Otto Loewi
Encyclopedia
Otto Loewi was a German
born pharmacologist
whose discovery of acetylcholine
helped enhance medical therapy. The discovery earned for him the Nobel Prize in Physiology or Medicine
in 1936 which he shared with Sir Henry Dale, whom he met in 1902 when spending some months in Ernest Starling's laboratory at University College, London. He has been referred to as the "Father of Neuroscience
."
, Germany
. He received his medical doctoral degree from University of Strasbourg
(then part of Germany) in 1896 where he also was a member of the fraternity Burschenschaft Germania Strassburg.
During 1897-1898 he was assistant to Carl von Noorden, clinician at the City Hospital in Frankfurt. Soon, however, after seeing the high mortality in countless cases of far-advanced tuberculosis and pneumonia, left without any treatment because of lack of therapy, he decided to drop his intention to become a clinician and instead to carry out research in basic medical science, in particular pharmacology. In 1898, he succeeded in becoming an assistant of Professor Hans Horst Meyer
, the renowned pharmacologist at the University of Marburg, from 1904 Professor of Pharmacology in Vienna. In 1905, Loewi became Associate Professor at Meyer's laboratory, and in 1909 he was appointed to the Chair of Pharmacology in Graz.
During his first years in Marburg
, Loewi's studies were in the field of metabolism
. As a result of his work on the action of phlorhizin, a glucoside provoking glycosuria, and another one on nuclein metabolism in man, he was appointed «Privatdozent» (Lecturer) in 1900. Two years later he published his paper «Über Eiweisssynthese im Tierkörper» (On protein synthesis in the animal body), proving that animals are able to rebuild their proteins from their degradation products, the amino acids - an essential discovery with regard to nutrition.
Loewi investigated how vital organs respond to chemical and electrical stimulation. He also established their relative dependence on epinephrine
for proper function. Consequently, he learnt how nerve impulses are transmitted by chemical messengers. The first chemical neurotransmitter that he identified was acetylcholine.
In 1903, he accepted an appointment at the University of Graz
in Austria
, where he would remain until being forced out of the country in 1938. In 1905 he received Austrian citizenship.
He married Guida Goldschmiedt in 1908. They had three sons and a daughter. He was the last Jew hired by the University between 1903 and the end of the war.
After being arrested, along with two of his sons, on the night of the German invasion of Austria, March 11, 1938, Loewi was released on condition that he "voluntarily" relinquish all his possessions to the Nazis. Loewi moved to the United States in 1940, where he became a research professor at the New York University
College of Medicine. In 1946, he became a naturalized citizen of the United States
. In 1954, he became a Foreign Member of the Royal Society
. He died in New York City
on December 25, 1961.
Shortly after Loewi's death in late 1961, his youngest son bestowed the gold Nobel medal on the Royal Society
in London. He gave the Nobel diploma to the University of Graz
in Austria
in 1983, where it currently resides, along with a bronze copy of a bust of Loewi. The original of the bust is at the Marine Biological Laboratory
in Woods Hole, Massachusetts, Loewi's summer home from his arrival in the US until his death.
Before Loewi's experiments, it was unclear whether signalling across the synapse
was bioelectrical or chemical. Loewi's famous experiment, published in 1921, largely answered this question. According to Loewi, the idea for his key experiment came to him in his sleep. He dissected out of frogs two beating heart
s: one with the vagus nerve
which controls heart rate attached, the other heart on its own. Both hearts were bathed in a saline solution (i.e. Ringer's solution). By electrically stimulating the vagus nerve, Loewi made the first heart beat slower. Then, Loewi took some of the liquid bathing the first heart and applied it to the second heart. The application of the liquid made the second heart also beat slower, proving that some soluble chemical released by the vagus nerve was controlling the heart rate. He called the unknown chemical Vagusstoff
. It was later found that this chemical corresponded to Acetylcholine
(Kandel, et al. 2000).
Loewi's investigations “On an augmentation of adrenaline release by cocaine” and “On the connection between digitalis and the action of calcium” were profound concepts and were studied relentlessly by others decades later.
He also clarified two mechanisms of eminent therapeutic importance: the blockade and the augmentation of nerve action by certain drugs.
He is almost as famous for the means by which the idea for his experiment came to him as he is for the experiment itself. On Easter Saturday 1923, he dreamed of an experiment that would prove once and for all that transmission of nerve impulses was chemical, not electrical. He woke up, scribbled the experiment onto a scrap of paper on his night-stand, and went back to sleep.
The next morning he arose very excited because he knew this dream had been very important. But he found, to his horror, that he couldn't read his midnight scribbles. That day, he said, was the longest day of his life, as he could not remember his dream. That night, however, he had the same dream. This time, he immediately went to his lab to perform the experiment. From that point on, the consensus was that the Nobel was not a matter of "if" but of "when."
Thirteen years later, Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Sir Henry Hallett Dale
.
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
born pharmacologist
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
whose discovery of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
helped enhance medical therapy. The discovery earned for him the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
in 1936 which he shared with Sir Henry Dale, whom he met in 1902 when spending some months in Ernest Starling's laboratory at University College, London. He has been referred to as the "Father of Neuroscience
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
."
Biography
Loewi was born in FrankfurtFrankfurt
Frankfurt am Main , commonly known simply as Frankfurt, is the largest city in the German state of Hesse and the fifth-largest city in Germany, with a 2010 population of 688,249. The urban area had an estimated population of 2,300,000 in 2010...
, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
. He received his medical doctoral degree from University of Strasbourg
University of Strasbourg
The University of Strasbourg in Strasbourg, Alsace, France, is the largest university in France, with about 43,000 students and over 4,000 researchers....
(then part of Germany) in 1896 where he also was a member of the fraternity Burschenschaft Germania Strassburg.
During 1897-1898 he was assistant to Carl von Noorden, clinician at the City Hospital in Frankfurt. Soon, however, after seeing the high mortality in countless cases of far-advanced tuberculosis and pneumonia, left without any treatment because of lack of therapy, he decided to drop his intention to become a clinician and instead to carry out research in basic medical science, in particular pharmacology. In 1898, he succeeded in becoming an assistant of Professor Hans Horst Meyer
Hans Horst Meyer
Hans Horst Meyer was a German pharmacologist. He studied medicine and did research in pharmacology. The Meyer-Overton hypothesis on the mode of action on general anaesthetics is partially named after him...
, the renowned pharmacologist at the University of Marburg, from 1904 Professor of Pharmacology in Vienna. In 1905, Loewi became Associate Professor at Meyer's laboratory, and in 1909 he was appointed to the Chair of Pharmacology in Graz.
During his first years in Marburg
Marburg
Marburg is a city in the state of Hesse, Germany, on the River Lahn. It is the main town of the Marburg-Biedenkopf district and its population, as of March 2010, was 79,911.- Founding and early history :...
, Loewi's studies were in the field of metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. As a result of his work on the action of phlorhizin, a glucoside provoking glycosuria, and another one on nuclein metabolism in man, he was appointed «Privatdozent» (Lecturer) in 1900. Two years later he published his paper «Über Eiweisssynthese im Tierkörper» (On protein synthesis in the animal body), proving that animals are able to rebuild their proteins from their degradation products, the amino acids - an essential discovery with regard to nutrition.
Loewi investigated how vital organs respond to chemical and electrical stimulation. He also established their relative dependence on epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
for proper function. Consequently, he learnt how nerve impulses are transmitted by chemical messengers. The first chemical neurotransmitter that he identified was acetylcholine.
In 1903, he accepted an appointment at the University of Graz
University of Graz
The University of Graz , a university located in Graz, Austria, is the second-largest and second-oldest university in Austria....
in Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
, where he would remain until being forced out of the country in 1938. In 1905 he received Austrian citizenship.
He married Guida Goldschmiedt in 1908. They had three sons and a daughter. He was the last Jew hired by the University between 1903 and the end of the war.
After being arrested, along with two of his sons, on the night of the German invasion of Austria, March 11, 1938, Loewi was released on condition that he "voluntarily" relinquish all his possessions to the Nazis. Loewi moved to the United States in 1940, where he became a research professor at the New York University
New York University
New York University is a private, nonsectarian research university based in New York City. NYU's main campus is situated in the Greenwich Village section of Manhattan...
College of Medicine. In 1946, he became a naturalized citizen of the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. In 1954, he became a Foreign Member of the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
. He died in New York City
New York City
New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
on December 25, 1961.
Shortly after Loewi's death in late 1961, his youngest son bestowed the gold Nobel medal on the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
in London. He gave the Nobel diploma to the University of Graz
University of Graz
The University of Graz , a university located in Graz, Austria, is the second-largest and second-oldest university in Austria....
in Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
in 1983, where it currently resides, along with a bronze copy of a bust of Loewi. The original of the bust is at the Marine Biological Laboratory
Marine Biological Laboratory
The Marine Biological Laboratory is an international center for research and education in biology, biomedicine and ecology. Founded in 1888, the MBL is the oldest independent marine laboratory in the Americas, taking advantage of a coastal setting in the Cape Cod village of Woods Hole, Massachusetts...
in Woods Hole, Massachusetts, Loewi's summer home from his arrival in the US until his death.
Research
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
was bioelectrical or chemical. Loewi's famous experiment, published in 1921, largely answered this question. According to Loewi, the idea for his key experiment came to him in his sleep. He dissected out of frogs two beating heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
s: one with the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
which controls heart rate attached, the other heart on its own. Both hearts were bathed in a saline solution (i.e. Ringer's solution). By electrically stimulating the vagus nerve, Loewi made the first heart beat slower. Then, Loewi took some of the liquid bathing the first heart and applied it to the second heart. The application of the liquid made the second heart also beat slower, proving that some soluble chemical released by the vagus nerve was controlling the heart rate. He called the unknown chemical Vagusstoff
Vagusstoff
Vagusstoff refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate. Discovered in 1921 by physiologist Otto Loewi, vagusstoff was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered...
. It was later found that this chemical corresponded to Acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
(Kandel, et al. 2000).
Loewi's investigations “On an augmentation of adrenaline release by cocaine” and “On the connection between digitalis and the action of calcium” were profound concepts and were studied relentlessly by others decades later.
He also clarified two mechanisms of eminent therapeutic importance: the blockade and the augmentation of nerve action by certain drugs.
He is almost as famous for the means by which the idea for his experiment came to him as he is for the experiment itself. On Easter Saturday 1923, he dreamed of an experiment that would prove once and for all that transmission of nerve impulses was chemical, not electrical. He woke up, scribbled the experiment onto a scrap of paper on his night-stand, and went back to sleep.
The next morning he arose very excited because he knew this dream had been very important. But he found, to his horror, that he couldn't read his midnight scribbles. That day, he said, was the longest day of his life, as he could not remember his dream. That night, however, he had the same dream. This time, he immediately went to his lab to perform the experiment. From that point on, the consensus was that the Nobel was not a matter of "if" but of "when."
Thirteen years later, Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Sir Henry Hallett Dale
Henry Hallett Dale
Sir Henry Hallett Dale, OM, GBE, PRS was an English pharmacologist and physiologist. For his study of acetylcholine as agent in the chemical transmission of nerve impulses he shared the 1936 Nobel Prize in Physiology or Medicine with Otto Loewi.-Biography:Henry Hallett Dale was born in Islington,...
.
External links
- Nobel Lectures, Physiology or Medicine 1922-1941, Elsevier Publishing Company, Amsterdam, 1965.
- Kandel EREric R. KandelEric Richard Kandel is an American neuropsychiatrist who was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons...
, Schwartz JH, Jessell TM. Principles of Neural SciencePrinciples of Neural ScienceFirst published in 1981 by Elsevier, Principles of Neural Science is a neuroscience textbook edited by Eric R. Kandel, James Schwartz, and Thomas Jessell. The original edition was 468 pages; now on the fourth edition, the book has grown to 1414 pages. The second edition was published in 1985, third...
, 4th ed. McGraw-HillMcGraw-HillThe McGraw-Hill Companies, Inc., is a publicly traded corporation headquartered in Rockefeller Center in New York City. Its primary areas of business are financial, education, publishing, broadcasting, and business services...
, New York (2000). ISBN 0-8385-7701-6 - Otto Loewi Biography. Nobel Foundation.
- From the Workshop of Discoveries Porter Lecture at the University of Kansas, 1953 (University of Kansas Press, Lawrence, 1953). Full-text PDF file.