The scientific case against animal experiments

Dr Robert Sharpe

Most people who oppose vivisection do so on moral grounds because they object to cruelty. But the case against animal experiments is strongly reinforced by scientific arguments. This is because people and animals are different in the way their bodies work and in their response to drugs and disease.
If animal experiments were a valid method of research, people would go to a veterinarian rather than a doctor when they felt ill! In fact, vivisection is an unscientific approach to medicine because of the constant risk of misleading results.

Clinical observations

Doctors have known for a long time that human disease can take a very different form when artificially induced in animals. During an investigation of cholera in the 1880s, the German experimenter Robert Koch repeatedly failed to induce the disease in animals (1). He was forced to rely on clinical observation of actual cases of human cholera and, as a result, succeeded in isolating the responsible germ and discovering how it was transmitted.
Another famous case is yellow fever. In 1990 researches carried out experiments on themselves because no animal was known to be susceptible to the disease. They were able to prove that yellow fever is transmitted by mosquitoes and to suggest preventive measures (2).

Pneumonia is another disease where the causative organisms are not generally harmful to laboratory animals (3). Scientists have also been unable to induce AIDS in animals. Closely related species such as chimpanzees do not develop the disease when inoculated with HIV (4).

Artificially-induced diseases

Even in cases where symptoms induced in animals resemble those found in human patients, there may still be underlying differences in physiology and body chemistry which invalidate experimental findings.

An example is research into stroke, where the condition is induced in animals by blocking blood vessels in the brain. Although there is a superficial similarity to the human disease, the animal experiments have still been misleading. Of 25 drugs found useful in treating animals with artificially-induced stroke over the past ten years, none have proved effecitive in clinical practise (5). In the January 1990 issue of the medical journal Stroke, researchers at the Mayo Clinic in the United States concluded that "ultimately the answers to many of our questions regarding the treatment of stroke do not lie with continued attempts to model the human situation perfectly in animals, but rather with the development of techniques to enable the study of ... living humans."

Another disease where the artificially-induced condition in animals bears a superficial resemblance to the human disorder is cancer. But is has long been known that animal tumours are biological different to human cancers. Indeed, a recent editorial in the cancer research journal Clinical Oncology stated that it is hard to find a single, common human cancer where management and expectation of cure has been markedly influenced by laboratory research (6). The editorial reached the same conclusion as the stroke researchers at the Mayo Clinic – that it is the study of human patients and not animal experiments which will ultimately yield relevant results.

Species differences

There are countless examples in the medical journals where drugs and other chemicals react differently in people and animals (7):

• cortisone produces birth defects in mice but not people, whilst thalidomide works the other way around;
• morphine calms people but excites cats, goats and horses;
• penicillin is highly poisonous to guinea pigs and hamsters;
• insulin causes birth defects in animals but not in people;
• the antibiotic chloramphenicol produces the blood disease aplastic anaemia in some human patients but it saves animals;
• in dogs, the muscle-relaxing drug tubocurarine causes a severe fall in blood pressure but is comparatively safe for people (8);
• and doses of aspirin used in human therapeutics are poisonous to cats.

Experiments sometimes claim that species differences are rare. But in fact they occur frequently. Surveys have shown that most of the side-effects occurring in people when they take a drug cannot be correctly predicted by animal experiments (7). Nor can the problem be overcome by using more species of animals.

This is illustrated by the drugs aspirin and fenclozic acid (7). Aspirin causes birth defects in rats, mice, cats, dogs, guinea pigs and monkeys but is considered safe for pregnant women. The arthritis drug, fenclozic acid, causes liver toxicity in people but not in rats, mice, dogs, monkeys, rabbits, guinea pigs, ferrets, cats, pigs and horses.

False sense of security

With such differences tests on animals can be either worthless or positively dangerous, because they provide a false sense of security. In fact, animal experiments have failed to warn doctors about many of the hazards of drug therapy. Recent examples are the heart drugs encainide and flecainide. They were marked in the United States during 1987 following the usual animal tests but are now thought to have caused as many as 3000 human deaths (9).

Other examples of drug side-effects that were not predicted by animal experiments include (7)

• the addictive properties of the benzodiazepine tranquillisers;
• the increased risk of blood clots caused by oral contraceptives;
• the deadly diarrhoea associated with antibiotics such as clindamycin;
• and the liver damage linked to a wide variety of medicines including antifungal drug Nizoral, the anaesthetic halothane, the arthritis drug Ibufenac and the antidepressant Zelmid.

Unforeseen hazards

Sometimes, unforeseen hazards lead to a drug's withdrawal from use. Selacryn, Oraflex, Merital, Zomax and Suprol are examples of drugs withdrawn on safety grounds from the U.S. marked since 1980 (10).

Far more commonly, the use of drugs is restricted or special warnings are sent to doctors. For instance, the U.S. General Accounting Office found that 51.5% of drugs marketed between 1976 and 1985 had to be be-labelled due to "serious" unexpected side-effects. These included heart, liver and kidney failure, severe blood disorders, birth defects, respiratory arrest, seizures and blindness. The labelling changes either limited the drug's use or added major warnings or precautions (10).

Relying on animal experiments is dangerous

Reliance on animal experiments can be detrimental in other areas of medical research. When scientists disregard human clinical findings in favour of animal test results, the consequences can be devastating.

An important example is the harmful effects of smoking. The discovery that smoking causes lung cancer was achieved through studies of human populations and potentially represents one of the most crucial contributions to health policy in recent times. Yet, unsuccessful attempts to induce lung cancer in laboratory animals by forcing them to breathe tobacco smoke cast doubt on the human studies and delayed health warnings for years, costing thousands of lives (11).

The finding that excessive alcohol consumption leads to liver cirrhosis has been doubted by the failure to produce similar effects in nearly all laboratory animals (12). Only in baboons has cirrhosis been induced, although not in all animal researchers have confirmed this. Too much alcohol can also cause cancer, but once again this well-established clinical fact has been doubted because it has proved impossible to induce cancer in laboratory animals. Some researchers insist that alcohol should net be classified as a human carcinogen because the experimental evidence is lacking (13).

Another example where contradictory animal experiments have delayed acceptance of human findings, is asbestos-induced lung cancer (14). The first reports of a relationship between asbestos and lung cancer were made in England and Germany during the 1930s, following careful examination of people who have died from asbestos. As a result, in 1943 the German authorities declared asbestos-induced lung cancer an occupational disease.

But in some countries, especially America, the carcinogenic action of asbestos was doubted for many years because it proved impossible to induce the disease in animals. The debate continued until the 1960s despite further evidence from observations of asbestos workers. In 1967 experimenters finally managed to produce cancer in animals by dosing with asbestos. This was 30 years after the first reports of lung cancer in people, and more than two decades after Germany accepted the relationship between asbestos and lung cancer.

In November 1983 attention was drawn to an increased number of childhood leukaemia cases in the vicinity of a nuclear reprocessing and power plant at Sellafield in Britain. Although the incidence of leukaemia was ten times the national average, the official Committee of Inquiry decided that the nuclear facility was not the cause. Their conclusion was based on information from animal experiments. By preferring animal data to direct human observations, the risk of radiation were minimised (15).

Human-based research

These examples illustrate the danger of relying on animal experiments. Since it is impossible to tell which animal species, if any, will correctly predict human responses, there is the constant risk of misleading predictions. Far more could be achieved, and without harm to animals, by concentrating methods of direct relevance to people. These methods include human population studies (known scientifically as epidemiology), clinical investigation of people who are ill or who have died, observations of healthy volunteers, and test-tube experiments with human tissues. Such tissues can be obtained from therapeutic surgery, biopsies and postmortem specimens.

Just two examples illustrate the vital importance of human studies. First, the 19th century social reformers used human epidemiological studies to discover the causes of infectious disease and to bring about sanitary reform (16): the resulting improvements in public health were chiefly responsible for the improvement in life-expectancy experienced by many countries over the past century. Secondly, human clinical and epidemiological studies have identified the main causes of cancer, heart disease and strokes, thereby showing how today's major killer disease can be prevented (7).

Nevertheless, despite its greater relevance to medicine, human-based research is underrated and underfunded. For instance, America's National Institute of Health, which funds medical research on behalf of the government, spends about twice as much on animal experiments as it does on studies with people (17).

There is also declining interest in autopsies, a procedure which in the past has proved crucial to the proper understanding of disease. The situation has become so serious that Robert Anderson, chairman of the pathology department at the University of New Mexico School of Medicine, states (18) that "we know a lot more about the causes of death in old mice than we do about the causes of death in old people".

Test-tube studies with human tissues are also widely neglected. This is especially the case with pharmacology (19), the science of drugs. Pharmacologists determine exactly how drugs, and naturally occurring chemicals in the body, exert their effects on the tissues. This kind of information is valuable in providing a logical basis for developing new treatments. Unfortunately, pharmacologists rely mainly on tissues from animals despite numerous contradictory results.

For example, acetylcholine, a chemical produced by nerve endings, dilates the coronary arteries of dogs but has the opposite effect in human coronary arterial tissue (20). Another example is noradrenaline, which constricts human cerebral vessels but has no effect on similar vessels from cows (21). Yet another case is the family of naturally occurring substances called leukotrienes: they dilate blood vessels in the skin of people but have the opposite effect in similar tissues from guinea pigs (22).

Why is human-based research so neglected? One reason may be that human clinical studies require more skill, time and patience to avoid risks to participants, whereas scientists regard animals as disposable. Human studies are neglected because many scientists regard animal experiments as more convenient. This is due to the fact that some effort is needed to form working contacts with hospital staff to obtain adequate supplies of human tissues.

But by sacrificing accuracy for the greater convenience of animal research, experimenters do medicine a disservice. Young doctors and scientists must be made more aware of the hazards of vivisections and the greater relevance of human stuidies.

Conclusion

In conclusion, the mediaeval idea that lives can be saved by sacrificing animals must be rejected. We need a new generation of scientists who no longer regard animals as the disposable tools of research. Furthermore, the physiological and biochemical differences between people and animals stress the urgent need for human based research. It is in the interest of both human beings and animals that vivisection will be stopped, so that the energy and skill of scientific investigation is directed into better and safer channels.

References

1. R. Koch, British Medical Journal, 1884, Sept. 6, 454.
L.K. Altmann, Who goes first? The story of self-experimentation (New York, Random House 1987).
J.B. Robbins, Journal of Infection, 1979, vol. 1, Suppl.2, 61-72.
P. Newmark, Nature, 1989, Oct. 19, 566-567.
D.O. Weibers et al., Stroke, 1990, vol. 21, 1-3.
D.F.N. Harrison, Clinical Oncology, 1980, vol.6, 1-2
R. Sharpe, The cruel deception: the use of animals in medical research (Thorsons, 1988) and quotations there.
The UFAW Handbook on the Care and Management of Laboratory Animals, Ed. UFAW (Churchill Livingstone, 1976).
Washington Times, 1989, July 26.
FDA Drug Review: Postapproval Risks 1976-1985 (U.S. General Accounting Office, April 1990).
Medical Research Modernisation Committee: a critical look at animal research (New York, 1990).
O. Ray: Drugs, Society and Human Behaviour (C.V. Mosby Company, 1978); C.C. Ainley et al., Journal of Hepatology, 1988, vol.7, 85-92.
L. Tomatis et al., Japanese Journal of Cancer researcg, 1989, vol. 80, 795-807.
P.E. Enterline, in: Epidemiology and Health Risk Assessment, Ed. L. Gordis (Oxford University Press, 1988).
E. Millstone, in: Animal Experimentation: The Consensus Changes, Ed. G. Langley (Macmillian, 1989).
W.W. Holland and A.H. Wainwright, Epidemiologic Reviews, 1979, vol.1, 211-232.
Alternatives to animal use in research, testing and education, Congress of the U.S. Office of Technology Assessment, 1986.
The Scientists, 1989, oct.30, 14.
E. Mullner-Schweinitzer, Trends in Pharmacological science, 1988, vol.9, 221-223.
S. Kalsner, Journal of Physiology, 1985, vol. 358, 509-526.
K. Schnor and R. Verheggen, Trends in pharmacological science, 1988, vol.9, 71-74.
P.J. Piper et al., Annals of the New York Academy of Sciences, 1988, vol.524, 133-141.