Background

Gerhard Domagk was born on October 30, 1895, in Lagow, Brandenburg, Germany (now Poland). His father, Paul Domagk, was a school headmaster; his mother was Martha Reimer.

Education

Domagk decided to study medicine while still at a scientifically oriented grammar school in Liegnitz (now Legnica). During his first term at the University of Kiel, World War I broke out and Domagk volunteered for active service with a German grenadier regiment. After being wounded he transferred to the German army medical corps and received his Doctor of Medicine degree at Kiel in 1921.

Career

For a short while, Domagk worked as an assistant to the chemist Ernest Hoppe-Seyler and in 1924 became a reader (privat-dozent) in pathology at the University of Greifswald. In 1925 he accepted a similar post at the University of Münster.

Domagk became an extraordinary professor of general pathology and pathological anatomy at Münster in 1928 and ordinary professor in 1958.

In 1924 Domagk published a paper on the defensive function of the reticuloendothelial system against infections. As a result of that paper and of his well-known interest in chemotherapy, the directors of the I. G. Farbenindustrie appointed him - at the age of thirty-two - director of research at their laboratory for experimental pathology and bacteriology at Wuppertal-Elberfeld. It was the turning point of his career.

Since Paul Ehrlich’s discovery of arsphenamine in 1909, chemotherapy had advanced in the field of protozoan and tropical diseases, but hardly any progress had been made in regard to bacterial infections of man; and the I. G. Farbenindustrie had decided on further testing of potential antibacterial agents, along the lines laid down by Ehrlich. Domagk’s interest centered on the so-called azo dyes, in which one hydrogen atom had been replaced by a sulfonamide group. These dyes, which had been developed as early as 1909 by H. Hörlein and his collaborators, conferred on textiles a high resistance to washing and light, because of their intimate combination with wool proteins.

In 1932 Domagk’s colleagues, the chemists Fritz Mietzsch and Josef Klarer, synthesized a new azo dye, hoping that it would prove to be a fast dye for treating leather. It was -4' sulfonamide-2-4-diaminoazobenzol, which they named prontosil rubrum. Domagk early recognized its protective power against streptococcal infections in mice and its low toxicity, but he withheld publication of his findings until 1935.

As early as 1933 A. Förster had reported the dramatic recovery of an infant with staphylococcal septicemia after treatment with prontosil rubrum, but Domagk’s discovery - after so many years of fruitless searching for specific antibacterial agents - was received with a great deal of skepticism. In 1936 L. Colebrook and M. Kenny of the British Medical Research Council confirmed Domagk’s findings and concluded that “the clinical results together with the mouse experiments support the view that there is more hope of controlling these early streptococcal infections by the administration of this or some related chemotherapeutical agent than by any other means at present available.”

In the first paper on prontosil published in the United States, P. H. Long and E. A. Bliss mentioned Domagk only as one of the investigators of prontosil, but in the same issue of the Journal of the American Medical Association, its editor gave Domagk full credit for his significant paper and hoped that “further investigations will disclose a definite group of disorders characterized by high virulence and mortality which can be materially helped by appropriate chemotherapy.” Their hopes were indeed fulfilled, but only after workers at the Pasteur Institute in Paris - the Trefuels, F. Nitti, D. Bovet, and E. Fourneau - had established that the azo component of prontosil dissociated in vivo and that the liberated sulfonamide radical was responsible for the antibacterial effect. This was a very important discovery because sulfonamide could be produced far more cheaply than prontosil.

Ironically enough, at that very time an agar plate containing an even more powerful antibacterial agent - penicillin - lay forgotten in St. Mary’s Hospital in London. Its owner, Alexander Fleming, had become highly interested in prontosil and the sulfonamide derivatives that followed, but in his many papers on antibacterial and antiseptic treatment published between 1938 and 1940, he never mentioned penicillin, the antistaphylococcal action of which he had first observed in 1928.

In October 1939, sponsored by American, French, and British scientists, Domagk was awarded the Nobel Prize in physiology or medicine. He duly acknowledged the great honor to the rector of the Caroline Institute; but some weeks later, after having been arrested by the Gestapo, he declined the prize in a letter drafted for him by the German authorities. In 1947 he received the prize again.

After World War II, with the antibiotics having joined the therapeutic armamentarium against acute bacterial diseases, Domagk’s interests shifted to the chemotherapy of tuberculosis. The euphoria induced by the discovery of streptomycin had by that time given way to considerable disillusionment because of the rapidly increasing numbers of streptomycin-resistant strains of the tuberculosis mycobacterium.

Together with R. Behnisch, F. Mietzsch, and H. Schmidt, Domagk reported in 1946 on the tuberculostatic action in vitro of the thiosemicarbazones of which the 4'-acetyl-aminobenzaldehyde (Conteben, Tibione) seemed to be the most promising compounds. Because of their many and dangerous toxic side effects the thiosemicarbazones never became popular in clinical medicine, but for many years they were used as “second-line drugs” against mycobacteria that were resistant to one or more of the standard antituberculous drugs.

The work of Domagk and his colleagues with the thiosemicarbazones resulted, however, in a supremely important accidental discovery. In 1945 V. Chorine had reported on the tuberculostatic action of the nicotinamides, and his findings were rediscovered by D. McKenzie, L. Malone, S. Kushner, J. J. Oleson, and Y. Subba Row in 1948. This produced no practical results until it became known that the active agents of the nicotinamides were derivatives of isonicotinic acids. In 1951 H. H. Fox tried to prepare isonico-tinaldehyde-thiosemicarbazone. An intermediate product, isonicotinoylhydrazine (isoniazid), was tested in New York’s Sea View Hospital in 1952 and has since become one of the most potent and reliable drugs in the treatment of tuberculosis.

Finally, Domagk turned to the greatest challenge of all, the chemotherapy of cancer. He experimented mostly with ethylene-iminoquinones, but success evaded him as it did so many other workers in that field. In a letter quoted by Colehrook he wrote: “One should not have too great expectations of the future of cytostatic agents.”

The dawn of the new chemotherapeutic era in Germany was no accident, if only for the traditional close association between the chemical industry and medical research in that country. Nevertheless, twenty-seven years passed between P. Gelmo’s first preparation of a sulfonamide in 1908, during Ehrlich’s lifetime, and its recognition by Domagk as an elixirium magnum sterilisans. Gelmo’s original paper, “Sulphamides of P-aminobenzene Sulphonic Acid,” is in Journal fur praktische Chemie, 77 (1908).

He died at Burberg, Baden-Württemberg, on April 24, 1964.

Achievements

• 

  Gerhard Domagk was a gistinguished bacteriologist and pathologist who was awarded the Nobel Prize in Physiology or Medicine for his discovery of the antibacterial effects of prontosil. His discovery profoundly changed the prognosis of many dangerous and potentially fatal diseases such as puerperal fever, erysipelas, cerebrospinal meningitis, and pneumonia.
  
  His paper “Ein Beitrag zur Chemotherapie der bakteriellen Infektionen” has become not only a classic but - measured by strict experimental and statistical yardsticks - a masterpiece of careful and critical evaluation of a new therapeutic agent.
  
  He received many high honors and an honorary professorship of the University of Valencia, and he became doctor honoris causa of many European and American universities. He was especially pleased by the award of the Paul Ehrlich Gold Medal and by his election as a foreign correspondent of the Royal Society of London.

Works

More photos

• book

  • Ansprache des Ministerpräsidenten Fortschritte auf dem Gebiet der experimentellen Krebsforschung 1954

Membership

Domagk was a member of the Royal Society, the German Academy of Sciences Leopoldina, and the North Rhine-Westphalia Academy for Sciences and Arts.

• 

  Royal Society , United Kingdom

• 

  German Academy of Sciences Leopoldina , Germany

• 

  North Rhine-Westphalia Academy for Sciences and Arts , Germany

Personality

It is characteristic of Domagk’s intensive scientific curiosity and humane outlook that he wrote at the end of his life: “If I could start again, I would perhaps become a psychiatrist and search for a causal therapy of Mental Disease which is the most terrifying problem of our times.”

Connections

Domagk married Gertrud Struebe on May 30, 1925. They had four children. His only daughter, Hildegard, was one of the first patients to be treated successfully with prontosil rubrum for a severe streptococcal infection.

Father:

Paul Domagk

Mother:

Martha Reimer

Spouse:

Gertrud Struebe

Son:

Jorg Domagk

Son:

Wolfgang Domagk

Son:

Göta Domagk

Daughter:

Hildegard Domagk

colleague:

Fritz Mietzsch

colleague:

Josef Klarer

colleague:

R. Behnisch

colleague:

F. Mietzsch

colleague:

H. Schmidt

References

• The Demon Under the Microscope In The Demon Under the Microscope, Thomas Hager chronicles the dramatic history of sulfa, the first antibiotic and the drug that shaped modern medicine.
  2007
• Gerhard Domagk and the Discovery of Sulfa
  2002
• Nobel Lectures in Physiology or Medicine 1922-1941
  1999