14. Animals and Humans: Remarkably Similar
The assertion that animal experimentation is a “failed technology” (1) is the linchpin of the pseudoscientific attack on animal-based biomedical research that has been waged over the last two decades. However, it is an undeniable fact that our knowledge of the function of the organs of the human body stems almost solely from research in other animals.
For example, the investigation of the function of the heart by William Harvey (2) was one of the earliest adventures in experimental medicine. Harvey’s conclusion, that the movements of the heart caused the blood to circulate round the body, derived from observations in cold-blooded animals such as a living snake or toad as well as in the pig. Today, the rodent is the most widely used order for experimental work. It is evident that there is no difference in the way the conducting tissue in the heart of the rat or the human triggers the sequential contraction of the individual muscle fibres, so that the blood is caused to circulate first through the lungs then throughout the body.
The similarity extends to pathology, for should a coronary artery of the rat heart be ligated, thus preventing the flow of blood to a portion of the heart muscle, bursts of irregular heart beats occur – bigeminy, ventricular tachycardia – just as happens in patients suffering from acute myocardial ischaemia induced by coronary occlusion. Exactly as in patients, a proportion of rats so treated will die due to ventricular fibrillation unless resuscitation techniques are applied.
The mechanisms whereby the major organs are controlled and co-ordinated are likewise identical in man and laboratory species. The chemical messengers released from nerve cells in the brain and the peripheral nervous system to effect a response in adjacent cells are identical in all mammals. Thus, for example, the increase in heart rate induced by circulating adrenaline or by noradrenaline released from sympathetic nerves in the heart can be blocked in both humans and rat by beta-adrenoceptor antagonists such as propranolol. Indeed even the selective blockade, by the more recent drugs, of the beta receptors on the heart as compared to those on the lung (preferred by asthmatics) is observed in the rat as well as man.
The more long-term regulation of organ activity of humans, that exerted by the endocrine system, is of course also analogous in laboratory animals. In fact in the absence of animal experimentation it is doubtful if knowledge of the functions of say, the pituitary and thyroid glands would be much different from the views current in the mid nineteenth century. At that time it was thought that they were concerned with the production of mucus to moisten the nasal and tracheal membranes respectively.
It is a fact that the hormones, insulin, obtained from the pancreases of pigs or cows, powdered thyroid gland of pig, thyrotropin obtained from cow pituitaries, calcitonin obtained from parathyroid glands of salmon, adrenocorticotrophic hormone from the pituitaries of “mammals used for food” and oxytocin and vasopressin from pig posterior pituitary glands have all been used in patients to correct hormone deficiencies or for diagnostic purposes. This surely speaks more powerfully for the similarity of the physiologies of these species rather than for patent differences.
One could of course fill a textbook with further evidence but these very general examples serve to illustrate the basic similarities in the physiology and biochemistry of all mammals and even non-mammalian species.
The Arguments
What are the arguments used by those attacking the validity of animal experiments? How do they attempt to justify their claims?
Diseases
First there is the claim that animals don’t suffer from the same pathological conditions as man and therefore cannot be used to study human diseases which, it is alleged, are entirely different. In fact there are many animal diseases which are the exact analogy of those in humans. The veterinary surgeon Cornelius (3) has published a list of some 350 diseases suffered by animals which have an exact human counterpart. The paper of Cornelius is mentioned by the antivivisectionist Sharpe (4, p. 116) who quite erroneously claimed that Cornelius gives “a long list of animal models of human disease” (my emphasis), implying that these were induced, whereas in fact Cornelius was describing diseases that occurred spontaneously in animals. Cornelius went further to suggest that the study of such diseases was “a neglected medical resource” and called for coordinated interprofessional efforts between human and veterinary centres. This issue is also well-covered in a source readily available to the general public – the section on “Animal Disease” in Encyclopaedia Britannica. This contains a large list of diseases common to animals and humans and states: “it is likely that, for every known human disease, an identical or similar disease exists in at least one other species.”
Reaction to drugs
The second argument is the claim that animals respond differently to drugs. It is often stated that there are vast differences between lethal doses in animals and humans (4, p. 98). The problems in making such a claim are clear. Whilst it is relatively easy on the one hand to obtain a satisfactory estimate of the range of toxicity of a substance in an animal species it is not possible in humans. One must rely on data from suicides or accidental poisoning where one can never be absolutely confident of the amount ingested or the amount possibly lost by vomiting or stomach wash etc. Furthermore, individual variation in humans due to genetic constitution, age (many cases of poisoning occur in children), alcoholism, concurrent ingestion of alcohol or other drugs, existing disease etc., render any but the most vague estimate of toxic dose impossible.
Similarly spurious are the claims of a particular drug morbidity produced in an animal species but not in humans. One of the most preposterous is the allegation by Sharpe (4, p. 72) that aspirin is a proven teratogen in rats and other species yet, despite being widely used by pregnant women has failed to produce any malformation. The studies in which aspirin was shown to be teratogenic in rat used doses of 250 mg/kg/day, from three days prior to mating to the end of pregnancy (5), or 300 mg/kg/day from the 9th to the 12th day of pregnancy (6). Transposed to the human (assuming a woman of 55kg) it would mean a regimen of 46 aspirin tablets per day for the whole of pregnancy or 55 tablets every day from the 12th to the 17th week of pregnancy (Fig. 14.1).
Not surprisingly, clinical data with this sort of regimen does not exist, however McNeil (7) cited 8 cases of fetal abnormalities in children from mothers who habitually took large doses of aspirin during pregnancy, and in a retrospective study by Richards (8) of 833 patients who ingested large amounts of aspirin during the first trimester, there was a significant rise in malformation.
One can similarly destroy the rather bizarre assertion that a hormone naturally produced by the body – insulin – “produces deformities in laboratory animals but not in people” (4, p. 72). In these studies (9) pregnant rabbits were given 20 units of insulin per day for between 2 and 13 days (a dose sufficient to cause hypoglycaemic convulsions for five hours each day) and many abnormal fetuses were born. Again, no comparable clinical data exists but one would hardly be surprised if pregnant women subjected to this treatment produced deformed children.
A final example is the perennial canard that morphine calms people but causes “maniacal excitement in cats” (4, p. 71). The source of this statement is obscure but the veterinarians Davis and Donnelly (10) showed that doses of morphine equivalent to those used in humans (i.e. 0.1 mg/kg) “produced analgesia with no excitement in experimental cats,” and the current edition of a standard textbook of veterinary pharmacology (11) states: “Even in the cat, it is now accepted that very low doses (of morphine) can produce analgesia without excitement.” A high dose of morphine (1 mg/kg) will produce excitement in cats, as it will in humans (12).
The flaws in the arguments raised by those proposing that animal experiments are “bad science” are easily exposed by reading primary sources readily obtainable in any science library. The selection and promulgation of abstracts that transmit a persuasive misrepresentation of scientific method does nothing for the furtherance of scientific or ethical principles.
An earlier version of this chapter was published as: Animals and humans – remarkably similar. RDS News January 1993 8-10.
References
- Sharpe, R (1989) Animal Experiments – A Failed Technology, in Animal Experimentation. The consensus Changes. Oxford: Macmillan Press.
- Harvey, W (1628) An Anatomical Disputation Concerning the Movement of the Heart and Blood in Living Creatures. Trans by Gweneth Whitteridge. 1976 London: Blackwell Scientific Publications.
- Cornelius CE (1969) Animal models – A neglected medical resource. New Eng J Med 281 934-43.
- Sharpe R (1988) The Cruel Deception: The Use of Animals in Medical Research. London: Thorsons.
- McColl J D, Globus M & Robinson S (1965) Effect of some therapeutic agents on the developing rat fetus. Toxicol appl Pharmacol 7 409-17.
- Wilson J G, Ritter E J, Scott W J & Fradkin R (1977) Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and monkeys. Toxicol appl Pharmacol 41 67-78.
- McNeil J R (1973) The possible teratogenic effects of salicylates on the developing fetus. Clin Paediat 12 347-50.
- Richards I D G (1969) Congenital malformations and environmental influences in pregnancy. Brit J Prevent & Soc Med 23 218-25.
- Kalter H & Warkany J (1959) Experimental production of congenital malformations in mammals by metabolic procedure. Physiol Rev 39 69-115.
- Davis L E & Donnelly E J (1968) Analgesic drugs in the cat. J Am Vet Med Ass 153 1161-67.
- Brander et al. (1991) Veterinary Applied Pharmacology and Therapeutics. 5th ed. Philadelphia: Bailliere Tindall.
- Goodman & Gilman (1980) The Pharmacological Basis of Therapeutics. 6th edition. New York: Macmillan.