November 2009

RETROSPECTIVE

Seymour Kaufman (1924–2009)

 

kaufman

The American Society for Biochemistry and Molecular Biology recently lost another of its distinguished and longtime members. Seymour Kaufman, a scientist emeritus and former chief of the laboratory of neurochemistry at the National Institute of Mental Health, passed away at the age of 85 in Bethesda, Md.

Seymour was renowned for his contributions toward the characterizations of the partial reactions in processes catalyzed by mixed function oxidases, particularly those involved in the hydroxylation of aromatic amino acids. He identified tetrahydrobiopterin as an essential co-factor in these hydroxylation reactions. Seymour established, by direct enzyme assays, that it is indeed the lack of the phenylalanine hydroxylase enzyme that is responsible for the human genetic disease classical phenylketonuria. Subsequently, he identified other genetic variants of phenylketonuria that result from deficiencies in enzyme activities involved in the synthesis and processing of tetrahydrobiopterin, the co-factor in the phenylalanine hydroxylation reaction.

Seymour was born in Brooklyn, N.Y., on March 13, 1924. His earliest interests were not in science; at a young age, he showed artistic talents that led him to attend New York’s High School of Music and Art. The curriculum there was markedly deficient in science. Although Seymour never lost his interest in the arts, he, like so many others of his generation, was diverted to ambitions in science by reading Paul DeKruif’s “Microbe Hunters” during his senior year. This new interest initially was unfocused and fluctuated between basic chemistry and biochemistry. Eventually, having learned that the University of Illinois had an outstanding chemistry department and understanding that a strong background in chemistry would also be invaluable in biochemistry, he applied to the school and was admitted in 1941. During his undergraduate and graduate studies at the University of Illinois, he took most of the organic chemistry and biochemistry courses available and acquired extensive knowledge and experience in organic and synthetic chemistry, which proved to be valuable later in his career. His primary interest became biochemistry after he took W. C. Rose’s course in intermediary metabolism during his senior year in college. His interest was heightened while doing research for his master’s degree at the University of Illinois with Carl Vestling. It was this work with Vestling that led to Seymour’s first publication in the Journal of Biological Chemistry in 1946 (1).

After receiving his master’s degree in 1946, Seymour enrolled as a Ph.D. candidate under Hans Neurath in the department of biochemistry at Duke University. There, he worked with George Schwert and John Snoke on proteolytic enzymes, which stimulated an interest in enzymology that would remain with Seymour throughout his career. It was also in Neurath’s lab that he met Elaine Elkins, another of Neurath’s graduate students, who later became his wife.

After acquiring his Ph.D. in 1949 and doing a brief postdoctoral fellowship with Neurath, Seymour joined Severo Ochoa’s department of pharmacology at New York University, first as a postdoctoral fellow and then as an assistant professor. He remained there for approximately five years and matured into an outstanding enzymologist and scientist. The department had an extraordinarily stimulating atmosphere and was home to many great scientists. There was also the powerful influence of Ochoa’s character, personality and modus operandi. He was completely dedicated and focused on his research and uncompromisingly rigorous in its execution. Although Seymour probably would have denied it, he later displayed some of these traits while directing his own lab.

It was in Ochoa’s department that Seymour made his first important contribution to biochemistry. This was the characterization of the partial reactions in the conversion of alpha-ketoglutarate to succinate in the tricarboxylic acid cycle and the elucidation of the mechanism of the substrate-level phosphorylation associated with this step.

Giulio Cantoni had been in Ochoa’s lab during part of the time that Seymour was there and was very impressed with him. Cantoni later became chief of the laboratory of cellular pharmacology at the newly established NIMH and recruited Seymour as an independent research biochemist. In Ochoa’s lab, Seymour had been more or less required to work on projects of Ochoa’s choosing. Cantoni’s offer of complete freedom to choose his own research project was probably an important consideration in his decision to accept Cantoni’s offer and to join to the NIMH in 1954.

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