The Pre-Antibacterial Era
Weapons against bacterial diseases improved just before the turn of
the 20th century. The advent of the germ theory of disease, which
proposed that microorganisms are the causes of many diseases, caused a
revolutionary change in the understanding of the vital role of microbes
in infectious diseases. Specific microbial pathogens were
identified as the causative agents of many diseases, and a race
immediately began to find effective means to kill these implicated
The first recorded microbial by-product shown to have antimicrobial activity was the blue pigment from Bacillus pyocyaneus (now Pseudomonas aeruginosa) which stopped the growth of some kinds of bacteria in the test tube. This was serendipitously observed by E. de Freudenreich (Germany) in 1888. Rudolf Emmerich and Oscar Loew (Germany), who later named the substance “pyocyanase”, performed clinical trials in 1889 showing some effectiveness against many of the infectious diseases of that time. This understandably raised excitement in the scientific community, however, this compound’s instability and inherent toxicity in patients later made it clear that pyocyanase had no real clinical application, and thus its popularity eventually declined16.
Another German physician, named Paul Ehrlich, tirelessly searched for a “magic bullet” that could selectively kill microorganisms. After several failures, in 1910 he finally came up with an arsphenamine chemical dye they referred to as compund 606 and later named Salvarsan - the first chemical compound shown to cure a human disease, syphilis 22, 25, 28.
Alexander Fleming, more notable for his discovery of penicillin in the later years, reported in 1920 of a naturally occurring antibacterial substance in human tears that causes lysis in some bacterial cells. He later called this lysozyme. Unfortunately, this too did not realize clinical application because of its limited effect on mostly non-pathogenic bacteria, and because it could not be produced in quantities large enough for further trials12,16.