The action of bacteria as pathogenic agents is in great part merely an instance of their general action as producers of chemical change, yet bacteriology as a whole has become so extensive, and has so important a bearing on subjects widely different from one another, that division of it has become essential. The science will accordingly be treated in this section from the pathological standpoint only. It will be considered under the three following heads, viz. (1) the methods employed in the study; (2) the modes of action of bacteria and the effects produced by them; and (3) the facts and theories with regard to immunity against bacterial disease.

The demonstration by Pasteur that definite diseases could Historical summary. be produced by bacteria, proved a great stimulus to research in the etiology of infective conditions, and the result was a rapid advance in human knowledge. An all-important factor in this remarkable progress was the introduction by Koch of solid culture media, of the "plate-method," etc., an account of which he published in 1881. By means of these the modes of cultivation, and especially of separation, of bacteria were greatly simplified. Various modifications have since been made, but the routine methods in bacteriological procedure still employed are in great part those given by Koch. By 1876 the anthrax bacillus had been obtained in pure culture by Koch, and some other pathogenic bacteria had been observed in the tissues, but it was in the decade 1880-1890 that the most important discoveries were made in this field. Thus the organisms of suppuration, tubercle, glanders, diphtheria, typhoid fever, cholera, tetanus, and others were identified, and their relationship to the individual diseases established.

In the last decade of the 19th century the chief discoveries were of the bacillus of influenza (1892), of the bacillus of plague (1894) and of the bacillus of dysentery (1898). Immunity against diseases caused by bacteria has been the subject of systematic research from 1880 onwards. In producing active immunity by the attenuated virus, Duguid and J. S. Burdon-Sanderson and W. S. Greenfield in Great Britain, and Pasteur, Toussaint and Chauveau in France, were pioneers. The work of Metchnikoff, dating from about 1884, has proved of high importance, his theory of phagocytosis (vide infra) having given a great stimulus to research, and having also contributed to important advances. The modes by which bacteria produce their effects also became a subject of study, and attention was naturally turned to their toxic products. The earlier work, notably that of L. Brieger, chiefly concerned ptomaines (vide infra), but no great advance resulted. A new field of inquiry was, however, opened up when, by filtration a bacterium-free toxic fluid was obtained which produced the important symptoms of the disease - in the case of diphtheria by P. P. E. Roux and A. Yersin (1888), and in the case of tetanus a little later by various observers.

Research was thus directed towards ascertaining the nature of the toxic bodies in such a fluid, and Brieger and Fraenkel (1890) found that they were proteids, to which they gave the name "toxalbumins." Though subsequent researches have on the whole confirmed these results, it is still a matter of dispute whether these proteids are the true toxins or merely contain the toxic bodies precipitated along with them. In the United Kingdom the work of Sidney Martin, in the separation of toxic substances from the bodies of those who have died from certain diseases, is also worthy of mention. Immunity against toxins also became a subject of investigation, and the result was the discovery of the antitoxic action of the serum of animals immunized against tetanus toxin by E. Behring and Kitazato (1890), and by Tizzoni and Cattani. A similar result was also obtained in the case of diphtheria. The facts with regard to passive immunity were thus established and were put to practical application by the introduction of diphtheria antitoxin as a therapeutic agent in 1894. The technique of serum preparation has become since that time greatly elaborated and improved, the work of P. Ehrlich in this respect being specially noteworthy.

The laws of passive immunity were shown to hold also in the case of immunity against living organisms by R. Pfeiffer (1894), and various anti-bacterial sera have been introduced. Of these the anti-streptococcic serum of A. Marmorek (1895) is one of the best known. The principles of protective inoculation have been developed and practically applied on a large scale, notably by W. M. W. Haffkine in the case of cholera (1893) and plague (1896), and more recently by Wright and Semple in the case of typhoid fever. One other discovery of great importance may be mentioned, viz. the agglutinative action of the serum of a patient suffering from a bacterial disease, first described in the case of typhoid fever independently by Widal and by Grünbaum in 1896, though led up to by the work of Pfeiffer, Gruber and Durham and others. Thus a new aid was added to medical science, viz. serum diagnosis of disease. The last decade of the 19th century will stand out in the history of medical science as the period in which serum therapeutics and serum diagnosis had their birth.

In recent years the relations of toxin and antitoxin, still obscure, have been the subject of much study and controversy. It was formerly supposed that the injection of attenuated cultures or dead organisms - vaccines in the widest sense - was only of service in producing immunity as a preventive measure against the corresponding organism, but the work of Sir Almroth Wright has shown that the use of such vaccines may be of service even after infection has occurred, especially when the resulting disease is localized. In this case a general reaction is stimulated by the vaccine which may aid in the destruction of the invading organisms. In regulating the administration of such vaccines he has introduced the method of observing the opsonic index, to which reference is made below. Of the discoveries of new organisms the most important is that of the Spirochaete pallida in syphilis by Schaudinn and Hoffmann in 1905; and although proof that it is the cause of the disease is not absolute, the facts that have been established constitute very strong presumptive evidence in favour of this being the case.