Dr. Yalow’s measurement method — an “assay,” in scientific parlance — initially transformed the study of hormones, and in particular insulin, which regulates the concentration of sugar in the bloodstream. She and her scientific partner, Solomon A. Berson, who died in 1972, used the technique to make pathfinding observations about diabetes.
The power of the technique was immediately recognized by scientists in other fields.
Radioimmunoassay, or RIA, became an essential tool in diagnostic and research labs and transformed blood banks, where it was used to detect pathogens such as the hepatitis B virus that had been unwittingly passed on to people getting transfusions.
“The technique revolutionized medicine,” said William A. Bauman, a physician and researcher at the Mount Sinai School of Medicine in New York. “Before them, there was a lot of guesswork in medicine. They took away the guesswork.”
“Her method contributed enormously not only to endocrinology but to all the biological sciences,” said Andrew V. Schally, a researcher at the Veterans Affairs hospital in Miami who shared the 1977 Nobel Prize for physiology or medicine with Dr. Yalow and Roger Guillemin. Her co-winners used radioimmunoassay to study the action of hormones produced by the brain. (The first woman to win the Nobel in physiology or medicine was Gerty Cori, in 1947.)
Like Schally, Dr. Yalow did her most important work in the VA medical system, in her case at the Bronx VA Hospital. Schally recalled Thursday that when they won the Nobel Prize, murmurs in Congress about shutting down the VA system came to an abrupt end.
Radioimmunoassay depends on the ability of antibodies, which are Y-shaped proteins produced by the immune system, to bind with other molecules. For example, a molecule of an antibody against insulin will bind and hold a molecule of insulin.
However, another insulin molecule can knock the first one off and replace it, like children competing in a game of musical chairs. That competition between radioactively “labeled” and unlabeled molecules is the basis for the test.
In their original experiment, Dr. Yalow and Berson labeled insulin with radioactive iodine atoms and mixed it with a solution containing antibodies to insulin. The researchers then added a sample of human plasma that contained an unknown quantity of insulin.
Some of the insulin molecules then competed with the radiolabeled insulin for attachment to the antibody. Measuring the amount of free radiolabeled insulin by a Geiger counter or some other method gives an indirect but precise estimate of the amount of insulin in the plasma sample.
This principle is now the basis for hundreds of tests.
“It turns out that much of biology involves messenger systems that have great similarity to hormones — things like growth factors and cytokines that allow cells to communicate,” said Jesse Roth, former scientific director of the National Institute of Diabetes and Digestive and Kidney Diseases. “The application of this technique was not just in endocrinology but basically in all of biology.”
In their own laboratory, Dr. Yalow and Berson used RIA to prove that patients with type 1 diabetes, which usually comes on in childhood, had very little insulin in their blood, while patients with type 2 diabetes, which begins in adulthood, had circulating insulin to which their tissues were at least partly resistant.
Their work was also essential in the creation of a new field, nuclear medicine, that uses radioactive isotopes to trace the distribution of substances in the body and pinpoint organs affected by disease.
Dr. Yalow was born Rosalyn Sussman in New York on July 19, 1921. Her father ran a shop that sold twine and other items. Neither of her parents finished high school.
She attended an all-girl public high school in the Bronx, and then Hunter College, a public college for women that is now part of the City University of New York. She majored in physics.
When Enrico Fermi visited Columbia in 1939 and described nuclear fission, she said she was “hanging from the rafters.” However, doing graduate work in physics was considered a long shot for a woman.
After graduating from Hunter, she had a part-time secretarial job with a biochemist at Columbia’s medical school, which she hoped to parlay into access to graduate courses.
When she was given a spot as a graduate student and teaching assistant at the University of Illinois at Urbana-Champaign, “I tore up my stenography books,” she wrote in an autobiographical essay for the Nobel committee after winning her prize.
She was virtually the only woman doing science graduate work at the university. In her first year, she received A grades in her courses, except for an A-minus in an optics laboratory. That prompted the chairman of the physics department to say that “women do not do well in laboratory work,” she wrote in her Nobel essay.
At Illinois she met Aaron Yalow, a fellow physics graduate student. They were married in 1943. They had two children, who survive her. Her husband died in 1992.
After receiving a doctorate in physics, Dr. Yalow joined the Bronx VA full time in 1950 and developed its radioisotope service.
Her 22-year collaboration with Berson, a physician trained in internal medicine, was unusually close. After he died from a heart attack, the emotionally restrained Dr. Yalow “wept openly, continuously” at his funeral, according to a 1998 biography written by a onetime member of her lab, Eugene Straus, who died in April. She got permission to have her laboratory named the Solomon A. Berson Research Laboratory “so that his name will continue to be on my papers as long as I publish,” she wrote.
Neither Dr. Yalow nor Berson patented the radioimmunoassay technique, thinking it should be available to everyone. Bauman said that was true of their ideas as well, which they freely shared with scientists who sojourned in Dr. Yalow’s lab.
She once turned down an organization’s invitation to be its “woman of the year,” saying she thought such a designation was demeaning. After she retired she said, “I feel it is now my duty to speak to young women, to encourage them to have careers, and particularly careers in science.”
However, she also once wrote that “all women scientists should marry, rear children, cook and clean in order to achieve fulfillment, to be a complete woman.”
The couple had live-in help for much of their children’s childhoods. Dr. Yalow thought that “her children paid no price for the demands of her scientific career,” according to Straus’s biography. Her daughter is quoted as saying that “she just wasn’t physically around. . . . She didn’t do the things that parents are supposed to do,” while also saying, “She was a pretty wonderful mother.”