Gerhard Domagk

Biography Domagk was born in Lagow, Brandenburg, German Empire (now Poland). His father Paul Richard Domagk was a school teacher. He had an elder brother Erich, who died in childhood, and a younger sister, Charlotte. When he was five, in 1900, his father was transferred to Sommerfeld (now Lubsko, Poland). He immediately entered the Bismarck School where he completed elementary education in 1910. Then, he attended Herzog-Heinrich School in Liegnitz where he completed secondary education in 1914.

Domagk entered the University of Kiel in 1914 to study medicine. As the First World War broke out, the university was closed and he returned to Sommerfeld. He joined the German Grenadier Regimen 7 as a volunteer along with 15 of his old school friends. In his first experience of war at Flanders in October 1914, he barely escaped death where 11 of his school friends were killed. He was transferred to eastern front in Poland in December 1914, where he was shot on the head. He was transported to Lichterfelde near Berlin where he recovered from the injury. There he was given a training as medical orderly. In May 1915, he rejoined the eastern front as a medic. He recalled the horrors and suffering, especially of infections, at the battlefields, saying "There horrible impressions kept pursuing me during my whole life, and made me think how I could take measures against bacteria... I then swore, in case I would return to my home alive, to work and work to make a small contribution to solve that problem."

As the war ended in November 1918, Domagk resumed his medical course at Kiel. His doctoral thesis titled Beeinflussung der Kreatininausscheidung durch Muskelarbeit (Influence of Creatinine Excretion in the Urine through Muscular Activity) was supervised by Max Buerger and with that he earned his degree in 1921. He supported Domagk's research on phagocytosis, an immune process discovered by Russian zoologist Elie Metchnikoff, so far as permitting excessive use of electricity, constant photographic lights, and free roaming of experimental mice, all of which angered the janitor. Domagk's thesis "Destroying infectious diseases through the reticuloendothelium and the development of amyloid", was assessed as a worthy criterion for promotion to a full professor. However, Gross was appointed to the University of Münster, and he invited Domagk to join him as a lecturer at his proposed Department of Experimental Pathology.

In 1925, he married Gertrude Strube, at the time an advisor to the German Chamber of Commerce in Basel. Later they had three sons and a daughter. However, another source states that he joined the IG Farben in 1927.

Domagk died from a heart attack at his villa in the Black Forest village of Burgberg near Königsfeld, Schwarzwald. He was a Christian.

Achievements

Prontosil Domagk's responsibility at IG Farben was to test the new compounds, chemical dyes, for antimicrobial activities. Werner Schulemann, Friedrich Mietzsch, Hans Mauss and Joseph Klarer were largely responsible for providing a continuous supply of chemicals to be screened. Since the end of the 19th century, azo dyes, developed and used for colouring textile and other materials, were found to have medicinal properties against infections. For example, German biologist Paul Ehrlich used methylene blue, a type of azo dye, to kill malarial parasites in experimental animals, and cured two persons from malaria in 1891. Later, Ehrlich and his students found that some azo dyes were effective against African sleeping sickness. Following such leads, IG Farben devoted to studying and chemically modifying azo dyes for potential medicines.

Development In early 1930s, Mietzsch and Klarer synthesised a benzene derivative of azo dye, which was chemically related to (an analogue of) chrysoidine. The compound had an addition of sulphonamide group as a side chain, thus becoming sulfamidochrysoidine. They suspected that a unique chemical component of sulphonamide group in the new dye could be a possible drug candidate; as Mietzsch predicted: "[The sulphonamide parts were] the right substituents in the right positions on the azo group."

The exact date of synthesis is unknown. may not be true, as IG Farben received the patent of the first modified sulfamidochrysoidine on 7 November 1931. The other related compound received patent in December 1932. whereas the untreated 14 mice all died by the fourth day of experiment. This is still in practice when the infection had caused severe tissue damage even after antibiotics are available. In a notable incidence, Domagk's six-year-old daughter, Hildegarde, injured herself with a stitching needle while making Christmas decorations on 4 December 1935. She fell on the stairs and stabbed her hand with the needle, and the broken needle was stuck in her wrist. The needle was removed at a hospital. However, she developed severe inflammation and fever from the next day. As Domagk recounted:When the dressing was changed a few days later there was marked swelling of the hand, and despite removal of all the stitches the fever continued to rise rapidly. In spite of numerous incisions the inflammation phlegmon extended to the under-arm. A serious worsening of the general condition and dizziness occurred, so that we were gravely worried about the child. Since further surgical intervention was not possible, I asked permission of the treating surgeon to use Prontosil, after I had established by culture that streptococci were the cause of the illness. After making 14 incisions, the physician suggested that the only way to save Hildegarde was amputation of the arm. However, Hildegarde recovered following the Prontosil treatment and her arm was saved. Prontosil was used as the common name for both and the brand name of the drug after 1935. Domagk had used only the Streptozon type. He reported the development of the drug and his human application in the article "Chemotherapie der streptokokken-infektionen" ("Chemotherapy of streptococcus infection") in the October issue of Klinische Wochenschrift (later Journal of Molecular Medicine).

Confirmation The first independent research was done by English physician Leonard Colebrook at the Queen Charlotte's Maternity Hospital in London. Immediately after reading Domagk's paper, in 1935, Colebrook repeated the experiments on mice using both soluble Streptozon and the less soluble form and found that Streptozon was more effective but only in specific bacteria that caused puerperal fever. However, he found a serious side effect that the surviving mice developed severe kidney damages. This discouraged him from human clinical trials, but he encountered one woman who was terminally ill from puerperal fever. Without other options of treatment, he gave the Streptozon that cured the woman in a couple of days. He tested the drug again on another woman with the same result, to which he remarked: "Almost at once there was a surprising and most gratifying change." especially in the treatments of burns and urinary tract infections.

Zephirol In 1932, Domagk discovered the potential use of benzyldimethyldodecylammonium chloride as a powerful antimicrobial agent. After a series of tests with different bacteria, he published in 1935 as a disinfectant, naming it Zephirol. Domagk explained how Zephirol applied to the skin, such as before wearing gloves during surgery, could prevent infection. It led to a successful marketing as a common disinfectant. This was the discovery of quats, chemicals that are later used in a variety of consumer applications including as general antimicrobials (such as detergents and disinfectants), fabric softeners, and hair conditioners.

Cancer therapy Since 1936, Domagk also focussed on cancer treatment. In 1956, he reported the successful development of an anticancer drug which he designated E-39 (E for ethylenimine quinones). He was aware that precision drugs would be required to target specific cancers, as he remarked:In therapy we will have to be satisfied, for the present at least, with a certain equilibrium between body cell and tumorous cell, even if the tumor cannot be completely eliminated. We will be satisfied if we can slow down it growth, in order to preserve the life of a patient longer and under bearable conditions. Although the drug did not find way into prescription treatment of cancer, it was continued to be investigated and several related compounds are still under experimental studies.

Nobel Prize and issues In 1939, Domagk was selected by the Nobel Foundation to receive the Nobel Prize in Physiology or Medicine for the discovery of Prontosil as an antibiotic, the first commercially available drug effective against bacterial infections. However, the Nazi government banned him from attending the award ceremony. This was because Carl von Ossietzky, an outspoken anti-Nazi pacifist, had won the Nobel Peace Prize in 1935, which had angered the Nazi German government. Ossietzky was imprisoned and died in a concentration camp. In 1937 Adolf Hitler made an official decree that prohibited German nationals from accepting Nobel Prizes.

On 27 October 1939, Domagk received a telegram from the rector of the Karolinska Institute in Stockholm that he was to receive the Nobel Prize. He informed the rector of the University of Münster, Walter Mevius, who immediately submitted a petition to the German authorities to allow Domagk to receive the award. Domagk himself wrote to the NSDAP Office of the Führer, Hitler's headquarters, that should he be allowed to receive the award, he would donate 100,000 Deutsche Marks for the war cause.

Awards and honours Domagk was awarded the 1939 Nobel Prize in Physiology or Medicine. In the same year, Domagk was also awarded the Cameron Prize for Therapeutics of the University of Edinburgh. In 1941 Domagk was awarded the Medaglia Paterno (Rome) by the Kingdom of Italy and also the Von-Klebelsberg-Medal and Prize by the Kingdom of Hungary. He became a member of the German Academy of Sciences Leopoldina in 1942.

After the war, in 1947, Domagk was finally able to receive his Nobel Prize, but not the monetary portion of the prize due to the time that had elapsed. In 1951, he was one of seven Nobel Laureates who attended the 1st Lindau Nobel Laureate Meeting. He received the El Soleil del Perú in 1952, the Pour le mérite für Wissenschaften und Künste in 1952, the Spanish Civil de Sanidad in 1953, the del Lobertador from the Republic of Venezuela in 1957, the Medal of the Rising Sun 2nd Class from Japan in 1960, the Grand Cross with Star of the Order of Merit of the Federal Republic of Germany in 1955. In 1952, he was elected chairman of the German Society of Pathology.

Domagkpark, a public park, and Domagkstraße, a road, in Munich are named after Domagk. In Münster, a research foundation called Krebsforschung Professor Dr. Gerhard Domagk (Cancer Research Professor Dr. Gerhard Domagk) was established in 1961, and Gerhard-Domagk-Institut für Pathologie (Gerhard Domagk Institute of Pathology) is created in the University of Münster.