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CHAPTER 2 ANIMAL MODELS OF HUMAN DISEASES In the preceding chapter, I pointed out that the logic behind comparative medicine is that of doing research by analogy, and I outlined in general terms some of the fields in which this method has been successfully used. In this chapter , I shall look more closely at some model systems. First, however, I shall consider the ways in which suitable models for human problems are found. Basically, there are two approaches to the discovery of such models: starting from the animal or starting from man. In the first case, someone working with animals, usually a veterinarian , notices that an animal disease which he encounters resembles a human disease which he knows about, and he draws attention to the possible value of the former as a model for the latter. Clearly, the recognition of these opportunities depends on the veterinarian being acquainted with human pathology. In the second case, the researcher starts from the human disease and makes a deliberate search for an analogous condition in animals. Here, again, it is necessary for the person concerned to have some knowledge of both human and 41 Frontiers in Comparative Medicine animal disease in order to draw analogies which have significant implications for further research. The first point I wish to make, then, is that comparative medicine calls for research workers whose knowledge is broader than normally met in people trained exclusively in either the veterinary or the medical field. Veterinary education always extends across several species of animals, so usually it is easier for the veterinarian to acquire a general knowledge of human diseases than it is for a medical man to acquire knowledge of diseases of animals. It might be argued that collaboration between a medic and a veterinarian renders it unnecessary for either to know the other's field, but this is only partly true, and, in my view, it is a second best to combining the knowledge in one mind. Dependence on collaboration lessens the chance of unforeseen discovery. Whichever way one looks at it, however, it is necessary to bridge the gap that normally exists between human and veterinary medicine. Animal models are most often found in domestic animals and especially the companion animals, dogs and cats, because they are often kept to old age and given more individual veterinary attention than farm animals. The next most fruitful Source is laboratory animals, because they are usually autop- $ied. Animals in zoos are another source of models and, no doubt, there is a great potential in wild animals, among which, however, there are practical difficulties in finding models. Lower vertebrates and invertebrates also offer scope lor comparative studies, and one recalls that the concept of phagocytic cells as part of our defense mechanism originated from Metchnikoff s observation on starfish larvae. Once a few animals are found with the disease in question, It is sometimes possible to breed from them selectivelyto produce groups of animals for experimentation and even to intensify the disease condition. Inbreeding of mice has been 42 Animal Models of Human Diseases extensively practiced to produce strains which are especially suitable for studying certain diseases. For example, the New Zealand black mouse is a well-known model in immunopathology . An animal model may be a true counterpart to the human disease, and in that case direct comparisons and transfer of information can take place; but often the best model that is available differs from the human condition in a number of respects, and this situation calls for careful judgment and insight in interpreting the comparisons. In these cases, it is especially important to bear in mind that the object of the study is not so much to transfer results directly from animal to man as to reach an understanding of the underlying mechanisms of the particular disease in the relevant physiological context. That is why a model may be useful even when it is not an exact counterpart. The essence of the comparative method is that one uses the animal model to elucidate the basic disease processes and to develop appropriate technical methods. One then employs this knowledge to investigate the human problem. Virtually any medical problem can be approached in the comparative way. Leader and Leader (1971), Jones (1969), Cornelius (1969), and others have produced extensive catalogues of animal models of human diseases. The National Academy of Sciences publishes a series entitled Animal Models for Biomedical Research, and the Institute of Laboratory Animal Resources includes details of animal...


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