Otto Heinrich Warburg

1. Otto Heinrich Warburg By: Alina Ungureanu & Stephanie Segreto

2. Biography Otto Heinrich Warburg: • Born-October 8, 1883 in Germany • Died-August 1, 1970 in Berlin, Germany • Son of physicist Emil Warburg • Otto was a German physiologist and medical doctor. • He won a Nobel prize in Physiology and Medicine for his Warburg effect in 1931. • He was one of the twentieth century's leading biochemist

3. What Was Known Before? • The concept of glycolysis and metabolism was already known. • Warburg's early researches was in the polypeptide field, he also worked on the process of oxidation. • 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 fermentation.

4. Hypothesis (Warburg Effect) • Warburg hypothesized that cancer is caused by the fact that tumor cells mainly generate energy by non-oxidative breakdown of glucose • “Healthy" cells mainly generate energy from oxidative breakdown of pyruvate. • Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. • According to Warburg, cancer should be interpreted as a mitochondrial dysfunction.

5. The Warburg Effect • The Warburg effect is the inhibition of carbon dioxide fixation, and subsequently of photosynthesis, by high oxygen concentrations. The oxygenase activity of RuBisCO, which initiates the process of photorespiration, largely accounts for this effect. • In oncology, the Warburg effect is that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria like most normal cells. The latter process is aerobic. Tumour cells typically have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful • He postulated that this change in metabolism is the fundamental cause of cancer

6. The Warburg Effect • The Warburg effect has important medical applications, as high aerobic glycolysis by malignant tumours is utilized clinically to diagnose and monitor treatment responses of cancers by radiation as radiation kills cancerous cells.   • The effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumours, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's apoptosis program which would otherwise kill cancerous cells. • It may also be an effect associated with cell proliferation. Since glycolysis provides most of the building blocks required for cell proliferation, it has been proposed that cancer cells (and normal proliferating cells) may need to activate glycolysis despite the presence of oxygen in order to proliferate. There is also evidence that attributes some of the high aerobic glycolytic rates to an over expressed form of mitochondrially-bound hexokinase responsible for driving the high glycolytic activity.

7. One of his Lectures… • "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… " -- Dr. Otto H. Warburg in Lecture

8. Interpretations • His "Warburg effect" asserts that even when oxygen is plentiful, cancer cells continue to use glycolysis (a secondary system of producing energy, employed by normal cells only when oxygen is in short supply). • Thanks to Otto Heinrich Warburg, we can discover new ways of finding and treating cancer.

9. References • "Warburg effect - Wikipedia, the free encyclopedia." Wikipedia, the free encyclopedia. N.p., n.d. Web. 15 Nov. 2010. <http://en.wikipedia.org/wiki/Warburg_effect>. • "Warburg effect - Wikipedia, the free encyclopedia." Wikipedia, the free encyclopedia. N.p., n.d. Web. 15 Nov. 2010. <http://en.wikipedia.org/wiki/Warburg_effect>. • "Otto Heinrich Warburg - Wikipedia, the free encyclopedia." Wikipedia, the free encyclopedia. N.p., n.d. Web. 15 Nov. 2010. <http://en.wikipedia.org/wiki/Otto_Heinrich_Warburg>. • "Warburg Effect." How Stuff Works. N.p., n.d. Web. 15 Nov. 2010. <sci-ence.howstuffworks.com/dictionary/famous-scientists/biologists/otto-heinrich-warburg-info.htm >.