BY DAVID SHEMIN AND RONALD BENTLEY

DAVID RITTENBERG WAS a leader in the development of the isotopic tracer technique for the study of biochemical reactions in intermediary metabolism. In a brief but historic paper published in Science in 1935, Rittenberg and Rudolph Schoenheimer described work at the Department of Biochemistry at Columbia University’s College of Physicians and Surgeons. Their pioneering experiments used deuterium, ²H, the heavy, stable isotope of hydrogen, to trace the fate of various compounds in the animal body. The metabolites containing ²H had properties essentially indistinguishable from their natural analogs by the methods commonly used. Nevertheless, the presence of the isotope made it possible to trace their metabolic fate. Thus, if a ²H-containing compound, B, was isolated after feeding the ²H-labeled compound, A, to an animal, the metabolic conversion A → B was established. Prophetically, these authors noted that “the number of possible applications of this method appears to be almost unlimited.” Subsequent developments have shown that they were true prophets.

In the mid-1930s little was known about the chemical reactions used by living systems to synthesize and degrade cellular components. One difficulty was that methods for the isolation and purification of carbohydrates, lipids, and