Radioimmunoassay: Historical Aspects and General Considerations

Abstract

Radioimmunoassay (RIA) could be considered a serendipitous discovery in that it arose as fallout from investigations into what would appear to be an unrelated study. To test the hypothesis (Mirsky 1952) that maturity-onset diabetes might be a consequence of abnormally rapid degradation of insulin by an enzyme, insulinase, which was shown to be widely distributed in the body, we administered radioiodine-labeled insulin as a tracer to study the distribution and turnover of insulin in diabetic and nondiabetic subjects (Berson et al. 1956). We observed that the labeled insulin disappeared more slowly from the plasma of subjects with a history of insulin treatment than from the plasma of diabetic or nondiabetic subjects who had never received animal insulin. We soon demonstrated that the slower rate of removal was a consequence of the binding of insulin to an acquired antibody. Almost immediately we appreciated that the methodology used to study the kinetics of reaction of insulin with insulin-binding antibody and to determine the binding capacity of that antibody could be applied reciprocally to determine the concentration of insulin in body fluids. Although we first used the word immunoassay to describe the general methodology in 1957 (Berson and Yalow 1957), it was not until several years later that our assay had sufficient sensitivity to measure the concentrations of insulin in the circulation of humans (Yalow and Berson 1959).