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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 microbes. 

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

 

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Dr. Ehrlich

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Dr. Ehrlich set aim to find “magic bullets” specific substances which have specific affinities for pathogenic organisms at which they were aimed.


To achieve this, Ehrlich and his assistants tested hundreds of chemical substances. Ehrlich’s 606th preparation of an arsenobenzene compund was previously set aside in 1907 as being ineffective. But when Ehrlich asked a Japanese colleague named Hata, who had succeeded in infecting rabbits with syphilis, to test this discarded drug on these rabbits, they found that it was very effective. Thus came the birth of the first chemotherapeutic agent, later named Salvarsan.


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The impact of Dr. Ehrlich’s contribution to medicine can be best appreciated in the fact that his story was immortalized in a 1940 Warners Bros. movie entitled “Dr. Ehrlich’s Magic Bullet”.