Sunday, October 21, 2012

Cancer: Como se crea el cancer/The origen of cancer?

Scientific work and Nobel Prize
Otto Warburg, 1931
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 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.[3]

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).[4][5] Some sources reported 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.[6][7] According to the Nobel Foundation, this rumor is not true; although he was considered a worthwhile candidate, he was not selected for the prize.[4]

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 Szentgyörgyi-Krebs cycle).
Warburg’s combined work in plant physiology, cell metabolism and oncology made him an integral figure in the later development of systems biology.[8] He worked with Dean Burk in photosynthesis to discover the I-quantum reaction that splits the CO2, activated by the respiration. [9]

[edit] Cancer hypothesis

In 1924, Warburg hypothesized that cancer, malignant growth, and tumor growth are caused by tumor cells mainly generating energy (as e.g. adenosine triphosphate / ATP) by nonoxidative breakdown of glucose (a process called glycolysis) and the subsequent recycling of the metabolite NADH back to its oxidized form, for reuse in the glycolytic cycle to complete the process (known as fermentation, or anaerobic respiration). This is in contrast to "healthy" cells, which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end product of glycolysis, and is oxidized within the mitochondria. Hence, and according to Warburg, cancer should be interpreted as a mitochondrial dysfunction.

"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 [10]
Warburg continued to develop the hypothesis experimentally, and held several prominent lectures outlining the theory and the data.[11]

The concept that cancer cells switch to fermentation in lieu of aerobic respiration has become widely accepted, even if it is not seen as the cause of cancer. Some suggest the Warburg phenomenon could be used to develop anticancer drugs.[12] Meanwhile, cancer cell glycolysis is the basis of positron emission tomography (18-FDG PET), a medical imaging technology that relies on this phenomenon.[12][13]
Otto Heinrich Warburg

Otto Heinrich Warburg
Born(1883-10-08)October 8, 1883
Freiburg, Baden, Germany
DiedAugust 1, 1970(1970-08-01) (aged 86)
Berlin, West Germany
FieldsCell biology
InstitutionsKaiser Wilhelm Institute for Biology
Alma materUniversity of Berlin
University of Heidelberg
Doctoral advisorEmil Fischer
Ludolf von Krehl
Known forPathogenesis of cancer
Notable awardsIron Cross 1st class (1918)
Nobel Prize in Physiology or Medicine (1931)
Pour le Mérite (Civil Class) (1952)


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