Otto Heinrich Warburg
Otto Heinrich Warburg
|Died||1 August 1970 86) (aged|
|Alma mater|| University of Berlin |
University of Heidelberg
|Known for||Pathogenesis of cancer|
Warburg effect (oncology)
Warburg effect (plant physiology)
|Awards|| Iron Cross 1st class (1918)|
Nobel Prize in Physiology or Medicine (1931)
Pour le Mérite (Civil Class) (1952)
Foreign Member of the Royal Society
|Institutions||Kaiser Wilhelm Institute for Biology|
|Doctoral advisor|| Emil Fischer |
Ludolf von Krehl
Otto Heinrich Warburg ( // ; 8 October 1883 – 1 August 1970), son of physicist Emil Warburg, was a German physiologist, medical doctor, and Nobel laureate. He served as an officer in the elite Uhlan (cavalry regiment) during the First World War, and was awarded the Iron Cross (1st Class) for bravery. He was the sole recipient of the Nobel Prize in Physiology or Medicine in 1931. In total, he was nominated for the award 47 times over the course of his career.
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.Emil was a member of the illustrious Warburg family of Altona, and had converted to Christianity reportedly after a disagreement with his Conservative Jewish parents. Emil was also president of the Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat (True Senior Privy Counselor).
Otto Warburg studied chemistry under Emil Fischer, and earned his doctorate in chemistry in Berlin in 1906. He then studied under Ludolf von Krehl and earned the degree of doctor of medicine in Heidelberg in 1911.
Between 1908 and 1914, Warburg was affiliated with the Naples Marine Biological Station, (in Naples, Italy), where he conducted research. In later years, he would return for visits, and maintained a lifelong friendship with the family of the station's director, Anton Dohrn.
A lifelong equestrian, he served as an officer in the elite Uhlans (cavalry) on the front during the First World War, where he won the Iron Cross. Warburg later credited this experience with affording him invaluable insights into "real life" outside the confines of academia. Toward the end of the war, when the outcome was unmistakable, Albert Einstein, who had been a friend of Warburg's father Emil, wrote to Warburg at the behest of friends, asking him to leave the army and return to academia, since it would be a tragedy for the world to lose his talents. Einstein and Warburg later became friends, and Einstein's work in physics had a great influence on Warburg's biochemical research.[ citation needed ]
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 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".In particular, he discovered that animal tumors produce significant quantities of lactic acid. 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.
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.
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). Although banned from teaching, he was allowed to carry on his research.
According to the Reichsbürgergesetz from 1935 (cf. Nuremberg Laws) Warburg was considered by the Nazis a half-Jew (Halbjude) resp. Mischling and in September 1942 he issued an official request for equal status ("Gleichstellung") with Germans, which was granted.
In 1941, Warburg lost his post briefly when he made critical remarks about the regime, but a few weeks later a personal order from Hitler's Chancellery ordered him to resume work on his cancer research. Göring also arranged for him to be classified as one-quarter Jewish.
It is believed that Warburg was so totally dedicated to his work that he was prepared not only to stay in Germany but also to accept the Nazi treatment of his Jewish colleagues and his Jewish relatives.This was despite his having received an offer from the Rockefeller Foundation to continue to fund his work if he emigrated. After the end of the Second World War, he made inquiries about moving to the United States of America, but his approach then was turned down.
In 1943 Warburg relocated his laboratory to the village of Liebenburg on the outskirts of Berlin to avoid ongoing air attacks.
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).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. 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.
Three scientists who worked in Warburg's lab, including Sir Hans Adolf Krebs, went on to win the Nobel Prize in future years. 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.He worked with Dean Burk in the study of photosynthesis to discover the I-quantum reaction that splits CO2, activated by respiration.
Warburg hypothesized that cancer growth is caused by tumor cells generating energy (as, e.g., adenosine triphosphate/ATP) mainly by anaerobic breakdown of glucose (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, 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.
Warburg continued to develop the hypothesis experimentally and gave several prominent lectures outlining the theory and the data.
Today, mutations in oncogenes and tumor suppressor genes are thought to be responsible for malignant transformation, and the metabolic changes Warburg thought of as causative are now considered to be a result of these mutations.
However, 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, more strongly supports Warburg’s original theory than the somatic mutation theory for the origin of malignant transformation and cancer.
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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 anglophile, Otto Warburg was thrilled when Oxford University awarded him an honorary doctorate.[ citation needed ] He was awarded the Order Pour le Mérite in 1952 and was known to tell other universities not to bother with honorary doctorates. He would ask officials to mail him medals he had been awarded so as to avoid a ceremony that would separate him from his beloved laboratory.[ citation needed ]
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".
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".
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.
Warburg never married and resided in the Kaiser Wilhelm Institute with his faithful companion, Jacob Heiss, a personal friend and the secretary and manager of the Kaiser Wilhelm Institute. Warburg pursued his research until the age of 86.
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.
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.
Paul Ehrlich was a Nobel prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. He is credited with finding a cure for syphilis in 1909. He invented the precursor technique to Gram staining bacteria. The methods he developed for staining tissue made it possible to distinguish between different types of blood cells, which led to the capability to diagnose numerous blood diseases.
Sir Hans Adolf Krebs was a German-born British biologist, physician and biochemist. He was a pioneer scientist in the study of cellular respiration, a biochemical process in living cells that extracts energy from food and oxygen and makes it available to drive the processes of life. He is best known for his discoveries of two important sequences of chemical reactions that take place in the cells of humans and many other organisms, namely the citric acid cycle and the urea cycle. The former, often eponymously known as the "Krebs cycle", is the key sequence of metabolic reactions that provides energy in the cells of humans and other oxygen-respiring organisms; and its discovery earned Krebs a Nobel Prize in Physiology or Medicine in 1953. With Hans Kornberg, he also discovered the glyoxylate cycle, which is a slight variation of the citric acid cycle found in plants, bacteria, protists, and fungi. Krebs died in 1981 in Oxford, where he had spent 13 years of his career from 1954 until his retirement in 1967 at the University of Oxford.
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Günter Blobel was a Silesian German and American biologist and 1999 Nobel Prize laureate in Physiology for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell.
Humboldt University of Berlin is a university in the central borough of Mitte in Berlin, Germany. It was established by Frederick William III on the initiative of Wilhelm von Humboldt, Johann Gottlieb Fichte and Friedrich Ernst Daniel Schleiermacher as the University of Berlin in 1809, and opened in 1810, making it the oldest of Berlin's four universities. From 1810 until its closure in 1945, it was named Friedrich Wilhelm University. During the Cold War the university found itself in East Berlin and was de facto split in two when the Free University of Berlin opened in West Berlin. The university received its current name in honour of Alexander and Wilhelm von Humboldt in 1949.
Fritz Albert Lipmann was a German-American biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded the Nobel Prize in Physiology or Medicine in 1953.
Otto Fritz Meyerhof was a German physician and biochemist who won the Nobel Prize in Physiology and Medicine in 1922.
Bert Sakmann is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch clamp. Bert Sakmann was Professor at Heidelberg University and is an Emeritus Scientific Member of the Max Planck Institute for Medical Research in Heidelberg, Germany. Since 2008 he leads an emeritus research group at the Max Planck Institute of Neurobiology.
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Johannes Andreas Grib Fibiger was a Danish physician and professor of anatomical pathology at the University of Copenhagen. He was the recipient of the 1926 Nobel Prize in Physiology or Medicine "for his discovery of the Spiroptera carcinoma". He demonstrated that the roundworm which he called Spiroptera carcinoma could cause stomach cancer in rats and mice. His experimental results were later proven to be a case of mistaken conclusion. Erling Norrby, who had served as the Permanent Secretary of the Royal Swedish Academy of Sciences and Professor and Chairman of Virology at the Karolinska Institute, declared Fibiger's Nobel Prize as "one of the biggest blunders made by the Karolinska Institute."
Albert Claude was a Belgian-American cell biologist and medical doctor who shared the Nobel Prize in Physiology or Medicine in 1974 with Christian de Duve and George Emil Palade. His elementary education started in a comprehensive primary school at Longlier, his birthplace. He served in the British Intelligence Service during the First World War, and got imprisoned in concentration camps twice. In recognition of his service, he was granted enrolment at the University of Liège in Belgium to study medicine without any formal education required for the course. He earned his Doctor of Medicine degree in 1928. Devoted to medical research, he initially joined German institutes in Berlin. In 1929 he found an opportunity to join the Rockefeller Institute in New York. At Rockefeller University he made his most groundbreaking achievements in cell biology. In 1930 he developed the technique of cell fractionation, by which he discovered the agent of the Rous sarcoma, components of cell organelles such as mitochondrion, chloroplast, endoplasmic reticulum, Golgi apparatus, ribosome and lysosome. He was the first to employ the electron microscope in the field of biology. In 1945 he published the first detailed structure of cell. His collective works established the complex functional and structural properties of cells.
In oncology, the Warburg effect is a form of modified cellular metabolism based on aerobic fermentation found in cancer cells, which tend to favor anaerobic glycolysis rather than the oxidative phosphorylation pathway which is the preference of most other cells of the body. In tumor cells, the last product of glycolysis, pyruvate, is converted into lactate. This observation was first made by Nobel laureate Otto Heinrich Warburg who was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme".
The Charité – Universitätsmedizin Berlin is one of Europe's largest university hospitals, affiliated with Humboldt University and Free University Berlin. With numerous Collaborative Research Centers (CRC) of the Deutsche Forschungsgemeinschaft it is one of Germany's most research-intensive medical institutions. From 2012 to 2019, it was ranked by Focus as the best of over 1000 hospitals in Germany. In 2019 Newsweek ranked the Charité as fifth best hospital in the world and best in Europe. More than half of all German Nobel Prize winners in Physiology or Medicine, including Emil von Behring, Robert Koch and Paul Ehrlich, have worked at the Charité. Several politicians and diplomats have been treated at the Charité, including German Chancellor Angela Merkel, who underwent meniscus treatment at the Orthopaedic Department, and Julia Timoschenko from Ukraine.
Emil Gabriel Warburg was a German physicist who during his career was professor of physics at the Universities of Strassburg, Freiburg and Berlin. He was president of the Deutsche Physikalische Gesellschaft 1899–1905. His name is notably associated with the Warburg element of electrochemistry.
The Warburg hypothesis, sometimes known as the Warburg theory of cancer, postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria. The term Warburg effect in oncology describes the observation that cancer cells, and many cells grown in vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire. In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment. The Warburg hypothesis was that the Warburg effect was the root cause of cancer. The current popular opinion is that cancer cells ferment glucose while keeping up the same level of respiration that was present before the process of carcinogenesis, and thus the Warburg effect would be defined as the observation that cancer cells exhibit glycolysis with lactate production and mitochondrial respiration even in the presence of oxygen.
Dean Burk was an American biochemist, medical researcher, and a cancer researcher at the Kaiser Wilhelm Institute and the National Cancer Institute. In 1934, he developed the Lineweaver–Burk plot together with Hans Lineweaver.
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