The germ-theory of disease is another question of general bearing, and it will be dealt with briefly here. After the discovery of bacteria by Leeuwenhoek, in 1687, some medical men of the time suggested the theory that contagious diseases were due to microscopic forms of life that passed from the sick to the well. This doctrine of _contagium vivum_, when first promulgated, took no firm root, and gradually disappeared. It was not revived until about 1840. If we attempt briefly to sketch the rise of the germ-theory of disease, we come, then, first to the year 1837, when the Italian Bassi investigated the disease of silkworms, and showed that the transmission of that disease was the result of the passing of minute glittering particles from the sick to the healthy. Upon the basis of Bassi's observation, the distinguished anatomist Henle, in 1840, expounded the theory that all contagious diseases are due to microscopic germs. The matter, however, did not receive experimental proof until 1877, when Pasteur and Robert Koch showed the direct connection between certain microscopic filaments and the disease of splenic fever, which attacks sheep and other cattle. Koch was able to get some of these minute filaments under the microscope, and to trace upon a warm stage the different steps in their germination. He saw the spores bud and produce filamentous forms. He was able to cultivate these upon a nutrient substance, gelatin, and in this way to obtain a pure culture of the organism, which is designated under the term anthrax. He inoculated mice with the pure culture of anthrax germs, and produced splenic fever in the inoculated forms. He was able to do this through several generations of mice. In the same year Pasteur showed a similar connection between splenic fever and the anthrax. This demonstration of the actual connection between anthrax and splenic fever formed the first secure foundation of the germ-theory of disease, and this department of investigation became an important one in general biology. The pioneer workers who reached the highest position in the development of this knowledge are Pasteur, Koch, and Lister. [Illustration: Fig. 92.--Louis Pasteur (1822-1895) and his Granddaughter.]