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free toxic fluid was obtained which produced the important symptoms of the disease—in the case of diphtheria by Roux and 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 II. Pathological. Behring and Kitasato (1890), and by Tizzoni and Cattani. The action of bacteria as pathogenic agents is in great A similar result was also obtained in the case of diphtheria. part merely an instance of their general action as pro- The facts with regard to passive immunity were thus ducers of chemical change, yet bacteriology as established, and were put to practical application by the Bacterio- a wp0je pas become so extensive, and has so introduction of diphtheria antitoxin as a therapeutic agent important a bearing on subjects widely different in 1894. The technique of serum preparation has become from one another, that division of it has become essential. since that time greatly elaborated and improved, the work The science will accordingly be treated in this section from of Ehrlich in this respect being specially noteworthy. The the pathological standpoint only. It will be considered laws of passive immunity were shown to hold also in the under the three following heads, viz. (1) the methods em- case of immunity against living organisms by Pfeiffer ployed in the study; (2) the modes of action of bacteria (1894), and various anti-bacterial sera have been introand the effects produced by them; and (3) the facts and duced. Of these the anti-streptococcic serum of Marmorek theories with regard to immunity against bacterial disease. (1895) is probably the most important. The principles The demonstration by Pasteur (see ScHizoMYCETES,AW:y. of protective inoculation have been developed and pracBrit., ninth ed.) that definite diseases could be produced tically applied on a large scale, notably by Haffkine in the by bacteria, proved a great stimulus to research case of cholera (1893) and plague (1896), and recently by Historical ^ ^ etj0j0gy 0f infective conditions, and the Wright and Semple in the case of typhoid fever. One result was a rapid advance in human knowledge. other discovery of great importance may be mentioned, viz., An all-important factor in this remarkable progress was the agglutinative action of the serum of a patient suffering the introduction by Koch of solid culture media, of the from a bacterial disease, first discovered in the case of “ plate-method,” Ac., an account of which he published in typhoid fever independently by Widal and by Griinbaum 1881. By means of these the modes of cultivation, and in 1896, though led up to by the work of Pfeiffer, Gruber especially of separation, of bacteria were greatly simplified. and Durham, and others. Thus a new aid was added to Various modifications have since been made, but the routine medical science, viz., serum diagnosis of disease. It will methods in bacteriological procedure still employed are in thus be seen that the last decade of the 19th century was great part those given by Koch. By 1876 the anthrax largely occupied with the investigation of toxins, of quesbacillus had been obtained in pure culture by Koch, and tions of immunity, and of the properties of the serum of some other pathogenic bacteria had been observed in the immunized animals; it will stand out in the history of tissues, but it was in the decade 1880-90 that the most medical science as the period in which serum therapeutics important discoveries were made in this field. Thus the and serum diagnosis had their birth. The methods employed in studying the relation of bacteria of suppuration, tubercle, glanders, diphtheria, typhoid fever, cholera, tetanus, and others were identified, bacteria to disease are in principle comparatively simple, and their relationship to the individual diseases established. but considerable experience and great care are Metbods e In the last decade of the 19th century the chief discoveries necessary in applying them and in interpreting of st°dy. were of the bacillus of influenza (1892), and of the bacillus results. In any given disease there are three of plague (1894).1 Immunity against diseases produced by chief steps, viz. (1) the discovery of a bacterium in the bacteria has been the subject of systematic research from affected tissues by means of the microscope ; (2) the obtain1880 onwards. In producing active immunity by the ing of the bacterium in pure culture ; and (3) the production attenuated virus, Duguid andBurdon-Sanderson, and Green- of the disease by inoculation with a pure culture. By means field in Great Britain, and Pasteur, Toussaint, andChauveau of microscopic examination more than one organism may in France, were pioneers. The work of Metchnikoff, dating sometimes be observed in the tissues, but one single organfrom about 1884, has proved of high importance, his ism by its constant presence and special relations to the theory of phagocytosis having proved a great stimulus to tissue changes can usually be selected as the probable cause research, and having also contributed to important advances. of the disease, and attempts towards its cultivation can then The modes by which bacteria produce their effects also be made. Such microscopic examination requires the use became a subject of study, and attention was naturally of the finest lenses and the application of various staining turned to their toxic products. The earlier work, notably methods. In these latter the basic aniline dyes in solution that of Brieger, chiefly concerned ptomaines (vide infra), are almost exclusively used, on account of their special but no great advance resulted. A new field of inquiry affinity for the bacterial protoplasm. The methods vary was, however, opened up when, by filtration, a bacterium- much in detail, though in each case the endeavour is to colour the bacteria as deeply, and the tissues as faintly, as 1 A bacillus (B. icteroides) was described as the cause of yellow possible. Sometimes a simple watery solution of the dye fever by Sanarelli in 1897, but the etiology of this disease must still is sufficient, but very often the best result is obtained by (1901) be considered as subjudice.

/. Bakt. II. Abt. B. i. 1895, p. 1.—Molisch. Die Pflanze in Hire Bcziehungen zum Disen. Jena, 1892. Pigment Bacteria : Ewart. “On the Evolution of Oxygen from Coloured Bacteria.” Linn. Journ., 1897, vol. xxxiii. p. 123. Oxydases and Enzymes: Green. The Soluble Ferments and Fermentation. Cambridge, 1899. Action of Light, &c.: Marshall Ward. “The Action of Light on Bacteria.” Phil. Trans., 1893, p. 961, and literature. Resistance to Cold, &c. : Ravenel. Med. News, 1899, vol. Ixxiv. — Macfadyen and Rowland. Proc. Ji. Soc. vol. Ixvi. pp. 180, 339, and 488.—Farmer. -“Observations on the Effect of Desiccation of Albumin upon its Coagulability.” Ibid. p. 329. Pathogenic Bacteria: Baumgarten. Pathologische Mykologie, 1890; and numerous special works in medical literature. Ehrlich. “ On Immunity with Special Reference to Cell-life.” Proc. R. Soc. vol. Ixvi. p. 424. Bacteriosis: Migula, ' l.c. p. 322, has collected the literature.—Woods. “Stigmonose, a Disease of Carnations, &c.” U.S. Dept, of Agriculture. Bull. No. 19, 1900. Symbiosis: Marshall Ward. “Symbiosis.” Ann. of Dot. vol. xiii. p. 549, and literature. (h. M. W.)