The Beginning of Protein Physical Chemistry. Determinations of Protein Molecular Weights. The Work of Edwin Joseph Cohn
Year: 2002
Type: article
Abstract: Studies in the Physical Chemistry of the Proteins. V. Molecular Weights of the Proteins (Cohn, E. J., Hendry, J. L., and Prentiss, A. M. (1925) J. Biol. Chem.63, 721–766) Edwin Joseph Cohn (1892–1953) began his college education at Amherst College as a humanities student but developed an interest in science and, with the encouragement of Jacques Loeb, transferred to the University of Chicago where he received both his Bachelors (1914) and Ph.D. degrees in Chemistry. During his Ph.D. work he had been strongly influenced by Lawrence J. Henderson of Harvard who was the first Chairman of the Department of Physical Chemistry at Harvard Medical School. Cohn had done some of his thesis work with Henderson, and from that experience he decided that proteins would be his life's work. After his Ph.D., he worked with Thomas D. Osborne in New Haven who had been studying plant proteins for many years and was one of the few protein chemists in the United States. With the beginning of World War I, Cohn moved to Harvard to again work with Henderson on a war project studying the physical chemistry of bread making. The shortage of wheat made this an important project. After the war, he studied in Copenhagen with S. P. L. Sorensen who had shown that egg albumin, although a large molecule of approximately 40,000 daltons, formed solutions that obey the classical laws of physical chemistry. In 1920, he returned to the United States and was invited by Henderson to play a leading role in the Department of Physical Chemistry. Henderson's research interests were taking him away from the department, and Cohn was put in charge. His research initially was an extension of studies done with Osborne and Sorensen and focused on solubility and acid-base properties of casein, zein, and serum globulins. It was an interesting time in the study of proteins because there was not complete agreement that proteins were actually discrete molecules. Among colloid chemists, it was thought that proteins were not true molecules but aggregates of small peptides held together by noncovalent interactions. One of the most prominent of the colloid school was The Svedberg in Uppsala, who would later develop the ultracentrifuge and also eventually recognize that proteins were indeed discrete molecules. It would, however, take another decade to finally bury the colloid view although Cohn never considered their views seriously (1Edsall J.T. Biographical Memoir for Edwin Joseph Cohn. 20. National Academy of Sciences, Washington, D. C.1961: 47-72Google Scholar). The Cohn paper selected as this Journal of Biological Chemistry (JBC) Classic represents a very thorough examination and comparison of the molecular weights of several proteins as determined by various methods. The methods include molecular weight determination by osmotic pressure and by composition. The compositional studies used various reference components, iron for hemoglobin, copper for hemocyanin, sulfur for many proteins, and low frequency amino acids. The compositional analysis would provide a minimal molecular weight and other information from dialysis, and ultrafiltration, reported in a subsequent paper, would allow a calculation of the even multiple of the minimal molecular weight for the intact protein. Drawing on data from many sources, he concludes this paper with the estimated minimal molecular weights of 14 proteins. Although all of the estimates are wrong, the important conclusion is that proteins are large, discrete molecules, which at the time was an important conclusion. Cohn continued his studies of protein solubility and increasingly focused on amino acids and peptides and eventually on serum proteins. In the course of these latter studies he developed sound physical-chemical approaches to fractionation of serum proteins, including salting in/salting out, alcohol precipitation, etc. that would be of enormous practical importance as the United States prepared for World War II. In 1940, the National Research Council recognized the need for providing material for blood transfusions for the war effort. It was the hope initially that bovine albumin could be used as a “plasma expander” for the prevention of shock. In 1941 Cohn published a review, “The Properties and Functions of Plasma Proteins with consideration of the Methods for their Separation and Purification” (3Cohn E.J. The properties and functions of the plasma proteins with a consideration of the methods for their separation and purification.Chem. Rev. 1941; 28: 395Crossref Scopus (26) Google Scholar). With his vast experience with serum proteins, he was enlisted to direct an effort for large scale purification of bovine albumin. He wisely also worked on the isolation of human albumin as well because bovine albumin was never proven safe for humans. In the course of this work, Cohn insisted that the full complexity of plasma be appreciated, and fractionation was designed to produce particular components for specific purposes: albumin for transfusion and shock treatment, fibrinogen and prothrombin for clotting problems, and γ-globulins for certain diseases. The scale of the national effort was enormous, and with the support of the Office of Scientific Research and Development and blood from the Red Cross, over a half-million transfusions of albumin were prepared in the United States between 1942 and 1945. Cohn was the driving force behind this effort. Driven by the war effort, the understanding of plasma proteins was advanced enormously. Cohn provided a very fruitful training ground for many of the most important protein chemists of a generation. John Edsall, Jeffries Wyman, and Alex von Muralt were all in the Cohn laboratory at the same time. He was a demanding mentor and supervisor. He is described by John Edsall, “In applying pressure to get things done he was often imperious and demanding, sometimes rude to the point of insult. Certainly he made many enemies by his extreme forcefulness and sometimes by an aggressiveness which went beyond obvious necessity” (1Edsall J.T. Biographical Memoir for Edwin Joseph Cohn. 20. National Academy of Sciences, Washington, D. C.1961: 47-72Google Scholar). Among many honors, Cohn was the first Harvard professor of the life sciences to be named University Professor, and he received the Medal of Merit from the U.S. Government for his war efforts (1Edsall J.T. Biographical Memoir for Edwin Joseph Cohn. 20. National Academy of Sciences, Washington, D. C.1961: 47-72Google Scholar).
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: W1602174015