Gerhard Domagk

German bacteriologist and pathologist

• Born: October 30, 1895
• Birthplace: Lagow, Germany
• Died: April 24, 1964
• Place of death: Burgberg, West Germany (now Germany)

Domagk was awarded the Nobel Prize in Physiology or Medicine in 1939 (he accepted the award in 1947) for his discovery that a synthesized dye, prontosil, was an effective treatment for streptococcal infections in mice. This discovery led to the development of sulfa drugs, the first successful chemical means for dealing with bacterial infections.

Early Life

Gerhard Domagk (GAYR-hahrt DOH-mahk) was the son of a teacher. He attended a scientifically oriented grammar school in Liebnitz and decided at a young age to study medicine. When it was time to enter college, he chose the University of Kiel; his first term, however, was interrupted by World War I. Domagk volunteered for active service when war was declared and joined a German grenadier regiment. In 1915, he was wounded and was transferred to the army medical corps, where he stayed for the remainder of the war.

After the war, he returned to the university and completed his medical degree in 1921. He chose not to enter medical practice but instead became an assistant to the chemist Ernst Felix Hoppe-Seyler. In 1924, Domagk joined the University of Greifswald as a reader in pathology and, that same year, published a paper on the defensive functions of the reticuloendothelial system against infections, “Untersuchungen über die Bedeutung des retikuloendothelialen Systems für die Vernichtung von Infektionserregern und für die Enstehung des Amyloids.” In this paper he dealt with infection and chemotherapy for the first time, research that would lead directly to his most important achievement. In 1925, he married Gertrud Strube, with whom he would have three sons and one daughter.

In the late 1920’s, on the strength of his 1924 paper and his interest in chemotherapy, Domagk accepted a position as director of research in the experimental pathology and bacteriology laboratories of I. G. Farbenindustrie in Wuppertal-Elberfeld. At the age of thirty-two, Domagk had arrived at the most important crossroad of his career.

Life’s Work

Domagk devoted his professional life to investigating the use of chemotherapeutic agents in the treatment of human illness, specifically bacterial infections, tuberculosis, and cancer. In 1909, the German bacteriologist and biochemist Paul Ehrlich had discovered the drug arsphenamine, which was useful in treating syphilis; this drug’s use had led to the development of several other chemotherapeutic agents for the treatment of diseases caused by protozoa and rare bacteria. Until Domagk’s work, however, little progress had been made in dealing with bacterial infections through chemical attack.

The dye firm of I. G. Farbenindustrie hired Domagk to investigate systematically the potential medical uses for the firm’s new dyes. He began to study the so-called azo dyes, which shared a particular group of atoms called a sulfonamide group, instead of the expected hydrogen atom. One of these dyes was an orange-red synthetic given the name prontosil rubrum. It had been developed in 1932 by two of Domagk’s colleagues at the firm, Fritz Mietzsch and Josef Klarer, as a treatment for leather. That same year, Domagk discovered that injections of prontosil provided a successful treatment for streptococcal infections in mice. Furthermore, the agent itself was not as toxic to the mice as compounds tested previously.

For reasons that have never been clearly explained, Domagk did not reveal his findings publicly until 1935, when he published “Ein Beitrag zur Chemotherapie der bakteriellen Infektionen” (a contribution to the chemotherapy of bacterial infection). By that time, the dye’s usefulness as a treatment for bacterial infections had been confirmed: Another scientist, A. Förster, had reported the recovery of an infant suffering from a staphylococcal infection. Moreover, Domagk had experienced the effectiveness of the treatment in his own family. When his young daughter Hildegarde was accidentally pricked with a needle, contracting a streptococcal infection from which she nearly died, Domagk turned in desperation to prontosil injections. The treatment saved her life. Nevertheless, Domagk’s announcement that he had found the first specific treatment for bacterial infection was greeted skeptically by the scientific community. It was not until 1936, when the British Medical Research Council and the American Medical Association verified his findings, that prontosil received the notice it deserved. When it was used to save the life of Franklin D. Roosevelt, Jr., the son of the president of the United States, the drug’s fame spread even more widely.

Under the study of scientists around the world, further refinements were made. At the Pasteur Institute in Paris, scientists discovered that it was not necessary to use the entire prontosil rubrum molecule to achieve the desired effect: It was actually the sulfonamide group alone that worked against the bacterial agents. Since sulfonamide had been synthesized for decades and could be produced less expensively than prontosil, this discovery was good news. What followed was a series of sulfa compounds, each useful for the treatment of a specific infection. For the first time, medical science could offer some hope to those afflicted with pneumonia, spinal meningitis, gonorrhea, and other potentially fatal illnesses.

In 1939, Domagk was informed that he had been chosen to receive the Nobel Prize in Physiology or Medicine, having been nominated by British, French, and American scientists. He immediately expressed his thanks in a letter to the Caroline Medico-Chirurgical Institute in Stockholm, whose members select the winners. Unfortunately, he was arrested by the Gestapo in November, held prisoner for a week, and forced to decline the prize. Ever since Carl von Ossietzky, a German pacifist and a prisoner of a concentration camp, had been awarded the Nobel Peace Prize in 1935, Adolf Hitler had forbidden Germans to accept the Nobel Prize. A second letter, prepared by the minister of education, declined Domagk’s award, and he was persuaded to sign it. Under regulations, Domagk’s prize money was turned back to the Nobel Foundation after one year, but his medal and diploma were saved for him. In 1947, after Hitler’s death and the war’s end, Domagk traveled to Stockholm to accept his award.

By the end of World War II, antibiotics were becoming widely available, and Domagk turned his attention to the battle against tuberculosis. For a time it had appeared that streptomycin, discovered by the American scientist Selman Waksman, would prove to be an effective treatment; however, it soon became clear that new streptomycin-resistant strains of the tuberculosis-causing bacteria were rapidly evolving. Domagk and several colleagues experimented with sulfonamide derivatives and eventually placed their hopes in the compounds called thiosemicarbazones. In 1946, Domagk and three others announced that these compounds appeared to be successful in the laboratory; in clinical studies, however, the substance was found to damage the liver. Because of this and other harmful side effects, these compounds were used only in rare cases when an infection resisted treatment with more common drugs. Another drug, called isonicotinic acid hydrazide, or isoniazid, was developed elsewhere at almost the same time and tested extensively in 1952; this proved to be a safe and effective treatment for tuberculosis.

Toward the end of his life, Domagk devoted his energies to searching for chemotherapeutic agents to fight cancer. He hoped to find a substance that would attack only tumor cells, leaving normal cells unharmed. Like so many others, he was unsuccessful in this search. His inability to meet his greatest challenge, however, in no way diminishes the importance of his achievements over a long career. By the time he retired, he had been awarded in addition to the Nobel Prize the Paul Ehrlich Gold Medal, the Cameron Medal of Edinburgh, several honorary degrees in the United States and throughout Europe, and membership in the Royal Society of London. On April 24, 1964, Gerhard Domagk died in Burgberg, West Germany, at the age of sixty-eight.

Significance

Directly and indirectly, Domagk’s work with the azo dyes served to usher in a new medical age. Prior to his discovery that prontosil rubrum could be used to treat bacterial infection and the subsequent development of a series of sulfonamides, or “sulfa drugs,” there was no chemical defense against this type of disease; as a result, illnesses such as streptococcal infection, gonorrhea, and pneumonia held terrors that now are difficult to imagine. A small injury could easily lead to death.

By following the clues suggested by the synthetic sulfa drugs and how they worked to prevent the reproduction of bacteria, other scientists were able to develop an even more powerful type of drug the antibiotic. When René Dubos discovered that natural organisms could also be used to fight bacteria, interest was renewed in work by Alexander Fleming that had gone unnoticed for eleven years the development of penicillin. Antibiotics, such as penicillin and streptomycin, have become some of the most important tools in fighting disease. Antibiotics have replaced sulfa drugs for most uses, in part because they cause fewer side effects, but sulfa compounds are still commonly used for, among other things, the treatment of urinary tract infections. Together, sulfa drugs and antibiotics have offered the possibility of a cure to millions, who previously had had no chance to survive.

Bibliography

Colebrook, L. “Gerhard Domagk.” Biographical Memoirs of the Royal Society 10 (1964): 39-50. Written to commemorate the occasion of Domagk’s death and to honor him as a member of the Royal Society of London, this article is the most complete and most readable biography generally available.

Colebrook, L., and M. Kenny. “Treatment of Human Puerperal Infections and Experimental Infections in Mice with Prontosil.” Lancet, 1936: 1279-1286. An important study, as it provided the British Medical Research Council’s confirmation of Domagk’s findings and declared prontosil to be the best hope then available for fighting streptococcal infection. A highly technical study, for advanced readers.

Hager, Thomas. The Demon Under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Harmony Books, 2006. Recounts in an accessible style the efforts of Domagk and others to develop sulfa drugs.

Long, Perrin H. “The Progress of Science: Award of the Nobel Prize in Physiology and Medicine to Dr. Gerhard Domagk.” Scientific Monthly 50 (1940): 83-84. Contains a brief biography and a readable explanation of Domagk’s research. Written just after Domagk had turned down the Nobel Prize, this article provides an interesting historical perspective.

Sourkes, Theodore L. Nobel Prize Winners in Medicine and Physiology, 1901-1965. New York: Abelard-Schuman, 1966. Presents a brief biographical sketch, excerpts from the Nobel lecture describing Domagk’s discovery in his own words, and an explanation of the importance of the work. The range covered demonstrates clearly how most scientific inquiry develops from earlier work.

Spink, Wesley W. “Present Status of Sulfonamide Therapy.” Merck Report, April, 1951, 17-19. Offers interesting information about the mortality rates for certain infections before the advent of the sulfa drugs. Provides a vivid and fascinating context for understanding the importance of Domagk’s discovery.