Prontosil and the Sulfonamide Drugs

In the 1920s and 1930s a scratch could kill. Streptococcal and staphylococcal infections were major killers in Europe and the United States, along with pneumococcal disease and tuberculosis, and pneumonia and tuberculosis took even young adults.

Gerhard Domagk, a pathologist, was recruited from the University of Münster in 1927 by the pharmaceutical division of IG Farbenindustrie, the new German chemical conglomerate. He set up a pharmacology laboratory and worked with two chemists, Fritz Mietzsch and Josef Klarer, testing compounds related to synthetic dyes. Domagk insisted on testing them in living animals and kept working with compounds that failed against bacteria in glassware. In 1931 the chemists produced an azo dye carrying a sulfonamide group, KL 695, which did nothing in the test tube but was weakly active in mice infected with streptococci. Some 35 compounds later they made KL 730, which had strong antibacterial effects in infected mice. It was named prontosil rubrum and patented as Prontosil.

Domagk spent three years on the drug before publishing his first report in 1935. By then Prontosil had been used in patients with streptococcal and staphylococcal infections. One of them was his six-year-old daughter, Hildegard, who developed a severe streptococcal infection from an unsterilized needle. She recovered, though the drug left her skin permanently reddened.

Prontosil was the first of the sulfa drugs, all related to the compound sulfanilamide. The 1939 Nobel Prize in Physiology or Medicine went to Domagk for the discovery of its antibacterial effects. German law under Hitler forbade citizens to accept the prize, and after Domagk accepted it the Gestapo arrested him and made him send a letter declining it. He received the medal in 1947, by which time the prize money had been redistributed.