Benedict's Solution, a Reagent for Measuring Reducing Sugars: the Clinical Chemistry of Stanley R. Benedict

Benedict's Solution, a Reagent for Measuring Reducing Sugars: the Clinical Chemistry of Stanley R. Benedict
Stanley Rossiter Benedict was born in Cincinnati in 1884. While a student at the University of Cincinnati he worked with J. F. Snell, and together they published nine papers describing new analytical methods in inorganic chemistry. This research experience as a college student provided the intellectual foundation for his career. After a mistaken year in medical school at Cincinnati, he went to Yale, to the Department of Physiological Chemistry, to study with Russell Chittenden and Lafayette Mendel where he received training in metabolism and physiology. He received his Ph.D. in 1908, 2 years after entering graduate school. (Current students take note.) In 1910, he became Professor of Chemistry at Cornell University Medical College, the position he held until his death in 1936 at the age of 52 (1).

In a biographical review of Benedict's career, E. V. McCollum wrote,“ It is not possible to give an accurate account of the scientific work of Stanley Benedict without at the same time discussing the parallel researches of Otto Folin... they succeeded, through many years of intensive investigations, in devising and refining analytical procedures for determination of minute amounts of the principal non-protein constituents of blood and urine so that, for the first time, chemical analysis became a highly useful technic (sic) for the discovery of the chemical processes in the normal functioning of the body” (1).

Of Benedict's relationship with Folin, Shaffer wrote, “Both excelled in designing very clever analytical methods of the widest usefulness, and in using these tools with rare success for the discovery of new facts about metabolism. In spite of seventeen years difference in their age (Folin was the older), of the rivalry and controversy sometimes evident in their papers, there early developed between them a warm friendship which reveals the fine character of both. They were kindred spirits” (2). (We will present a classic paper by Otto Folin in a subsequent installment of JBC Classics, stay tuned.)

As McCollum and Shaffer described, Benedict's major contributions to biochemistry were in devising analytical methods. Although he published many papers in the Journal of Biological Chemistry (JBC), the paper reprinted here seemed appropriate to characterize a distinguished career. It had been known for many years that the common sugars had carbonyl groups and were therefore, “reducing sugars.” That is, they were oxidized by a variety of metal ions, Ag+, Fe3+, and Cu2+. Treatment with hot alkali fragments the sugars, and the resulting products reduce Cu2+ to Cu+ with the formation of a precipitate of Cu2O. As noted in the paper, Benedict's goal was to improve this general method to make the reagent less corrosive and more stable. He accomplished this by substituting carbonate for hydroxide as the alkali component, to reduce the corrosiveness, and by substituting citrate for tartrate as the agent to chelate the Cu2+, to make the reagent more stable.

Benedict's Solution, or one of the many variants that evolved over the years, was used as the reagent of choice for measuring sugar content for more than 50 years. It was the most common test for diabetes and was the standard procedure for virtually all clinical laboratories. Saul Roseman remembers that all inductees into the army during World War II had their urine tested for sugar with Benedict's Solution.1 Although Benedict's assay was the method of choice for more than 50 years, it suffered from lack of sugar specificity and was eventually supplanted by the use of enzymatic methods such as glucose oxidase.
Benedict's test for reducing sugars....
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