Otto Heinrich Warburg

Otto Heinrich Warburg (German pronunciation:

Otto Heinrich Warburg was born in Freiburg im Breisgau in 1883, close to the Swiss border. Otto's mother was the daughter of a Protestant family of bankers and civil servants from Baden. His father, Emil Warburg, had converted to Protestantism as an adult, although Emil's parents were Orthodox Jews.^[4] Emil was a member of the illustrious Warburg family of Altona. Emil was also president of the Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat (True Senior Privy Counselor).

Otto Warburg studied chemistry under

While working at the Marine Biological Station, Warburg performed research on oxygen consumption in

In 1918, Warburg was appointed professor at the

The Nobel laureate George Wald, having completed his Ph.D. in zoology at Columbia University, received an award from the U.S. National Research Council to study with Warburg. During his time with Warburg, 1932–1933, Wald discovered vitamin A in the retina.

Survival under the Nazis

When the Nazis came to power, people of Jewish descent were forced from their professional positions, although the Nazis made exceptions. Warburg had a Protestant mother and a father with Jewish heritage (who had converted to Protestantism).^[7] According to the Reichsbürgergesetz from 1935 (cf. Nuremberg Laws) Warburg, as a "half-Jew" was labeled a Halbjude or Mischling.^[8]

Warburg was also at risk due to his relationship with Jacob Heiss, with whom he lived and worked.^[9] Beginning around 1918, Heiss served variously as Warburg's personal aid, secretary, and administrative assistant.^[10] The couple lived together in an elegant villa in Dahlem, in Berlin.^[9][11][12]

Warburg was banned from teaching, but allowed to carry on his research.^[7] In 1941, Warburg briefly lost his post for making remarks critical of the Nazi regime, but in a few weeks was able to resume his research following a personal order from Hitler's Chancellery. Hermann Göring also arranged for him to be classified as one-quarter Jewish.^[7] In September 1942, Warburg made an official request for equal status ("Gleichstellung") with German Aryans, which was granted.^[8]

The Nazis were willing to allow Warburg to work because of his focus on metabolism and cancer. Hitler was obsessed with cancer, having lost his own mother to breast cancer at an early age.^[9][12][13] The decisive factor was Warburg's distinguished military service in the Great War, as Jewish veterans were often exempted from the loss of citizenship mandated by the Nuremberg laws. Warburg's Germanic physiognomy may also have weighed in his favor, as Hitler's Chancellery is known to have factored in eye color and face shape when evaluating Aryanization applications.^[14]

Warburg disagreed with the Nazi regime, and refused to acknowledge the Nazi salute, to the point of provoking retaliation from its officers. Authors have speculated on why he stayed in Germany under the Reich. Apple suggests that, like many others, he did not imagine how bad things could get. His own egotism may have led him to underestimate the potential threat posed by the Nazis.^[9] Others have suggested that Warburg was so totally devoted to his work that he was prepared not only to stay in Germany but to tolerate the treatment of his Jewish colleagues and relatives by the Nazis.^[15] An anecdote from Birgit Vennesland, who became a director at Warburg's institute in West Berlin in 1968, is suggestive. She said that Warburg's advice for an acquaintance who was experiencing emotional difficulties was "Tell him not to think about anything but science—think about absolutely nothing else—only science."^[16]

In 1943 Warburg relocated his laboratory to the village of Liebenburg on the outskirts of Berlin to avoid ongoing air raids.^{[citation needed]} The Rockefeller Foundation reportedly offered to continue funding his work if he emigrated. After the war ended, Warburg inquiried about the prospect of moving to the United States, but was turned down.^{[citation needed]}

Nomination for a second Nobel Prize

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 flavin (in yellow enzymes).^[17][18] Some sources report that he was selected to receive the award that year, but was prevented from receiving it by Adolf Hitler's regime, which had issued a decree in 1937 that forbade Germans from accepting Nobel Prizes.^[19][20] According to the Nobel Foundation, this rumor is not true; although he was considered a worthy candidate, he was not selected for the prize at that time.^[17]

Three scientists who worked in Warburg's lab, including Sir

Warburg hypothesized that

Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.

— Otto H. Warburg, ^[22]

Warburg continued to develop the hypothesis experimentally and gave several prominent lectures outlining the theory and the data.^[23]

Today,

A recent reevaluation of the data from nuclear/cytoplasm transfer experiments, where nuclei from cancer cells are placed in normal cytoplasm and where nuclei from normal cells are placed in cancer cytoplasm, support the role of metabolism in cancer and the mitochondria in aiding tumor suppression.^[25][26] Still, as evident from the references therein, this promising phenomenon still fails to explain the origin of cancer as Warburg originally proposed. While Warburg's hypothesis certainly inspired the scientific community to further investigate the field of cancer metabolism, his tendency to oversimplify^[27] perhaps prevented him from accepting the vastly complex role and interactions between both the mitochondria and nucleus, or more generally, metabolism and mutations.^{[28][29][30][31]}

Later years

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Otto Warburg edited and had much of his original work published in The Metabolism of Tumours (tr. 1931) and wrote New Methods of Cell Physiology (1962). An unabashed

When frustrated by the lack of acceptance of his ideas, Warburg was known to quote an aphorism he attributed to Max Planck: "Science advances one funeral at a time".^[32][33]

Seemingly utterly convinced of the accuracy of his conclusions, Warburg expressed dismay at the "continual discovery of cancer agents and cancer viruses" that he expected to "hinder necessary preventive measures and thereby become responsible for cancer cases".^[23]

When Josef Issels was tried and convicted for promoting the Issels treatment, an ineffective regimen claimed to treat cancer, Warburg offered to testify on Issels' behalf at his appeal to the German Supreme Court. All of Issels' convictions were overturned.^[34]

Warburg resided in the Kaiser Wilhelm Institute with his companion of 50 years, Jacob Heiss, the secretary and manager of the Kaiser Wilhelm Institute.^{[citation needed]} Warburg pursued his research until the age of 86. He left his entire estate to Heiss.^[9]

In 1968, he suffered a broken femur. This was complicated by deep vein thrombosis. He died in 1970 from pulmonary embolism and was buried in a Christian cemetery.^[35]

The Otto Warburg Medal

The Otto Warburg Medal is intended to commemorate Warburg's outstanding achievements. It has been awarded by the German Society for Biochemistry and Molecular Biology (Gesellschaft für Biochemie und Molekularbiologie) since 1963. The prize honors and encourages pioneering achievements in fundamental biochemical and molecular biological research. The Otto Warburg Medal is regarded as the highest award in Germany for biochemists and molecular biologists. It has been endowed with prize money, sponsored by the publishing company Elsevier/BBA.^[36]

Bibliography

• Warburg effect inversion
• Oncometabolism
• List of Jewish Nobel laureates

References