Resumen de Development and Proliferation of Radioimmunoassay Technology
Radioimmunoassay (RIA) developed as a fallout from investigations concerning the nature of maturity-onset diabetes. We studied the metabolism of 131I-labeled insulin in nondiabetic and diabetic subjects to determine whether rapid insulin metabolism was responsible for Type 2 diabetes. Unexpectedly, we observed that radioactive insulin disappeared more slowly from the plasma of patients who had received insulin than from the plasma of subjects never treated with insulin. While immunologists of the mid-1950s did not believe that a 6,000-dalton peptide could be immunogenic, we found that the retarded rate of insulin disappearance was due to binding of labeled insulin to insulin-binding antibodies. This first use of radioisotopic methods for detection of soluble antigen-antibody complexes introduced a revolution in theoretical immunology. It is now appreciated that very small peptides can be antigenic and that the equilibrium constants for antigen-antibody reactions can be as great as 1014 liters per mole, a value up to 108 times greater than predicted by Pauling's theory of 1940. The RIA for insulin was developed when we realized that the concentration of insulin in a solution could be determined by comparing its inhibitory effect on the binding of radioactive insulin to antibody with the inhibitory effect of known insulin standards. Our initial observations with insulin suggested that antigenicity was a more general property than had been appreciated, and since non-antibody materials with specific binding characteristics were also available, RIA and related techniques quickly proliferated for the detection and measurement of a vast array of substances in our own laboratory and around the world.
