The laboratory animal today and to-morrow

FOREWORD THE LABORATORY ANIMAL TODAY AND TO-MORROW The importance of the quality of the laboratory animals in research is unanimously recognized. We are glad that the NATO has considered the problem as important enough to organize an advanced study symposium in Harrogate, England and to arrange publication of a selection of the papers presented on this occasion. It is a fact that the majority of investigators are not particularly interested in laboratory animals as such. But in the solution of problems in fundamental and applied research, as in genetics and heredity, infectious diseases and immunology, problems of cell ultrastructure and cell physiology, radiobiology, standardization of drugs, in problems related to cardiovascular diseases and cancer, the laboratory animal becomes more and more a tool of major importance. Therefore, the raising and maintenance of laboratory animals of quality become a task which is impossible to overlook. The production and maintenance of various primary type colonies become an urgent necessity if we want to secure for investigators material adequate to meet the requirements resulting from the actual trends of research in medicine and biology. In this domain, thanks to recent developments, we have considerably increased our knowledge. We know how to organize and maintain production units derived from primary colonies and how to produce large numbers of animals during a limited number of generations without risking serious departure from the original specifications. As regards the construction and operation of buildings for those units, many investigators and scientific animal breeders have acquired great experience. Earlier designs, as well as materials, have been markedly improved. We are now able to exclude parasitic infestation and the entrance of pathogenic bacteria, thanks to the construction of barrier-type buildings suitably equipped with such a refinement as a vacuum system for the evacuation of soiled bedding and excrement, as well as vacuum transport for sterilized supplies. This type of building can be constructed to raise and maintain caesarean-derived animals for long periods of time, in the condition they are in when first introduced into the building. Thus we are now prepared for mass production of routine laboratory animals of high quality. These should without a doubt include pathogen-free animals from pure-line origin. Further the question arises of the need, not only for specific pathogen-free animals, but, also for germ-free animals of reputed strains. Such material will provide investigators in many fields with a tool which will undoubtedly give more uniform response to well-defined experimental problems. The need for germ-free animals is a major problem in production but is in my view essential. It is highly desirable to raise caesarean-derived animals and to maintain them in an aseptic environment during their whole lifespan and for several generations to solve many fundamental problems of physiology and molecular biology. The necessity for raising species especially suitable for certain types of research and other than those most commonly used (e.g. mice and rats) like some types of farm animals (such as miniature pigs or rabbits), domestic animals 0ike cats and dogs), and certain varieties of primates, is another question of growing importance. The demand by physiologists and

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pathologists for animals o f this type is increasing every year. There are laboratories where certain types of investigation are impaired by the lack of such biological tools. Highly inbred strains selected during the period of inbreeding may be necessary for features desirable in specific fields. Up to now, we have aimed at a high degree of homozygosity in our inbred lines and specificity in our closed colony stocks based upon certain definite tests. A high degree of uniformity in our experimental animals is undoubtedly necessary if we want uniform results. As is well known, skin grafting is the test generally considered best for finding out whether a line is homozygous. But skin grafting can, after all, only cover a small proportion of the total number of genes present in the genome. Therefore, it is obvious that there is a need for tests that will make it possible to scan other different types of loci. Progress has already been made in this direction. It has been shown during this meeting how recessive characteristics, gene dependent, can segregate from other well-known, easily-detectable characteristics and how by breeding it is possible to establish pure lines which may or may not possess the features required. However, we agree that there is still a long way to go before we shall have at our disposal the pure lines desirable to cover the majority of needs in the many fields where laboratory animals are used. Thus, it is urgent to devise simple methods for selection of special lines, as well as adequate methods for the scanning and testing of the different sets of genes required. There is also a profound need for the acquisition of more information concerning the gene functions as well as the mechanism through which the genes act by means of the messenger RNA to fulfil the many functions of the cytoplasm. Do regulating genes exist in mammals as they seem to exist in micro-organisms ? If so, there must exist environmental factors acting on the end product: the repressors, that are enhancing factors as well as depressing factors. A better knowledge of such mechanisms would help the geneticist to develop new scientific methods of selection and to establish pure lines possessing definite sets of characteristics. It may be that immunological methods could play a role, by taking advantage of the antigenicity of D N A and RNA as such, or better still, of carefully selected polypeptides linked to a protein moiety. Gene function, and the mechanism through which information is transcribed by the messenger, is related to the whole question of viral infection. Would it be possible to raise animals virus free, or free from specific types of virus ? This is undoubtedly a problem of molecular biology and will have to be tackled if we want to approach the solution of problems related to tissue or organ grafting and cancer. Problems possible to solve with suitable animals are so numerous and exist in so many different disciplines that although we hesitate to elaborate yet others come to mind. One problem directly related to the production of laboratory animals in general is the question of food and nutrition. To my mind, this question has not attracted enough attention if one realizes that problems like fecundity, cardiovascular diseases and cancer are at least partly related to nutrition. Allow me also to mention a few problems in radiobiology concerning adaptation, mutation, protection and recovery. Needless to say that such problems are of paramount importance at the dawn of the atomic era. The problem of aging and longevity must also receive attention. The role played by heredity in the mechanism of carcinogenesis needs urgent clarification. We have devoted much effort in selecting strains susceptible to cancer. Is it possible to select strains resistant to chemically- or radiologically-induced cancer, even if virus or immunological methanisms are involved ? On the other hand, what are the essential changes in the D N A and RNA of cancer cells ? And, related to this problem,

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to what extent is it possible to influence mutations induced by definite mutagenic agents through environmental factors ? No doubt, in solving so many fundamental problems, the need exists not only for pathogen-free animals and for hybrids of weU-known ancestry, but also for new types of homozygous lines characterized by definite sets of genes. We may predict that this need will become more imperative in the future. Therefore, we hope that authorities responsible for the promotion of science will understand this and actively encourage the creation of modern scientific breeding centres in universities and commercial organizations not only in the western world, but also in developing countries. Let us hope tlmt the International Committee of Laboratory Animals (ICLA), which has already done so much to promote the development of the scientific animal, will once again pioneer in the right direction. Let us thank NATO for their understanding and their generous help and let us hope that NATO and other international organizations, like WHO and the Council for International Organizations of Medical Sciences (CIOMS) which have been so co-operative, will continue to understand the importance of this problem for the scientific development of biology and the benefit of humanity. J. n . MAISIN

Institut du Cancer, Louvain, Belgium