Krebs was born inHildesheim, Germany, to Georg Krebs, anear, nose, and throat surgeon, and Alma Krebs (née Davidson).[9] He was ofJewish ancestry and was the middle of three children.[10] He had an elder sister, Elisabeth, and a younger brother, Wolfgang.[11]
Memorial plaque at the parental home of Sir Hans Adolf Krebs in Hildesheim
Krebs attended school at theGymnasium Andreanum in his home town.[9] Near the end ofWorld War I, in September 1918, six months short of completing his secondary school education, he wasconscripted into theImperial German Army.[10] He was allowed to take an emergency examination for his high school diploma, which he passed with such a high score that he suspected the examiners of being "unduly lenient and sympathetic".[12] With the end of the war two months later, his conscription ended.[10]
Krebs decided to follow his father's profession and entered theUniversity of Göttingen in December 1918 to study medicine. In 1919, he transferred to theUniversity of Freiburg.[9] In 1923, he published his first scientific paper on atissue staining technique. He did this work under the guidance of Wilhelm von Mollendorf starting it in 1920.[11] He completed his medical course in December 1923. To obtain aDoctor of Medicine degree, and a medical license, he spent one year at the Third Medical Clinic in theUniversity of Berlin.[9] By then he had turned his professional goal from becoming a practising physician to becoming a medical researcher, particularly in biochemistry. In 1924, he studied at the Department of Chemistry at the Pathological Institute of theCharité Hospital, inBerlin, for training in chemistry and biochemistry.[13] He earned hisMD degree in 1925 from theUniversity of Hamburg.[10][14][15]
In 1926, Krebs joinedOtto Heinrich Warburg as a research assistant at theKaiser Wilhelm Institute for Biology inDahlem, Berlin.[16] He was paid 4800marks per year. After four years in 1930, with 16 publications to his credit, his mentor Warburg urged him to move on and he took up the position of Assistant in the Department of Medicine at the Municipal Hospital inAltona (now part ofHamburg). The next year he moved to the Medical Clinic of theUniversity of Freiburg. At Freiburg, he was in charge of about 40 patients, and was at liberty to do his own research. Before a year was over at Freiburg, he, with research studentKurt Henseleit, published their discovery of the ornithine cycle of urea synthesis, which is the metabolic pathway forurea formation. It is now known as theurea cycle, and is sometimes also referred to as the Krebs–Henseleit cycle. Together they also developed a complexaqueous solution (abuffer), orperfusionex vivo, for studying blood flow in arteries, which is now called the Krebs–Henseleit buffer.)[17][18] In 1932, he published the basic chemical reactions of the urea cycle, which established his scientific reputation.
Krebs's life as a respected German scientist came to an abrupt halt in 1933 because of his Jewish ancestry. With the rise ofHitler'sNazi Party to power, Germany decreed theLaw for the Restoration of the Professional Civil Service, which decreed the removal of all non-Germans, and anti-Nazis, from professional occupations. Krebs received his official dismissal from his job in April 1933, and his service was terminated on 1 July 1933. An admirer,Sir Frederick Gowland Hopkins at theUniversity of Cambridge, immediately came to his rescue, and persuaded the university to recruit Krebs to work with him in the Department of Biochemistry.[19] By July 1933, he was settled in Cambridge with financial support from theRockefeller Foundation.
Although Germany restricted him to bringing only his personal belongings, he was fortunate that the government agents allowed him to take his equipment and research samples to England. They proved to be pivotal to his later discoveries, especially themanometer developed by Warburg specifically for the measurement of oxygen consumption in thin slices of tissues; it was the basis for his research.[20]
He was appointed as Demonstrator in biochemistry in 1934, and in 1935 theUniversity of Sheffield offered him a post of Lecturer in Pharmacology, with a more spacious laboratory and double the salary. He worked there for 19 years. The University of Sheffield opened a Department of Biochemistry, now Department of Molecular Biology and Biotechnology, in 1938 and Krebs became its first Head, and eventually a Professor in 1945. During his time it became one of the leading departments of biochemistry in the world.[21] Krebs took over the running of theSorby Research Institute in 1943. In 1944, the BritishMedical Research Council established the MRC Unit for Cell Metabolism Research at Sheffield, and Krebs was appointed the Director. With this, his laboratory became so large that the locals jokingly nicknamed it "Krebs's Empire".
He moved with his MRC unit to theUniversity of Oxford in 1954 asWhitley Professor of Biochemistry, the post he held until his retirement in 1967. The editorial board ofBiochemical Journal extended their good wishes on his retirement, but in return he promised to keep them busy, by producing scientific papers. He continued his research, and took his MRC unit to the Nuffield Department of Clinical Medicine at theRadcliffe Infirmary, Oxford. From there he published over 100 research papers.[14][15][22][23]
Krebs met Margaret Cicely Fieldhouse (30 October 1913 – May 1993)[24] when he moved to Sheffield in 1935. They married on 22 March 1938. Krebs later described his life in Sheffield as "19 happy years".[14] They had two sons, Paul (born 1939) and John (born 1945), and a daughter, Helen (born 1942).[25] John (Sir John Krebs, and later Baron Krebs) became a renownedornithologist, Professor at the University of Oxford, Principal ofJesus College, Oxford, andMember of the British House of Lords.[26]
In 1932, Krebs worked out the outlines of the urea cycle with a medical student Kurt Henseleit at theUniversity of Freiburg. While working at the Medical Clinic of the University of Freiburg, Krebs metKurt Henseleit, with whom he investigated the chemical process ofurea formation. In 1904, two Germans, A. Kossel and H. D. Dakin, had shown thatarginine could be hydrolysed by the enzymearginase to formornithine and urea in inorganic reaction.[28] Based on this reaction, Krebs and Henseleit postulated that in living cells, similar reaction could occur, and that ornithine andcitrulline could be the intermediate reactions.[29][30] Krebs started working on the possible method for the synthesis of arginine. Using his Warburg manometer, he mixed a slice of liver with purified ornithine and citrulline. He found that citrulline acted as acatalyst in the metabolic reactions of urea fromammonia andcarbon dioxide. He and Henseleit published their discovery in 1932. Thus theurea cycle (or "ornithine cycle") was established, and it was the first metabolic cycle to be discovered.[20][31]
At theUniversity of Sheffield, Krebs andWilliam Arthur Johnson investigatedcellular respiration by whichoxygen was consumed to transfer energy from the breakdown ofglucose. Krebs had earlier suggested to Warburg while they worked together in Germany that by using amanometer it could be possible to detect the oxygen consumption and identify the chemical reaction inglucose metabolism. Warburg had flatly rejected the idea. In Sheffield, Krebs vigorously worked to identify a possible chemical reaction and came up with numerous hypothetical pathways. Using the manometer he tested those hypotheses one by one. One hypothesis involvingsuccinate,fumarate, andmalate proved to be useful because all these molecules increased oxygen consumption in the pigeon breast muscle. In 1937, German biochemistsFranz Knoop and Carl Martinus had demonstrated a series of reactions usingcitrate that producedoxaloacetate. Krebs realised that these molecules could be the missing intermediates for such reaction. After four months of experimental works to fill in the gaps, Krebs and Johnson succeeded in establishing the sequence of the chemical cycle, which they called the "citric acid cycle".[32][33] It is also known as the "Krebs cycle" or "tricarboxylic acid (TCA) cycle".
Krebs sent a short manuscript account of the discovery toNature on 10 June 1937. On 14 June, he received a rejection letter from the editor, saying that the journal had "already sufficient letters to fill correspondence columns for seven or eight weeks", and encouraging Krebs to "submit it for early publication to another periodical."[34]
Krebs immediately prepared a longer version titled "The Role of Citric Acid in Intermediate Metabolism in Animal Tissues", which he sent to the Dutch journalEnzymologia after two weeks and was published in two months.[3][35] It was followed by a series of papers in different journals.[36][37][38]
Krebs continued to add more details to his citric acid cycle. The discovery ofacetyl-CoA in 1947 byFritz Albert Lipmann was another major contribution.[4][39] However, this new discovery posed a problem in his classic reaction. In 1957, he, withHans Kornberg, found that there were additional crucial enzymes. One wasmalate synthase, which condenses acetate with glyoxylate to form malate, and the other wasisocitrate lyase, which provides glyoxylate for the reaction by cleaving it from isocitrate.[8] These two reactions did not follow the normal citric acid cycle, and hence the pathway was named the glyoxylate bypass of the citric acid cycle, but is now known as theglyoxylate cycle.[20][40]
In July 2015, Krebs's Nobel Prize medal was auctioned off for £225,000 (around $351,225).[47][48] The proceeds were used to found the Sir Hans Krebs Trust, which provides funding for doctoral students in the biomedical field and support chemists who had to flee their home countries.[49]
The University of Oxford had a building named Hans Krebs Tower, which was occupied by the Department of Biochemistry. In 2008, a new building for the Department of Biochemistry was constructed, on which a plaque was placed on 20 May 2013 by theAssociation of Jewish Refugees.[50] The plaque was unveiled by John, Lord Krebs, and the inscription reads:[51]
Professor Sir Hans Krebs FRS 1900 – 1981 Biochemist & discoverer of the Krebs cycle Nobel Prize Winner 1953 worked here 1954 – 1967
The Department of Physiology, Anatomy and Genetics at Oxford University hosts the Sir Hans Krebs Prize Lecture Series.[52]The last three recipients have been: Jeffrey Friedman M.D., PhD (2019) Professor Sir Stephen O'Rahilly MD FRS FMedSci (2022) and in 2023 - Professor Dame Frances Ashcroft FRS FMedSci[53]
The University of Sheffield has The Krebs Institute, founded in 1988. It is a research centre covering interdisciplinary programmes in biochemical research.[54]
TheBiochemical Society offers Krebs Memorial Scholarship to a postgraduate (PhD) student working in biochemistry or an allied biomedical science at any British university. As of 2014, the scholarship is worth £18,500 and is given for a year, but is extendable up to three years.[59]
^Weber, George (2001). "Sir Hans A. Krebs Centenary Lecture: cancer and clinical targeting".Advances in Enzyme Regulation.41 (1):1–29.doi:10.1016/S0065-2571(00)00026-1.PMID11417529.
^Leigh, F W (2009). "Sir Hans Adolf Krebs (1900–81), pioneer of modern medicine, architect of intermediary metabolism".Journal of Medical Biography.17 (3):149–154.doi:10.1258/jmb.2009.009032.PMID19723965.S2CID207200346.
^Holmes, Frederic Lawrence (1991).Hans Krebs. Monographs on the History and Philosophy of Biology. Oxford University Press. p. 121.ISBN978-0-19-536128-5. Retrieved12 June 2024.
^abcWillcocks, Elizabeth (1 June 2003)."A lucky man". Royal Society of Chemistry.
^Bailey, Leslie E; Ong, Seok D (1978). "Krebs–Henseleit solution as a physiological buffer in perfused and superfused preparations".Journal of Pharmacological Methods.1 (2):171–175.doi:10.1016/0160-5402(78)90022-0.
^Kinne-Saffran, E; Kinne, RK (1999). "Vitalism and synthesis of urea. From Friedrich Wöhler to Hans A. Krebs".American Journal of Nephrology.19 (2):290–294.doi:10.1159/000013463.PMID10213830.S2CID71727190.
^Graßhoff, Gerd; May, Michael (2003). "Hans Krebs' and Kurt Henseleit's Laboratory Notebooks and Their Discovery of the Urea Cycle-Reconstructed with Computer Models". In Holmes, Frederic L.; Renn, Jürgen;Rheinberger, Hans-Jörg (eds.).Reworking the Bench : Research Notebooks in the History of Science. Dordrecht: Kluwer Academic Publishers. pp. 269–294.doi:10.1007/0-306-48152-9_13.ISBN978-1-4020-1039-2.
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