The Stadtman Way A Tale of Two Biochemists at NIH

In the early 1970s, Thressa's direction of research was suddenly changed by the unexpected, serendipitous observation that selenium was required for synthesis of a particular protein. At that time, Thressa was examining the biochemical properties of glycine reductase, the enzyme that catalyzes the reductive degradation of glycine, by isolating and purifying its protein components separately. With this study, she sought to explain a seemingly casual, but puzzling, finding in her laboratory: why did some batches of C. sticklandii, grown under conditions deemed to be optimal for the production of glycine reductase, exhibit virtually no ability to reduce glycine to acetate? 

In every such instance, the lack of enzymatic activity could be attributed to the absence of one component, called protein A, in the preparation. Finding that this protein component was not continuously produced during the entire phase of growing the bacteria, Thressa began to search for nutrient factors that might help or inhibit the production of protein A. After testing various inorganic minerals, she discovered that the addition of selenium to the bacterial culture medium greatly increased the production of protein A and immediately restored the activity of glycine reductase to its highest level. To determine further whether selenium was an actual component of protein A, Thressa conducted an experiment in which she grew C. sticklandii in a culture medium containing radioactive selenium. This resulted in the incorporation of radioactivity in protein A. By the end of June 1972, Thressa finally had enough evidence to announce the existence of a selenium-containing protein. Protein A of glycine reductase was a selenoprotein!