Department of

Biochemistry

The Department of Biochemistry—A Brief Historical Perspective

benedict

Stanley R. Benedict
Chairman 1913-1936

 

 

Biochemistry at Weill Cornell Medical College (formerly Cornell University Medical College: CUMC) started as part of the Department of Physiological Chemistry & Chemical Pathology. The Department of Chemistry was founded in 1913 under the Chairmanship of Stanley R. Benedict, and the name was changed to the Department of Biochemistry in 1932. Vincent du Vigneaud, Alton Meister, and Frederick R. Maxfield have served as Department Chairs. During the tenure of the first three Chairs research within the Department was closely associated with the interests of the Chairs.

Stanley Benedict was recruited to CUMC in 1910 as an Assistant Professor of Chemistry in the Department of Physiological Chemistry and Chemical Pathology, having already achieved some degree of prominence with the publication of his method for the determination of sugars in urine and blood, using what came to be known as Benedict’s Reagent (J. Biol. Chem. 5: 485-487, 1908;)http://www.jbc.org/cgi/content/full/277/16/e5. This method remained the basis for sugar determinations in biological fluids for almost 50 years, and it was the most common test for diabetes. The method suffered from a lack of sugar specificity and was eventually supplanted in the late 1950’s by more specific and sensitive enzymatic methods.

Benedict received his Ph.D. in 1908 from Yale University (two years after entering graduate school!). In 1913, Benedict was appointed Professor and Chair of the Department of Chemistry at CUMC and remained Chair of the Department until his death in 1936. During his tenure, the overarching focus of research within the Department was in the development of methodology for analysis of metabolites and the application of these methods in metabolic studies and in the detection of disease. In addition to the method for sugar determination, methods were developed for analysis of metabolites such as urea, creatine/creatinine, uric acid, and ammonia. From 1926 to 1936, Benedict also served as the Managing Editor of J. Biol. Chem. Among other honors, he was a member of the National Academy of Sciences and President of the American Society of Biological Chemists. (A biographical memoir of Benedict by Elmer V. McCollum can be viewed at: http://books.nap.edu/html/biomems/sbenedict.pdf.

Vincent du Vigneaud succeeded Benedict as Chair in 1938. Du Vigneaud received his Ph.D. from the Rochester University School of Medicine in 1927 and became Head of the Biochemistry Department at the George Washington University School of Medicine in 1932. He had a lifelong interest in the chemistry and biochemistry sulfur-containing compounds, including, amino acids and peptides. Du Vigneaud, along with Mildred Cohn (who began her career as a post-doctoral fellow with du Vigneaud and went on to become a National Medal of Science recipient) pioneered the efforts to use isotopic tracers to study the metabolism of S-containing compounds. One of the earliest mass spectrometers used in the study of metabolic pathways was built at CUMC in the Department of Biochemistry by Cohn and Julian Rachele with the encouragement of du Vigneaud. Such pioneering work led to an era of explosive productivity within the Department and the training of a whole generation of young scientists, many of whom went on to distinguished careers in Biochemistry.

The research achievements during the du Vigneaud era are too numerous to detail. The major advances included: Elucidating the metabolic relationship between methionine and homocysteine, thus paving the way to the study of biological methyl transfer; the use of methionine in the biosynthesis of cysteine; the use of 1-carbon compounds in the de novo synthesis of what were then termed “labile” methyl groups; determination of the S-containing vitamin, biotin; and, during World War II, participation in the joint effort to develop a method for the chemical synthesis of the S-containing antibiotic, penicillin. The most recognized research efforts led to purification of the posterior pituitary hormones oxytocin and vasopressin, determination of their structure and proof of their structures by chemical synthesis, representing the first chemical synthesis of a biologically active peptide hormone. Du Vigneaud’s research was recognized with the Nobel Prize in Chemistry in 1955 (“… for his work on the chemistry and biochemistry of sulfur-containing molecules, with special reference to his work on oxytocin.”) http://nobelprize.org/nobel_prizes/chemistry/laureates/1955

The development of the methodology for the synthesis of biologically active peptide hormones allowed du Vigneaud and his colleagues to explore the relationship between the chemical structures of the hormones and their biological activity by investigating the effects of systematic amino acid residue modification on function. Du Vigneaud retired in 1967 to become Professor Emeritus at Cornell University, Ithaca. Following his death in 1978, an endowment from the du Vigneaud family laid the foundation for the annual Vincent du Vigneaud Symposium, one of the most popular forums for the presentation of research by both the students in the Graduate School.

Alton Meister was appointed the Chair of the Department of Biochemistry in 1967. He received his M.D. from CUMC in 1945 and spent several years at the National Cancer Institute, during which he made important contributions to the diagnosis of heart attacks from changes in the isozymic patterns of lactate dehydrogenase in plasma. Before his recruitment here, Meister was Chair of Biochemistry at Tufts University Medical College with a pervasive interest in the biochemistry of amino acids, to which he had already made major contributions, not the least of which was authorship of the 2-volume, comprehensive monograph, Biochemistry of Amino Acids. His arrival at CUMC signaled a profound shift in the Department’s research focus. Meister’s research was aimed at elucidating the enzymatic pathways by which amino acids are synthesized, interconverted and catabolized. The research programs of most of the faculty within the Department revolved around these central themes. Major projects within the Department involved the understanding of how the vitamins, pyridoxine and riboflavin, participate in amino acid metabolism, the mechanism and regulation of enzymes that catalyze the formation of amide bonds. Other Department faculty studied protein-protein interactions and the structure of proteins using biophysical methods such as ultracentrifugation and electron microscopy.

The research that drew the most widespread attention was Meister’s studies on the enzymology of glutathione metabolism. The sum of the reactions involved in the synthesis and catabolism of glutathione were shown to comprise a cycle, termed by Meister the gamma–glutamyl cycle. Research on this cycle generated a great deal of interest in the biochemistry and physiology of glutathione, opening up several lines of research into its protective roles, involvement in the synthesis of the bioactive molecules such as the leukotrienes, discovery of the metabolic basis of the inherited disease, 5-oxoprolinuria, etc.

In addition to his prolific research productivity, Meister served for many years as Editor of Advances in Enzymology, and Associate Editor of the Journal of Biological Chemistry and the Annual Review of Biochemistry. He was a member of the National Academy of Sciences and recipient of several prestigious awards http://www.jbc.org/cgi/content/full/282/38/e30. Meister stepped down as Chair in 1992.

Frederick Maxfield was appointed Chair in 1995, after an interval of three years, during which Esther Breslow served as Acting Chair. Before his recruitment, Maxfield was Professor of Pathology and Physiology at the Columbia University College of Physicians and Surgeons. He had received his Ph.D. in Biophysical Chemistry from Cornell University, Ithaca. The focus of research has shifted towards cellular biophysics and structural biology with several independent groups engaged in studies in molecular structure determination, molecular mechanisms of membrane trafficking, protein folding, and signal transduction.

Medical student teaching remains an important role of department faculty. In a major revision of the Basic Science curriculum in the Medical College, the department-based courses were replaced with integrated courses that use various modalities to teach the basic sciences in the first 2 years of the medical program. The Biochemistry faculty members are principally involved in the first Basic Science course, Molecules, Genes, and Cells.

du Vigneaud

Vincent Du Vigneaud Chairman 1938-1967
Nobel Laureate
in Chemistry 1955


meister

Alton Meister
Chairman 1967-1992


maxfield

Frederick Maxfield
Chairman 1995-present