The First Radioimmunoassay

Overview

The first radioimmunoassay (RIA) was developed by Rosalyn Yalow and Solomon Berson at the Bronx Veterans Administration Medical Center in the late 1950s. Their seminal 1960 paper in the Journal of Clinical Investigation, titled "Immunoassay of Endogenous Plasma Insulin in Man," reported a method for measuring insulin at concentrations orders of magnitude below what had previously been possible.

The principle was elegant. If unlabeled (non-radioactive) analyte and labeled analyte are mixed with a limited quantity of specific antibody, the two forms compete for binding sites. The more unlabeled antigen present, the less labeled antigen binds to the antibody. By separating antibody-bound from free tracer and counting radioactivity, the concentration of unlabeled analyte in the unknown sample can be determined with reference to a standard curve.

Yalow and Berson's starting observation — that diabetic patients who had received insulin injections harbored anti-insulin antibodies — was itself controversial, because contemporary immunology held that small proteins like insulin should not be immunogenic. The ability to demonstrate and measure these antibodies with a sensitive assay vindicated their hypothesis and, in the process, opened a new era of clinical chemistry.

Key People

• Rosalyn Yalow (1921–2011): Medical physicist who co-developed RIA.
• Solomon Berson (1918–1972): Physician-scientist and Yalow's collaborator, who died before the Nobel.
• David Sokal: Early clinical collaborator on diabetes-related immunology.
• Ralph E. Peterson and Seymour Lieberman: Contributed to adaptation of RIA to steroid hormones.

Timeline

• 1956: Yalow and Berson report anti-insulin antibodies in diabetic patients.
• 1959: First description of the insulin RIA principle at a scientific meeting.
• 1960: Landmark JCI paper describes the method.
• Mid-1960s: RIA is adapted for growth hormone, glucagon, ACTH, and many other hormones.
• 1970s: RIA becomes standard in endocrine laboratories worldwide.
• 1977: Yalow receives the Nobel Prize.

Background

Before RIA, endocrine laboratories relied on bioassays (for example, measuring insulin by its effect on blood glucose in animals) or on bulk chemical methods. Both approaches were slow, expensive, and imprecise. The RIA method provided quantitative, specific, and sensitive measurements with a small plasma sample — transforming what could be done in both research and clinical settings.

The use of iodine-125 as a common labeling isotope, the development of antibody standards, and the eventual commercialization of reagent kits (for example, those from Behringwerke, Serono, and Abbott) expanded the reach of RIA into virtually every hospital endocrinology laboratory. The earliest RIAs for insulin, growth hormone, and human chorionic gonadotropin remained workhorses of endocrine diagnostics for decades.

Modern Relevance

Today, the radioisotope form of RIA has largely been replaced by non-radioactive immunoassays — ELISA, chemiluminescent immunoassay, electrochemiluminescence, and similar platforms — that retain the antibody-based detection but substitute enzymatic, fluorescent, or electrochemical labels for radioactivity. These successors trace their conceptual lineage directly to the original RIA.

The first RIA also remains a touchstone for the philosophy of quantitative biology. Yalow and Berson refused to patent the technique, enabling rapid global adoption and saving many patient lives. The paper is still widely cited as an illustration of the power of physical methods in clinical science. For related topics, see radioimmunoassay-method and rosalyn-yalow.

Related Compounds

• Insulin
• Growth hormone
• ACTH
• Glucagon
• hCG