Otto Warburg, A Giant of Modern Cellular Biology
Reporter: Larry H Bernstein, MD, FCAP
Otto Heinrich Warburg (Photo credit: Wikipedia)
Otto Heinrich Warburg (October 8, 1883 – August 1, 1970), son of physicist Emil Warburg, was a German physiologist, medical doctor and Nobel laureate.
Otto Heinrich Warburg was born on October 8, 1883, in Freiburg, Baden. His father, the physicist Emil Warburg, was President of the Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat. He was a member of the Warburg family, a prominent family and financial dynasty of German Jewish descent, noted for their varied accomplishments in physics, classical music, art history, pharmacology, physiology, finance, private equity and philanthropy. They are believed to be descended from the Venetian Jewish del Banco family, in the early 1500s one of the wealthiest Venetian families. The Warburgs fled from Italy to Warburg in Germany in the 16th century before moving to Altona, near Hamburg in the 17th century taking their surname from the city of Warburg. The brothers Moses Marcus Warburg(1763 – 1830) and Gerson Warburg (1765 – 1826) founded the M. M. Warburg & Co. banking company in 1798 that is still in existence.
Otto studied chemistry under the great Emil Fischer, and gained the degree, Doctor of Chemistry (Berlin), in 1906. He then studied under von Krehl and obtained the degree, Doctor of Medicine (Heidelberg), in 1911.
He served as an officer in the elite Uhlan (cavalry regiment) during the First World War, and won the Iron Cross (1st Class) for bravery. Warburg was one of the 20th century’s leading biochemists. [1] He won the Nobel Prize of 1931. In total, he was nominated an unprecedented three times for the Nobel prize for three separate achievements.
While working at the Marine Biological Station, Warburg performed research on oxygen consumption in sea urchin eggs after fertilization, and proved that upon fertilization, the rate of respiration increases by as much as sixfold. His experiments also proved iron is essential for the development of the larval stage.
In 1918, Warburg was appointed professor at the Kaiser Wilhelm Institute for Biology in Berlin-Dahlem (part of the Kaiser-Wilhelm-Gesellschaft). By 1931 he was named director of the Kaiser Wilhelm Institute for Cell Physiology, which was founded the previous year by a donation of the Rockefeller Foundation to the Kaiser Wilhelm Gesellschaft (since renamed the Max Planck Society).
Warburg’s early researches with Fischer were in the polypeptide field.
At Heidelberg he worked on the process of oxidation. His special interest in the investigation of vital processes by physical and chemical methods led to attempts to relate these processes to phenomena of the inorganic world. His methods involved detailed studies on the assimilation of carbon dioxide in plants, the metabolism of tumors, and the chemical constituent of the oxygen transferring respiratory ferment. Warburg was never a teacher, and he has always been grateful for his opportunities to devote his whole time to scientific research. His later researches at the Kaiser Wilhelm Institute have led to the discovery that the flavins and the nicotinamide were the active groups of the hydrogen-transferring enzymes.
This, together with the iron-oxygenase discovered earlier, gives a complete account of the oxidations and reductions in the living world. Warburg investigated the metabolism of tumors and the respiration of cells, particularly cancer cells, and in 1931 was awarded the Nobel Prize in Physiology for his “discovery of the nature and mode of action of the respiratory enzyme.”[2]
The award came after receiving 46 nominations over a period of nine years beginning in 1923, 13 of which were submitted in 1931, the year he won the prize. This discovery opened up new ways in the fields of cellular metabolism and cellular respiration. He hypothesized, among other things, that cancerous cells can live and develop, even in the absence of oxygen. Warburg also wrote about oxygen’s relationship to the pH of cancer cells’ internal environments, since fermentation was a major metabolic pathway of cancer cells.
Three scientists who worked in Warburg’s lab, including Sir Hans Adolf Krebs, went on to win the Nobel Prize. Among other discoveries, Krebs is credited with the identification of the citric acid cycle (or Szent györgyi-Krebs cycle).
In 1944, Warburg was nominated for a second Nobel Prize in Physiology by Albert Szent-Györgyi, for his work on nicotinamide, the mechanism and enzymes involved in fermentation, and the discovery of flavine (in yellow enzymes). Although he was considered a worthwhile candidate, he was not selected for the prize.
References
- Krebs, HA (1972), “Warburg Heinrich Warburg. 1883-1970”, Biographical Memoirs of Fellows of the Royal Society (The Royal Society) 18: 628–699,doi:10.1098/rsbm.1972.0023
- ^ NobelPrize.org, The Nobel Prize in Physiology or Medicine 1931accessed April 20, 2007
- Warburg O (1956), “On the origin of cancer cells”, Science 123 (3191): 309–14, doi:10.1126/science.123.3191.309, PMID 13298683
- ^ a b Kim JW, Dang CV (2006), “Cancer’s molecular sweet tooth and the Warburg effect”, Cancer Res. 66 (18): 8927–30, doi:10.1158/0008-5472.CAN-06-1501, PMID 16982728
- Som P; Atkins HL; Bandoypadhyay D et al. (1 July 1980), “A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection”, J. Nucl. Med. 21 (7): 670–5, PMID 7391842
- Chernow, Ron (1993), The Warburgs: The Twentieth-Century Odyssey of a Remarkable Jewish Family, New York, NY: Random House, ISBN 0-679-41823-7
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[…] See original article: Otto Warburg, A Giant of Modern Cellular Biology « Pharmaceutical … […]
I find it fascinating that Krebs was one of his students. I actually looked up the initial paper that Warburg wrote on oxygen utilization, pH and cancer and it reads like poetry. Papers are not written like that anymore. I was actually thinking about posters including biographies of scientists who had contributed seminal works in their field. Wonderful post.
Dr. Williams,
SInce you have a neck for History of Molecular Biology,
May I refer you to a Historian of Molecular Biology among Ours, Contributors’ Biographies, my sister, Dr. Pnina G. Abir-Am
https://pharmaceuticalintelligence.com/contributors-biographies/pnina-g-abir-am-phd-historian-of-molecular-biology/
I do encourage any EAW to incorporate biographical material in their posts. Please see
https://pharmaceuticalintelligence.com/?s=Nobel+Prize
I am now reading Krebs biography of Warburg. Fascinating. His father played the piano, and Einstein played the violin. They were very close, and they played duets in Emil’s house. After Otto was wounded in WWI and was ready to go back, Einstein wrote to him and said that his talent was too great to be lost in war, and to think about it. Max Planck and Walter Nernst were in the circle of friends. I think it was Nernst who went to the Kaiser Wilhelm and told him that Germany did not have the resources to win a drawn out war (probably a factor in Hitler’s Blitzkrieg). Emil made a major contribution to Einstein’s work on the photoelectric effect, and I think that Boltzmann had a major influence on his Brownian Movement – before relativity theory. Otto did consider Einstein’s advice and he thought, we’ll lose the war.
The Warburg family went back to the 16th century. The family moved to Hamburg, and then to a town near Hamburg when the Warburg mayor was asked to convert to christianity. There was a brilliant artist cousin, and two banking giants in London. That factors into Warburg’s being an angliophile!
Otto wanted to do better than his father, which is indeed incredible.
His father and Einstein went to the Kaiser and arranged for the Kaiser Wilhelm Institute. When Hitler came to power, they moved it out of Berlin. It was funded by the Rockefeller Foundation. He was told he had no teaching obligations, and he could walk in the woods and THINK. Think he did well, as well as the laboratory experiments. I didn’t realize the association he had with Otto Meyerhoff, who must have been the 3rd Nobel Laureate to come out of his lab.
He had a team of 6 technicians who were highly skilled, which I think is comparable to Nate Kaplan’s having Francis Stolzenbach and Johannes Everse. He also had postdoctoral fellows.
He initially discovered that the sea urchin embryo grows quickly and requires a lot of energy. He then went back to the work of Pasteur on the generation of lactic acid by bacteria, and lactic acid production is stopped in the presence of oxygen…Warburg termed that aerobic glycolysis. He was interested in why cancer cells grow quickly, and in the presence of oxygen. He ground up liver and discovered that liver “particles”, not then known as mitochondria, were responsible, and he concluded that the metabolic process required structure.
Leloir later referred to this in his Nobel Prize acceptance, but he was unaware that Warburg didn’t intend to mean that the process couldn’t be done in a system without the lipid structure. He was able to demonstrate that it had to have a metal catalyst. He also went on to isolate the pyridine nucleotide coenzymes, adenine, adenine nucleotides, and flavines.
He redesigned the apparatus used for studying respiration, and he grew slices of tissue in the Warburg apparatus and measured the O2 utilization, whereas, he had years earlier done experiments with stoichiometric titration. He was able to establish that cancer cells grow, and that they rely on aerobic glycolysis.
I didn’t know the profound influence of Warburg when I went to NO Kaplan’s lab with continued support from my pathology chairman, AA Liebow, when funds were cut – I was put on an NIH Cardiovascular Training Grant. Kaplan would not use the terms NAD, NADP, NADH, and NADPH. Kaplan and Colowick had both been together in Fritz Lippman’s Lab at Johns Hopkins and were involved in the discovery of coenzyme A. This opened up a more complete understanding of the mitochondrial function, high energy ~P, and then with Fyodor Lynen – lipid synthesis,
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this has generated a long lasting discussion
On Thu, Jul 24, 2014 at 1:29 PM, Pharmaceutical Intelligence wrote:
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