Succeeding in Science Despite the Odds; Studying Metabolism with NMR by Mildred Cohn
Year: 2004
Type: article
Abstract: A Study of Oxidative Phosphorylation with O18-labeled Inorganic Phosphate (Cohn, M. (1953) J. Biol. Chem. 201, 735–750) Nuclear Magnetic Resonance Spectra of Adenosine Di- and Triphosphate. II. Effect of Complexing with Divalent Metal Ions (Cohn, M., and Hughes, T. R. (1962) J. Biol. Chem. 237, 176–181) Mildred Cohn was born in New York City in 1913. When she was young, her father told her she could achieve anything she chose to, but not without some difficulty because she was both female and Jewish. With her parents' encouragement, Cohn moved rapidly through the New York public school system and graduated from high school at age 14. She decided to go to Hunter College in Manhattan, then an all-girls college, and majored in chemistry and minored in physics. Hunter's attitude toward science education at that time can be summed up by the chairman of the chemistry department who declared that it was not ladylike for women to be chemists and that his sole purpose was to prepare his students to become chemistry teachers. When Cohn graduated from Hunter College in 1931 she tried to get a scholarship for graduate studies in chemistry but was unsuccessful. She enrolled in Columbia University nonetheless and used her savings to pay for her education. At Columbia, she studied under Nobel laureate Harold Urey but had to drop out after a year because of lack of money. She then took a job with the National Advisory Committee of Aeronautics and after a few years was able to earn enough money to return to Columbia. Working with Urey, she studied ways of separating different isotopes of carbon and received her Ph.D. in physical chemistry in 1937. Unfortunately, jobs were scarce in 1938, during the years of the Great Depression, and academic positions for women were even more scarce. Industrial recruiters regularly posted notices announcing that, “Mr. X of Y Company will interview prospective doctorate recipients—Male, Christian”(1Wasserman E. The Door in the Dream: Conversations with Eminent Women in Science. Joseph Henry Press, Washington, D. C.2000: 43-46Google Scholar). 1All biographical information on Mildred Cohn was taken from Refs. 1Wasserman E. The Door in the Dream: Conversations with Eminent Women in Science. Joseph Henry Press, Washington, D. C.2000: 43-46Google Scholar and 4Person First Cohn Mildred The Scientist. 2003; 17: 16Google Scholar.1All biographical information on Mildred Cohn was taken from Refs. 1Wasserman E. The Door in the Dream: Conversations with Eminent Women in Science. Joseph Henry Press, Washington, D. C.2000: 43-46Google Scholar and 4Person First Cohn Mildred The Scientist. 2003; 17: 16Google Scholar. With Urey's help, Cohn was able to obtain a postdoctoral position at George Washington University with future Nobel prize winner Vincent du Vigneaud. In du Vigneaud's laboratory, Cohn pioneered the effort to use isotopic tracers to follow the metabolism of sulfur-containing compounds, the subject of a previous Journal of Biological Chemistry (JBC) Classic (2JBC Classics Du Vigneaud V. Cohn M. Chandler J.P. Schenck J.R. Simmonds S. J. Biol. Chem. 1941; 140 (http://www.jbc.org/cgi/content/full/279/51/e11): 625-641Abstract Full Text PDF Google Scholar). Cohn worked with du Vigneaud for 9 years and moved with him to New York when he went to Cornell Medical College. In 1946, Cohn went to Washington University in St. Louis to work with Carl and Gerty Cori, Nobel prize laureates and authors of a previous JBC Classic (3JBC Classics Cori C.F. Cori G.T. J. Biol. Chem. 1928; 79: 321-341Abstract Full Text PDF Google ScholarCori G.T. Colowick S.P. Cori C.F. J. Biol. Chem. 1938; 124: 542-555Abstract Full Text PDF Google ScholarCori G.T. Colowick S.P. Cori C.F. J. Biol. Chem. 1939; 127: 771-782Abstract Full Text PDF Google ScholarGreen A.A. Cori G.T. J. Biol. Chem. 1943; 151: 21-29Abstract Full Text PDF Google ScholarCori G.T. Green A.A. J. Biol. Chem. 1943; 151 (http://www.jbc.org/cgi/content/full/277/29/e18): 31-38Abstract Full Text PDF Google Scholar), who were studying biological catalysts. There, she did independent research, mainly focusing on using isotopes and NMR to study metabolic processes. Cohn was promoted to Associate Professor in Biochemistry in 1958 but left Washington University 2 years later to move to the University of Pennsylvania School of Medicine. She became a full Professor in 1961 and retired as Benjamin Rush Professor Emerita of Biochemistry and Biophysics in 1982. Once, when asked what her most exciting scientific moments were (4Person First Cohn Mildred The Scientist. 2003; 17: 16Google Scholar), Cohn replied, “In 1958, using nuclear magnetic resonance, I saw the first three peaks of ATP (5Cohn M. Hughes T.R. Phosphorus magnetic resonance spectra of adenosine diphosphate and triphosphate. I. Effect of pH.J. Biol. Chem. 1960; 235: 3250-3253Abstract Full Text PDF PubMed Google Scholar). That was exciting. [I could] distinguish the three phosphorus atoms of ATP with a spectroscopic method, which had never been done before. Another paper, in 1962 (the second JBC Classic reprinted here), was about the effect of metal ions on the phosphorus spectrum of ATP. And earlier, I found that oxygen in inorganic phosphate exchanged with water through oxidative phosphorylation (the first JBC Classic reprinted here).” Cohn's study of oxidative phosphorylation came at a time when it was known that phosphorylation occurred concomitantly with oxidation in the electron transport chain. However, no one had yet discovered the nature of the interaction of the electron transport system with phosphate or any part of the phosphorylating system. Cohn approached this problem by tracking the loss of O18 from inorganic phosphate during oxidative phosphorylation in rat liver mitochondria. In the first JBC Classic reprinted here, she describes her findings as, “a new reaction which occurs in oxidative phosphorylation associated with the electron transport system has been observed in the rat liver mitochondria with α-ketoglutarate, a ā-hydroxybutyrate, and succinate as substrates. This reaction manifests itself by a replacement of O18 with normal O16 in inorganic phosphate labeled with O18 and parallels the phosphorylation which is associated with the oxidation.” Cohn concluded that water must be involved in this reaction because there was no other source of oxygen large enough to account for the amounts she saw introduced into inorganic phosphate. In the second JBC Classic Cohn describes her use of NMR to examine the structural changes in ADP and ATP caused by various divalent metal ions. Cohn knew that divalent ions were involved in enzymatic reactions of ADP and ATP but didn't know their functions. Using NMR, she measured the changes in the chemical shifts in the peaks of the ATP and ADP phosphorus nuclei in the presence of Mg2+, Ca2+, and Zn2+ as well as the paramagnetic ions Cu2+, Mn2+, and Co2+. By analyzing the resultant spectra, she was able to determine which metals bound to which phosphate groups and thus gained insight into the nature of the metal complexes formed. Cohn received many awards and honors for her contributions to science, including the National Medal of Science in 1982, “for pioneering the use of stable isotopic tracers and nuclear magnetic resonance spectroscopy in the study of the mechanisms of enzymatic catalysis,” as well as election to the National Academies of Science in 1971. She also served the American Society of Biological Chemists (ASBC), now American Society for Biochemistry and Molecular Biology (ASBMB), in many ways. She was President of the Society in 1978 and was on the Federation of American Societies for Experimental Biology (FASEB) Board from 1978 to 1980 as ASBC representative. In addition, Cohn was the first woman to be appointed to the JBC Editorial Board. Despite her success, Cohn's father was right about the difficulties she would encounter in her life. “My career has been affected at every stage by the fact that I am a woman, beginning with my undergraduate education, which was very inferior in chemistry, and physics was not even offered [as a major] at Hunter College, unlike the excellent science education that my male counterparts received at City College,” she notes. “In my day, I experienced discrimination in academia, government, and industry.”
Source: Journal of Biological Chemistry
Language: English
Subfield: History and Philosophy of Science
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1586451999