Who is otto warburg

In , he was guest in the laboratory of Barron at Johns Hopkins Medical School, where he performed the experiments on the enzymatic nature of chemical reductions in blood cells. On this visit, with the support of Jacob Loeb, he also negotiated with the Rockefeller Foundation, who was interested in establishing research institutes in Germany. The Institute of Cell Physiology was inaugurated in December and Otto Warburg became to be its one and only director.

The year was also the one in which Otto Warburg received the Nobel Prize in Medicine and Physiology for unraveling the oxygen-transferring ferment of respiration [ 17 ]. His father had missed this event by only a few months, having died in July. A controversial and enigmatic issue is how Warburg could continue working in Berlin during the Third Reich, since his Jewish colleagues had departed or been expelled.

Warburg himself was half-Jewish, but like his father considered himself to be a German Christian and even denied being related to the other Jewish descendants in the family.

On the other hand, he was quite aware of the political situation from the very beginning and supported his Jewish coworkers in getting jobs outside of the country; he advised Hans Krebs to take a position in England. His rather disrespectful behavior toward a visiting governmental official jeopardized the institute being delivered with required chemicals. Moreover, in , he was to be removed from his position as a director.

However, probably mediated through indirect contacts to officials close to Hitler, he was allowed to keep this position and continue working in the institute. One explanation proposed for this salvation is that Hitler, having had a benign larynx polyp removed, was obsessed with cancer phobia and probably hoped for a rapid cure to be discovered. In , due to the bombings on Berlin, Warburg along with very few remaining coworkers had to move the laboratory to a small location in the countryside northwest of Berlin [ 4 ].

After the war, it took some years until Warburg could go back to acceptable working conditions. The Russians had confiscated the laboratory equipment. His institute in Dahlem in West Berlin was occupied by American troops.

He was examined on his role in Nazi Germany. However, he finally was elected as a member of the Academy of Sciences reestablished in East Berlin , of which his father along with Albert Einstein and Max Planck had already been members. Eventually, in , he traveled to the USA, accepting the invitations from Robert Emerson at the University of Illinois and Dean Burk at the Cancer Institute at Bethesda to perform experiments on photosynthesis in their laboratories.

In the summer of , he also visited Woods Hole in Cape Cod and the Cancer Institute at Bethesda, where he met friends, expatriates, and critical colleagues, with anecdotal incidences of polemic scientific disputes. During the last period of his life, Warburg continued working on both photosynthesis and tumor metabolism, particularly on the role of respiration in tumorigenesis.

For the latter, he now also used cultures of cells which had been isolated from normal tissues by trypsinization based on a method which had just been developed by Dulbecco and Vogt [ 19 , 20 ]. He presented these concepts at prestigious meetings, one being the Annual Meeting of the Nobel Laureates in in Lindau, an island in the Lake of Constance Germany.

On this occasion, he received much scientific dissent. It is inferred that Melvin Calvin, who had received the Nobel Prize on photosynthesis in and had expanded his interests to carcinogenesis, may have avoided these harsh confrontations with Warburg by not attending the Lindau meetings until , after the death of Warburg [ 24 ].

Warburg considered cancer to be a nutritional problem, one that could be avoided by maintaining an appropriate natural diet. This line of thinking led him to consider the administration of vitamin supplements, which would enhance respiration and was considered to be a natural and safe application. Already in the s, Warburg, who was asserted having cancer phobia, practiced his own recommendations in maintaining a disciplined lifestyle: he grew his own vegetables, drew water from an unpolluted well, had his bread baked with grains from wheat not treated with pesticides, and kept his own poultry.

And, he did sports: long walks, horseback riding, or sailing [ 3 ]. After his favorite sister Lotte died of cancer in , Warburg also quit smoking [ 4 ]. Warburg, being sensitized to the dangers of smoking, alcohol, and drugs, proposed to the German Ministry of Health to reduce cigarette smoking, motor vehicle exhausts, air pollution, and chemical additives in foods as cancer prevention measures.

This was in and at that time without avail [ 3 ]. For one, there is the Warburg effect, i. While this is a reproducible observation, the scientific controversies continue on how the Warburg effect is related to the origin of cancer, what it means in molecular terms, how it can be connected to the genomics, proteomics, and molecular biology of cancer cells, and last but not least, how it can be utilized for diagnostics and therapy. The renaissance of the Warburg effect has put cancer metabolism back into the lime light of cancer research.

Probably the most controversial legacy for tumor metabolism is the hypothesis on the origin of cancer: that damaged respiration is solely responsible for the tumor type metabolism. In spite of its disaffirmation by numerous data and alternative explanations [ 31 ] providing evidence that there are also tumor cells which have apparently normal mitochondria and respiratory activity, what makes this hypothesis so attractive? A popular hypothesis always has two sides. The shiny side of the coin is the myriad of ideas it evokes and the new experiments and concepts it stimulates, especially when the hypothesis comes from a Nobel Laureate.

On the other side, however, there is the danger of oversimplification and non-reflected universal application, as well as the uncritical acceptance of a hypothesis as a given fact. For the latter, Warburg alone cannot be held responsible—it is the challenge and responsibility of every scientist to question the validity of a hypothesis.

We now have available many new investigative tools allowing us to elaborate on the observations and conclusions made by Otto Warburg about 90 years ago. He has set an example of meticulous work, bringing forth a gain of knowledge, which is now taken for granted as common textbook knowledge. He has, moreover, set an example for ingenious thinking, even if not all of it has been proven right. Reflecting this statement could also be a Warburg effect.

Oxygen as a factor in photosynthesis. Biol Rev Camb Philos Soc. Racker E. Bioenergetics and the problem of tumor growth: an understanding of the mechanism of the generation and control of biological energy may shed light on the problem of tumor growth.

Am Sci. Krebs H, Schmid R. Otto Warburg Zellphysiologe - Biochemiker - Mediziner Grosse Naturforscher. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH; Google Scholar. Werner P. Otto Warburg - Von der Zellphysiologie zur Krebsforschung. Berlin: Verlag Neues Leben; Warburg O, Minami S.

Klin Wochenschr. Article Google Scholar. Minami S. Biochem Zeitschr. CAS Google Scholar. The metabolism of chicken tumors. J Natl Canc Inst. Warburg O. Gleadle, J. Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: evidence against a regulatory role for Src kinase.

Blood 89 , — Jiang, B. V-SRC induces expression of hypoxia-inducible factor 1 HIF-1 and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Osthus, R. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc.

Ahuja, P. Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.

Shim, H. USA 94 , — This paper reports the first direct link between the oncogene MYC and the regulation of energy metabolism. Christofk, H. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Mazurek, S. Pyruvate kinase type M2 and its role in tumor growth and spreading. Cancer Biol. David, C. References 72—74 document the role of PKM2, an alternatively spliced form of PK, in cancer metabolism.

Dang, C. Robey, R. Deprez, J. Phosphorylation and activation of heart 6-phosphofructokinase by protein kinase B and other protein kinases of the insulin signaling cascades.

Arsham, A. Akt and hypoxia-inducible factor-1 independently enhance tumor growth and angiogenesis. Laughner, E. Fan, Y. Akt and c-Myc differentially activate cellular metabolic programs and prime cells to bioenergetic inhibition. Robey, I. Regulation of the Warburg effect in early-passage breast cancer cells. Neoplasia 10 , — Yun, J. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.

Ramanathan, A. Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Kikuchi, H. Sears, R. Ras enhances Myc protein stability. Cell 3 , — Gordan, J. Cancer Cell 14 , — Zundel, W. Genes Dev. Blagosklonny, M. Agani, F. Bensaad, K. TIGAR, a pinducible regulator of glycolysis and apoptosis. Vousden, K. Nature Rev. Cancer 9 , — Cheung, E.

The role of p53 in glucose metabolism. Cell Biol. Matoba, S. Ruiz-Lozano, P. Cell Growth Differ. This paper, reference 92 and reference 94 link p53 to glucose metabolism and mitochondrial function. Brand, K. Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. Newsholme, E. Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Moreadith, R. The pathway of glutamate and glutamine oxidation by tumor cell mitochondria.

Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29 , — Gao, P. Wise, D. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Yuneva, M. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. References — link MYC to the regulation of glutamine metabolism and glutamine dependency. Wang, J.

Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Weinberg, F. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Cadoret, A. Oncogene 21 , — Matsuno, T. Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma. Linder-Horowitz, M. Glutaminase activities and growth rates of rat hepatomas. Dal Bello, B.

Glutamine synthetase immunostaining correlates with pathologic features of hepatocellular carcinoma and better survival after radiofrequency thermal ablation. Burke, Z. Gastroenterology , — Alternative fuel — another role for p53 in the regulation of metabolism. Hu, W. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Open in a separate window. Figure 1. Krebs H. Oxford: Clarendon Press; Farrer D. The Warburgs. London: Michael Joseph; Chernow R.

Medawar J, Pyke D. Rosenbaum E, Sherman AJ. Ghiretti F. Review of Otto Warburg. Hist Philos Life Sci. Warburg OH. On the origin of cancer cells. NobelMedia AB Accessed Nov 6, The Prime Cause and Prevention of Cancer. The chemical constitution of respiration ferment. Clin Orthop Relat Res. Nat Rev Cancer. Inborn and acquired metabolic defects in cancer. J Mol Med Berl ; 89 — The Warburg effect: insights from the past decade. Pharmacol Ther. Therapeutic targeting of cancer cell metabolism.

Najafov A, Alessi DR. Uncoupling the Warburg effect from cancer. Induction of the Warburg effect by Kaposi Sarcoma herpes virus. Search for Maria or Betty Warburg. In most non-cancerous cells, on the other hand, fermentation will not occur if oxygen supply is sufficient. He suggests that cells turn into cancer cells by switching from respiration to fermentation. This could happen if the enzymatic machinery required for respiration is damaged or respiration is not possible due to a lack of oxygen, for instance.

To do so, he suggests to strengthen the enzymatic machinery responsible for cellular respiration, thus making the switch to fermentation - and cancer - less likely. This strengthening could easily be achieved by supplementing food with the micronutrients i.

Today we know that his idea is - unfortunately - too good to be true.