Gerhard Domagk
Gerhard Domagk | |
---|---|
antibiotics[2] | |
Spouse | Gertrud Strube |
Children | One daughter and three sons |
Awards | Cameron Prize for Therapeutics of the University of Edinburgh (1939) Nobel Prize in Medicine (1939) Paul Ehrlich and Ludwig Darmstaedter Prize (1956) Fellow of the Royal Society (1959)[1] |
Scientific career | |
Fields | Bacteriology |
Gerhard Johannes Paul Domagk (German pronunciation:
He is credited with the discovery of sulfonamidochrysoidine (KL730) as an antibiotic for which he received the 1939 Nobel Prize in Physiology or Medicine. The drug became the first commercially available antibiotic and marketed under the brand name Prontosil.[3][4]
While working in the pathology department of the
Domagk was chosen to receive the 1939 Nobel Prize in Physiology or Medicine "for the discovery of the antibacterial effects of prontosil,"[5] but the Nazi government prohibited him from receiving the award. In 1947, after the fall of Nazi Germany, he was officially given the Nobel diploma and delivered the Nobel lecture.[6]
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.[7]
Domagk entered the
As the war ended in November 1918, Domagk resumed his medical course at Kiel. His doctoral thesis titled Beeinflussung der Kreatininausscheidung durch Muskelarbeit[10] (Influence of Creatinine Excretion in the Urine through Muscular Activity)[11] was supervised by Max Buerger and with that he earned his degree in 1921.[12] Between 1922 and 1923, he worked as an assistant to Georg Hoppe-Seyler at Kiel.[11]
In 1923, he met Walter Gross, the Director of the Institute of Pathology at the
In 1925, he married Gertrude Strube, at the time an advisor to the German Chamber of Commerce in Basel.[15] Later they had three sons and a daughter.[11]
At Münster, Domagk felt that the new department was not flourishing as he anticipated and was underpaid. The IG Farben branch at Elberfeld (later Wuppertal) noticed him and offered him to lead their institute of experimental pathology. When he informed of this opportunity to his university authority in July 1927, and that he would stay if at least he was given a position of associate professor; he never received a response. He took a sabbatical leave for two years without pay, and decided to accept IG Farben's offer in 1929.[16] However, another source states that he joined the IG Farben in 1927.[11]
Domagk was appointed director of the Institute of Pathology and Bacteriology, started working at the IG Farben laboratories at Wuppertal where he continued the studies of Josef Klarer and Fritz Mietzsch, based on works by Paul Ehrlich, to use dyes, at that time a major product of the company, as antibiotics. He changed his focus to tuberculosis and chemotherapy. He remained in that position until his retirement in 1961.[11]
Along with
Domagk died from a heart attack at his villa in the Black Forest village of Burberg near Königsfeld, Schwarzwald.[19]
Achievements
Prontosil
Domagk's responsibility at IG Farben was to test the new compounds,
Development
In early 1930s, Mietzsch and Klarer synthesised a benzene derivative of azo dye, which was chemically related to (an analogue of) chrysoidine.
The exact date of synthesis is unknown.[24] An account that the IG Farben leader Heinrich Hörlein suggested the use of sufur group to azo dyes "some time in 1932"[26] may not be true, as IG Farben received the patent of the first modified sulfamidochrysoidine on 7 November 1931.[27] The other related compound received patent in December 1932.[25] Initial experiments in 1931 indicated poor antibacterial effect against bacterial cultures. It was not known at the time that the active component of Prontosil was the sulphonamide and not the azo group, as they expected. In addition, the sulphonamides by themselves were not antibacterials, but only became active drug after metabolism inside the body. This is why the first tests (in vitro) on bacterial cultures failed.[25]
Discovery of antibacterial activity
In early 1931,[27] Domagk immediately tested the compound in mice that were having bacterial infection, and found that it was effective against Gram-positive bacteria.[28] He designated a code for the compound D 4145 (D for Domagk).[26] He induced infection at the belly (peritonitis) of mice using clinical specimens (isolates) of Streptococcus pyogenes. In the first experiment, he infected 26 mice by injecting the bacteria, and he injected a single dose of Prontosil to 12 of the infected mice, while the rest 14 were simply kept infected (as controls) without Prontosil treatment. All the Prontosil-injected mice survived, meaning they were cured of the streptococcal infection,[20][29] whereas the untreated 14 mice all died by the fourth day of experiment.[24] There were several more experimental tests, and a clinical trial in which a boy was cured of streptococcal infection in 1933.[20] In February 1935, Domagk reported his experiments in the journal Deutsche Medizinische Wochenschrift as "Ein Beitrag zur Chemotherapie der bakteriellen Infektionen" ("A contribution to the chemotherapy of bacterial infections").[30][25]
At the time, there was no medical cure for streptococcal infection, and infected body parts had to be surgically removed to prevent further spread of the infection.[31] This is still in practice when the infection had caused severe tissue damage even after antibiotics are available.[32] 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.[33][34] 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.[33]
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.[25]
By 1935, Mietzsch and Klarer had prepared two forms of the compound, one is poorly soluble in water while the other is highly soluble. The water-soluble compound was given a name Streptozon (specifically Streptozon S, for the soluble sodium salt) after the bacterium with which it was originally experimented, and the less water-soluble was called Prontosil (specifically Prontosil rubrum).[35] 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.[36] He reported the development of the drug and his human application in article "Chemotherapie der streptokokken-infektionen" ("Chemotherapy of streptococcus infection") in the October issue of Klinische Wochenschrift (later Journal of Molecular Medicine).[37]
Confirmation
The first independent research was done by English physician
Sulfonamides had revolutionary antibacterial effectiveness for their time, surpassing
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.
Cancer therapy
Since 1936, Domagk also focussed on cancer treatment. 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 ca slow down it growth, in order to preserve the life of a patient longer and under bearable conditions.[50] Although the drug did not find way into prescription treatment of cancer, it was continued to be investigated[51][52] and several related compounds are still under experimental studies.[53][54][55]
Nobel Prize and issues
In 1939, Domagk was selected by the
On 27 October 1939, Domagk received a telegram from the rector of the
Two years after the end of World War II and the Nazi regime, the Nobel Foundation gave the Nobel medallion and a diploma to Domagk in 1947. However, the monetary prize was not given as it was already returned to the foundation.[28]
Awards and honours
Domagk was awarded the 1939 Nobel Prize in Physiology or Medicine. In the same year, Domagk was also awarded the
After the war, in 1947, Domagk was finally able to receive his Nobel Prize,[59] 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.[60] 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.[11]
Domagk became a Foreign Member of the Royal Society in 1959; his short biography was published by the Royal Society in 1964.[1][56]
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.[11]
References
- ^ .
- PMID 3525495.
- PMID 7040718.
- PMID 14120818.
- S2CID 54410112.
- ^ "The Nobel Prize in Physiology or Medicine 1939 Gerhard Domagk". Nobelprize.org. Retrieved 2 July 2010.
- ISBN 978-3-8258-6164-3.
- ISBN 9783825861643.
- ISBN 9783825861643.
- OCLC 793770685.
- ^ S2CID 215810336.
- ^ ISBN 9783825861643.
- S2CID 10695542.
- ISBN 9783825861643.
- ISBN 9783825861643.
- ISBN 9783825861643.
- ^ Einstein, Albert; Nathan, Otto; Norden, Heinz (1968). Einstein on peace. Internet Archive. New York, Schocken Books. pp. 539, 670, 676.
- ^ "[Carta] 1950 oct. 12, Genève, [Suiza] [a] Gabriela Mistral, Santiago, Chile [manuscrito] Gerry Kraus". BND: Archivo del Escritor. Retrieved 19 October 2023.
- ^ ISSN 0362-4331. Retrieved 5 October 2022.
- ^ .
- ^ .
- PMID 5652361.
- ISSN 0025-729X.
- ^ S2CID 71576734.
- ^ S2CID 27970581.
- ^ PMID 19283418.
- ^ S2CID 4120072.
- ^ OCLC 162572834.
- ^ ISSN 0262-4079.
- S2CID 70515565.
- PMID 17865165.
- PMID 8197532.
- ^ ISSN 0098-7484.
- ISBN 978-1-59726-645-1, retrieved 4 March 2023
- .
- ^ .
- S2CID 5722987.
- PMID 21378618.
- S2CID 19923455.
- S2CID 195807205.
- S2CID 234297557, retrieved 7 September 2022
- S2CID 71926126.
- ISSN 0066-4227.
- ^ Lim, XiaoZhi (2022). "Do we know enough about the safety of quat disinfectants?". cen.acs.org. Retrieved 5 October 2022.
- S2CID 146809199.
- PMID 27572084.
- S2CID 30564489.
- S2CID 260087274.
- S2CID 30047404.
- ISSN 0036-8075.
- S2CID 44270951.
- S2CID 71993710.
- S2CID 236235376, retrieved 5 October 2022
- S2CID 58630060.
- PMID 27089214.
- ^ a b c Schück, Henrik; Ragnar Sohlman; Anders Österling; Göran Liljestrand; Arne Westgren; Manne Siegbahn; August Schou; Nils K. Ståhle (1950). "The Prize in Physiology and Medicine: The Nobel Prizes in Wartime". In Nobel Foundation (ed.). Nobel: The Man and His Prizes. Stockholm: Klara Civiltryckeri. pp. 167–179.
- 23 December 2006)
- ^ "NobelPrize.org". Archived from the original on 2 February 2007.
- PMC 5823360.
- ^ "1st Lindau Nobel Laureate Meeting – Laureates". www.mediatheque.lindau-nobel.org. Retrieved 9 January 2018.
External links
- Gerhard Domagk on Nobelprize.org including the Nobel Lecture on 12 December 1947 Further Progress in Chemotherapy of Bacterial Infections
- Biography at Bayer