the U.S., with an estimated 1,300 still remaining in research laboratories, according to The Humane Society of the United States. ["An Introduction to Primate Issues"], The Humane Society of the United States, retrieved July 13, 2006. 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.

There are indications that NHP use is on the rise, in part because biomedical research funds in the USA have more than doubled since the 1990s["Senate completes NIH doubling in 2003"]. In the U.S., the Oregon and California National Primate Research Centers and New Iberia Research Center have expanded their facilities["ONPRC Outdoor shelters"]["CNPRC expanding"][New 12,000 sq ft facility at New Iberia]; in 2000 the National Institutes of Health (NIH) invited applications for the establishment of new breeding specific pathogen free colonies["NIH RFA for new breeding colonies"]; and a new breeding colony projected to house 3,000 NHPs has been set up in Florida["Panther Tracts at Primate Products"]. 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. ["2004-2008 Strategic Plan: Challenges and Critical Choices"], National Center for Research Resources, National Institutes of Health. 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.

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. ["Statistics of Scientific Procedures on Living Animals"] , Great Britain, 2004, p. 16 Cynomolgous macaques and rhesus macaques are the most commonly used species.

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. Langley, Gill. "Next of Kin: A Report on the Use of Primates in Experiments," British Union for the Abolition of Vivisection, June 2006, p.33-34. The second largest category of research using primates is "fundamental biological research." This includes inducing brain damage in order to research Parkinson's, studying visual and auditory functions, and cognitive research. Langley, Gill. "Next of Kin: A Report on the Use of Primates in Experiments," British Union for the Abolition of Vivisection, June 2006, p.37.

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. ["Statistics of Scientific Procedures on Living Animals"] , Great Britain, 2004, p. 87

NHP use in xenotransplantation

Medical journalists Jenny Bryan and John Clare have called these 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." Bryan, Jenny & Clare, John. Organ Farm, Carlton Books, 2001.

Cats

Types of experiment

Pure research

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

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

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

• Experiments into behaviour, to understand how organisms detect and interact with each other and their environment. Fruit flies, worms, mice and rats are all widely used in research into mechanisms of vision, [link] taste, [link] hearing, [link] touch, [link] and smell. [link] In addition studies of brain function, such as memory and social behaviour, often use rats and birds. [link] 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 [link] [link]. 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 [link]. Scientists studying mechanisms of evolution use a number of animal species, including mosquitos [link], sticklebacks [link], cichlids [link] and lampreys [link], due to their niche physiology, morphology, ecology or phylogeny.

Toxicology testing

Drug testing

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

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 [link] (pdf, p44), demands "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration". Subacute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it becomes toxic, in order to discover the effects of the build up of toxic metabolites. Testing for chronic toxicity can last up to two years and, in the European Union, is required to utilize "two species of mammals, one of which must be non-rodent" [link] (pdf, p45). The data gained from this period can be used to calculate the maximum tolerable dose; that is, the dose where signs of toxicity begin to occur.
• efficacy studies, which test whether experimental drugs work by inducing the appropriate illness in animals using an animal model of the disease. The drug is then administered in a double-blind controlled trial. This is intended to allow scientists to determine the effect of the drug and the dose-response curve.
• Specific tests on reproductive function, embryonic toxicity or carcinogenic potential can all be required by law, dependent of the result of other studies and type of drug being tested.

Cosmetics testing

Products in Europe not tested on animals carry this symbol

Products not tested on animals in the UK carry this British Union for the Abolition of Vivisection logo

U.S. and Canadian products that carry this Coalition for Consumer Information on Cosmetics (CCIC) logo do not test their products or ingredients on animals

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

Cosmetic testing on animals includes:

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

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

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

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

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

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

Cosmetics manufacturers who genuinely do not test on animals generally use the following for safety testing of their products:

• reliance on existing natural or synthetic ingredients, compounds and substances, which have already been extensively tested on animals;
• avoiding novel ingredients or combinations of ingredients that have not been fully tested and may not be safe;
• testing on human volunteers/clinical trials.

Controversy

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

Huntingdon Life Sciences

PETA filmed staff inside a British laboratory owned by Huntingdon Life Sciences (HLS), Europe's largest animal-testing facility, punching puppies in the face, screaming at them, and simulating sex acts while taking blood samples [Undercover video footage of HLS employees beating a puppy], filmed at the Huntingdon Research Centre, England. (video). Footage shot in the U.S. appeared to show technicians dissecting a live monkey [Undercover video footage of HLS employees apparently dissecting a live monkey], filmed at the HLS Princeton Research Centre, NJ, USA. (video).

Covance

Image by Friedrich Mülln

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 are kept isolated in small wire cages with little or no natural light, no environmental enrichment, and high noise levels from staff shouting and playing the radio [Undercover footage of staff in Covance screaming at and mocking monkeys] (video).

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

University of Cambridge

In February 2005, while applying for a judicial review of laboratory practices in the United Kingdom, BUAV told the High Court in London that internal documents from the University of Cambridge's primate-testing labs showed that monkeys had had the tops of their heads sawn off to induce a stroke, and were then left alone after the procedure for 15 hours overnight, with no veterinary care, because staff only worked from nine to five. [link] The BUAV judicial challenge followed a 10-month undercover investigation by BUAV into three research programmes at Cambridge in 1998. BUAV's lawyer, David Thomas, told the court: "The whole system is very secretive and the public does not get to see what is really going on." [link]

The experiments involved the use of hundreds of macaque monkeys, who were deliberately brain damaged for the purpose of research into strokes and Parkinson's disease. The macaques were first trained to perform behavioral and cognitive tasks. Researchers then caused brain damage either by removing parts of the macaque's brains or by injecting toxins. The monkeys were then re-tested to determine how the damage had affected their skills. They were deprived of food and water to encourage them to perform the tasks, with water being withheld for 22 out of every 24 hours. [link] [link] (video)

The Home Office investigated the BUAV report and the judge hearing BUAV's application for a judicial review rejected the allegation that the Home Secretary had been negligent in granting the university a licence. [link] [link] The Research Defence Society, a lobby group representing 5,000 medical researchers and institutions in the UK, wrote in a summmary of the case: "[F]or this research into stroke monkeys were fully anaesthetised, a piece of the skull bone was removed (in the same way as for human neurosurgery), one blood vessel was permanently blocked, the skull bone was replaced, the muscle and skin resewn and appropriate pain killers given. On recovery from anaesthesia, monkeys were kept in an incubator, offered food and water and monitored at regular intervals until the early evening. They were then allowed to sleep in the incubators until the next morning. No monkeys died unattended during the night after stroke surgery." [link]

University of California, Riverside

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

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

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

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

Columbia University

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

Alternatives to animal testing

Most scientists and governments say they agree that animal testing should cause as little suffering to animals as possible, and that animal tests should only be performed where necessary. The "three Rs" [link] are guiding principles for the use of animals in research in many countries:

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

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

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

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

Institutes researching (and organizations funding) alternatives to animal testing include:

• The Johns Hopkins Center for Alternatives to Animal Testing
• The University of California Center for Animal Alternatives
• Dr Hadwen Trust
• The Fund for the Replacement of Animals in Medical Experiments [link]
• The National Centre for Replacement, Refinement and Reduction of Animals in Research [link]
• The 3R Research Foundation [link]

The arguments in brief

Advocates of animal testing

• It would be unethical to test substances or drugs with potentially adverse side-effects on human beings. [link]
• Controlled experiments involve introducing only one variable at a time, which is why animals are experimented on while confined inside a laboratory. Human beings could not be confined in this way. [link]
• There is no substitute for the living systems necessary to study interaction among cells, tissue, and organs. Animals are good surrogates because of their similarities to humans. [link]
• There is no substitute for psychiatric studies (e.g., antidepressant clinical trials) that require behavioral data.
• Animals have shorter life and reproductive spans, meaning that several generations can be studied in a relatively short time.
• Animals can be bred especially for animal-testing purposes, meaning they arrive at the laboratory free from disease.
• Humans that use medicine derived from animal research are healthier. [link]
• Animals receive more sophisticated medical care because of animal tests that have led to advances in veterinary medicine. [link]
• There have been several examples of substances causing death or injury to human beings because of inadequate animal testing. [link]
• Over 10 times more animals are killed and harmed in everyday life (eg. pest control , euthanasia of unwanted pets, hunting, and agriculture) than in animal experiments.
• Activists manipulate and fabricate facts, therefore their claims are not reliable.
• Alternatives to certain kinds of animal testing are unknown.
• Wherever practical alternatives exist, they are often likely to be introduced for economical reasons, like testing on rodents instead of primates because of their lower cost of keeping.

Opponents of animal testing

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