Magic bullet, or shot in the dark?

Posted: 05 07, 2015

The concept of a magic bullet comes from the ancient Germanic folktale of Freischutz, a marksman who made a deal with the devil for bullets that would hit whatever target he desired.

Drawing on the folktale, Paul Ehrlich developed the concept of a magic bullet that destroys pathogens, but not the host. Before he became famous, the young Paul Ehrlich spent his days developing and testing dyes for the selective staining of cells. He wasn’t always so selective…Paul’s hands and face were often mottled with the brightly colored dyes. It was through this work that he developed his “side chain theory” to explain the choosiness of the dyes. In his theory, dyes associated with cells through a chemical side chain, or receptor, which bound the dye with lock-and-key specificity. The idea seems obvious to us now, but at the time it was so groundbreaking that its application to immunology earned Ehrlich half of the 1908 Nobel Prize in Medicine.

paul ehrlich

A year later in 1909, along with synthetic chemist Alfred Bertheim, and bacteriologist Sahachiro Hata, Ehrlich finally identified his first magic bullet; one arsenic compound out of more than 300 tested was toxic to the microorganism that causes syphilis, but not to the human host. The successful compound was called Salvarsan (“the arsenic that saves”) by the pharmaceutical company, and was an overwhelming success. The competition wasn’t exactly stiff, as a combination of mercury and isolation was the alternative. More than being a miracle cure, Salvarsan’s legacy is that it validated Ehrlich’s theory, and set the stage for the development of the now famous field that Ehrlich named “chemotherapy.”

In the folktale, the devil reserves some of the magic bullets for his own nefarious purposes, occasionally wreaking havoc.  Now, more than a century later, we’re still dealing with serious drug “side” effects. It seems Ehrlich’s magic bullet metaphor might have more apt than he intended.


by Erinn C. Brigham


More about the cell staining work behind Paul’s side chain theory of immunity:–circa-1900/

The image above is from the cover of the Annals of the Rheumatic Diseases:


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This article by Erinn C. Brigham was co-published on the SWAC Blog, The Pipettepen:


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