A Selective Critique of Animal Experiments in Human-Orientated Biological Research.
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| Title: | A Selective Critique of Animal Experiments in Human-Orientated Biological Research. |
|---|---|
| Language: | English |
| Authors: | Webb, G. P. |
| Source: | Journal of Biological Education. Fall 1990 24(3):191-197. |
| Peer Reviewed: | Y |
| Page Count: | 7 |
| Publication Date: | 1990 |
| Intended Audience: | Practitioners; Researchers |
| Document Type: | Journal Articles Opinion Papers |
| Descriptors: | Biological Sciences, Biomedicine, College Science, Higher Education, Laboratory Animals, Laboratory Procedures, Medical Research, Research Methodology, Research Problems, Science Education |
| ISSN: | 0021-9266 |
| Abstract: | The advantages and justifications for using small animals in human-oriented research are reviewed. Some of the pitfalls of extrapolating animal-derived data to humans are discussed. Several specific problems with animal experimentation are highlighted. (CW) |
| Journal Code: | CIJAPR1991 |
| Entry Date: | 1991 |
| Accession Number: | EJ419082 |
| Database: | ERIC |
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| FullText | Text: Availability: 1 Value: <anid>AN9611215395;JBI01FAL.90;1996Dec16.09:37;v2.3</anid> <title id="AN9611215395-1">A SELECTIVE CRITIQUE OF ANIMAL EXPERIMENTS IN HUMAN-ORIENTATED BIOLOGICAL RESEARCH </title> <hd id="AN9611215395-2"> Abstract </hd> <p>The advantages and justifications for using small animals in human-orientated research are briefly over-viewed. Some of the potential pitfalls of extrapolating animal-derived data to humans are then discussed more fully, using examples biased towards nutrition. A number of particular problems of animal experimentation are highlighted.' the applicability of the results of controlled, deliberately' reductionist, laboratory experiments to arguments about free-living animals and humans,' species differences in nutrient requirements,' differences in pattern of feeding and type of diet of mammalian species; and various facets of the problem of scaling from small to large species. The enormous contribution of animal experimentation to the advancement of human biological understanding is accepted, but by focusing attention of biological educators on examples, perceived by the author to have involved inappropriate cross-species extrapolation, it is hoped that this paper may help to increase the future effectiveness and reduce waste of experimental animals. </p> <hd id="AN9611215395-3"> Justification and aims of the paper </hd> <p>Experiments with small laboratory animals are a vital tool in biomedical research, but few science courses contain a formal teaching clement on the role and validity of animal experiments for human-orientated argument. In this paper, the logical assumptions, benefits, and problems of this type of research approach are discussed using examples biased towards the author's area of experience--nutrition. Animal experiments, or even experiments with bacteria, may be productively used to generate testable hypotheses about human biology. In practice, however, results from animal experiments are sometimes extrapolated to humans with little experimental confirmation in humans and with inadequate consideration of biological factors which make such projections unsafe. Practical and ethical limitations may make direct testing of animal-generated hypotheses in humans difficult, and experimenters may be limited to testing those human observations that are obtainable, for consistency with an hypothesis. </p> <p>The major contribution of animal experimentation to human biology is acknowledged, but the general thesis presented is that, on occasion, a lack of rigour in the extrapolation of animal-derived data to humans may have encouraged dubious or incorrect conclusions. By persuading potential researchers, through those who teach them, to consider more fully the difficulties of interpreting human-orientated animal experiments, this paper may make a contribution toward increasing the effectiveness of laboratory animal use. </p> <hd id="AN9611215395-4"> The basic dilemma </hd> <p>The concept of evolution from a common ancestor unifies the biological sciences and carries with it the implicit assumption that certain fundamental processes are common in different life-forms. Paradoxically, this same theory also highlights the uniqueness of each life-form: each mammal is the product of a long process of random change and selection to exploit a particular ecological niche. A mouse is thus not a slightly misshapen small-scale model of a human, a paradigm that has to be consciously resisted when projecting experimental results between species. </p> <p>Evolution has produced an array of life-forms to exploit all potential nutrient sources, thus implying great diversity in nutritional strategies and requirements. Perhaps the only universal nutritional rule is the minimal one--nutrition must supply a source of energy and the elements of which the organism is composed. </p> <hd id="AN9611215395-5"> Benefits and problems--an overview </hd> <p>Compared with experiments on humans, the use of animals allows increased precision, reliability, and contrallability of experiments, as well as extending the range of experiments that are ethically, technically, or economically feasible. However, when the results of such experiments are applied to humans a whole new dimension is added to the problem of validity. </p> <p>A number of key measurements are of fundamental importance in nutritional investigations. For example, the quantity of nutrients consumed, body size and composition, energy expenditure, and nutrient turnover. Direct measurements are often difficult or impossible in free-living humans, but given care and commitment can usually be made with some precision in laboratory animals. The problems in humans are highlighted by the observation that 25 per cent of all communications involving human experimentation (n=87) in the 1988 Proceedings of the Nutrition Society were either descriptions and evaluations of new methods or re-evaluations of existing methods. </p> <p>In experimentation, responses to imposed variation are measured; a major design aim is to eliminate unrequired variation. Animals can be kept under identical environmental conditions, with identical diets, and maintained pathogen-free. Use of inbred strains greatly reduces genetic variation. With experimental animals there are fewer restrictions on the nature or severity of treatments that can be used; invasive measurements can be made, harmful mutations propagated, and animals killed at the end of the experiment for post-mortem investigations. </p> <p>The small size, short generation-time, and large litter size of rodents makes them relatively inexpensive for experimental use, and they account for more than 80 per cent of experimental animal usage in the UK (HMSO, 1985). Their wide use over many years means that we have a thorough background knowledge of their physiology, biochemistry, and nutritional requirements; this should give a sound basis for the interpretation of new findings. </p> <p>The nature of the diet and pattern of feeding of mammals differs widely--they may be grazers (eating or ruminating for 16h per day) or gorgers (eating large, infrequent meals corresponding to a kill)--they may be carnivore, herbivore, or omnivore. Such biological features of experimental species tend to be disregarded by human-orientated researchers and results interpreted anthropocentrically. </p> <p>Laboratory animal usage facilitates the conduct of rigidly controlled experiments, but the artificial conditions of such experiments may limit the applicability of the results even to wild animals of the same species. Experiments are performed under a specific set of background conditions and the assumption usually made that essentially similar results would be obtained under different conditions; this assumption will not always hold. Changes in background conditions may substantially alter the nature or magnitude of an experimental response. Factorial design of experiments can detect such interactions but it is often, in practice, difficult to predict which factors are liable to interact. </p> <p>The problem of scaling across species is both complex and multi-faceted. How does one relate dosages or nutrient requirements determined in a 20 g mouse to a 70 kg human? How does one allow for the huge variation across species in the relative burdens of pregnancy and lactation? What relationship is there between metabolic rate and body size and what implications does this have when small animals are used as models for humans in studies on thermoregulation, energy balance, and obesity? The growth and maturation rates of different mammals vary widely and humans also live much longer than laboratory animals. </p> <hd id="AN9611215395-6"> Measurement problems in nutrition research </hd> <p>Webb and Jakobson (1980) discussed the relative problems of assessing body fat content in mice and humans. Animal experimenters have the ultimate choice of precise chemical analysis of the carcass. All human measures, however, are indirect estimates with relatively low sensitivity and precision; there is also no realistic possibility of their validation and calibration against the absolute measure. </p> <p>Accurate measurements of nutrient intake are straightforward in laboratory animals, as a single, mixed and pelleted food is often used. In humans, retrospective methods are often used, where subjects are asked to recall what they ate in say the previous 24 hours (24 h recall.). Potential errors are readily apparent due to: memory errors; dishonest reporting; errors in estimating portion sizes and components; and in the use of tables to convert foods into energy and nutrient values. Prospective methods (e.g. 7-day intake weighed by the subjects) reduce some of these errors but may be invalidated by sentient subjects changing their consumption in response to monitoring. </p> <hd id="AN9611215395-7"> Controlled experiments--essential but can mislead </hd> <p>The increased capacity to control experiments is a major advantage of animal use. Purified diets, devoid of individual putative nutrients, can be administered for prolonged periods and the nutrient added back to confirm its curative effect on any resultant symptoms of deficiency. Such an approach has been invaluable in the identification of vitamins and other essential nutrients. The dietary requirement for essential fatty acids was demonstrated in the rat several decades before unequivocal confirmation in humans (see Pass-more and Eastwood, 1986). </p> <p>The long-term safety of food additives is principally based on chronic feeding experiments in animals. Single additives can be fed at high doses to otherwise identically maintained animals over their whole lifespan. Such single-variable experiments, however, preclude the possibility of interactions between additives, or between additives and particular dietary or other environmental factors. A well-documented example of such interaction between two factors, is that between monoamine oxidase inhibitors (anti-depressants) and tyramine-containing foods (e.g. cheese) in raising blood pressure. A critique of food additive testing may be found in Millstone (1985); such arguments may well apply to toxicity testing of other substances. </p> <p>Reduction of genetic variability is regarded as an advantage of animal use but there is a need for caution when extrapolating from a narrow gene pool to a wide one. Sibling matings over many generations produce strains of rodents where individuals can be regarded as being homozygous and syngeneic--tissue can be transplanted between individuals of such strains without risk of rejection, as it can only be between identical twins in humans. Festing (1986) has contended that, because of enhanced reproducibility, syngeneic strains,should be used more widely: 'one of the basic assumptions of science is that experiments should be reproducible' (Festing, 1979). The danger is that if such strains are indeed a single genotype then one is effectively testing an individual response and thus possible idiosyncratic reactions may apply to whole strains. Would an experiment on an individual from an isolated tribe with a long tradition of incestuous marriage, always yield results applicable to people in general, let alone to phylogenetically distant species like rats or mice? </p> <p>Controlled experimental conditions may give a false impression if uncritically applied to humans or even to wild animals of the same species. The laboratory rat is fed a dry diet with pap water only, and as thirst is a universally experienced sensation, then it might be concluded that thirst is a dominant controlling influence over water balance. A civilised human, however, eats much wet food and drinks for taste, social reasons, and drug content, thus relegating thirst to a much less dominant role. Laboratory rats were regarded as model regulators of food intake but it is now clear that, given access to a variety of palatable, energy-rich foods, they are, like humans, prone to overeat and become obese (Rothwell and Stock, 1979). </p> <hd id="AN9611215395-8"> Differences between species in requirements for nutrients </hd> <p>Experiments in laboratory and agricultural species, stretching back over two centuries, have demonstrated the principle that all mammals require an exogenous supply of protein and essential amino acids. Monogastric animals require these essential amino acids to be present in the food they eat, but in ruminants much protein digested and absorbed in the intestine is bacterial protein produced during ruminal fermentation. Ruminants can live without any dietary protein provided they are given a suitable nitrogen source. Webb (1989) suggested that the high growth rates, and therefore very high protein requirements, of most laboratory and agricultural species encouraged inflated estimates of the protein requirements of children, and thus contributed to the now discredited idea of a huge deficit in world protein availability. </p> <p>Primates and guinea-pigs are exceptional amongst mammals in having a dietary requirement for vitamin C (ascorbic acid); most other mammals synthesize ascorbic acid from glucose. Thus the guinea-pig alone amongst the laboratory species is suitable for the study of vitamin C deficiency; the use of other rodents is clearly precluded. </p> <p>On occasion, animals are chosen as a research tool because of, rather than in spite of, their differences to humans. Thus the rabbit provided a model for studying hypothalamic control of pituitary gonadotrophin output because, unlike in most other mammals, the act of mating induces an ovulatory surge of gonadotrophin output. More controversially, Pauling (1972) has used the rats rate of vitamin C synthesis (2658 mg kg[-1] day[-1]) to support his influential view that gram quantities of the vitamin are required for optimal human health (1.8-4.1g day[-1] by simple mass scaling). </p> <hd id="AN9611215395-9"> Differences in the nature of the diet and pattern of feeding </hd> <p>Dietary cholesterol was regarded as a major factor in human atherosclerosis but current UK dietary guidelines give low priority to restriction of cholesterol intake (James, 1983). Frantz and Moore (1969) concluded that this cholesterol hypothesis derived from three observations: (a) the presence of cholesterol in atherosclerotic plaques; (b) the production of atherosclerosis by feeding animals (principally rabbits) cholesterol; (c) humans' high plasma cholesterol and epidemiological association of hypercholesteraemia with atherosclerosis. According to these authors, therefore, the animal experiments were the most important factor in directly linking dietary cholesterol with atherosclerosis. It has long been known that rabbits develop atherosclerotic vascular lesions when fed large amounts of cholesterol but they are uniquely sensitive to cholesterol (Constantinides, 1965). Selye (1970) suggested that had rats rather than rabbits been the usual experimental animal at the turn of the century then the phenomenon of cholesterol-induced atherosclerosis might never have been discovered. Differences in species sensitivity to cholesterol might be due to phylogenetic adaptation, thus, vegetarian rabbits, unlike carnivores or omnivores, may be metabolically ill-equipped to deal with cholesterol loading (Constantinides, 1965). </p> <p>The observation that gorging (i.e. meal-feeding or tube-feeding) in rodents increases energetic efficiency and adiposity, encouraged the belief that isocaloric 'nibbling' regimes are preferable to infrequent meals in the treatment of human obesity, despite relatively little experimental confirmation in humans (see Fabry, 1969). </p> <hd id="AN9611215395-10"> Nutritional requirements in pregnancy and lactation </hd> <p>Logic would suggest that pregnancy and lactation are times of heightened nutritional requirement in all mammals. The magnitude of the nutritional burden of pregnancy and lactation is, however, likely to vary widely between species. Table 1 illustrates this, showing litter mass as a proportion of pre-pregnant maternal mass in several species and also the time taken for these newborn animals to double their birth mass. After nine months of pregnancy, a human female gives birth to an infant which represents around 6 per cent of her body mass and she must then supply nutrients via her milk to enable this infant to double its birth mass in 4-6 months. A female mouse produces a litter representing 40 per cent of her mass in about three weeks and she must then provide nutrients in her milk to enable these pups to double their birth mass in five days. </p> <p>Cross-species comparisons suggest that primates have small offspring in relation to their gestation length and that the metabolic stresses are less than for comparably sized non-primates (Payne and Wheeler, 1968). Behavioural and physiological adjustments in human pregnancy make actual extra nutritional requirements very small or perhaps even non-existent in this country. Pregnant women reduce their activity and resting metabolism (DHSS, 1969; Prentice, 1989); the efficiency of iron and calcium absorption also increases markedly in pregnancy (see Passmore and Eastwood, 1986). </p> <hd id="AN9611215395-11"> Scaling of dosages </hd> <p>Conversion of dosages across species depends not only upon species sensitivity per se but also on size differences. Schmidt-Nielsen (!972) speculate. d about a likely suitable dose of LSD for an elephant. He produced a range of doses depending on whether scaling was based on relative masses, relative metabolic rates, or relative brain sizes. The dose chosen for the elephant will also depend upon whether a relatively sensitive species (man) or an insensitive species (cat) is chosen as the reference species (see table 2). </p> <p>The figures in table 2 highlight the capacity for variability when scaling dosages across species and they undermine, for example, the validity of Pauling's (1972) suggestion that the rat's rate of vitamin C synthesis, scaled on a mass basis, supports the proposition that gram quantities are needed for optimal human health. </p> <hd id="AN9611215395-12"> Body size, metabolic rate, and the energy costs of homeothermy </hd> <p>Although absolute metabolic rate increases with increasing body size across mammalian species, when standardized for body mass, it declines with increasing body size. Thus standardized metabolic rate for a large cow is around 55 kJ kg[-1] day[-1] but for a small mouse around 840 kJ kg[-1] day[-1] (Kleiber, 1965). </p> <p>Double log regressions of metabolic rate against body mass suggest an approximate relationship defined by: </p> <p>metabolic rate = k mass[0.75] </p> <p>Although temperature regulation may not be the primary stimulus governing this relationship (Bligh, 1973), it must be more energy expensive for smaller animals with their relatively large surface areas to maintain homeothermy. </p> <p>Heldmaier (1971) found a negative association between size and non-shivering thermogenic capacity with cold-acclimatized mice, which were, for example, able to increase oxygen consumption fourfold by non-shivering mechanisms. Heldmaier attributed this to the unfavourable mass-surface relation in small mammals making an effective heating system to maintain homeothermy essential. Foster and Frydman (1979) showed that brown adipose tissue is probably the major site of this non-shivering thermogenesis in rodents. </p> <p>Non-shivering thermogenesis is, however, considered unimportant to adult humans, with a capacity to increase oxygen consumption by non-shivering thermogenesis of only 10-20 per cent at most (Joy, 1963). Behavioural mechanisms, shivering, and physiological heat conservation are the predominant responses to cold in humans. Large animals, such as humans, can increase their thermal insulation several-fold in response to cold stress through changes in surface blood flow, whereas small mammals have a very limited capability in this respect (Kleiber, 1975; Jakobson, 1981). Human babies, however, are unable to shiver and they do employ non-shivering thermogenesis in thermoregulation and have active brown adipose tissue (Aherne and Hull, 1966). </p> <p>Some mammals abandon energy-expensive homeothermy when adverse climatic or food supply conditions prevail. The ability of some mammals to hibernate is well known, and some small mammals exhibit shallow, daily torpor in response to food deprivation (Hudson, 1978). During bouts of torpor, core temperature may drop to around 20 degrees C for several hours. </p> <p>Mice have generally been regarded as true homeotherms and lowered body temperatures interpreted by experimenters as failures or defects of homeothermy (Webb, Jagot, and Jakobson, 1982), but several studies (Hudson and Scott, 1979; Webb et al., 1980 and 1982) clearly show that laboratory mice can become torpid when fasted. This finding has wide significance because mice are a major laboratory species and it may affect the interpretation of experimental results using mice, particularly in energy balance studies. </p> <p>Although one factor favouring continued use of rodents experimentally is the assumption of wide background knowledge of the species, here is an example of a fundamantal aspect of the biology of the commonest laboratory animal overlooked by most human-orientated investigators. </p> <hd id="AN9611215395-13"> Body size and the energy costs of exercise </hd> <p>Different assumptions about scaling can change the whole perspective in the energy balance field. Table 3 shows some much-quoted calculations of the energy costs of a 10 km walk in three species (Miller and Mumford, 1966). These authors used body mass<sups>0.75</sups> to calculate basal metabolism and used 2 kJ kg<sups>-1</sups> km<sups>-1</sups> as the energy cost of walking because 'simple mechanics suggest that the energy cost of walking is related directly to body weight'. Taylor, Schmidt-Nielsen, and Raab (1970) found that the energy cost of running declined markedly with increasing species size. They produced a regression equation relating body mass to the minimum energy cost of running; a human expended roughly twice the expected energy of a similar sized quadruped, perhaps reflecting the extra energy cost of bipedal locomotion. This equation has been used to recalculate Miller and Mumford's example (table 4) and quite different results are obtained. </p> <hd id="AN9611215395-14"> Animal models of obesity--have they misled human nutritionists? </hd> <p>Obesity has traditionally been viewed as due to a failure to regulate food intake coupled with inactivity, that is gluttony and sloth; the etymology of the word obese (from the Latin esus 'eaten') betrays this prejudice. Early experiments with animal models of obesity focused largely on the hypothalamic mechanisms that regulate food intake (reviewed by Mayer, 1956) and thus this prevailing 'regulatory' paradigm of obesity causation was reinforced and became prominent in many nutrition texts (e.g. Davidson and Passmore, 1963). The concept of discrete nuclei within the hypothalamus regulating hunger and satiety to produce an accurately metered supply of energy to precisely fulfill requirements and maintain optimal body mass was prominent, but has lost favour in recent years. The current edition of Davidson's nutrition text (Passmore and Eastwood, 1986) has expunged all reference to hypothalamic regulation of food intake. </p> <p>An alternative view is that the obese people within a society are not necessarily those who eat the most and exercise the least, but rather that they are the least well-equipped to deal with extra energy intake by adaptive increases in energy expenditure, that is diet-induced thermogenesis (see Rothwell and Stock, 1979). According to this 'metabolic' view of obesity, some people remain lean despite overfeeding by 'burning off' the excess energy whereas those prone to obesity store it as fat. The increasing prevalence of obesity in affluent countries would be because conditions are created which permit expression of this variable and inherited, metabolic tendency towards corpulence. </p> <p>The mutant obese-hyperglycaemic mouse (ob/ob) has been widely used and has played an important role in encouraging the metabolic view of obesity. Ob/ ob mice, when restricted to the same intake as lean litter-mates, still get fatter and heavier. Thus, overeating is demonstrably not a prerequisite for obesity and the ob/ob mouse represents a popular and 'unequivocally' metabolic experimental obesity -- surely a formative influence on thinking? (see Mayer, 1960). Ob/ob mice were shown to have a low body temperature and poor cold tolerance (see Mayer, 1960) and this imperfect homeothermy would be expected to increase metabolic efficiency and contribute to the obesity. Several investigators have suggested abnormalities in the structure and/or functioning of brown adipose tissue (BAT) in ob/ob mice as a likely cause of their aberrant homeothermy, and thus their obesity (see Himms-Hagen, 1985). Providing rats with access to a variety of palatable, energy rich foods encourages overfeeding and obesity, but Rothwell and Stock (1979), in a highly influential paper, reported that some rats remained lean despite apparent massive overeating. They reported evidence of increased amounts and activity of BAT in these persistently lean animals and suggested that the site of diet-induced thermogenesis was BAT. Thus Rothwell and Stock provided a credible and stimulating hypothesis (linking several models of obesity) to account for body mass regulation via diet-induced thermogenesis in BAT. They gave preliminary evidence of active BAT in adult humans even though BAT is regarded as playing little role in human thermoregulation. </p> <p>Does the demonstration of murine torpor influence the interpretation of the apparent defective thermoregulation of ob/ob mice? Webb et al. (1982) suggested that if ob/ob mice have a defective satiety mechanism (as proposed by Coleman, 1978), then physiologically they would respond as if in a permanently food-restricted state. One might expect to find high food intake, restricted activity, and reduced thermoregulatory (and dietary) thermogenesis--all characteristic of oh/oh mice. Webb et al. (1982) and Jagot, Jakobson, and Webb (1983) reported occasional frank torpor in ad libitum fed ob/ob mice but if torpor is loosely defined as a state of reduced thermogenesis, reduced core temperature, and profound inactivity then torpidity is the usual state of ob/ob mice. Himms-Hagen (1985) even argues that the basic defect in the oh/oh mouse probably lies in a centrally determined high propensity for entry into torpor! </p> <p>Webb and Geissler (unpublished) asked nutritionists and other obesity workers to rate (on a 1-5 scale) the relevance of animal work to improving the understanding and treatment of human obesity. Figure 1 shows the responses to this question. For the whole sample, the middle option (<reflink idref="bib3" id="ref1">3</reflink>) was the mode and there was some skewing of responses toward the 'very relevant' end of the scale. The pattern for experimenters who had used animals is totally different, with 1 (very relevant) being the mode and all but one respondent giving an answer of 3 or less. The results for those who had used only human subjects in research or clinicians tended to be skewed towards the 'not relevant' end of the scale. </p> <p>Thus, predictably, those who work with animal models have much more faith (perhaps too much?) in their relevance, than clinicians, or experimenters using human subjects. </p> <hd id="AN9611215395-15"> Acknowledgements </hd> <p>I would like to thank my colleagues Drs Mary Fysh and Paul Rogers for their constructive criticism of the draft manuscript. I also acknowledge the advice and criticism of Dr Catherine Geissler throughout a period of study leave spent at King's College, London where several of these ideas were crystallized. </p> <p>Table I Relationship between maternal mass, offspring mass, and time to double birth mass in a variety of species, to illustrate the variation in relative burdens of pregnancy and lactation in different animals. (Data taken largely from Widdowson, 1981 and Blaxter, 1961.) </p> <ct id="AN9611215395-16">Legend for Chart: A - Species B - Mass of mother (kg) C - Mass of average litter as percentage of maternal mass D - Time to double birth mass (days) A B C D House mouse 0.025 40 5 Rat 0.200 25 6 Guinea-pig 0.560 68 14 Rabbit 1. 175 196 Cat 2.75 16 7 Sheep 37 10 10 Chimpanzee 46 4 100 Human 56 6 180 Cow 600 7 47 Table 2 A range of possibly suitable doses of LSD for an elephant derived by different scaling methods. (Data from Schmidt-Nielsen, 1972.) Dose (mg) Based on relative body masses and dose effective in the cat 297 * Based on relative metabolic rates of elephant and cat 80 Based on relative body masses and dose effective in humans 8 * Based on relative metabolic rates of human and elephant 3 [a] Based on relative brain size of human and elephant 0.4</ct> <p>* Detoxification and excretion may be related to metabolic rate </p> <p>[a] LSD may be concentrated in the brain. </p> <p>Table 3 The calculated energy costs of a 10 km walk in three species. (After Miller and Mumford, 1966.) </p> <ct id="AN9611215395-17">Legend for Chart: A - Species B - Mass (kg) C - Daily maintenance energy requirement (k J) D - Energy required for 10 km walk (k J) E - Energy cost of walk as percentage of maintenance A B C D E Elephant 3700 280 500 77 400 22 Human 65 12 550 1380 10 Rat 0.3 250 8 3 Assumptions: Metabolic rate = mass<sups>0.75</sups> Energy cost of walking = 2 kJ kg<sups>-1</sups> km<sups>-1</sups></ct> <p>Table 4 Recalculation of energy costs of walking in table 3 using the formula of Taylor et al. (1970) </p> <ct id="AN9611215395-18">Legend for Chart: A - Species B - Mass (kg) C - Daily maintenance energy requirement (k J) D - Energy required for 10 km walk (k J) E - Energy cost of walk as percentage of maintenance A B C D E Elephant 3700 280 500 15 470 5.5 Human 65 12 550 2720 21.7 Rat 0.3 250 54 21.5 Assumptions: Metabolic rate = mass<sups>0.75</sups> Energy cost of walking = 8.46 x mass<sups>-04</sups> (double for humans) (ml O<subs>2</subs> g<sups>-1</sups> km<sups>-l</sups>) 1 litre O<subs>2</subs>=21 kJ.</ct> <p>GRAPH: Figure 1 Questionnaire respondents' opinions on the relevance of animal work to the understanding or treatment of human obesity. All respondents were either members of the Nutrition Society or the Association for the Study of Obesity. (Unpublished data of Webb and Geissler.) </p> <hd id="AN9611215395-19"> References </hd> <p>Aherne, W. and Hull, D. (1966) Brown adipose tissue and heat production in the newborn infant. Journal of Pathology and Bacteriology, 91, 223-230. </p> <p>Blaxter, K. L. (1961) Lactation and the growth of the young. In Milk: The mammary gland and its secretion, Vol. II, ed, Kon, S. K. and Cowie, A. T. New York: Academic Press. </p> <p>Bligh, J. (1973) Temperature regulation in mammals and other vertebrates. Amsterdam: North-Holland Publishing Company. </p> <p>Coleman, D. L. (1978) Obesity and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia, 14, 141-148 </p> <p>Constantinides, P. (1965) Experimental atherosclerosis. Amsterdam: Elsevier. </p> <p>Davidson, S. and Passmore, R. (1963) Human nutrition and dietetics second edition. Edinburgh: Livingstone. </p> <p>DHSS (1969) Department of Health and Social Security. Recommended intakes of nutrients for the United Kingdom. (Report on Public Health and Medical Subjects, No. 120.) London: Her Majesty's Stationery Office. </p> <p>Fabry, P. (1969) Feeding patterns and nutritional adaptations. 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| Items | – Name: Title Label: Title Group: Ti Data: A Selective Critique of Animal Experiments in Human-Orientated Biological Research. – Name: Language Label: Language Group: Lang Data: English – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Webb%2C+G%2E+P%2E%22">Webb, G. P.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="SO" term="%22Journal+of+Biological+Education%22"><i>Journal of Biological Education</i></searchLink>. Fall 1990 24(3):191-197. – Name: PeerReviewed Label: Peer Reviewed Group: SrcInfo Data: Y – Name: Pages Label: Page Count Group: Src Data: 7 – Name: DatePubCY Label: Publication Date Group: Date Data: 1990 – Name: Audience Label: Intended Audience Group: Audnce Data: Practitioners; Researchers – Name: TypeDocument Label: Document Type Group: TypDoc Data: Journal Articles<br />Opinion Papers – Name: Subject Label: Descriptors Group: Su Data: <searchLink fieldCode="DE" term="%22Biological+Sciences%22">Biological Sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Biomedicine%22">Biomedicine</searchLink><br /><searchLink fieldCode="DE" term="%22College+Science%22">College Science</searchLink><br /><searchLink fieldCode="DE" term="%22Higher+Education%22">Higher Education</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+Animals%22">Laboratory Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+Procedures%22">Laboratory Procedures</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+Research%22">Medical Research</searchLink><br /><searchLink fieldCode="DE" term="%22Research+Methodology%22">Research Methodology</searchLink><br /><searchLink fieldCode="DE" term="%22Research+Problems%22">Research Problems</searchLink><br /><searchLink fieldCode="DE" term="%22Science+Education%22">Science Education</searchLink> – Name: ISSN Label: ISSN Group: ISSN Data: 0021-9266 – Name: Abstract Label: Abstract Group: Ab Data: The advantages and justifications for using small animals in human-oriented research are reviewed. Some of the pitfalls of extrapolating animal-derived data to humans are discussed. Several specific problems with animal experimentation are highlighted. (CW) – Name: CodeSource Label: Journal Code Group: SrcInfo Data: <searchLink fieldCode="JC" term="%22CIJAPR1991%22">CIJAPR1991</searchLink> – Name: DateEntry Label: Entry Date Group: Date Data: 1991 – Name: AN Label: Accession Number Group: ID Data: EJ419082 |
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| RecordInfo | BibRecord: BibEntity: Languages: – Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 191 Subjects: – SubjectFull: Biological Sciences Type: general – SubjectFull: Biomedicine Type: general – SubjectFull: College Science Type: general – SubjectFull: Higher Education Type: general – SubjectFull: Laboratory Animals Type: general – SubjectFull: Laboratory Procedures Type: general – SubjectFull: Medical Research Type: general – SubjectFull: Research Methodology Type: general – SubjectFull: Research Problems Type: general – SubjectFull: Science Education Type: general Titles: – TitleFull: A Selective Critique of Animal Experiments in Human-Orientated Biological Research. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Webb, G. P. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 1990 Identifiers: – Type: issn-print Value: 0021-9266 Numbering: – Type: volume Value: 24 – Type: issue Value: 3 Titles: – TitleFull: Journal of Biological Education Type: main |
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