[13] This modification is made for the author by Messrs. Down Bros., St. Thomas's Street, London, S. E. [14] Manufactured by Messrs. Francis Lepper, 56, Great Marlborough Street, London, W. XVIII. THE STUDY OF EXPERIMENTAL INFECTIONS DURING LIFE. The possession of pathogenetic properties by an organism under study is indicated by the "infection" of the experimental animal--a term which is employed to summarise the condition resulting from the successful invasion of the tissues of the experimental animal by the micro-organisms inoculated and by their multiplication therein. Infection is considered to have taken place: 1. When the death of the animal is produced as a direct consequence of the inoculation. 2. When without necessarily producing death the inoculation causes local or general changes of a pathological character. 3. When either with or without death, or local or general changes occurring, certain substances make their appearance in the body fluids, which can be shown (_in vitro_ or _in vivo_) to exert some profound and specific effect when brought into contact with subcultivations of the organism originally inoculated. The important factors in the production of infection are: A. Seed. Virulence of organism. Dose of organism. B. Soil. Resistance offered by the cells of the experimental animal. The first two factors, although variable, are to a certain extent under the control of the experimenter. Thus by suitable means the virulence of an organism can be exalted or attenuated, whilst the size of the dose may be increased or diminished. The third factor also varies, not only amongst different species of animals, but also amongst different individuals of the same species. The essential causes of this variation are not so obvious, so that beyond selecting the animals intended for similar experiments with regard to such points as age, size or sex, but little can be done to standardise cell resistance. Immediately an animal has been inoculated a period of clinical observation must be entered upon, which should only terminate with the death of the animal. The general observations should at first and if the infection is an acute one, be made daily--later, and if the animal appears to be unaffected or if the infection is chronic, both general and special observations should be carried out at weekly intervals. If the animal appears to be still unaffected, it should be killed with chloroform vapour at the end of two or three months and a complete post-mortem carried out. A. The ~general observations~ should take cognisance of: 1. _General appearance._ The experimental animal should be inspected daily, not only with a view to detecting symptoms due to the experimental infection, but also to prevent any intercurrent infection, naturally acquired, from escaping notice (_vide_ page 337).