Gerty T. Cori

The scientist Gerti T. Cory (1896-1957) made important discoveries in biochemistry, especially carbohydrate metabolism, and in 1947, along with her husband, received the Nobel Prize in medicine or physiology. She later studied glycogen storage diseases and the role of enzymes in sugar metabolism.

Collaborating with her husband, scientist Gerty T. Cori made important discoveries about the human body's metabolism of sugar. She won the Nobel Prize in physiology or medicine in 1947 and later went on to study diseases known as glycogen storage disorders, demonstrating the significant role enzymes play in metabolism.

Gerty T. Cori made significant contributions in two major areas of biochemistry, which increased understanding of how the body stores and uses sugars and other carbohydrates. For much of her early scientific career, Cori performed pioneering work on sugar metabolism (how sugars supply energy to the body), in collaboration with her husband, Carl Ferdinand Cori. For this work they shared the 1947 Nobel Prize in physiology or medicine with Bernardo A. Houssay, who had also carried out fundamental studies in the same field. Cori's later work focused on a class of diseases called glycogen storage disorders. She demonstrated that these illnesses are caused by disruptions in sugar metabolism. Both phases of Gerty Cori's work illustrated for other scientists the importance of studying enzymes (special proteins that permit specific biochemical reactions to take place) for understanding normal metabolism and disease processes.

Gerty Theresa Radnitz was the first of three girls born to Otto and Martha Neustadt Radnitz. She was born in Prague, then part of the Austro-Hungarian Empire, on August 15, 1896. Otto was a manager of sugar refineries. It is not known if his work helped shape his eldest daughter's early interest in chemistry and later choice of scientific focus. However, her maternal uncle, a professor of pediatrics, did encourage her to pursue her interests in science. Gerty was first taught by tutors at home, then enrolled in a private girls' school. At that time, girls were not expected to attend a university. In order to follow her dream of becoming a chemist, Gerty first studied at the Tetschen Realgymnasium. She then had to pass a special entrance exam (matura) that tested her knowledge of Latin, literature, history, mathematics, physics, and chemistry.

In 1914 Gerty Radnitz entered the medical school of the German University of Prague (Ferdinand University). There she met a fellow classmate, Carl Ferdinand Cori, who shared her interest in doing scientific research. Together they studied human complement, a substance in blood that plays a key role in immune responses by combining with antibodies. This was the first of a lifelong series of collaborations. In 1920 they both graduated and received their M.D. degrees.

Shortly after graduating, they moved to Vienna and married. Carl worked at the University of Vienna's clinic and the University of Graz's pharmacology department, while Gerty took a position as an assistant at the Karolinen Children's Hospital. Some of her young patients suffered from a disease called congenital myxedema, in which deposits form under the skin and cause swelling, thickening, and paleness in the face. The disease is associated with severe dysfunction of the thyroid gland, located at the base of the neck, which helps to control many body processes, including growth. Gerty's particular research interest was in how the thyroid influenced body temperature regulation.

Immigrates to United States

In the early 1920s, Europe was in the midst of great social and economic unrest in the wake of World War I, and in some regions, food was scarce; Gerty suffered briefly from malnourishment while working in Vienna. Faced with these conditions, the Coris saw little hope there for advancing their scientific careers. In 1922 Carl moved to the United States to take a position as biochemist at the New York State Institute for the Study of Malignant Diseases (later the Roswell Park Memorial Institute). Gerty joined him in Buffalo a few months later, becoming an assistant pathologist at the institute.

Life continued to be difficult for Gerty Cori. She was pressured to investigate malignant diseases, specifically cancers, which were the focus of the institute. Both she and Carl did publish studies related to malignancies, but studying cancer was not to be the focus of either Gerty's or Carl's work. During these early years in the United States, the Coris' publications covered topics from the biological effects of X rays to the effects of restricted diets on metabolism. Following up on her earlier work on the thyroid, Gerty published a report on the influence of thyroid extract on paramecium population growth, her first publication in English.

Colleagues cautioned Gerty and Carl against working together, arguing that collaboration would hurt Carl's career. However, Gerty's duties as an assistant pathologist allowed her some free time, which she used to begin studies of carbohydrate metabolism jointly with her husband. This work, studying how the body burns and stores sugars, was to become the mainstream of their collaborative research. During their years in Buffalo, the Coris jointly published a number of papers on sugar metabolism that reshaped the thinking of other scientists about this topic. In 1928 Gerty and Carl Cori became naturalized citizens of the United States.

In 1931 the Coris moved to St. Louis, Missouri, where Gerty took a position as research associate at Washington University School of Medicine; Carl was a professor there, first of pharmacology and later of biochemistry. The Coris' son, Carl Thomas, was born in 1936. Gerty become a research associate professor of biochemistry in 1943 and in 1947 a full professor of biochemistry. During the 1930s and 1940s the Coris continued their work on sugar metabolism. Their laboratory gained an international reputation as an important center of biochemical breakthroughs. No less than five Nobel laureates spent parts of their careers in the Coris' lab working with them on various problems.

For their pivotal studies in elucidating the nature of sugar metabolism, the Cori's were awarded the Nobel Prize for physiology or medicine in 1947. They shared this honor with Argentine physiologist Bernardo A. Houssay, who discovered how the pituitary gland functions in carbohydrate metabolism. Gerty Cori was only the third woman to receive a Nobel Prize in science. Previously, only Marie Curie and Iréne Joloit-Curie had been awarded such an honor. As with the previous two women winners, Cori was a co-recipient of the prize with her husband.

Significance of the Coris' Research

In the 1920s, when the Coris began to study carbohydrate metabolism, it was generally believed that the sugar called glucose (a type of carbohydrate) was formed from another carbohydrate, glycogen, by the addition of water molecules (a process known as hydrolysis). Glucose circulates in the blood and is used by the body's cells in virtually all cellular processes that require energy. Glycogen is a natural polymer (a large molecule made up of many similar smaller molecules) formed by joining together large numbers of individual sugar molecules for storage in the body. Glycogen allows the body to function normally on a continual basis, by providing a store from which glucose can be broken down and released as needed.

Hydrolysis is a chemical process that does not require enzymes. If, as was believed to be the case in the 1920s, glycogen were broken down to glucose by simple hydrolysis, carbohydrate metabolism would be a very simple, straightforward process. However, in the course of their work, the Coris discovered a chemical compound, glucose-1-phosphate, made up of glucose and a phosphate group (one phosphorus atom combined with three oxygen atoms—sometimes known as the Cori ester) that is derived from glycogen by the action of an enzyme, phosphorylase. Their finding of this intermediate compound, and of the enzymatic conversion of glycogen to glucose, was the basis for the later understanding of sugar metabolism and storage in the body. The Coris' studies opened up research on how carbohydrates are used, stored, and converted in the body.

Cori had been interested in hormones (chemicals released by one tissue or organ and acting on another) since her early thyroid research in Vienna. The discovery of the hormone insulin in 1921 stimulated her to examine its role on sugar metabolism. Insulin's capacity to control diabetes lent great clinical importance to these investigations. In 1924 Gerty and Carl wrote about their comparison of sugar levels in the blood of both arteries and veins under the influence of insulin. At the same time, inspired by earlier work by other scientists (and in an attempt to appease their employer), the Coris examined why tumors used large amounts of glucose.

Their studies on glucose use in tumors convinced the Coris that much basic research on carbohydrate metabolism remained to be done. They began this task by examining the rate of absorption of various sugars from the intestine. They also measured levels of several products of sugar metabolism, particularly lactic acid and glycogen. The former compound results when sugar combines with oxygen in the body.

The Coris measured how insulin affects the conversion of sugar into lactic acid and glycogen in both the muscles and liver. From these studies, they proposed a cycle (called the Cori cycle in their honor) that linked glucose with glycogen and lactic acid. Their proposed cycle had four major steps: (1) blood glucose becomes muscle glycogen, (2) muscle glycogen becomes blood lactic acid, (3) blood lactic acid becomes liver glycogen, and (4) liver glycogen becomes blood glucose. Their original proposed cycle has had to be modified in the face of subsequent research, a good deal of which was carried out by the Coris themselves. For example, scientists learned that glucose and lactic acid can be directly inter-converted, without having to be made into glycogen. Nonetheless, the Coris' suggestion generated much excitement among carbohydrate metabolism researchers. As the Coris' work continued, they unraveled more steps of the complex process of carbohydrate metabolism. They found a second intermediate compound, glucose-6-phosphate, that is formed from glucose-1-phosphate. (The two compounds differ in where the phosphate group is attached to the sugar.) They also found the enzyme that accomplishes this conversion, phosphoglucomutase.

By the early 1940s the Coris had a fairly complete picture of carbohydrate metabolism. They knew how glycogen became glucose. Rather than the simple non-enzymatic hydrolysis reaction that, twenty years earlier, had been believed to be responsible, the Coris' studies painted a more elegant, if more complicated picture. Glycogen becomes glucose-1-phosphate through the action of one enzyme (phosphorylase). Glucose-1-phosphate becomes glucose-6-phosphate through the action of another enzyme (phosphoglucomutase). Glucose-6-phosphate becomes glucose, and glucose becomes lactic acid, each step in turn mediated by one specific enzyme. The Coris' work changed the way scientists thought about reactions in the human body, and it suggested that there existed specific, enzyme-driven reactions for many of the biochemical conversions that constitute life.

Resumes Early Interest in Pediatric Medicine

In her later years, Cori turned her attention to a group of inherited childhood diseases known collectively as glycogen storage disorders. She determined the structure of the highly branched glycogen molecule in 1952. Building on her earlier work on glycogen and its biological conversions via enzymes, she found that diseases of glycogen storage fell into two general groups, one involving too much glycogen, the other, abnormal glycogen. She showed that both types of diseases originated in the enzymes that control glycogen metabolism. This work alerted other workers in biomedicine that understanding the structure and roles of enzymes could be critical to understanding diseases. Here again, Cori's studies opened up new fields of study to other scientists. In the course of her later studies, Cori was instrumental in the discovery of a number of other chemical intermediate compounds and enzymes that play key roles in biological processes.

At the time of her death, on October 26, 1957, Cori's influence on the field of biochemistry was enormous. She had made important discoveries and prompted a wealth of new research, receiving for her contributions, in addition to the Nobel Prize, the prestigious Garvan Medal for women chemists of the American Chemical Society as well as membership in the National Academy of Sciences. As the approaches and methods that she helped pioneer continue to result in increased scientific understanding, the importance of her work only grows greater.

Further Reading

Cori, Carl F., American Chemists and Chemical Engineers: Gerty Theresa Cori, American Chemical Society, 1976.

Dictionary of Scientific Biography, Scribner, 1971.

Magill, Frank N., The Nobel Prize Winners, Physiology or Medicine: 1944-1969, Salem Press, 1991 □

Cori, Gerty Theresa Radnitz

(b. Prague, Austria-Hungary [now Czechoslovakia], 15 August 1896; d. St. Louis, Missouri, 26 October 1957),

biochemistry.

The daughter of Otto and Martha Radnitz, Gerty Cori graduated from a school for girls in 1912. Since she wished to study chemistry, she was obliged to prepare for the university entrance examination (matura). After passing the examination at the Tetschen Realgymnasium in Prague she entered the medical school of the German University of Prague (Ferdinand University) in 1914. She received the M.D. degree in 1920 and married a fellow student, Carl Ferdinand Cori, in August of the same year. After two years at the Karolinen Children’s Hospital in Vienna, where she worked on the problem of temperature regulation in a case of congenital myxedema before and after thyroid therapy, she came to the United States to join her husband at the New York State Institute for the Study of Malignant Diseases in Buffalo, New York. In 1931 the Coris went to the Washington University School of Medicine in St. Louis, Missouri, where Gerty Cori was appointed research associate in the department of pharmacology. In 1946 the Coris moved to the department of biochemistry at the same university, and in 1947 Gerty Cori became professor of biochemistry, the post she occupied at her death. She had one son, C. Thomas Cori, born in 1936.

At Buffalo, in spite of institutional pressure for Gerty Cori to work on selected aspects of cancer, the Coris initiated a close collaboration in research on the metabolism of carbohydrates in animals. Their first joint report on this subject appeared in 1923; and during the succeeding dozen years they described, in a series of important papers, the effects of the hormones epinephrine and insulin on carbohydrate metabolism. During the course of this work the Coris demonstrated that epinephrine increases the rate of conversion of liver glycogen to glucose, an effect counteracted by insulin, and also that epinephrine increases the rate of conversion of muscle glycogen to lactate, with the formation of hexosemonophosphate. A closer study of the hexosemonophosphate led the Coris to discover and to isolate, in 1936, a new phosphorylated intermediate (glucose-1-phosphate) in carbohydrate metabolism. In 1938 they described its enzymatic interconversion with glucose-6-phosphate, already known to be formed by the phosphorylation of glucose in an enzyme-catalyzed reaction involving adenosine triphosphate (ATP). The Coris then demonstrated that the formation of glucose-1-phosphate from glycogen is effected by a new enzyme, phosphorylase, that catalyzes the cleavage and synthesis of polysaccharides. Before these discoveries had been made, it was widely believed that the metabolic breakdown of glycogen involved its hydrolysis to glucose; the Coris showed the existence of an enzymatic mechanism for the phosphorolysis of the glycosidic bonds of a polysaccharide.

The crystallization and characterization of rabbit muscle phosphorylase (fully described in 1943) laid the groundwork for later studies by the Coris and others on the hormonal control of its enzymatic activity. Furthermore, the Coris identified and isolated other enzymes involved in the formation and breakdown of the highly branched glycogen molecule; this knowledge made it possible for them to effect the first synthesis of glycogen in the test tube. For these achievements Carl and Gerty Cori were awarded the 1947 Nobel Prize in physiology or medicine, which they shared with Bernardo A. Houssay of Argentina. Gerty Cori was the third woman to receive a Nobel Prize in science, the other two being Marie Curie and Irene Joliot-Curie.

In subsequent work Gerty Cori used the enzymes involved in the biological cleavage of glycogen as tools for the chemical definition of its molecular structure. This was achieved in 1952, almost exactly 100 years after the discovery of glycogen by Claude Bernard. The insights into the chemistry of glycogen, and of the enzymes concerned with its biological transformations, made it possible for Gerty Cori to illuminate in 1953 the nature of the glycogen storage diseases in children. She recognized two groups of disorders, one involving excessive amounts of normal glycogen and the other characterized by abnormally branched glycogen, and showed them to be a consequence of deficiencies or changes in particular enzymes of the metabolic pathway. Gerty Cori’s work thus demonstrated the central importance of the isolation and characterization of individual enzymes, both for the structural definition of the macromolecules on which they act and for the understanding of dysfunctions of metabolic processes in which these enzymes participate.

BIBLIOGRAPHY

I. Original Works. Among Gerty Cori’s most important papers are “The Formation of Hexosephosphate Esters in Frog Muscle,” in Journal of Biological Chemistry, 116 (1936), 119–128, written with C. F. Cori; “Crystalline Muscle Phosphorylase. II. Prosthetic Group,” ibid., 151 (1943), 31–38, written with A. A. Green; “Crystalline Muscle Phosphorylase. III. Kinetics,” ibid., 39–55, written with C. F. Cori and A.A. Green; “The Enzymatic Conversion of Phosphorylase a to b,” ibid., 158 (1945), 321–332, written with C. F. Cori; “Action of Amylo-1, 6-Glucosidase and Phosphorylase on Glycogen and Amylopectin,” ibid., 188 (1951), 17–29, written with J. Larner; “Glucose-6-phosphatase of the Liver in Glycogen Storage Disease,” ibid., 199 (1952), 661–667, written with C. F. Cori; and “Glycogen Structure and Enzyme Deficiencies in Glycogen Storage Disease,” in Harvey Lectures, 48 (1952–1953), 145–171.

II. Secondary Literature. On Gerty Theresa Cori or her work, see C. F. Cori, “The call of Science,” in Annual Review of Biochemistry, 38 (1969), 1–20; B. A. Houssay, “Carl F. and Gerty T. Cori,” in Biochimica et biophysica acta, 20 (1956), 11–16; and S. Ochoa and H. M. Kalckar, “Gerty T. Cori, Biochemist,” in Science, 128 (1958), 16–17.

Joseph S. Fruton

CORI, GERTY THERESA

CORI, GERTY THERESA (née Radnitz ; 1896–1957), Nobel laureate in medicine and physiology. Cori was born in Prague, where she graduated in medicine from the German University in 1920. That year she married her fellow student and lifelong scientific collaborator, Carl Cori, and converted to Catholicism from Judaism. The Coris joined the staff of the New York State Institute for the Study of Malignant Disease in Buffalo, New York (1922–31), before moving to Washington University, St. Louis, in 1931 where she was professor of biochemistry from 1947 until her death. The Coris became U.S. citizens in 1928. They were awarded the Nobel Prize in 1947 (shared with Bernardo Houssay) for their work on carbohydrate metabolism in which they discovered how glucose is stored as glycogen in the liver and muscles, and broken down to glucose as an energy source (a process termed the Cori cycle). They also described the effects of insulin and other hormones on glucose metabolism. The Coris' honors included election to the U.S. National Academy of Sciences.

[Michael Denman (2^nd ed.)]