Investigations by Konrad Bloch (born 1912) of the complex processes by which animal cells produce cholesterol have increased our understanding of the biochemistry of living organisms.
Konrad Bloch's research established the vital importance of cholesterol in animal cells and helped lay the groundwork for further research into treatment of various common diseases. For his contributions to the study of the metabolism of cholesterol, he was awarded the 1964 Nobel prize for Physiology or Medicine.
Konrad Emil Bloch was born on January 21, 1912 in the German town of Neisse (now Nysa, Poland) to Frederich (Fritz) D. Bloch and Hedwig Bloch. Sources list his mother's maiden name variously as Steiner, Steimer, or Striemer. After receiving his early education in local schools, Bloch attended the Technische Hochschule (technical university) in Munich from 1930 to 1934, studying chemistry and chemical engineering. He earned the equivalent of a B.S. in chemical engineering in 1934, the year after Adolf Hitler became chancellor of Germany. As Bloch was Jewish, he moved to Switzerland after graduating and lived there until 1936.
While in Switzerland, he conducted his first published biochemical research. He worked at the Swiss Research Institute in Davos, where he performed experiments involving the biochemistry of phospholipids in tubercle bacilli, the bacteria that causes tuberculosis.
In 1936, Bloch emigrated from Switzerland to the United States; he would become a naturalized citizen in 1944. With financial help provided by the Wallerstein Foundation, he earned his Ph.D. in biochemistry in 1938 at the College of Physicians and Surgeons at Columbia University, and then joined the Columbia faculty. Bloch also accepted a position at Columbia on a research team led by Rudolf Schoenheimer. With his associate David Rittenberg, Schoenheimer had developed a method of using radioisotopes (radioactive forms of atoms) as tracers to chart the path of particular molecules in cells and living organisms. This method was especially useful in studying the biochemistry of cholesterol.
Cholesterol, which is found in all animal cells, contains 27 carbon atoms in each molecule. It plays an essential role in the cell's functioning; it stabilizes cell membrane structures and is the biochemical "parent" of cortisone and some sex hormones. It is both ingested in the diet and manufactured by liver and intestinal cells. Before Bloch's research, scientists knew little about cholesterol, although there was speculation about a connection between the amount of cholesterol and other fats in the diet and arteriosclerosis (a buildup of cholesterol and lipid deposits inside the arteries).
While on Schoenheimer's research team, Bloch learned about the use of radioisotopes. He also developed, as he put it, a "lasting interest in intermediary metabolism and the problems of biosynthesis." Intermediary metabolism is the study of the biochemical breakdown of glucose and fat molecules and the creation of energy within the cell, which in turn fuels other biochemical processes within the cell.
After Schoenheimer died in 1941, Rittenberg and Bloch continued to conduct research on the biosynthesis of cholesterol. In experiments with rats, they "tagged" acetic acid, a 2-carbon compound, with radioactive carbon and hydrogen isotopes. From their research, they learned that acetate is a major component of cholesterol. This was the beginning of Bloch's work in an area that was to occupy him for many years—the investigation of the complex pattern of steps in the biosynthesis of cholesterol.
Bloch stayed at Columbia until 1946, when he moved to the University of Chicago to take a position as assistant professor of biochemistry. He stayed at Chicago until 1953, becoming an associate professor in 1948 and a full professor in 1950. After a year as a Guggenheim Fellow at the Institute of Organic Chemistry in Zurich, Switzerland, he returned to the United States in 1954 to take a position as Higgins Professor of Biochemistry in the Department of Chemistry at Harvard University. Throughout this period he continued his research into the origin of all 27 carbon atoms in the cholesterol molecule. Using a mutated form of bread mold fungus, Bloch and his associates grew the fungus on a culture that contained acetate marked with radioisotopes. They eventually discovered that the two-carbon molecule of acetate is the origin of all carbon atoms in cholesterol. Bloch's research explained the significance of acetic acid as a building block of cholesterol, and showed that cholesterol is an essential component of all body cells. In fact, Bloch discovered that all steroid-related substances in the human body are derived from cholesterol.
The transformation of acetate into cholesterol takes 36 separate steps. One of those steps involves the conversion of acetate molecules into squalene, a hydrocarbon found plentifully in the livers of sharks. Bloch's research plans involved injecting radioactive acetic acid into dogfish, a type of shark, removing squalene from their livers, and determining if squalene played an intermediate role in the biosynthesis of cholesterol. Accordingly, Bloch traveled to Bermuda to obtain live dogfish from marine biologists. Unfortunately, the dogfish died in captivity, so Bloch returned to Chicago empty-handed. Undaunted, he injected radioactive acetate into rats' livers, and was able to obtain squalene from this source instead. Working with Robert G. Langdon, Bloch succeeded in showing that squalene is one of the steps in the biosynthetic conversion of acetate into cholesterol.
Bloch and his colleagues discovered many of the other steps in the process of converting acetate into cholesterol. Feodor Lynen, a scientist at the University of Munich with whom he shared the Nobel Prize, had discovered that the chemically active form of acetate is acetyl coenzyme A. Other researchers, including Bloch, found that acetyl coenzyme A is converted to mevalonic acid. Both Lynen and Bloch, while conducting research separately, discovered that mevalonic acid is converted into chemically active isoprene, a type of hydrocarbon. This in turn is transformed into squalene, squalene is converted into anosterol, and then, eventually, cholesterol is produced.
In 1964, Bloch and his colleague Feodor Lynen, who had independently performed related research, were awarded the Nobel Prize for Physiology or Medicine "for their discoveries concerning the mechanisms and regulation of cholesterol and fatty acid metabolism." In presenting the award, Swedish biochemist Sune Bergström commented, "The importance of the work of Bloch and Lynen lies in the fact that we now know the reactions that have to be studied in relation to inherited and other factors. We can now predict that through further research in this field … we can expect to be able to do individual specific therapy against the diseases that in the developed countries are the most common cause of death." The same year, Bloch was honored with the Fritzsche Award from the American Chemical Society and the Distinguished Service Award from the University of Chicago School of Medicine. He also received the Centennial Science Award from the University of Notre Dame in Indiana and the Cardano Medal from the Lombardy Academy of Sciences the following year.
Bloch continued to conduct research into the biosynthesis of cholesterol and other substances, including glutathione, a substance used in protein metabolism. He also studied the metabolism of olefinic fatty acids. His research determined that these compounds are synthesized in two different ways: one comes into play only in aerobic organisms and requires molecular oxygen, while the other method is used only by anaerobic organisms. Bloch's findings from this research directed him toward the area of comparative and evolutionary biochemistry.
Bloch's work is significant because it contributed to creating "an outline for the chemistry of life," as E.P. Kennedy and F.M. Westheimer of Harvard wrote in Science. Moreover, his contributions to an understanding of the biosynthesis of cholesterol have contributed to efforts to comprehend the human body's regulation of cholesterol levels in blood and tissue. His work was recognized by several awards other than those mentioned above, including a medal from the Societe de Chimie Biologique in 1958 and the William Lloyd Evans Award from Ohio State University in 1968.
Bloch served as an editor of the Journal of Biological Chemistry, chaired the section on metabolism and research of the National Research Council's Committee on Growth, and was a member of the biochemistry study section of the United States Public Health Service. Bloch has also been a member of several scientific societies, including the National Academy of Sciences, to which he was elected in 1956, the American Academy of Arts and Sciences, and the American Society of Biological Chemists, in addition to the American Philosophical Society.
Bloch and his wife, the former Lore Teutsch, met in Munich and married in the United States in 1941. They have two children, Peter and Susan. Bloch is known for his extreme modesty; when he was awarded the Nobel Prize, the New York Times reported that he refused to have his picture taken in front of a sign that read, "Hooray for Dr. Bloch!" He enjoys skiing and tennis, as well as music.
Modern Men of Science, McGraw-Hill, 1966, pp. 46-47.
Nobel Prize Winners, H.W. Wilson Company, 1987, p. 104.
Kennedy, E.P. and F. H. Westheimer, "Nobel Laureates: Bloch and Lynen Win Prize in Medicine and Physiology," in Science, October 23, 1964, pp. 504-506.
New York Times, October 16, 1964, pp. 1 and 3. □
Born: January 21, 1912
Died: October 15, 2000
Konrad Bloch's investigations of the complex processes by which animal cells produce cholesterol have increased our understanding of the biochemistry of living organisms and have helped further research into treatment of various common diseases. For his contributions to the study of how the body creates cholesterol, he was awarded the 1964 Nobel Prize in Physiology or Medicine.
Early years and education
Konrad Emil Bloch was born on January 21, 1912, in the German town of Neisse (now Nysa, Poland) to Frederich (Fritz) D. Bloch and Hedwig Bloch. After receiving his early education in local schools, Bloch attended the Technische Hochschule (technical university) in Munich, Germany, from 1930 to 1934. He quickly developed an interest in organic chemistry, partly through the influence of his teacher, Hans Fischer. Also at this time he was inspired while attending lectures by leading chemists of the time, including Adolph Windaus (1876–1959), Rudolph Willstatter (1872–1942), and Heinrich Wieland (1877–1957).
He earned a degree in 1934, the year after Adolf Hitler (1889–1945) became chancellor (leader) of Germany. Bloch moved to Switzerland after graduating and lived there until 1936. While in Switzerland he conducted his first published biochemical research. He worked at the Swiss Research Institute in Davos, where he performed experiments involving the biochemistry of the bacteria (microscopic parasites) that causes tuberculosis, a deadly disease that attacks the lungs and bones.
In 1936 Bloch left Switzerland for the United States, where he earned his doctorate degree in biochemistry in 1938 at the College of Physicians and Surgeons at Columbia University. Bloch joined the school's faculty and later accepted a position at Columbia on a research team led by Rudolf Schoenheimer (1898–1941). With his associate David Rittenberg, Schoenheimer had developed a method of using radioisotopes (radioactive forms of atoms) to track the path of particular molecules in cells and living organisms. This method was especially useful in studying the biochemistry of cholesterol.
Cholesterol, which is found in all animal cells, contains twenty-seven carbon atoms in each molecule. It plays an essential role in the cell's functioning, as it stabilizes cell membrane (walls of the cell). Before Bloch's research, scientists knew little about cholesterol, although many believed there was a connection between the amount of cholesterol and other fats in the diet and arteriosclerosis (an unhealthy buildup of cholesterol deposits inside the arteries).
Conducts research on cholesterol
After Schoenheimer died in 1941, Rittenberg and Bloch continued to conduct research on cholesterol. From their research they learned that acetate (a salt of acetic acid, an important acid found in the body) is a major part of cholesterol. This was the beginning of Bloch's work for many years—the investigation of the complex pattern of steps in the cholesterol's biosynthesis, the production of complex cells from simple cells.
Between 1946 and 1954 Bloch continued his research into the origin of all twenty-seven carbon atoms in the cholesterol molecule. Bloch's research explained the significance of acetic acid as a building block of cholesterol, and showed that cholesterol is an essential component of all body cells. In fact, Bloch discovered that all steroid-related substances (hormones, or substances released by organs for the organic process) in the human body are derived from cholesterol.
In 1941, Bloch married Lore Teutsch, whom he met in Munich. They had two children, Peter and Susan.
Awarded Nobel Prize
In 1964 Bloch and his colleague Feodor Lynen, who had independently performed related research, were awarded the Nobel Prize for Physiology or Medicine. The same year Bloch was honored with the Fritzsche Award from the American Chemical Society and the Distinguished Service Award from the University of Chicago School of Medicine.
Bloch's work is significant because it contributed to creating "an outline for the chemistry of life," as E. P. Kennedy and F. M. Westheimer of Harvard wrote in Science.More importantly, his contributions to understanding the biosynthesis of cholesterol have contributed to efforts to understand the human body's regulation of cholesterol levels in blood and tissue.
Bloch was known for his extreme modesty. When he was awarded the Nobel Prize, the New York Times reported that he refused to have his picture taken in front of a sign that read, "Hooray for Dr. Bloch!" On October 15, 2000, Bloch died of heart failure at the Lahey Clinic in Burlington, Massachusetts. He was eighty-eight years old.
According to the Harvard University Gazette, Dean Jeremy R. Knowles called Bloch, "a marvelously perceptive biochemist and genius," and added that Bloch's "deep understanding of metabolism laid the chemical foundations of today's biology."
For More Information
Modern Men of Science. New York: McGraw-Hill, 1966, pp. 46–47.
Nobel Prize Winners. New York: H. W. Wilson Co., 1987, p 104.
Kennedy, E. P. and F. H. Westheimer. "Nobel Laureates: Bloch and Lynen Win Prize in Medicine and Physiology." Science (October 23, 1964): pp. 504–506.
Bloch, Konrad Emil
BLOCH, Konrad Emil
(b. 21 January 1912 in Neisse, Germany [now Poland]; d. 15 October 2000 in Burlington, Massachusetts), Nobel Prize–winning scientist whose discovery of the basic steps in cholesterol synthesis would ultimately lead to a lowering of the death rate from coronary artery disease.
The son of Fritz Bloch and Hedwig Streimer, Bloch studied at the Technische Hochschule in Munich, Germany, where he was drawn to organic chemistry, especially the structure of natural products. Bloch, who was Jewish, left Munich in 1934, the year after Adolf Hitler became chancellor of Germany and the Nazi authorities told him that he must end his studies. With a degree in chemical engineering (1934), he moved to Davos, Switzerland, and worked in a tuberculosis sanitarium, where he investigated the phospholipids of tubercle bacilli.
After immigrating to the United States in 1936, Bloch joined the Department of Biochemistry at Columbia University and studied under Hans T. Clarke. He received his Ph.D. in 1938, joined Rudolf Schoenheimer's laboratory, and became interested in intermediary metabolism and problems of biosynthesis. The following year, Bloch and collaborator David Rittenberg initiated the work on the biological synthesis of cholesterol that was to occupy much of his subsequent career. Naturalized as a U.S. citizen in 1944, Bloch accepted an appointment at the University of Chicago in 1946. In 1954 he was appointed Higgins Professor of Biochemistry in the Department of Chemistry at Harvard University, and became chairman of the department in 1968.
Bloch and Feodor Lynen, who was on the faculty of the Max Planck Institute in Munich, received the Nobel Prize in medicine and physiology in 1964 for their work on cholesterol and fatty acid metabolism. Although cholesterol had been isolated nearly 200 years earlier from human gallstones and its chemical structure had been elucidated during the first two decades of the twentieth century, scientists knew little about how cholesterol is formed.
Bloch's research focused on the biosynthesis within the body that turned acetic acid into cholesterol. Using the radioisotope carbon-14, Bloch, in collaboration with David Rittenberg, confirmed that cholesterol was, in part, derived from the two-carbon acetate molecule. In experiments with rat livers, Bloch and colleagues identified the hydrocarbon squalene, which is produced in the liver, as an intermediate in cholesterol synthesis. A terpene (a hydrocarbon found in essential oils) with an open chain of thirty carbon atoms, squalene begins the folding necessary to produce the four rings of cholesterol. Bloch also discovered many of the other thirty-six overall steps needed to convert acetate (a salt or ester of acetic acid) into cholesterol. These steps are of vital importance, because malfunctions in the process of formation and metabolism of lipids are at the root of many cardiovascular diseases. At the time, death from cardiovascular disease was reaching what would turn out to be an all-time high. As a result, the Nobel Prize citation read, in part: "Circulatory diseases are the foremost cause of death in many parts of the world and the therapy against these diseases will in the future rest upon the firm foundation laid by professors Bloch and Lynen."
Bloch's research would be a vital factor in the 40 to 50 percent decrease in coronary heart disease that occurred in the United States after the late 1960s. For example, Bloch's discoveries concerning the steps that lead from the production of acetic acid to the production of cholesterol were of fundamental importance in the subsequent discovery of drugs called statins, which are used to treat high cholesterol by interfering with cholesterol synthesis. Bloch's research also showed that cholesterol is a vital component of all body cells and that it is a precursor of bile acids and one of the female sex hormones.
After winning the Nobel Prize, Bloch, an extremely modest man, refused to have his picture taken in front of a sign that read, "Hooray for Dr. Bloch!" Nevertheless, Bloch's extraordinary contribution to science and mankind was also recognized in 1964 with the Fritzsche Award from the American Chemical Society, as well as the Distinguished Service Award from the University of Chicago School of Medicine. In 1965, the University of Notre Dame honored him with the Centennial Science Award, and the Lombardy Academy of Sciences awarded him the Cardano Medal.
Despite his commitment to research, Bloch avoided the competition and animosity that often results from scientists "competing" to make new and important discoveries. His daily routine included visiting the laboratories of his coworkers to talk about their work and latest findings and to foster a spirit of cooperation. Bloch was also a dedicated teacher throughout the 1960s and beyond. Thousands of Harvard students took his basic biochemistry course, and many of them went on to become scientists and scholars.
Bloch continued to conduct research into the biosyn-thesis of cholesterol and other substances, including glutathione, a substance used in protein metabolism; the metabolism of olefinic fatty acids; and comparative and evolutionary biochemistry. A former associate editor of the Journal of Biological Chemistry, Bloch authored hundreds of scientific papers dealing with the metabolism of proteins and amino acids. He also wrote the popular 1997 book Blondes in Venetian Paintings, the Nine-banded Armadillo, and Other Essays in Biochemistry, in which he discussed various aspects of biochemistry and explained the chemical basis for numerous biological processes.
Bloch died at the age of eighty-eight in a Massachusetts hospital due to complications from congestive heart failure. He was survived by his wife of fifty-nine years, Lore, a Munich native to whom he was married on 15 February 1941. They had two children.
A source of information on the specifics of Bloch's cholesterol research is E. P. Kennedy and F. H. Westheimer, "Nobel Laureates: Bloch and Lynen Win Prize in Medicine and Physiology," Science (23 Oct. 1964): 504–506. A detailed description of the cholesterol research conducted by Bloch and colleagues can be found in Bloch's article "Summing Up," Annual Reviews of Biochemistry 56 (1987): 1–19. An obituary is in Nature 409 (Feb. 2001).
BLOCH, KONRAD (1912–2000), U.S. biochemist and Nobel laureate. Bloch was born in Neisse, Germany (now Poland) and graduated from the Technische Hochschule of Munich in 1934. Forced to leave because he was Jewish, Bloch found a temporary position at the Schweizerische Forschungsinstitut in Davos, Switzerland. In 1936 he immigrated to the United States (becoming an American citizen in 1944) and joined the Department of Biochemistry, College of Physicians and Surgeons, Columbia University. New York. After obtaining his doctorate at Columbia University in 1938, he became a member of the staff there. His collaboration with R. *Schoenheimer stimulated his interest in the biological origin of cholesterol and he began to concentrate on this field in 1941. In 1942 Bloch and David Rittenberg discovered that the two-carbon compound acetic acid was the major building block in the 30 or more steps in the biosynthesis (natural formation) of cholesterol, a waxlike alcohol found in animal cells. In his search to determine how acetic acid molecules combine in this process, Bloch was also joined by Feodor Lynen and his collaborators in Munich and Sir John Warcup Cornforth and George Popják in England. Their discovery facilitated medical research on the relation of blood cholesterol levels to atherosclerosis; research in physiology; and research on the chemistry of terpenes, rubber, and other isoprene derivatives. In 1946 Bloch joined the University of Chicago, becoming professor of biochemistry in 1952. During his years at Chicago Bloch investigated the enzymatic synthesis of the tripeptide glutathione. As a Guggenheim fellow he spent the year 1953 at the Organisch-Chemisches Institut, Eidgenössische Technische Hochschule, in Zurich with L. Ruzicka, V. Prelog, and their colleagues. In 1954 Bloch was appointed Higgins Professor of Biochemistry in the Department of Chemistry, Harvard University, and in 1968 he became chairman of the department. He continued research on various aspects of terpene and sterol biogenesis, going on as well to the enzymatic formation of unsaturated fatty acids and biochemical evolution. He became emeritus professor in 1982. Bloch shared the 1964 Nobel Prize in physiology and medicine with Feodor Lynen for discoveries concerning the synthesis of cholesterol by the body from acetic acid.
He was a member of the American Chemical Society, U.S. National Academy of Sciences, American Academy of Arts and Sciences, and American Society of Biological Chemists, among others. He was associated with the Committee on Growth of the American Cancer Society, the Biochemical Section of the U.S. Public Health Service, and the National Institute of Neurological Diseases and Blindness. He served as an associate editor of the Journal of Biological Chemistry and published hundreds of papers. Apart from the topics mentioned, these dealt with creatinine, glutathione, amino acids generally, proteins, and several metabolic processes.
Chemical and Engineering News, 42 (Oct. 26, 1964), 34.
[Samuel Aaron Miller /
Ruth Rossing (2nd ed.)]