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.