The Science and Life behind the Prize: Rosalyn Sussman Yalow

“Initially, new ideas are rejected,” Rosalyn Yalow tells a group of young students. “Later they become dogma, if you’re right. And if you’re really lucky you can publish your rejections as part of your Nobel presentation.” The ideas Yalow refers to are her Nobel-prize winning innovations in the field of radioimmunoassay (RIA). As a medical physicist born in the 1920s, it’s no surprise that Yalow was only the second woman to win the Nobel Prize for medicine, which the Nobel Prize in Physiology or Medicine in 1977, shared with Roger Guillemin and Andrew V. Schally for unrelated research. Yalow’s technique for measuring substances in the human body was recognized for its myriad of potential uses and practical applications, such as screening blood donors for diseases. After awarding Yalow the prize, the Karolinska Institute in Sweden claimed that her research “brought a revolution in biological and medical research. We are witnessing the birth of a new era of endocrinology, one that starts with Yalow.”

Born in the lower east side to a Germany immigrant mother and a father of European descent, Yalow learned from a young age the harsh realities of being underprivileged. However, it was evident early on that academia might be her ticket for success and prosperity. Yalow’s earliest memory was of being a stubborn and determined child; so much so that her mother once claimed how fortunate it was that she chose an “acceptable” path. Yalow could easily have strayed and not been deflected from that downward spiral by any force.

Yalow became something of an autodidact through literature, learning to read even before kindergarten. Seeing as how they had no books at home, her older brother accompanied her to the library on regular trips to fulfill the thirst for knowledge she had as a child. Yalow was fascinated by the logic of science and its ability to explain the natural world, an interest that would prove to influence the rest of her life. Despite being committed to mathematics by the seventh grade, and humoring a brief flirtation with chemistry, Yalow returned back to her fateful path of physics. During the thirties, physics, particularly nuclear, was “the most exciting field in the world.” Yalow herself said, “Madame Marie Curie was on the reading list of every young aspiring female scientist.” She remembers listening to a colloquium in 1939 by Enrico Fermi on the discovery of nuclear fission. Although contextually associated with nuclear warfare, the radioisotopes also offered promise with their use in medical investigations.

Unfortunately, Yalow’s parents were not as enthusiastic about her interests. They thought it would be far more practical if she pursued a career as an elementary school teacher. Here is where that early onset stubbornness is displayed; Yalow chose to attend Hunter College, which was at the time all female, and studied physics. Yalow grew more and more interested in the field. She utilized her type skills to get a secretary position to leading biochemist at Columbia, Dr. Rudolf Schoenheimer, hoping this would help her get an in to grad school. However, that proved to be more difficult than anticipated. A skeptical Midwestern university once wrote, “She is from New York. She is Jewish. She is a woman,” and this was a common justification for rejection. After all, what legitimate grad schools would provide financial support for a woman in physics? Yalow eventually got her opportunity when she was offered a teaching assistantship at the University of Illinois.

Yalow was the only woman of a faculty of 400 at the College of Engineering, and the first one since 1917. Although her merit was taken well into consideration, the current events at the time are what helped Yalow in her circumstances. In 1941, the year of Pearl Harbor, the physics department lost most of its upperclassman to “secret work” elsewhere, leaving many empty spots to be filled, most of which went to young army/navy students in need of experience. Desperate to fill spots, many universities began offering up programs to women, but it took the threat of being shut down to offer scholarships to women.

Hunter had only offered a Physics program as Yalow was graduating, so her first year course work in Physics was minimal. Determined to catch up, she sat in on two undergrad courses for no credit, took three grad courses, and worked as a half-time teaching assistant for freshman physics. She was fortunate enough to work under a great professor with a reputation for inspiration, and emerged despite the heavy workload with straight As except for one A- in an Optics Laboratory. Most would call this a resounding achievement, but the chairman of the department responded, “that A- confirms that women do not do well at lab work.” Hard work and discrimination turned Yalow’s stubbornness into a determination to prove everyone wrong.

In January 1945, Yalow got her Ph.D. in Nuclear Physics. Her research began to focus on skills in making and using an apparatus for the measurement of radioactive substances. Yalow decided to accept an assistant engineer position in New York at Federal Telecommunications Laboratory, a research lab for ITT. She was their only female engineer. Finally back in New York, Yalow decided to work at Hunter after the research group left, teaching a pre-engineering program to returning veterans. For a mind like Yalow’s, maintain a home and working as a full time teacher was just not enough. She volunteered at leading medical physics Dr. Edith Quimby’s lab, who she met through her medical physicist husband’s connections at Montefiore Bronx. There, Yalow gained research experience in the medical applications of radioisotopes.

So what exactly is RIA? Radioisotopes are used to trace tiny quantities of even tinier proteins of various biological substances in aqueous fluids, especially human blood. Testing with RIA is dependent on two reagents. The first is the result of covalently bonding the radioactive isotope to a target molecule, and the second is the antibody, which reacts chemically with the target molecule, specifically. Both are used to measure the target signal by mixing with a fluid, which contains an unknown concentration. The radioactive half emits a signal that can be monitored. The unknown concentration supplies a target when it displaces the radioisotope molecule as it bonds to the antibody.

Dr. G. Failla, dean of American medical physicists spoke with Yalow, then picked up the phone as said, “Bernie, if you want to set up a radioisotope service, I have someone here you must hire.” When Dr. Failla had spoken. There was no choice; Yalow would work under the chief of radiotherapy service at the Bronx Veterans Administration Hospital. Until 1950, Yalow worked part-time and continued teaching at Hunter. During these years, she equipped and developed the Radioisotope Service, and commenced research projects with Dr. Roswit, among other physicians in a range of specializations. Dr. Roswit’s veteran group provided a small grant for the research, which was conducted in a lab comparable to a janitor’s closet, but the scientists still managed to generate eight publications in varying areas of clinical investigation.

Recognizing the growing potential, the hospital set up Radioisotope Service branches nation-wide. At this point, Yalow committed full time to her research. The Bronx VA Medical research program supported her lab from its inception and remained confident and encouraging towards Yalow for the entire process. Dr. Solomon A Berson was completing his residency in internal medicine when he too decided to join the Radioisotope service. This began a twenty-two year partnership, which lasted up until the day he died on April 11, 1972. Yalow began collaborating exclusively with Berson.

Studies in radioisotopes revealed their ability to track specific substances, such as focusing in on certain particles or proteins in the blood. The two first investigated applications of radioisotopes in blood volume determination, clinical diagnosis of thyroid diseases, and iodine metabolism kinetics. These techniques were extrapolated and used to study the distribution of globin and serum proteins (proteins present in blood plasma). These proteins serve many functions in relation to movement through and with blood, like transporting lipids, hormones, vitamins and metals in the circulatory system. These methods were then applied to peptides, which are distinguished from proteins on the basis of size. This research was conducted on hormones, and they used insulin since it was most readily available in a highly pure form. They noticed a retarded rate of disappearance of insulin from the circulation systems of subjects that were treated with the hormone. The conclusion was interesting regarding the reaction between insulin and antibodies, as all patients developed antibodies against animal insulin. They realized that this discovery was a tool for tacking the circulation of insulin in the bloodstream, and worked for several years on practical applications of this finding. “Thus the era of RIA can be said to have begun in 1959, and is now used to measure hundreds of substances of biologic interest in thousands of labs in this country and abroad, even in scientifically less advanced lands.”

Although originally used to test for diabetes mellitus, the advancement of the technologies allowed for the use on even smaller molecules, once thought too small for detection. Thus this early work was met with much resistance. They faced issues trying to get their research pertaining to insulin antibodies (which was fundamental to the advancement of RIA research) when most scientific journals refused. It was a bold discovery that challenged previously accepted understandings, as do most game-changer discoveries. Scientists just could not wrap their heads around the idea that antibodies could recognize molecules as small as insulin. Only after deleting a reference to antibodies did the Journal of Clinical Investigation accept their paper. Yalow’s research was applied to testing blood donors for hepatitis, detecting certain cancers, identifying hormone-related issues, and measuring the effectiveness of various antibiotics and drug doses.

Neither of the scientists had advanced post-doctoral training in medical investigation, but acted as one another’s strictest critic and thus greatest motivator. Yalow learned medicine not formally, but informally from Berson, “a master of physiology, anatomy, and clinical medicine.” With Berson’s death came a great loss to the field of investigative medicine in 1968, but Yalow decided to rename the lab they shared after him so that as she continued to publish papers, they would memorialize Berson’s contributions. Yalow continued her research with Dr. Eugene Straus in 1972, and together their lab produced great works as well as great workers. They trained many “professional children” as young investigators that dispersed globally as great leaders in clinical and investigative medicine. Yalow stuck to a certain philosophy in her lab, claiming “I have never aspired to have, nor do I now want, a laboratory or a cadre of investigators-in-training which is more expansive than I can personally interact with and supervise.”

Yalow remained dedicated to the fields of physics and medicine to the end of her career, acting as a distinguished service professor at a hospital now affiliated with the Mount Sinai School of Medicine, and remaining a member of the national academy of sciences. Yalow received numerous awards and honors over the years from both physical science and medicinal fields.

She died on May 30th, 2011, leaving behind a legacy of fantastic medical and physical discovery not only in the significance of her research, but also on the personal impact she created. Yalow became an inspiration to many young female physicists, and trained a workforce of great and world-renowned young scientists. Her work was revolutionary, as was her status as a female physicist, and both legacies acted as the basis for great movements in society.