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Research Alternatives


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Conservative scientists typically agree to what is called the 3 Rs:

  • Reduce the number of animals in an experiment

  • Refine techniques to reduce animal suffering

  • Replace the use of animals with non-animal methods

An example of both a reduction and a refinement to an existing animal test is the Limit Test, approved by the U.S. Food and Drug Administration (FDA) to replace the LD-50 (Lethal Dose 50) test. The LD-50 is an old toxicity test that measures the median amount of a substance required to kill half the test animals. The classic LD-50 requires a large number of animals (60-200), and causes acute toxicity and extreme suffering to most animals used.

 

As a result of both scientific and ethical objections, researchers and regulatory bodies such as the FDA developed various alternatives, including the Limit Test, which uses only 10-20 animals (reduction) and which exposes the animals to lower doses of the test drug, presumably causing less suffering (refinement).

 

However, this so-called "alternative" is still an animal test. It still uses animals, and it causes them to suffer considerably. And when drugs are tested for human medicine, the problems of species differences and laboratory stress still exist.

 

A truly alternative approach was developed by researchers from Sweden. Instead of reducing the number of animals used, scientists test substances in human cell cultures, eliminating the use of live animals altogether.

 

We will discuss only replacement alternatives, as these are the only research methods that overcome both the scientific and ethical problems associated with animal experimentation. Efficient and reliable non-animal methods that can replace experiments on animals include clinical research, epidemiology, cell and tissue cultures, and numerous other approaches.

 

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Clinical Research

Non-harmful study of actual patients (humans in medicine, animals in veterinary medicine) has always been the primary and most reliable method of research. It allows scientists to investigate diseases and conditions in the real world, and since no species differences or laboratory artifacts (distortions that result from artificial conditions) are involved, the conclusions of well-designed clinical studies can be trusted.

 

Non-invasive imaging devices, including CAT, MRI, PET, and SPECT scans, permit diseases to be observed and evaluated in living human patients, and have contributed greatly to modern medical knowledge.

 

Observation of human patients showed that smoking causes cancer, but animal studies funded by tobacco companies "proved" the reverse, delaying treatment and prevention programs for three decades.

 

Studies on human patients with heart disease revealed that a low-fat vegetarian diet, regular exercise, stopping smoking, and managing stress can halt and often reverse heart disease.1

 

World-renowned physician Henry Heimlich has been adamant in rejecting experiments on animals in favor of human clinical trials to develop inventions and techniques that have saved thousands of lives, including the Heimlich Maneuver for choking and drowning victims, the Heimlich throat tube to replace the esophagus, and the Heimlich Drainage Valve.

 

However, like any research method, clinical research has its drawbacks. First, it is often expensive and time consuming. Second, for obvious reasons, potentially dangerous procedures cannot be performed within the context of clinical research. For the latter, there are other, acceptable, alternatives.

 

Epidemiology (Population Studies)

The risk factors for heart disease — which are essential to know for prevention — were learned from population studies, as was the knowledge that second-hand smoke doubles the risk of lung cancer and also the cause of Legionnaires' diesase.2

 

Studies of populations with cancer or birth defects can lead to a better understanding of the cellular and molecular causes and processes of DNA damage, which can lead to more effective prevention and treatment.3

 

Post-Marketing Surveillance

A central database of information from post-marketing surveillance of drugs can enable the rapid identification of both dangerous and beneficial drug side effects. Clinical observation of side effects resulted in identifying the anti-cancer properties of prednisone, nitrogen mustard, and actinomycin D; the tranquilizing effect of chlorpromazine; and the mood-elevating effect of MAO inhibitor and tricyclic antidepressants.4

 

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Cell and Tissue Cultures

In vitro ("in glass," outside the body) methods allow test substances to be studied on cells or tissues in test tubes, instead of testing candidate drugs and other chemicals on live animals. In vitro studies have several advantages over traditional animal tests: first, human cells, rather than animal cells, can be used, bypassing the species-differences gap. Second, minute metabolic processes can be observed, and the cellular mechanisms of toxicity can be assessed.

 

In vitro cancer cell lines have proved to be less expensive and more reliable than all the mice experiments used by the U.S. National Cancer Institute from the 1950s to the 1980s to test 400,000 chemicals for their cancer-causing properties. The few substances found to be effective against cancer in mice had little effect on the major human cancer killers. In vitro tests using cells with human DNA can detect DNA damage more readily than animal tests.5

 

Vaccines made from human tissue cultures are more effective, safer, and less expensive than the monkey tissue vaccines previously made. They also avoid the serious danger of animal virus contamination. More sensitive and reliable cell culture techniques have also replaced many animal tests for viral vaccine safety.6

 

In vitro methods have been developed that can readily replace methods of developing antibodies that cause extreme suffering to animals.7  8 (See Monoclonal Antibodies.)

 

Animal researchers often argue that cell and tissue culture systems are too simplistic and that such methods may, at best, be used in the initial screen of candidate drugs; that because in vitro systems don't reflect the complex interactions characteristic of living animals, these methods are of limited value. Obviously, cell and tissue cultures are not whole animals, but animals are not humans either. Extrapolation from animal studies to humans may be as hazardous, or even more hazardous, than extrapolation from human cell and tissue cultures to living humans. Furthermore, advances in cell culture techniques enable researchers to at least partially model complex interactions. For example, the liver is a key organ in drug metabolism. Sophisticated in vitro systems now include human liver cells to metabolize the test drug, plus cells from a different human tissue to investigate toxic effects. Human cell cultures incorporating cells from several different body tissues offer the opportunity to model interactions among separate biological subsystems in vitro (endocrine, cardiovascular, and reproductive, for example).

 

Autopsies and Biopsies

Autopsies have contributed considerably to medical sciences. Discoveries about human anatomy were made and described based on postmortem examinations. Autopsies were crucial in understanding diseases such as heart disease, appendicitis, diabetes, and Alzheimer's. A drawback of autopsies is that you only see the final stage of the disease, a limitation not present in the case of biopsies, in which human tissues are taken from living patients to diagnose disease. Endoscopic biopsies demonstrated that colon cancers come from benign tumors called adenomas, while animal tests did not.9

 

Mathematical Models

Mathematical models using human clinical and epidemiological data are more reliable than data from animal studies. The data is used to generate hypotheses about complex disease processes. For example, a mathematical model showed that there are two types of breast cancer that appear to be identical under the microscope. One is very malignant, the other much less so. According to the model, the more malignant form requires early diagnosis and aggressive treatment, while in the less malignant form, surgical removal is sufficient.10

 

Innovative Technologies

Modern technology renders many experiments on live animals obsolete. For example, advanced software technologies are increasingly replacing the use of animals for teaching and demonstration purposes. Computer programs can illustrate and teach physiological and anatomical principles without harming animals, in both biological and clinical sciences. These methods offer a better alternative to many traditional types of research on animals by overcoming the species differences problem.

 

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Footnotes

1  D. Ornish, "Avoiding revascularization with lifestyle changes: The multicenter lifestyle demonstration project," American Journal of Cardiology, 1998;82:72T-76T. and CB Esselstyn Jr. "Updating a 12-year experience with arrest and reversal therapy for coronary heart disease," American Journal of Cardiology, 1999;84:339-341.

2 KM Anderson, PWF Wilson, PM Odell, WB Kannel, "An updated coronary risk profile," Circulation, 1991;83:356-362; and D Zaridze, D Maximovitch, G Zemlyanaya, ZN Aitakov, P Boffetta, "Exposure to environmental tobacco smoke and risk of lung cancer in non-smoking women from Moscow, Russia," International Journal of Cancer, 1998;75:335-8.).

3 GM Lower, "Human carcinogenesis: A disciplinary perspective," Medical Hypotheses, 1990;33:1-6.

4 L. Lasagna (ed), Postmarketing Surveillance of Multisource Drugs, Boston, Center for the Study of Drug Development, 1986; C.J van Boxtel, G. Wang, "Some observations on pharmacoepidemiology in Europe," Netherlands Journal of Medicine, 1997;51:205-212; O.H. Pearson, L.P. Eliel, R.W. Rawson, et al., "ACTH- and cortisone-induced regression of lymphoid tumors in man," Cancer, 1949;2:943-5; E. Boesen, Cytotoxic Drugs in the Treatment of Cancer, London, Edward Arnold, 1969, p. 24; W.B. Coley, "A preliminary note on the treatment of inoperable sarcoma by the toxic product of erysipelas," The Post-Graduate, 1893;8:278-286; A. Caldwell, Origins of Psychopharmacology: From CPZ to LSD, Springfield, Charles C. Thomas, 1970; H.E. Lehmann, N.S. Kline, "Clinical discoveries with antidepressant drugs," in M.J. Parnham, J. Bruinvels, (eds), Discoveries in Pharmacology, Volume 1. New York, Elsevier, 1983, pp. 209-221; F. Sulser, R. Mishra, "The discovery of tricyclic antidepressants and their mode of action," in M.J. Parnham, J. Bruinvels, (eds), Discoveries in Pharmacology, Volume 1, New York, Elsevier, 1983, pp. 233-247.

5 C. Stevens, "Statement before the House Subcommittee on Labor, Health, and Human Services," April 30, 1987; A. Pihl, "UICC Study Group on chemosensitivity testing of human tumors. Problems—applications—future prospects," International Journal of Cancer, 1986;37:1-5; C. Waldren, L. Correll, M.A. Sognier, T.T. Puck, "Measurement of low levels of x-ray mutagenesis in relation to human disease," Proceedings of the National Academy of Sciences, USA 1986;83:4839-4843.

6 L. Hayflick, "The choice of the cell substrate for human virus vaccine production," Laboratory Practice, 1970;19:58-62; A.J. Beale, "Use of tissue cultures for testing vaccines," Journal of the Royal Society of Medicine, 1978;71:681-686; L. Hayflick, "Human virus vaccines: Why monkey cells?" Science, 1972;176:183-184.

7 C. Hendriksen, J. Rozing, M. van der Kamp, W. de Leeuw, "The production of monoclonal antibodies: Are animals still needed?" Alternatives to Laboratory Animals, 1996;24:109-110.

8 Jin, Aishun, et al. "A rapid and efficient single-cell manipulation method for screening antigen-specific antibody–secreting cells from human peripheral blood." Nature Medicine. 16 August 2009. doi:10.1038/nm.1966.

9 R.B. Hill, R.E. Anderson, The Autopsy: Medical Practice and Public Policy, Boston, Butterworth, 1988; E.L. Opie, Disease of the Pancreas, Philadelphia, J.B. Lippincott, 1910; M. Barron, "The relation of the islets of Langerhans to diabetes with special reference to cases of pancreatic lithiasis," Surgery, Gynacology, and Obstetrics, 1920; 31:437-448; S.R. Kaufman, T. Czarnecki, I. Haralabatos, M. Richardson, "Animal Models of degenerative neurological diseases," Perspectives on Medical Research, 1991;3:9-48; D.J. Ahnen, "Are animal models of colon cancer relevant to human disease," Digestive Diseases and Sciences, 1985;30 (12 Suppl):103S-106S; S.E. Pories, N. Ramchurren,  I. Summerhayes, G. Steele, "Animal models for colon carcinogenesis," Archives of Surgery, 1993;128:647-653.

10 I.D. Bross, "Mathematical models vs. animal models," Perspectives on Animal Research, 1989; 1:83-108; L. Blumenson, I. Bross, "A mathematical analysis of the growth and spread of breast cancer," Biometrics, 1969;25:95-109.

 

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