Author: Kristin Stone

In contrast to product testing, in which some animal use is required by law, there is no law requiring the use of animals to study basic biology, or the pathology and treatment of human illness. Here, animal experiments are a carry-over from the early days of biology and medicine. Increasingly, however, other approaches are proving their worth as alternatives to harmful research on animals. These include the following:

Epidemiological Studies:Comparative studies of human populations allow doctors and scientists to discover the root causes of human diseases and disorders so that preventive action can be taken. The science of epidemiology is based on comparisons, for example, among disease rates in populations with differing levels of exposure to the factor under investigation. The discoveries of the relationships between smoking and cancer, cholesterol and heart disease, high-fat diets and common cancers, and chemical exposures and birth defects derive from epidemiology. Epidemiological investigations also demonstrated the mechanism of transmission of AIDS and virtually every other infectious disease, which in turn showed how these diseases can be prevented.

Clinical Studies:In the course of treating patients, much has been learned about the causes of diseases and disorders. Studies of human patients using sophisticated scanning technology (e.g., MRI, PET and CT) have isolated abnormalities in the brains of patients with Alzheimer’s disease, schizophrenia, epilepsy, and autism.

In Vitro Research: Cell and tissue culture (in vitro) studies are used to screen for anti-cancer, anti-AIDS, and other types of drugs. They have also become the preferred means of producing and testing a number of other pharmaceutical products, including vaccines, antibiotics, and therapeutic proteins. The AIDS virus was isolated in human serum, and in vitro methods are providing new insights into the virus’ effect on human cells. International tissue banks now provide hundreds of different types of human tissue to scientists investigating diabetes, cancer, cystic fibrosis, muscular dystrophy, glaucoma, and more than 50 other human diseases. In vitrogenetic research has isolated specific markers, genes, and proteins associated with Alzheimer’s disease, muscular dystrophy, schizophrenia, and other inherited diseases.

Human clinical, epidemiological, and in vitro studies are critical to the advancement of medicine. (Even animal researchers admit they need them, if only to confirm or reject the validity of their own experiments.) However, ethical research with human participants does require a different outlook. Animal researchers artificially induce disease; clinical investigators study people who are already ill or have died. Laboratory scientists want a “research subject” who can be manipulated as desired and killed when convenient; clinicians must do no harm to their patients or study participants. Animal researchers face the ultimate dilemma that their artificially created “animal model” can never fully reflect the human condition; clinical investigators know that the results of their work are directly relevant to people. Unfortunately, however, health charities and government research funding agencies currently devote more funds to animal research than investigations of our own species.

Humane Society International (HSI) Europe has been at the forefront of the campaign to establish a world-leading Centre of Excellence in non-animal research to accelerate the development of more ethical and reliable research methods. In May 2008, HSI co-hosted an event in the European Parliament with the Dr. Hadwen Trust for Humane Research and world-renowned primatologist Dr. Jane Goodall. During the event, HSI presented the Parliament with their joint report, Towards a European Science Without Animal Experiments [PDF] and a petition signed by 150,000 EU citizens.

Although some animal tests in use today were created nearly 80 years ago, most have never been formally validated (i.e., assessed in multiple laboratories to see if they reliably give the correct answers). However, there is a great deal of scientific evidence that some of the most common animal tests may be poor predictors of human effects. For example:

 Eye and skin irritation tests:

• Among 281 cases of accidental human eye exposure to 14 household products, investigators with the US Food and Drug Administration determined that rabbit test results correctly predicted human responses less than half the time. [1]
• Animal tests failed to correctly predict human skin reactions for nearly half of 65 consumer products examined. [2]
• Excessively high variability in test results and interpretation between labs. A comparison of test results across 24 labs documented variability up to 100%. [3]

Acute toxicity tests (often conducted using oral, inhalation and skin routes):

• Animal tests seriously underestimate human risk, as documented human sensitivity to some chemicals is as much as 2,000-times greater than in animals. [4]
• Only 65 percent agreement between rat and mouse test results for the same 50 chemicals. [5]
• “The information obtained from conventional acute toxicity studies is of little or no value in the pharmaceutical development process.” [6]

Birth defect tests (often conducted in both rats and rabbits):

• Tests in both rats and rabbits failed to detect the developmentally toxic effects of PCBs, ACE-inhibiting drugs, and other substances, and rabbits gave false negative results for toluene, tetracycline, diethylstilboestrol (DES), and other drugs. [7]
• Less than 74 precent agreement between rat, mouse and rabbit test results for the same chemicals. [8] 
• Testing in a second animal species increases the already high rate of false positive results. [9]

Cancer tests (usually conducted in both rats and mice):

• Failed to detect the hazards of asbestos, benzene, bromodichloromethane, cigarette smoke, dichlorovos, lindane, DDT, selenium sulfide, and many other substances, delaying consumer warnings and worker protection measures by decades in some cases. [10]
• Only 50-70 percent agreement between rat and mouse test results for the same chemicals. [11]

• Less than 60 percent agreement in the interpretation test results between labs for the same chemicals. [12]
• Many biological mechanisms leading to cancer in rodents are irrelevant to humans (e.g., buildup of alpha 2u-globulin in the kidneys of male rats, peroxisome proliferation in rodent livers, calcium phosphate-containing urinary buildup in rats). [13]
• Rodents possess cancer-prone organs for which there are no human equivalents (e.g., forestomach, Harderian gland, Zymbal’s gland). [14]
• Animals are sometimes administered 100-times or more the equivalent human intake of a chemical (e.g., to consume the level of the pesticide Alar that was fed to rats and mice in one study would require eating 28,000 pounds of apples daily for 10 years). [15]
• Commonly used strains of rats and mice are highly prone to spontaneous tumor development—even “control” animals who are not administered a test chemical—which confounds the interpretation of test results. [16]

As a direct consequence of the shortcomings cited above, pharmaceutical regulators have reported that fully 92% of drugs that pass preclinical (animal) testing fail clinical trials because animal studies so often “fail to predict the specific safety problem that ultimately halts development.” [17]

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¹ Freeberg FE, Griffith JF, Bruce RD, et al. Correlation of animal test methods with human experience for household products. Journal of Toxicology – Cutaneous and Ocular Toxicology 1, 53-64 (1984). 
² Robinson MK, McFadden JP & Basketter DA. Validity and ethics of the human 4-h parth test as an alternative method to assess acute skin irritation potential. Contact Dermatitis 45, 1-12 (2001).
³ Weil CS & Scala RA. Study of intra- and interlaboratory variability in the results of eye and skin irritation tests. Toxicology and Applied Pharmacology 19, 276-360 (1971). 
⁴ Müller R. Vergleich der im Tierexperiment und beim Menschen tödlichen Dosen wichtiger Pharmaka. Diss. Univ. Frankfurt/Main (1948).
⁵ Ekwall B, Barile FA, Castano A, et al. MEIC evaluation of acute systemic toxicity. Part VI. The prediction of human toxicity by rodent LD50 values and results from 61 in vitro methods. Alternatives to Laboratory Animals 26 (Suppl. 2), 617-58 (1998).
⁶ Chapman K & Robinson S. Challenging the requirement for acute toxicity studies in the development of new medicines.  London: UK National Centre for the 3Rs (2007).
⁷ Schardein JL. Chemically Induced Birth Defects, 3rd Ed. Rev. New York: Marcel Dekker (2000).
⁸ Hurtt ME, Cappon GD & Browning A. Proposal for a tiered approach to developmental toxicity testing for veterinary pharmaceutical products for food-producing animals. Food and Chemical Toxicology 41, 611-19 (2003).
⁹ Bremer S, Pellizzer C, Hoffmann S, Seidle T & Hartung T. The development of new concepts for assessing reproductive toxicity applicable to large scale toxicological programmes. Current Pharmaceutical Design 13, 3047-3058 (2007).
¹⁰ Seidle T. Chemicals and Cancer: What the Regulators Won’t Tell You. London: PETA Europe Ltd (2006).
¹¹ Gold LS & Slone TH. Prediction of carcinogenicity from two versus four sex-species groups in the carcinogenic potency database. Journal of Toxicology and Environmental Health 39, 143-57 (1993).
¹² Gottmann E, Kramer S, Pfahringer B, et al. Data quality in predictive toxicology: Reproducibility of rodent carcinogenicity experiments. Environmental Health Perspectives 109, 509-14 (2001).
¹³ Cohen SM. Bioassay bashing is bad science: Cohen’s response. Environmental Health Perspecitves 110, A737 (2002).
¹⁴ Cohen SM. Human carcinogenic risk evaluation: an alternative approach to the two-year rodent bioassay. Toxicological Sciences 80, 225-9. (2004).
¹⁵ ACSH [American Council on Science and Health]. Of Mice and Mandates: Animal Experiments, Human Cancer Risk and Regulatory Policies. New York: ACSH (1997).
¹⁶ Haseman JK, Hailer RJ & Morris RW. Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a National Toxicology Program update. Toxicologic Pathology 26, 428-41 (1998).
¹⁷ FDA [Food & Drug Administration]. Challenge and Opportunity on the Critical Path to New Medical Products. Bethesda, MD: FDA (2004).

In light of today’s global marketplace, a meaningful reduction in animal testing can only occur if different countries are prepared to recognise and accept the results of validated alternative methods. Otherwise, companies will be forced to perform different tests to satisfy different national requirements—which wastes not only time and money, but can actually increase the amount of animal testing that is done. 

Through the efforts of the European Centre for the Validation of Alternative Methods (ECVAM) and similar bodies in some member states, the EU has established itself as the world leader in the development and acceptance of non-animal/alternative test methods. More than two-dozen such methods have already been endorsed as scientifically valid, and many of these have also been adopted into EU testing regulations. Yet to date only a small handful of these methods have been formally endorsed by the US validation authority, ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) and accepted by relevant US federal agencies. Without a clear endorsement by ICCVAM, American regulators have been disinclined to accept alternative methods pioneered in the EU.

As a consequence, companies on both sides of the Atlantic are increasingly being forced to double-test their products in order to market them internationally (i.e., EU law prohibits animal use when an alternative approach is reasonably or practicably available, while US regulators remain skeptical of alternative methods, preferring to stick to familiar animal tests).

Humane Society International (HSI Europe) and the US-based Humane Society Legislative Fund are providing political and scientific support for bilateral discussions aimed at improving transatlantic regulatory co-operation in a number of areas. In particular, we are lobbying the US and EU to sign a formal Mutual Recognition Agreement concerning alternative test methods in order to expedite international acceptance and use of these life-saving technologies and prevent duplicate testing. A first step towards this has been taken with the creation of the International Cooperation on Alternative Test Methods (ICATM) between validation authorities in the EU, US, Japan and Canada.

The great majority of animal use for experimental purposes can best be described as “curiosity-driven” research. Animals who have been purpose-bred, captured from the wild, or purchased from pounds, animal shelters, and animal brokers can be subject to a seemingly limitless variety of experimental procedures in fields ranging from biology, psychology, biochemistry and physiology to genetic manipulation.

Such curiosity driven research stems, in part, from today’s “publish or perish” research environment, in which scientists are rewarded for the number of research papers they publish, rather than the contribution each study makes to the advancement of science or medicine. It is relatively easy to take an existing “animal model,” alter a few variables, and produce a publishable paper. Researchers can publish and advance themselves while showing little innovation. This translates into a system in which wasteful and medically irrelevant animal experimentation is all too commonplace.

Even animal research that is carried out for “medical purposes” tends to be far from relevant to human health. Part of the problem is that artificially induced disease in “animal models” is never identical to the naturally arising disorder in human beings. Animal species also differ in many biologically significant ways, making it that even more unlikely that research results will be correctly interpreted and then applied to the human condition in a meaningful way. Further doubt is cast on the validity of animal research because the species most often used in laboratory experiments are chosen largely on non-scientific grounds, such as cost, ease of handling, or simply habit. In addition, the results of animal experiments are so often variable and easily manipulated that researchers have used the results of animal studies to “prove” that cigarettes both do and do not cause cancer—depending on the source of funding.

Learn more about the issues:

• Comparison of treatment effects between animal experiments and clinical trials [PDF]
• Contributions to medical progress [PDF]
• Experimental treatments for stroke [PDF]
• Systematic reviews of human clinical utility [PDF]
• Translation of research evidence from animals to humans [PDF]
• Where is the evidence that animal research benefits humans?

A large number of laws and regulations have been enacted worldwide to control the marketing of drugs, vaccines, food additives, pesticides, industrial chemicals, and other substances of potential toxicological concern.

Such regulations often prescribe a specific regime of toxicity testing to generate information that will enable government regulators to determine whether the benefits of a particular substance outweigh its risks to human health and/or the environment.

Government statistics indicate that product testing accounts for approximately eight percent of all animal use for scientific purposes. Yet the use of animals in product testing figures prominently in the animal experiments controversy. It raises issues such as the ethics and humaneness of deliberately poisoning animals (sometimes to death), the appropriateness of harming animals for the sake of marketing a new cosmetic or household product, the applicability of animal data to humans, and the possibility of sparing millions of animals by developing alternatives to a handful of widely used procedures.

Humane Society International (HSI) does not consider animal-based toxicity studies to be an ethical or scientifically credible means of evaluating potential hazards to human health, wildlife, or the environment we all share. HSI is working to promote greater reliance on available non-animal testing methods, and is actively supporting a landmark call by eminent scientists for fundamental changes to the way product testing is conducted—to move from animal tests that are decades old, costly, slow and of dubious relevance to people, to ultra-modern, efficient and human-relevant non-animal methods.

In the time since the most commonly used toxicity tests were conceived, there has been a revolution in biology and biotechnology.

Advances in tissue engineering and robotics have given birth to rapid “high throughput” in vitro (cell culture) systems, while emerging technologies such as bioinformatics, genomics, proteomics, metabonomics, systems biology, and in silico (computer-based) systems offer still more potential alternatives to animal use.

In June 2007, the US National Academy of Sciences called for a major paradigm shift in toxicology that would “rely less heavily on animal studies and instead focus on in vitro methods that evaluate chemicals’ effects on biological processes using cells, cell lines, or cellular components, preferably of human origin. The new approach would generate more-relevant data to evaluate risks people face, expand the number of chemicals that could be scrutinized, and reduce the time, money, and animals involved in testing.” 

As public opposition towards animal testing has grown, animal use has been broadly prohibited where alternative methods are “reasonably and practicably available” (e.g., EU Directive 86/609 and legislation in the U.S. states of California [PDF], New Jersey [PDF] and New York [PDF]).

Animal testing bans may also be sector-specific, as in the case of the 7th Amendment to the EU Cosmetics Directive [PDF], which broadly prohibits the testing of cosmetics or their raw ingredients on animals in the EU, and with few exceptions, also bans the sale of cosmetics that have been tested on animals.

Some toxicity tests consume hundreds or thousands of animals per substance examined (e.g., lifetime cancer studies consume approximately 400 rats and 400 mice; a study of birth defects and developmental toxicity consumes 1,300 rats and/or 900 rabbits; and a study of sexual fertility and reproduction generally consumes 200 litters of rodent pups—or upwards of 2,600 animals) [1].

Moreover, some countries’ statistics on animal use indicate that toxicity testing accounts for up to 80% of the most painful procedures to which animals are subject for all experimental purposes (e.g., death as the endpoint in acute systemic toxicity studies) [2].

These concerns are exacerbated by the fact that some regulations prescribe dozens of separate animal tests to evaluate the full range of potential toxicities for a single substance (e.g., upwards of 12,000 animals may be consumed to test a single pesticide chemical according to U.S. regulations).

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¹OECD [Organisation for Economic Co-operation and Development]. OECD Guidelines for the Testing of Chemicals. Paris: OECD (2008).

²CCAC [Canadian Council on Animal Care]. Facts & Figures – CCAC Animal Use Survey: Number of Animals Used in 2006 per Purpose of Animal Use and Category of Invasiveness. Ottawa: CCAC (2008).

When it comes to human exploitation of primates, the animals are often just as valuable dead as they are alive. Their parts may be used in traditional medicine by people in some cultures and their bodies stuffed as hunting trophies by others. Worldwide demand for primate skins, meat and body parts is putting additional strain on their already dwindling populations. Unfortunately, in many cases the punitory fine for killing an animal for trade is much less than what a hunter can earn for selling it.

Primates in traditional medicine

In some places, particularly in Asia, people believe that consuming primate body parts will cure illness. For example, in India it is thought by many that eating monkey brain will treat rheumatism and that drinking monkey blood will cure asthma. Many of these traditions date back for centuries and are deeply entrenched. The fact that they are so widely accepted makes it very difficult for conservationists to step in and end such practices.

Hunting trophies

While it may be uncommon today to see a gorilla hand ashtray at a local bar, underground trade in primate parts is still occuring. The skin of the black and white colobus monkey, used traditionally in African clothing and, in the past, for coats and rugs in Europe and Japan, is considered particularly desirable. Hunting by foreigners who pay hefty amounts of money to visit Africa, Asia or South America and kill a primate as a trophy is another threat.

Sadly, even in countries where these types of activities are illegal, there are often not enough resources to enforce laws against them.

Living primates, whether captive-bred or wild-caught, have been exploited by humans for exotic pet trade, for our entertainment and in biomedical research. In each case, people have put their own needs and desires first, without enough thought for what is best for the animals.

The pet trade

The pet trade has long been a problem for primates. People are fascinated by their human-like characteristics, but have been unwilling to acknowledge the fact that primates make poor pets. A recent study of the trade in chimpanzees as pets showed that as many as 10 chimps die for every one who is successfully delivered to his overseas destination. Those who survive their capture and transportation go on to suffer a sad and lonely life as a pet. Primates are social creatures and, when taken away from their family group and natural habitat, they suffer psychological consequences. Monkeys and apes may also become aggressive as they age and more difficult to handle. The sad result is the neglect, abandonment or sale into bad circumstances of a great number of these animals, often leading to their untimely deaths.

Primates in entertainment

Primates held captive in roadside zoos or made to participate in circuses, films, shows and commercials are coerced into repetitive, unnatural behaviors, too often through negative rather than positive reinforcement. The performing animals we see are usually young, taken too soon from their mothers. At worst, they are abused; at best, they are improperly socialized. Like primates purchased as pets, many are cast aside when they mature and become unmanageable. The appearance of apparently cuddly chimps and other primates on television and in movies also helps perpetuate their inclusion in the pet trade.

Use in research labs

Approximately 55,000 primates are used in research labs every year in the U.S. alone. Among the most common are the crab-eating and rhesus macaque monkeys. Chimpanzees were once popular among laboratory researchers for the study of HIV until scientists found that the chimpanzee is a poor model because the virus affects chimps very differently from how it affects humans. Many remain warehoused in laboratories, while some are subjects of other experiments. Tragically, these long-lived animals may spend up to six decades locked up. Read about why Chimps Deserve Better.