ACS Honors Work of Carl and Gerty Cori

In his essay "remembering our Teachers" [J. Biol. Chem., 276, 3 (2001)], Arthur Kornberg of Stanford University reflected on his mentors Carl and Gerty Cori, their contributions in biochemistry, and the vicissitudes of the field. He wrote: "The spotlight on the biochemistry stage moves rapidly, leaving a star of yesterday in the dark and virtually forgotten. A substance, a procedure, or a biochemical event named after the star is eventually renamed and what seemed an assurance of immortality is gone. This has been the fate of the Cori cycle, the Cori ester, and of Carl and Gerty Cori as well."

Kornberg and Mildred Cohn--another of the Coris' more famous students--and more than 300 other attendees who sought to rekindle the memory of these stars, were on hand as the American Chemical Society designated as a National Historic Chemical Landmark the Coris' groundbreaking research on how the human body metabolizes glucose. The ceremony was held last month in St. Louis at the Washington University School of Medicine, where the Coris conducted much of their later research.

ACS President Charles P. Casey, a St. Louis native, was particularly delighted to be back home. In a brief address, he explained that "beginning in the 1920s, Carl and Gerty Cori conducted a series of pioneering studies that led to our current understanding of the metabolism of sugars. They elucidated the Cori cycle, the process by which the body reversibly converts glucose and glycogen, the polymeric storage form of this sugar," he said.

Furthermore, the couple isolated and purified many of the enzymes involved in glucose metabolism. "The work of the Coris advanced understanding of glycogen breakdown in cells and of metabolic regulation. Building on their work, others developed improved techniques to control diabetes," Casey said. He then presented a commemorative bronze plaque to chemist Mark Wrighton, chancellor of Washington University.

CARL CORI and Gerty Radnitz were both born in Prague in 1896. They met in Vienna while they were attending medical school and married in 1920. In the face of unrelenting anti-Semitism (Gerty was Jewish) and entrenched sexism, the young couple immigrated to the U.S. in 1922. They got jobs at the Institute for the Study of Malignant Diseases in Buffalo, N.Y., since renamed Roswell Park Memorial Institute. There, according to Kornberg, "they developed quantitative and precise methods to discover connections among what seemed then to be unconnected metabolic events: glucose converted to lactic acid during muscle contraction and stored as glycogen until needed again. The cycling of lactic acid and glucose between liver glycogen and muscle operated under the influence of hormones, including epinephrine and the newly discovered insulin." The Coris moved to St. Louis in 1931 when Carl accepted the chairmanship of the pharmacology department at Washington University School of Medicine. Gerty took a position as a researcher in the same department. In 1946, Carl became head of the school's department of biological chemistry. They were awarded the Nobel Prize in Physiology or Medicine in 1947.

By all accounts, the Coris were remarkable mentors, working with many researchers, "six more of whom would receive Nobel Prizes based on the training and outlook received at that time from the Coris and the ambience around them," Kornberg noted. The Coris-trained laureates are Severo Ochoa and Kornberg (Physiology or Medicine, 1959), Luis F. Leloir (Chemistry, 1970), Earl W. Sutherland Jr. (Physiology or Medicine, 1971), Christian de Duve (Physiology or Medicine, 1974), and Edwin G. Krebs (Physiology or Medicine, 1992).

The Coris had a truly collaborative relationship. Carl Cori summed up the nature of their partnership in his remarks at the Nobel banquet in 1947: "Our collaboration began 30 years ago when we were still medical students at the University of Prague and has continued ever since. Our efforts have been largely complementary, and one without the other would not have gone as far as in combination."

Gerty Cori died in 1957. In 1960, Carl married Anne Fitzgerald-Jones and in 1966, after retiring from Washington University, was appointed a visiting professor at Harvard Medical School. Carl Cori died in 1984.

Following the landmark ceremony, Kornberg gave Washington University's annual Carl & Gerty Cori Lecture. Kornberg, who spent the bulk of his career elucidating mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid, has switched the focus of his research from DNA replication to an entirely new subject: inorganic polyphosphate (poly P). He lectured on his work with the Coris and on poly P in biological systems.

Poly P is a linear polymer of many tens or hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. "Likely a prominent precursor in prebiotic evolution, poly P is now found in volcanic condensates, deep-oceanic steam vents, and in every living thing--bacteria, fungi, protozoa, plants, and mammals. Ignored in textbooks and dismissed as a 'molecular fossil,' our work has brought this molecule back to life," Kornberg said with great enthusiasm.

"The Cori cycle and the Cori ester have been renamed, and attributions to the Coris are reasonably buried in the dustbin of history. But the lives of Carl and Gerty Cori and their monumental achievements deserve to be remembered as much as those of the political, military, arts, and sports stars of their era," Kornberg said.