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Posts Tagged ‘Nobel Prize’


Otto Warburg, A Giant of Modern Cellular Biology

Reporter: Larry H Bernstein, MD, FCAP

 

 

Otto Heinrich Warburg

Otto Heinrich Warburg (Photo credit: Wikipedia)

Otto Heinrich Warburg (October 8, 1883 – August 1, 1970), son of physicist Emil Warburg, was a German physiologist, medical doctor and Nobel laureate.

Otto Heinrich Warburg was born on October 8, 1883, in Freiburg, Baden. His father, the physicist Emil Warburg, was President of the Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat. He was a member of the Warburg family, a prominent family and financial dynasty of German Jewish descent, noted for their varied accomplishments in physicsclassical musicart historypharmacologyphysiologyfinanceprivate equity and philanthropy. They are believed to be descended from the Venetian Jewish del Banco family, in the early 1500s one of the wealthiest Venetian families. The Warburgs fled from Italy to Warburg in Germany in the 16th century before moving to Altona, near Hamburg in the 17th century taking their surname from the city of Warburg. The brothers Moses Marcus Warburg(1763 – 1830) and Gerson Warburg (1765 – 1826) founded the M. M. Warburg & Co. banking company in 1798 that is still in existence.

Otto studied chemistry under the great Emil Fischer, and gained the degree, Doctor of Chemistry (Berlin), in 1906. He then studied under von Krehl and obtained the degree, Doctor of Medicine (Heidelberg), in 1911.

He served as an officer in the elite Uhlan (cavalry regiment) during the First World War, and won the Iron Cross (1st Class) for bravery. Warburg was one of the 20th century’s leading biochemists. [1] He won the Nobel Prize of 1931. In total, he was nominated an unprecedented three times for the Nobel prize for three separate achievements.
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’s early researches with Fischer were in the polypeptide field.

At Heidelberg he worked on the process of oxidation. His special interest in the investigation of vital processes by physical and chemical methods led to attempts to relate these processes to phenomena of the inorganic world. 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 ferment. Warburg was never a teacher, and he has always been grateful for his opportunities to devote his whole time to scientific research. His later researches at the Kaiser Wilhelm Institute have led to the discovery that the flavins and the nicotinamide were the active groups of the hydrogen-transferring enzymes.
This, together with the iron-oxygenase discovered earlier, gives a complete account of the oxidations and reductions in the living world. 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. This discovery opened up new ways in the fields of cellular metabolism and cellular respiration. He hypothesized, among other things, that cancerous cells can live and develop, even in the absence of oxygen. Warburg also wrote about oxygen’s relationship to the pH of cancer cells’ internal environments, since fermentation was a major metabolic pathway of cancer cells.
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 Szent györgyi-Krebs cycle).
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). Although he was considered a worthwhile candidate, he was not selected for the prize.

References

  1.  Krebs, HA (1972), “Warburg Heinrich Warburg. 1883-1970”, Biographical Memoirs of Fellows of the Royal Society (The Royal Society) 18: 628–699,doi:10.1098/rsbm.1972.0023
  2. ^ NobelPrize.org, The Nobel Prize in Physiology or Medicine 1931accessed April 20, 2007
  3.  Warburg O (1956), “On the origin of cancer cells”, Science 123 (3191): 309–14, doi:10.1126/science.123.3191.309PMID 13298683
  4. a b Kim JW, Dang CV (2006), “Cancer’s molecular sweet tooth and the Warburg effect”, Cancer Res. 66 (18): 8927–30, doi:10.1158/0008-5472.CAN-06-1501PMID 16982728
  5. Som P; Atkins HL; Bandoypadhyay D et al. (1 July 1980), “A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection”, J. Nucl. Med. 21 (7): 670–5, PMID 7391842
  6. Chernow, Ron (1993), The Warburgs: The Twentieth-Century Odyssey of a Remarkable Jewish Family, New York, NY: Random House, ISBN 0-679-41823-7
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Reporter: Aviva Lev-Ari, PhD, RN

On August 16, 2012 I received an e-mail on New@NEJM.org from this e-mail, I selected to post HERE, the

Cardiology Panel — NEJM Dialogue in Medicine, June 22, 2012

https://pharmaceuticalintelligence.com/2012/08/16/cardiology-panel-nejm-dialogue-in-medicine-june-22-2012/

While listening to the 1:35 minutes of the Video of the Cardiology Panel, the Nobel Prize for Nitric Oxide was mentioned. In light of the thrust, this Scientific Web Site has related to Nitric Oxide in Health and in Disease, I decided to cite here the entire Letter from the Nobel Prize Web Site.

October 12, 1998

The Nobel Assembly at Karolinska Institutet has today decided to award
the Nobel Prize in Physiology or Medicine for 1998 jointly to

Robert F. Furchgott, Louis J. Ignarro and Ferid Murad

for their discoveries concerning “nitric oxide as a signalling molecule in the cardiovascular system”.

Summary

Nitric oxide (NO) is a gas that transmits signals in the organism. Signal transmission by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell represents an entirely new principle for signalling in biological systems. The discoverers of NO as a signal molecule are awarded this year’s Nobel Prize.

Robert F Furchgott, pharmacologist in New York, studied the effect of drugs on blood vessels but often achieved contradictory results. The same drug sometimes caused a contraction and at other occasions a dilatation. Furchgott wondered if the variation could depend on whether the surface cells (the endothelium) inside the blood vessels were intact or damaged. In 1980, he demonstrated in an ingenious experiment that acetylcholine dilated blood vessels only if the endothelium was intact. He concluded that blood vessels are dilated because the endothelial cells produce an unknown signal molecule that makes vascular smooth muscle cells relax. He called this signal molecule EDRF, the endothelium-derived relaxing factor, and his findings led to a quest to identify the factor.

Ferid Murad, MD and pharmacologist now in Houston, analyzed how nitroglycerin and related vasodilating compounds act and discovered in 1977 that they release nitric oxide, which relaxes smooth muscle cells. He was fascinated by the concept that a gas could regulate important cellular functions and speculated that endogenous factors such as hormones might also act through NO. However, there was no experimental evidence to support this idea at the time.

Louis J Ignarro, pharmacologist in Los Angeles, participated in the quest for EDRF’s chemical nature. He performed a brilliant series of analyses and concluded in 1986, together with and independently of Robert Furchgott, that EDRF was identical to NO. The problem was solved and Furchgott’s endothelial factor identified.

When Furchgott and Ignarro presented their conclusions at a conference in July, 1986, it elicited an avalanche of research activities in many different laboratories around the world. This was the first discovery that a gas can act as a signal molecule in the organism.

Background

Nitric oxide protects the heart, stimulates the brain, kills bacteria, etc.
It was a sensation that this simple, common air pollutant, which is formed when nitrogen burns, for instance in automobile exhaust fumes, could exert important functions in the organism. It was particularly surprising since NO is totally different from any other known signal molecule and so unstable that it is converted to nitrate and nitrite within 10 seconds. NO was known to be produced in bacteria but this simple molecule was not expected to be important in higher animals such as mammals.

Further research results rapidly confirmed that NO is a signal molecule of key importance for the cardiovascular system and it was also found to exert a series of other functions. We know today that NO acts as a signal molecule in the nervous system, as a weapon against infections, as a regulator of blood pressure and as a gatekeeper of blood flow to different organs. NO is present in most living creatures and made by many different types of cells.
– When NO is produced by the innermost cell layer of the arteries, the endothelium, it rapidly spreads through the cell membranes to the underlying muscle cells. Their contraction is turned off by NO, resulting in a dilatation of the arteries. In this way, NO controls the blood pressure and its distribution. It also prevents the formation of thrombi.
– When NO is formed in nerve cells, it spreads rapidly in all directions, activating all cells in the vicinity. This can modulate many functions, from behaviour to gastrointestinal motility.
– When NO is produced in white blood cells (such as macrophages), huge quantities are achieved and become toxic to invading bacteria and parasites.

Importance in medicine today and tomorrow
Heart: In atherosclerosis, the endothelium has a reduced capacity to produce NO. However, NO can be furnished by treatment with nitroglycerin. Large efforts in drug discovery are currently aimed at generating more powerful and selective cardiac drugs based on the new knowledge of NO as a signal molecule.

Shock: Bacterial infections can lead to sepsis and circulatory shock. In this situation, NO plays a harmful role. White blood cells react to bacterial products by releasing enormous amounts of NO that dilate the blood vessels. The blood pressure drops and the patient may become unconscious. In this situation, inhibitors of NO synthesis may be useful in intensive care treatment.

Lungs: Intensive care patients can be treated by inhalation of NO gas. This has provided good results and even saved lives. For instance, NO gas has been used to reduce dangerously high blood pressure in the lungs of infants. But the dosage is critical since the gas can be toxic at high concentrations.

Cancer: White blood cells use NO not only to kill infectious agents such as bacteria, fungi and parasites, but also to defend the host against tumours. Scientists are currently testing whether NO can be used to stop the growth of tumours since this gas can induce programmed cell death, apoptosis.

Impotence: NO can initiate erection of the penis by dilating the blood vessels to the erectile bodies. This knowledge has already led to the development of new drugs against impotence.

Diagnostic analyses: Inflammatory diseases can be revealed by analysing the production of NO from e.g. lungs and intestines. This is used for diagnosing asthma, colitis, and other diseases.

NO is important for the olfactory sense and our capacity to recognise different scents. It may even be important for our memory.

Nitroglycerin
Alfred Nobel invented dynamite, a product in which the explosion-prone nitroglycerin is curbed by being absorbed in kieselguhr, a porous soil rich in shells of diatoms. When Nobel was taken ill with heart disease, his doctor prescribed nitroglycerin. Nobel refused to take it, knowing that it caused headache and ruling out that it could eliminate chest pain. In a letter, Nobel wrote: It is ironical that I am now ordered by my physician to eat nitroglycerin. It has been known since last century that the explosive, nitroglycerin, has beneficial effects against chest pain. However, it would take 100 years until it was clarified that nitroglycerin acts by releasing NO gas.

TO CITE THIS PAGE:
MLA style: “Physiology or Medicine for 1998 – Press Release”. Nobelprize.org. 16 Aug 2012 http://www.nobelprize.org/nobel_prizes/medicine/laureates/1998/press.html

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