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Remembrance Project: Origins of RIA

Abstract

How did RIA begin? It was a serendipitous discovery in that it was a fallout from our investigations into what might be considered an unrelated study. Prompted by the suggestion of Dr. I. Arthur Mirsky that maturityonset diabetes might not be due to an absolute deficiency of insulin secretion but rather to its abnormally rapid degradation by an enzyme which Mirsky called insulinase (1), Dr. Solomon A. Berson and I attempted to study the metabolism of ¹³¹I-insulin after iv administration to diabetic and nondiabetic subjects (2). We observed a slower rate of disappearance of the ¹³¹I-insulin from the plasma of subjects who had been treated with insulin whether or not they were diabetic. We postulated that the slower disappearance was a consequence of the binding of labeled insulin to antibodies that had developed in response to administration of foreign proteinsi. i.e. animal insulins. We used a variety of physicochemical systems, including, among others, paper electrophoresis, ultracentrifugal analysis, and salting out methods, to prove that the protein that bound insulin in the plasma of insulin-treated subjects had the characteristics of an antibody, an IgG immunoglobulin. This concept was not acceptable to immunologists of the mid-1950s. The original paper describing these findings was rejected by Science and initially rejected by the Journal of Clinical Investigation (JCI). The JCI letter of rejection was subsequently published in my Nobel Lecture (3).

Received May 31, 1991.

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