The German bacteriologist and experimental pathologist Gerhard Johannes Paul Domagk (1895-1964) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the antibacterial effects of prontosil.
Gerhard Domagk was born at Lagow, Brandenburg, on Oct. 30, 1895. He began the study of medicine at the University of Kiel in 1913. After World War I, throughout which he served in the army, he graduated in medicine at Kiel in 1921. In 1924-1925 he was a lecturer in pathology in the universities of Greifswald and Münster. He became director of research in experimental pathology and bacteriology on the staff of the I.G. Farbenindustrie at Wuppertal-Elberfeld in 1927.
Beginnings of Chemotherapy
Early in the 1900s a synthetic organic arsenic compound was used to treat experimental trypanosomiasis. Paul Ehrlich confirmed this and then began to search for a similar compound for the treatment of syphilis. Successive organic compounds were synthesized and tested. In 1910 he found that his 606th compound was very effective; he called it salvarsan. During the next 20 years efficient antimalarial remedies were synthesized, but there were no such remedies against the common bacterial and streptococcal infections of temperate climates, despite many attempts to solve this problem.
Chemotherapy of Bacterial Infections
Shortly after his appointment to the I.G. Farbenindustrie, Domagk was made responsible for another massive attempt to achieve chemotherapy of the bacterial infections. His chief chemists, Fritz Mietzsch and Joseph Klarer, synthesized organic compounds, and Domagk tested the activity of these compounds against various organisms, in cultures and in laboratory animals. For a long time they were unsuccessful. But some years earlier the two chemists had synthesized a red azo dye combined with a sulfonamide radical. Intended for treating leather, it was already on the market under the name Prontosil Rubrum. Their tests had shown that it had little activity against bacteria in cultures, but in 1932 preliminary tests suggested that it might be protective against streptococcal infections in mice. In December a crucial experiment was carried out, which showed conclusively that prontosil was very effective in protecting mice against a highly virulent streptococcus. These very satisfactory laboratory results were not published for over 2 years, partly because of doubt whether prontosil would be tolerated by human subjects. But Domagk personally had no doubt, because he had as a last resort given his daughter, who was near death as a result of a streptococcal infection, a dose of prontosil. She had miraculously recovered.
When Domagk published his laboratory results in 1935 he did not mention his daughter's case, but work on prontosil was at once started in several countries. It was shown that the action of prontosil was due to its sulfonamide radical, which alone was active, and that sulfanilamide, a similar sulfonamide compound, was as active as prontosil and cheaper to manufacture. This was the first of the many similar drugs synthesized and tested. These sulfonamides were shown to be effective in many diseases in addition to streptococcal infections, such as puerperal fever, pneumonia, and cerebrospinal fever.
For his work in this field Domagk was awarded the Nobel Prize in Physiology or Medicine for 1939, but he was forced by the Nazis to decline the award, which he had already accepted. After the war he was presented with the medal and the diploma, but the prize money had meanwhile reverted to the Nobel Foundation.
Chemotherapy of Tuberculosis
The effective discovery of the method of concentrating penicillin, the first of the antibiotics, in 1940 stimulated a search for other antibiotics and chemotherapeutic remedies that might be effective in treating tuberculosis. Domagk's chemical coworkers supplied him with the first of the thiosemicarbazones, and in 1946 he showed their power to inhibit the growth of the tubercle bacillus in culture. But as they caused liver damage they had later to be given up. Meanwhile, in 1944, the antibiotic streptomycin had been discovered, but its undoubted effectiveness in treating tuberculosis was found to be limited by its tendency to produce resistant strains of the bacillus. A little later the effectiveness of para-aminosalicylic acid (PAS) was discovered and also its value in delaying the appearance of resistant strains. But the thiosemicarbazones led to the discovery in 1951, by Domagk and others, of the activity of isonicotinic acid hydrazide (isoniazid). It was found that in man isoniazid was most efficient when combined with streptomycin and PAS.
Chemotherapy of Cancer
For 30 years, beginning in 1925, Domagk wrote numerous papers on experimental tumor formation. In 1955 he turned to the chemotherapy of malignant tumors. In 1958 he published his results obtained with ethyl-eneimino quinones and their derivative Trenimon. Although then promising, these results later remained unconfirmed.
Later Life
In 1958 the University of Münster conferred on Domagk the title of professor, and on his retirement from the I.G. Farbenindustrie he worked on cancer research at that university. His many honors included honorary degrees from six universities. In 1959 he was elected a Foreign Member of the Royal Society, and he was the recipient of the Paul Ehrlich Gold Medal and of the Cameron Prize of the University of Edinburgh. He died at Burberg, Baden-Württemberg, on April 24, 1964.
Further Reading
There is a biography of Domagk in Nobel Lectures: Physiology or Medicine, 1922-1941 (1965), which also contains his Nobel Lecture, not delivered until 1947. For the background of Domagk's discovery see I. Galdston, Behind the Sulfa Drugs (1943). For further developments see G. M. Findlay, Recent Advances in Chemotherapy (1930), especially the second (1939) and third (vol. 1, 1950) editions.
