the familiar notion of germs as a cause of disease also has a long history. in the sixteenth century, the italian girolamo fracastoro wrote about the new european outbreak of syphilis, hypothesizing that the contagious “seeds” of disease must be “alive” — multiplying — to sustain constant spread; otherwise, the infection would disappear.
but no one could see germs with the naked eye or the earliest microscopes. even after the nineteenth-century technical improvements to lenses, the existence of germs remained controversial. in the late nineteenth century, germ theory — the idea that tiny, living particles provoked human disease — was accepted, following the works of french chemist louis pasteur, scottish surgeon joseph lister, and german doctor robert koch. in 1882, koch proved that a specific bacterium was the cause of a specific disease: tuberculosis. he also laid down four rules, called “postulates,” by which observers could establish causal links between other germs and other diseases. we still use those rules.
koch’s four postulates included finding the germ in every case, growing it in pure culture, inoculating it, and recreating the disease in experimental animals. soon after, many well-recognized diseases with unmistakable symptoms were identified as the products of specific bacteria or other microorganisms. some germs had been visualized and hypothesized as human pathogens many years earlier; however, koch’s method helped to prove the relationship: dysentery (1883), cholera (1884), typhoid (1884), diphtheria (1884), pneumonia (1886), plague (1894), syphilis (1905). once germs were known to be the cause of specific diseases, the concept of a “magic bullet” dominated research, as scientists looked for drugs that would kill the germ and leave behind a healthy human. agents containing mercury, arsenic, and antimony were top of the list.