Animal Experimentation Issues

Understanding Research Charities' Comments about Animal Experimentation Programs

While many health charities and other institutions never fund animal experiments, others do.

In some cases, a lack of attention to alternatives is rationalized by various claims:

"Our animals are well treated...."

Even routine caging, isolation, handling, and shipping are stressful and sometimes terrifying for animals. A recent review of the scientific literature showing marked stress responses in animals undergoing routine laboratory procedures.

"Our standards for the treatment of animals meet or exceed all federal regulations regarding animal care and use...."

The Animal Welfare Act, the primary federal legislation "protecting" animals, does not apply to mice, rats, and birds. These animals are used in 80 to 90 percent of all experiments, yet they are given no protection.⁵ Even for animals to whom the Animal Welfare Act applies, the regulations in place are sorely deficient. Indeed, federal regulations do not prevent any experimental procedure, regardless of how painful it may be. While the Animal Welfare Act encourages the use of pain killers, experimenters can omit their use if they so choose.

Additionally, enforcement of laws that do exist is often inadequate. The U.S. Department of Agriculture Animal and Plant Health Inspection Service (APHIS), which is responsible for enforcing the AWA, reports that nearly half of all facilities are in violation of one or more provisions of the law.⁶ With only 73 inspectors for approximately 10,000 sites, inspections are rare and do not provide a real picture of a facility's animal use programs. Ron DeHaven, APHIS Animal Care Acting Deputy Administrator, admits that the agency's "intent is not to punish" facilities that violate animal protection laws, but rather to "work with them."

"Our institution is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), an independent, nonprofit organization which is the accepted standard of excellence for the humane care and use of laboratory animals...."

Like government regulations, AAALAC accreditation fails to provide any meaningful protection for animals. AAALAC even approves of multiple, major invasive procedures on individual animals.⁷ AAALAC prescribes standard procedures for monitoring and conducting animal experiments, but accreditation does not ensure that animals are well treated. For example, highly invasive surgeries on pregnant baboons have been conducted at AAALAC-approved laboratories at Cornell University. In one experiment, the baboons had catheters implanted deep in their thighs, electrodes sunk into their uteruses, and catheters inserted into the fetuses developing inside them. This extensive instrumentation was kept in the animals around the clock.⁸ Unfortunately, experiments of questionable clinical relevance that result in extreme suffering are routinely performed.

"Most of the animals we use are mice and rats...."

This may be true, however both mice and rats have highly developed central nervous systems, feel pain, and suffer from the stress of confinement. Indeed, because mice and rats are "unpopular" animals and are not protected under the Animal Welfare Act, they are more likely to be used in invasive experiments.

Rats and mice differ markedly from humans in many respects, making results from experiments on these animals difficult to extrapolate to humans in many cases. Tests of cancer-causing agents in rats and mice agree only 70 percent of the time⁹; the results would apply to humans even less often. Rats do not develop the same range of cancers as humans.¹⁰

"All research protocols are approved by our Institutional Animal Care and Use Committee (IACUC)...."

Approval by an IACUC gives no indication of whether animal experiments involve pain or stress. IACUCs routinely approve highly invasive, painful procedures. A recent three-year review showed that the IACUC approval process was no more reliable than the toss of a coin.

A panel composed of seven former IACUC members from various institutions,¹¹ with whom PCRM consulted in 1994, cited numerous proposals which caused suffering for animals and had little scientific merit, but were nevertheless approved by IACUCs. One involved castrating rabbits and/or giving them estrogen to study erectile problems. Another experiment involved killing horses as part of an effort to study exercise-induced bleeding. In other approved experiments, substances were administered to animals until 50 percent of them died; cocaine was given to pigs and piglets; and pigs were bled to the verge of death and revived.¹²

"We promote the use of alternatives to animal research whenever possible. When animals are required, we use as few as we can. Our researchers use animals only when absolutely necessary...."

Vague language such as this does not indicate a real commitment to replacing, or even reducing, the total numbers of animals used in experiments. Virtually every institution funding animal experiments claims that it uses animals only when necessary. Yet, countless examples have shown that animal experiments done in these same institutions are often of questionable scientific merit. For example, the March of Dimes funded an experiment which involved killing and comparing the brains of normal cats, kittens, cats who had one eye sewn shut for at least a year, and cats who were reared in complete darkness.¹² By the March of Dimes' own admission, no clinically relevant advances came from this study, yet March of Dimes' spokespersons continue to claim its researchers use animals only when "necessary."

NONANIMAL RESEARCH METHODS

Epidemiologic Studies

Comparative studies of human populations have provided important information about the causes of many diseases. 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 came from epidemiologic studies. Such studies also demonstrated the mechanism of transmission of AIDS, and showed how to prevent it.

In the course of treating patients, the causes of disease have often been elucidated. Studies of human patients using sophisticated scanning technology (CT, PET, and MRI) have isolated abnormalities in the brains of victims of Alzheimer's disease, schizophrenia, epilepsy, and autism. Dietary studies of patients with multiple sclerosis showed that adherence to a low-fat diet significantly reduced their death rate and the rate at which the debilitating disease progressed. Autopsy studies revealed that Alzheimer's disease patients have abnormal concentrations of aluminum in their brains.

An enormous amount of valuable in-vitro (test tube) research is conducted today. Cell and tissue cultures are used to screen anticancer and anti-AIDS drugs and to test for product irritancy. The AIDS virus was isolated in human serum, and in vitro methods are providing new insights into the virus' effect on human cells. The National Disease Research Interchange, a nonprofit clearinghouse, provides more than 130 kinds of human tissue to scientists investigating diabetes, cancer, cystic fibrosis, muscular dystrophy, glaucoma, and more than 50 other diseases. In-vitro genetic research has isolated specific markers, genes, and/or proteins for Alzheimer's disease, muscular dystrophy, schizophrenia, and other inherited disorders.

Computer programs can often predict the toxicity of chemicals, including their potential to cause cancer or birth defects, based on their molecular structure. Computer simulations have also replaced live animals in medical education.

Safety tests using human cells are, in some cases, more accurate than animal tests.

In the Multicenter Evaluation of In Vitro Cytotoxicity tests (MEIC), researchers from the U.S., Europe, Japan, and other countries tried 68 different test-tube methods to predict the toxicity of 50 different chemicals, such as aspirin, digoxin, diazepam (Valium), nicotine, malathion, and lindane. The effects of the chemicals in humans were already known from poison control centers. The study's goal was to see how well the cellular tests matched actual human experience and to compare them with data previously reported for animal tests.

Rat LD50 tests—lethal dose tests that measure the dose of a chemical that kills 50 percent of the animals given it—were only 59 percent accurate, and mouse tests were about 70 percent accurate. But the average human cell test was 77 percent accurate. Accuracy was boosted to 80 percent when results from three different human cell tests were combined.

With personnel formerly of Glaxo Wellcome, SmithKline Beecham, and Shire Pharmaceuticals, Pharmagene Laboratories, based in Royston, England, became the first company to conduct new drug development and testing using human tissues and sophisticated computer technologies exclusively. With tools from molecular biology, biochemistry, and analytical pharmacology, Pharmagene conducts extensive studies of human genes and investigates how drugs affect the actions of these genes or the proteins they make. While some have used animal tissues for this purpose, Pharmagene scientists believe that the discovery process is much more efficient with human tissues.

CONCLUSION

Those concerned about the treatment of animals and who want research to be relevant to human health are unlikely to find the claims about animal experiments comforting. A wide range of charities, businesses, and other institutions meet their research needs with exclusively nonanimal methods. Many feel more comfortable supporting these organizations instead of those that continue to fund animal experiments.

References
1. Yoshioka T, Feigenbaum L. Transgenic mouse model for central nervous system demyelination. Molec and Cell Biol 1991;11:11:5479-86.
2. Feigenbaum L, Hinrichs SH, Jay G, et al. JC virus and simian virus 40 enhancers and transforming proteins role in determining tissue specificity and pathogenicity. J Virol 1992;66:1176-82.
3. Pollock R, Jay G, Bieberich CJ, et al. Altering the boundaries of hox3.1 expression: evidence of antipodal gene regulation. Cell 1992;71:911-23.
4. Penn A, Snyder CA. Inhalation of sidestream cigarette smoke accelerates development of arteriosclerotic plaques. Circulation 1993;88:1820-5.
5. Orlans FB. Data on animal experimentation in the United States: what they do and do not show. Perspectives in Biol and Med 1994;Winter:37:2.
6. Dehaven R., U.S. Department of Agriculture Animal and Plant Health Inspection Service Animal Care Acting Deputy Admistrator. U.S. Department of Agriculture Animal and Plant Health Inspection Service Conference. Oral Testimony. 12 May 1998.
7. Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). "Position Statements." Multiple major surgical procedures. http://www.aaalac.org/position.htm (13 Nov 1997).
8. Nathanielsz PW, Honnebier MBOM, Mecenas C, Jenkins SL, Holland ML, Kemarest K. Effect of the oxytocin antagonist atosiban (1-Deamino-2-D-Tyr(OET)-4-Thr-8-Orn-Vasotocin/Oxytocin) on nocturnal myometrial contractions, maternal cardiovascular function, transplacental passage, and fetal oxygenation in the pregnant baboon during the last third of gestation. Biol Reproduction 1997;57:320-4.
9. Lave LB, Ennever FK, Rosenkranz HS, Omenn GS. Information value of the rodent bioassay. Nature 1988;336;631-3.
10. Detailed information and further primary source references on the problems with extrapolating rat experiments to humans are available in the PCRM factsheet, "Rats: Test Results That Don't Apply to Humans."
11. Jan Polon Novic (Letterman Army Institute of Research committee), Kim Sturla (Univ. of Calif.-Berkeley committee), Anne Phillips (Univ. of Tenn., Coll. of Veterinary Medicine committee), Thomas Poulton, M.D. (Creighton Univ. School of Medicine committee), Pamela Krausz (Univ. of Penn. committee), Steve Sapontzis, Ph.D. (Lawrence Berkeley Lab committee), Bruce Max Feldman, D.V.M. (Codon Co. committee).
12. Detailed information and further primary source references on IACUCs are available in the PCRM factsheet, "Animal Care and Use Committees: Structural Problems Impair Usefulness."
13. Sur M, Frost D, Hockfield S. Expression of a surface-associated antigen on y-cells in the cat lateral nucleus is regulated by visual experience. J Neuroscience 1988;8:3:874-82.

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