Rosalyn Yalow and Radioimmunoassay: A Discovery That Transformed Hormone Testing Worldwide

A converted janitor's closet, a diabetic husband, and one stubborn physicist's refusal to be told no became the foundation of modern hormone testing.
Rosalyn Yalow holding a pipette in her laboratory, surrounded by reagent bottles, circa Bronx VA Hospital
Dr. Rosalyn Yalow in her laboratory. From a converted storage room at the Bronx VA Hospital, she developed a technique that would fundamentally rewrite modern endocrinology.Women of influence via wikimedia commons
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A humble janitor's closet is the place where Radio-Immuno Assay (RIA) got kick started. The Bronx VA Hospital gave a young female physicist a converted storage closet and told her to investigate which radioactive isotopes might be useful for medicine. There was no way at the time to quantify hormones present in the bloodstream in very small amounts. For a doctor who suspected thyroid dysfunction, a growth disorder, or diabetes, there were not many tools at his disposal. Such patients were managed based on purely clinical suspicion.

Rosalyn Yalow changed that and became the second woman, and the first American-born woman, to receive the Nobel Prize for Physiology or Medicine in 1977.

What Is Radioimmunoassay, and Why Was It Important?

Radioimmunoassay (RIA) involves tagging the substance with a radioactive isotope, to study its behaviour in relation to an antibody, thereby making it possible to quantitatively measure amounts of it down to the billionth of a gram. Prior to that, scientists could reliably study only antigen-antibody reactions that produced visible clumps or precipitates, but not with such precision. For understanding the sensitivity of this test, we can imagine RIA could detect an equivalent amount of one teaspoon of sugar diluted in an enormous lake about 62 miles long. As per her Nobel Lecture of 1977, Yalow was able to list over a hundred different substances that RIA could detect such as hormones, drugs, vitamins, enzymes, viruses, etc..

How Did Yalow and Berson Discover Radioimmunoassay?

Solomon Berson became part of Yalow's small group of VA researchers in 1950, and he collaborated with her for the next 22 years. Yalow and Berson began their research project by trying to improve blood volume measurements with radioisotopes, and later moved on to insulin. One reason was that pure insulin was easily available; another reason was the fact that Yalow's husband Aaron had diabetes.

Berson and Yalow tagged insulin with radioactive iodine, injected it to volunteers including themselves, and measured the rate at which insulin was removed from the blood stream by collecting samples after hours had passed.

They found that in patients who had previously been treated with insulin, the radioactive insulin cleared from the bloodstream far more slowly than in people who'd never been treated. Those patients received insulin derived from beef or pork, and their immune systems started treating it as foreign, building antibodies that bound to it and held it in circulation longer. That alone was a real finding for treating insulin resistance. But classifying a hormone as something capable of triggering an antibody response broke with the prevailing wisdom of the time.

When they tried to publish their research in the Journal of Clinical Investigation in 1955, the journal rejected it. It took a year and a resubmission before the journal accepted it, under the title "Insulin-I131 Metabolism in Human Subjects: Demonstration of Insulin-Binding Globulin in the Circulation of Insulin-Treated Subjects." That paper went on to become one of the most cited in the journal's history, and the method radioimmunoassay, which laid the foundation for modern immunoassays.

Dr. Rosalyn Yalow celebrating her 1977 Nobel Prize in Physiology or Medicine, the ultimate validation of a revolutionary theory that the scientific establishment initially refused to publish.
Dr. Rosalyn Yalow celebrating her 1977 Nobel Prize in Physiology or Medicine, the ultimate validation of a revolutionary theory that the scientific establishment initially refused to publish.Keystone via wikimedia commons

Did Radioimmunoassay Help Lead to Modern Diabetes Drugs Like Ozempic?

Yalow mentored researchers from around the world, and one of them, John Eng, used her RIA technique in 1992 to identify a new substance in Gila monster venom. He called it exendin-4. A synthetic version, exenatide, won FDA approval in 2005 as the first GLP-1 receptor agonist, the drug class that exploded in popularity in the 2020s for diabetes management and weight loss. A lab technique built to study insulin in the 1950s eventually traced a path to the drugs reshaping diabetes care today. RIA became one of the laboratory tools that enabled researchers to identify and study hormones such as exendin-4.

Her influence didn't stay confined to one country, either. Another of her mentees, physician-researcher Narayana Panicker Kochupillai, carried the same technical legacy back to India, going on to lead endocrinology research there on thyroid hormones and iodine deficiency. Looking at that lineage, one retrospective has suggested Yalow might fairly be remembered as something like the field's founding figure, "the Mother of Endocrinology", though that's an informal label rather than an official title, more a way of pointing at how far her influence traveled through the people she trained.

What Else Can Radioimmunoassay Measure?

Applications multiplied fast once the method existed. Blood banks used it to screen for hepatitis B. Children with growth hormone deficiency could finally be diagnosed and treated. It became part of prenatal screening, newborn testing, and drug testing in sports. Many specific uses have since been refined or replaced by newer assay technologies, but the underlying principle, precisely quantifying substances the body produces in vanishingly small amounts, never went away. It's still what makes most modern lab panels possible.

Why Was Radioimmunoassay Eventually Replaced?

Although RIA revolutionized laboratory medicine, many laboratories have gradually shifted to non-radioactive immunoassays such as enzyme-linked immunosorbent assays (ELISA), chemiluminescent immunoassays, and automated immunoassay platforms. These methods provide similar sensitivity while avoiding radioactive materials. Nevertheless, RIA established the principles that modern immunoassays continue to use.

Gloved hand loading a rack of blood sample tubes into an automated laboratory analyzer
Today's automated analyzers run on the same antigen-antibody principle Yalow established, without the radioactive tracers.Pexels

Was Rosalyn Yalow a Champion for Women in Science?

Rosalyn mentored women she believed had real potential. Yet she was on record opposing organizations built specifically for women in science, reasoning that their existence implied women needed to be treated differently from men1. Other accounts describe her feeling a particular responsibility, after the Nobel, to encourage girls toward science5. Both things seem to be true. She once said: "It bothers me that there are now organizations for women in science, which means they think they have to be treated differently from the men. I don't approve”.

Conclusion

Rosalyn Yalow passed away in 2011, yet the DNA of modern medicine will always be hers. The thyroid hormone tests, the test that ensures there is no hepatitis in the donor blood, the laboratory methods that helped advance GLP-1 research, they all lead back to the one simple question put forward in a converted basement in Bronx. The story of a Nobel Prize is often an idealized tale; the reality behind this success lies in the fact that Rosalyn had to endure a rejection, to come up with something that ran counter to all existing literature, and to do so as a woman in physics.

References

  1. "Rosalyn Yalow." Women Who Changed Science. NobelPrize.org, Nobel Prize Outreach (2025).

  2. "Rosalyn Yalow." Jewish Women's Archive (2022).

  3. Berson, S. A., Rosalyn S. Yalow, A. Bauman, M. A. Rothschild, and K. Newerly. "Insulin-I131 Metabolism in Human Subjects: Demonstration of Insulin-Binding Globulin in the Circulation of Insulin-Treated Subjects." Journal of Clinical Investigation 35, no. 2 (1956): 170–190. https://doi.org/10.1172/JCI103262.

Rosalyn Yalow holding a pipette in her laboratory, surrounded by reagent bottles, circa Bronx VA Hospital
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