Abstract

In 1960 Berson and Yalow published a method for the radioimmunoassay (RIA) of plasma insulin based on the concept that the extent to which unlabeled insulin displaces labeled insulin from anti-insulin antibody is proportional to the concentration of unlabeled insulin. The RIA for insulin has greatly increased knowledge of the physiology of glucose homeostasis and of the diverse causes of diabetes mellitus. Beyond this, the insight on which the RIA-or, more broadly, the competitive protein-binding assay-is based has provided the means to measure nanomolar or picomolar concentrations of a vast array of compounds in plasma and tissues. Directly or indirectly, the RIA has profoundly affected every branch of medicine. This essay reviews the ideas that were current in the medical research community when Berson and Yalow began their work and the observations and reasoning process that led them to their seminal discovery.

Highlights

  • In 1960 Berson and Yalow published a method for the radioimmunoassay (RIA) of plasma insulin based on the concept that the extent to which unlabeled insulin displaces labeled insulin from anti-insulin antibody is proportional to the concentration of unlabeled insulin

  • IN 1960 BERSON AND YALOW published a method for the measurement of plasma insulin by radioimmunoassay (RIA).The insight that enabled them to conceptualize the RIA—that the extent to which unlabeled insulin displaces labeled insulin from anti-insulin antibody is proportional to the concentration of unlabeled insulin—had been described in a paper published four years earlier (Berson et al 1956).That insight and the experimental ingenuity required to convert it to a procedure for the precise measurement of plasma insulin and other pep

  • This essay reviews some of the ideas and observations that shaped the intellectual climate in which Berson and Yalow began their studies of plasma insulin, summarizes these studies and Berson and Yalow’s analysis of the technical problems that can complicate the validation of RIAs, and concludes with a few comments on the insulin RIA as a stimulus to the development of other hormonal assays, during the decade following its publication

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Summary

Introduction

In 1960 Berson and Yalow published a method for the radioimmunoassay (RIA) of plasma insulin based on the concept that the extent to which unlabeled insulin displaces labeled insulin from anti-insulin antibody is proportional to the concentration of unlabeled insulin. The 1956 paper was followed by kinetic studies of the rates of formation and dissociation of insulin-antibody complexes when I131-labeled beef insulin and antisera from insulin-treated patients were incubated at different relative concentrations (Berson and Yalow 1958, 1959a).

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