In the first place, the ancient question of "spontaneous generation" received fresh impetus from the difficulty of keeping such minute organisms as bacteria from reaching and developing in organic infusions; and, secondly, the long-suspected analogies between the phenomena of fermentation and those of certain diseases again made themselves felt, as both became better understood. Needham in 1745 had declared that heated infusions of organic matter were not deprived of living beings; Spallanzani (1777) had replied that more careful heating and other precautions prevent the appearance of organisms in the fluid. Various experiments by Schwann, Helmholtz, Schultz, Schroeder, Dusch and others led to the refutation, step by step, of the belief that the more minute organisms, and particularly bacteria, arose de novo in the special cases quoted. Nevertheless, instances were adduced where the most careful heating of yolk of egg, milk, hay-infusions, etc., had failed, - the boiled infusions, etc., turning putrid and swarming with bacteria after a few hours.

In 1862 Pasteur repeated and extended such experiments, and paved the way for a complete explanation of the anomalies; Cohn in 1872 published confirmatory results; and it became clear that no putrefaction can take place without bacteria or some other living organism. In the hands of Brefeld, Burdon-Sanderson, de Bary, Tyndall, Roberts, Lister and others, the various links in the chain of evidence grew stronger and stronger, and every case adduced as one of "spontaneous generation" fell to the ground when examined. No case of so-called "spontaneous generation" has withstood rigid investigation; but the discussion contributed to more exact ideas as to the ubiquity, minuteness, and high powers of resistance to physical agents of the spores of Schizomycetes, and led to more exact ideas of antiseptic treatments. Methods were also improved, and the application of some of them to surgery at the hands of Lister, Koch and others has yielded results of the highest value.

Long before any clear ideas as to the relations of Schizomycetes to fermentation and disease were possible, various thinkers at different times had suggested that resemblances existed between the phenomena of certain diseases and those of fermentation, and the idea that a virus or contagium might be something of the nature of a minute organism capable of spreading and reproducing itself had been entertained. Such vague notions began to take more definite shape as the ferment theory of Cagniard de la Tour (1828), Schwann (1837) and Pasteur made way, especially in the hands of the last-named savant. From about 1870 onwards the "germ theory of disease" has passed into acceptance. P. F. O. Rayer in 1850 and Davaine had observed the bacilli in the blood of animals dead of anthrax (splenic fever), and Pollender discovered them anew in 1855. In 1863, imbued with ideas derived from Pasteur's researches on fermentation, Davaine reinvestigated the matter, and put forth the opinion that the anthrax bacilli caused the splenic fever; this was proved to result from inoculation.

Koch in 1876 published his observations on Davaine's bacilli, placed beyond doubt their causal relation to splenic fever, discovered the spores and the saprophytic phase in the life-history of the organism, and cleared up important points in the whole question (figs. 7 and 9). In 1870 Pasteur had proved that a disease of silkworms was due to an organism of the nature of a bacterium; and in 1871 Oertel showed that a Micrococcus already known to exist in diphtheria is intimately concerned in producing that disease. In 1872, therefore, Cohn was already justified in grouping together a number of "pathogenous" Schizomycetes. Thus arose the foundations of the modern "germ theory of disease;" and, in the midst of the wildest conjectures and the worst of logic, a nucleus of facts was won, which has since grown, and is growing daily. Septicaemia, tuberculosis, glanders, fowl-cholera, relapsing fever, and other diseases are now brought definitely within the range of biology, and it is clear that all contagious and infectious diseases are due to the action of bacteria or, in a few cases, to fungi, or to protozoa or other animals.

Fig. 2. Germination of spores of Bacillus ramosus.

Fig. 2. - The various phases of germination of spores of Bacillus ramosus (Fraenkel), as actually observed in hanging drops under very high powers.

A. The spore sown at 11 A.M., as shown at a, had swollen (b) perceptibly by noon, and had germinated by 3.30 P.M., as shown at c: in d at 6 P.M., and e at 8.30 P.M.; the resulting filament is segmenting into bacilli as it elongates, and at midnight (f) consisted of twelve such segments.

B, C. Similar series of phases in the order of the small letters in each case, and with the times of observation attached. At f and g occurs the breaking up of the filament into rodlets.

D. Germinating spores in various stages, more highly magnified, and showing the different ways of escape of the filament from the spore-membrane. (H. M. W.)

Other questions of the highest importance have arisen from the foregoing. About 1880 Pasteur first showed that Bacillus anthracis cultivated in chicken broth, with plenty of oxygen and at a temperature of 42-43° C., lost its virulence after a few "generations," and ceased to kill even the mouse; Toussaint and Chauveau confirmed, and others have extended the observations. More remarkable still, animals inoculated with such "attenuated" bacilli proved to be curiously resistant to the deadly effects of subsequent inoculations of the non-attenuated form. In other words, animals vaccinated with the cultivated bacillus showed immunity from disease when reinoculated with the deadly wild form. The questions as to the causes and nature of the changes in the bacillus and in the host, as to the extent of immunity enjoyed by the latter, etc., are of the greatest interest and importance. These matters, however, and others such as phagocytosis (first described by Metchnikoff in 1884), and the epoch-making discovery of the opsonins of the blood by Wright, do not here concern us (see II. below).