November 2009

RETROSPECTIVE

When Seymour arrived at the NIMH, he found that Cantoni’s laboratory was still under construction and would not be fully operational for several months. Although he was initially disappointed, he used this delay to deliberate on the choice of his first research project. He finally settled on the enzymatic hydroxylation of phenylalanine to tyrosine. The problem not only satisfied his interest in organic chemistry and his desire to contribute to biomedical research, but it was appropriate for the NIMH (even though he was not obligated to work on problems directly related to the brain), as the inability to convert phenylalanine to tyrosine results in phenylketonuria, which is characterized by mental deficiency.

Using partially purified enzymes from rat and sheep livers, Seymour developed a system that converted phenylalanine to tyrosine in vitro. In addition to oxygen, the reaction required NADPH and a boiled rat liver extract (i.e., “kochsaft”), indicating that there was an essential co-factor in the reaction. In a series of classical biochemical studies, he identified the co-factor as tetrahydropteridine and showed that it was formed from 7,8-dihydropteridine in the presence of NADPH. It was subsequently found that this compound is also an essential co-factor in other aromatic amino acid hydroxylations.

In 1968, the significance of Seymour’s contributions to neuroscience and to the research program of the NIMH was recognized by his appointment as chief of the laboratory of neurochemistry at the NIMH. From then on, his work largely, but not exclusively, concentrated on phenylketonuria. He finally proved that classical phenylketonuria was due to the lack of the phenylalanine hydroxylase enzyme. He also identified other variants of phenylketonuria, which were due not to lack of phenylalanine hydroxylase but to other enzymes involved in the synthesis of the essential co-factor tetrahydropteridine.

Seymour’s status in the world of biochemistry and his outstanding research contributions were honored by his selection to serve two terms on the editorial board of the American Journal of Biochemistry, election to the National Academy of Sciences and the American Academy of Arts and Sciences, the Meritorious Presidential Rank Award and the American Chemical Society Hillebrand Prize.

Although Seymour had decided that he lacked the talent to be a successful artist, he never lost his interest in art. He acquired an impressive collection of lithographs, woodcuts and paintings, some by Henri de Toulouse-Lautrec, whose work he particularly admired. His home also was filled with a number of sculptures produced by his daughter Emily, a very successful sculptor, who has one of her sculptures on display in the Hirshhorn Museum in Washington, D.C.

Seymour also had other interests to which, in his typical fashion, he was passionately devoted. Tennis was one of them. Although he lacked natural athletic talents and had never received any formal coaching, he developed a quite creditable tennis game, mainly because of his competitive nature. He hated to lose. He also developed a strong taste for good food. This probably evolved from several trips to France, during which he was introduced to the culinary magic of several of the three-star restaurants in the Michelin Guide.

Sadly, Seymour passed away on June 23, 2009. He had been ill for several years, but, during that time, he never lost his zest for life. He is survived by his wife, Elaine; son, Allan; daughters, Emily and Leslie; three grandchildren, Lisa, Joshua, and Amanda; and two sisters, Lilly Wolfe and Dottie Laiserin. He will be greatly missed by his family, friends, associates and by all in the biochemical community. Below, we offer thoughts and reflections from several of Seymour’s friends and colleagues.

The one word that best describes Seymour Kaufman’s approach to research is “careful.” He felt that to publish an erroneous datum or draw an unjustified conclusion would be a disaster, because it might deflect the progress of science. He once said that he spent 10 percent of his time being 90 percent sure and the remainder being 99.9 percent sure. Though this often delayed his publications, they never could have been any more respected by those who knew him well. His ability to draw valid conclusions and useful hypotheses from data was unsurpassed. His curiosity made the process of investigation a treasure hunt.

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