Carl F. Cori

Czech American biochemist

• Born: December 5, 1896; Prague, Austria-Hungary (now Czech Republic)
• Died: October 20, 1984; Cambridge, Massachusetts

Carl Cori and his wife, Gerty Cori, were Czech American biochemists who discovered the eponymous Cori cycle, the mechanism by which lactic acid produced during metabolism is converted to glucose in the liver.

Primary field: Biology

Specialties: Biochemistry; physiology

Early Life

Carl Ferdinand Cori was born in Prague, then part of the Austro-Hungarian Empire, on December 5, 1896. He was the second of three children born to Dr. Carl Isidor Cori, who had earned both a medical degree and a doctorate in zoology, and Maria Lippich Cori, daughter of Ferdinand Lippich, a professor of mathematical physics and the developer of the polarimeter. When Cori was two years old, the family moved to Trieste, Italy, where his father had been appointed director of the Marine Biological Station. In addition to the scientific opportunities in marine biology and oceanography provided by his father, the young Cori was exposed to the geology and history of the region, resulting in a lifelong interest in archeology. Living in Trieste, Cori was also exposed to a wide variety of ethnic and religious communities. He became fluent in Italian, one of eight languages he would learn to speak over the course of a lifetime.

From 1906 to 1914, Cori was enrolled in the Trieste Gymnasium (secondary school), where he was educated primarily in the classics. Graduating in 1914, Cori entered the German University of Prague with the intent to study medicine. Among his fellow students was Gerty Radnitz, with whom he shared both a love of science and of the outdoors. They soon began collaborating on their research.

In 1916, with Austria-Hungary engaged in World War I, Cori was drafted into the army, where he first served with the ski troops before being assigned to a bacteriological laboratory with the sanitary corps. After surviving bouts of typhoid fever and several incidents in dealing with military bureaucracy, Cori was assigned to a hospital on the Piave River near the front lines in Italy. Fluent in Italian, Cori also dealt with illness and health concerns among the local civilian population.

Life’s Work

At the end of the war in 1918, Cori returned to Prague. In 1920, he finished his medical degree and moved to Vienna, Austria, for his postdoctoral studies. In August of that year, he married Gerty Radnitz. They would have one son, Carl Thomas, born in 1936.

While in Vienna, Cori carried out research at the Pharmacological Institute at the University of Vienna while continuing his clinical work. Meanwhile, Gerty Cori carried out her own postdoctoral studies at Vienna’s Carolinen Children’s Hospital. The near-starvation conditions in Vienna—the result of the outcome of the war and the refusal of physicians to accept the dietary supplements provided by the American Relief Administration—resulted in her developing xerophthalmia, a vitamin A deficiency. She was able to overcome the condition only by returning to Prague.

Cori remained in Vienna to continue his research, a rarity given the economic crisis at the time. He was able to continue thanks to his father, who sent him a shipment of frogs to study. Moving both the frogs and his research to the University of Graz in Austria and working with German pharmacologist Otto Loewi, Cori was able to study the mechanism of seasonal variation of vagus nerve action on the heart. His data came to the attention of another German pharmacologist, Hans Horst Meyer, a retired member of the institute. Meyer recommended Cori to Dr. Harvey Gaylord, director of the State Institute for the Study of Malignant Diseases (now the Roswell Park Memorial Institute) in Buffalo, New York. Gaylord had been trying to hire a biochemist for the institute and Cori accepted his offer, arriving early in 1922.

Cori’s wife Gerty joined him shortly thereafter, where she was appointed to the pathology department at the institute. They would remain there for nine years, becoming naturalized citizens of the United States in 1928 and continuing the collaborative research that marked their professional careers—despite the resistance they encountered at having a woman on an equal level with men in the laboratory. While the Coris performed some research on the origins and causes of cancer, it was here that they began their lifelong work on carbohydrate metabolism. They published some eighty papers during their time in Buffalo.

The Coris’ interest in carbohydrate chemistry stemmed from several sources. Gerty’s father suffered from diabetes, a fatal affliction at the time. It was said he had asked Gerty to investigate the cause of abnormal glucose levels, which characterized the disease. In 1923, German physiologist Otto Warburg had observed abnormal levels of lactic acid built up in tumor cells, which coincided with Coris’ study of cancer. The Coris wanted to investigate how glucose metabolism was regulated and, in particular, how the hormones insulin and epinephrine functioned in regulation. They observed that insulin increased the conversion of glucose to glycogen in muscle, but decreased conversion in the liver. Epinephrine produced the opposite effect. Their results also suggested an intermediate to the pathway would be in the blood; lactic acid was found to be that intermediate. The interconversion of glucose and glycogen became known as the lactic acid cycle, or Cori cycle. The Coris’ subsequent 1929 publication of an extensive review of carbohydrate metabolism placed them in the forefront of the field.

In 1931, the Coris moved to St. Louis, Missouri, where Carl subsequently became chair of the Department of Pharmacology at the Washington University School of Medicine. In addition to his research, Cori was also expected to deliver thirty to forty lectures to the medical students. The Coris’ carbohydrate research in Buffalo had produced an unusual finding: the conversion of glycogen to lactic acid is also accompanied by a loss of inorganic phosphate in the tissue. Continuing this area of research in St. Louis, the Coris determined that a missing intermediate was produced: a hexose (six-carbon) sugar phosphate (glucose-1-phosphate). The sugar phosphate became known as the Cori ester, and the enzyme that catalyzed its formation was termed a phosphorylase. In 1947, the Coris were awarded the Nobel Prize in Physiology or Medicine for their discovery of the Cori cycle.

Following World War II, Cori resigned as chair of the Department of Pharmacology to accept a similar position in the Department of Biochemistry, where he remained for twenty-one years. His research during the remainder of his academic career focused on the enzymes of carbohydrate metabolism. Most of this work dealt with enzymes that function in the oxidation of sugars, such as glucose, in what is known as the glycolytic pathway, as well as enzymes involved in the metabolism of glycogen. Gerty Cori was particularly interested in what were known as glycogen-storage diseases, which she continued to work on in collaboration with her husband until her death in 1957. In 1960, Cori married Anne Fitzgerald-Jones.

In 1966, Cori retired from Washington University and moved to Harvard University in Cambridge, Massachusetts, where he was appointed Visiting Professor of Biological Chemistry at the School of Medicine. He continued his research at Massachusetts General Hospital during his last years, remaining active until his death on October 20, 1984.

Impact

The Coris’ work opened a new area of medical research, that of carbohydrate chemistry, focusing on the interconversion between glucose and glycogen. The Coris also discovered the cellular functions of the enzyme and its analogous counterparts. Prior to their research, the prevailing hypothesis was that large biological polymers could only be synthesized within a living cell. Using three purified enzymes, the Coris demonstrated that it was possible to synthesize large molecules, such as glycogen, in a test tube.

The Coris also found that a second molecule, adenosine monophosphate (AMP), is required to activate one form of the phosphorylase. This was the first example of an activator that functions in what became known as an allosteric mechanism. After identifying the first allosteric control, the Coris were able to identify other enzymes that metabolized carbohydrates.

The publications that grew out of the Coris’ collaborative research not only characterized the primary enzymes of carbohydrate metabolism but also provided the background for understanding the structure and synthesis of carbohydrates in the body. The Coris’ legacy was beyond that of their own research. The biochemical techniques they developed for purification and analysis of enzymes were adapted by their colleagues carrying out analogous research in metabolic processes.

Bibliography

Cori, Carl F. “The Call of Science.” Annual Review of Biochemistry 38 (1969): 1–21. Print. Autobiography of the author. Cori describes his life in science and the research that led to receiving the 1947 Nobel Prize.

McGrayne, Sharon Bertsch. Nobel Prize Women in Science: Their Lives, Struggles, and Momentous Discoveries. Secaucus, NJ: Carol, 1993. Print. Includes a biography of Gerty Cori and her professional and personal collaboration with her husband, Carl Cori. Emphasizes the Coris’ contributions in biochemistry.

Salway, J. G. Medical Biochemistry at a Glance. 3rd ed. Malden: Wiley-Blackwell, 2012. Print. Covers the relevance of biochemistry to clinical medicine. Summarizes metabolic pathways, including the Cori cycle and its regulation. Illustrations, index.

Worek, Michael, ed. Nobel: A Century of Prize Winners. Ontario: Firefly, 2008. Print. Profiles two hundred Nobel Prize winners, including Carl and Gerty Cori. Includes illustrations to explain scientific concepts and photographs of the laureates.