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Yalow, Rosalyn Sussman (1921- )

Yalow, Rosalyn Sussman (1921- )

American medical physicist

Rosalyn Sussman Yalow was co-developer of radioimmunoassay (RIA), a technique that uses radioactive isotopes to measure small amounts of biological substances. In widespread use, the RIA helps scientists and medical professionals measure the concentrations of hormones, vitamins, viruses , enzymes , and drugs, among other substances. Yalow's work concerning RIA earned her a share of the Nobel Prize in physiology or medicine in the late 1970s. At that time, she was only the second woman to receive the Nobel Prize in medicine. During her career, Yalow also received acclaim for being the first woman to attain a number of other scientific achievements.

Yalow was born on July 19, 1921, in The Bronx, New York, to Simon Sussman and Clara Zipper Sussman. Her father, owner of a small business, had been born on the Lower East Side of New York City to Russian immigrant parents. At the age of four, Yalow's mother had journeyed to the United States from Germany. Although neither parent had attended high school, they instilled a great enthusiasm for and respect of education in their daughter. Yalow also credits her father with helping her find the confidence to succeed in school, teaching her that girls could do just as much as boys. Yalow learned to read before she entered kindergarten, although her family did not own many books. Instead, Yalow and her older brother, Alexander, made frequent visits to the public library.

During her youth, Yalow became interested in mathematics. At Walton High School in the Bronx, her interest turned to science, especially chemistry. After graduation, Yalow attended Hunter College, a women's school in New York that eventually became part of the City University of New York. She credits two physics professors, Dr. Herbert Otis and Dr. Duane Roller, for igniting her penchant for physics. This occurred in the latter part of the 1930s, a time when many new discoveries were made in nuclear physics. It was this field that Yalow ultimately chose for her major. In 1939, she was further inspired after hearing American physicist Enrico Fermi lecture about the discovery of nuclear fission, which had earned him the Nobel Prize the previous year.

As Yalow prepared for her graduation from Hunter College, she found that some practical considerations intruded on her passion for physics. In fact, Yalow's parents urged her to pursue a career as an elementary school teacher. Yalow herself also thought it unrealistic to expect any of the top graduate schools in the country to accept her into a doctoral program or offer her the financial support that men received. "However, my physics professors encouraged me and I persisted," she explained in Les Prix Nobel 1977.

Yalow made plans to enter graduate school via other means. One of her earlier college physics professors, who had left Hunter to join the faculty at the Massachusetts Institute of Technology, arranged for Yalow to work as secretary to Dr. Rudolf Schoenheimer, a biochemist at Columbia University in New York. According to the plan, this position would give Yalow an opportunity to take some graduate courses in physics, and eventually provide a way for her to enter a graduate a school and pursue a degree. But Yalow never needed her plan. The month after graduating from Hunter College in January 1941, she was offered a teaching assistantship in the physics department of the University of Illinois at Champaign-Urbana.

Gaining acceptance to the physics graduate program in the College of Engineering at the University of Illinois was one of many hurdles that Yalow had to cross as a woman in the field of science. For example, when she entered the University in September 1941, she was the only woman in the College of Engineering's faculty, which included 400 professors and teaching assistants. She was the first woman in more than two decades to attend the engineering college. Yalow realized that she had been given a space at the prestigious graduate school because of the shortage of male candidates, who were being drafted into the armed services in increasing numbers as America prepared to enter World War II.

Yalow's strong work orientation aided her greatly in her first year in graduate school. In addition to her regular course load and teaching duties, she took some extra undergraduate courses to increase her knowledge. While in graduate school she also met Aaron Yalow, a fellow student and the man she would eventually marry. The pair met the first day of school and wed about two years later on June 6, 1943. Yalow received her master's degree in 1942 and her doctorate in 1945. She was the second woman to obtain a Ph.D. in physics at the University.

After graduation the Yalows moved to New York City, where they worked and eventually raised two children, Benjamin and Elanna. Yalow's first job after graduate school was as an assistant electrical engineer at Federal Telecommunications Laboratory, a private research lab. Once again, she found herself the sole woman as there were no other female engineers at the lab. In 1946, she began teaching physics at Hunter College. She remained a physics lecturer from 1946 to 1950, although by 1947, she began her long association with the Veterans Administration by becoming a consultant to Bronx VA Hospital. The VA wanted to establish some research programs to explore medical uses of radioactive substances. By 1950, Yalow had equipped a radioisotope laboratory at the Bronx VA Hospital and decided to leave teaching to devote her attention to full-time research.

That same year, Yalow met Solomon A. Berson, a physician who had just finished his residency in internal medicine at the hospital. The two would work together until Berson's death in 1972. According to Yalow, the collaboration was a complementary one. In Olga Opfell's Lady Laureates, Yalow is quoted as saying, "[Berson] wanted to be a physicist, and I wanted to be a medical doctor." While her partner had accumulated clinical expertise, Yalow maintained strengths in physics, math, and chemistry. Working together, Yalow and Berson discovered new ways to use radioactive isotopes in the measurement of blood volume, the study of iodine metabolism , and the diagnosis of thyroid diseases. Within a few years, the pair began to investigate adult-onset diabetes using radioisotopes. This project eventually led them to develop the groundbreaking radioimmunoassay technique.

In the 1950s, some scientists hypothesized that in adult-onset diabetes, insulin production remained normal, but a liver enzyme rapidly destroyed the peptide hormone, thereby preventing normal glucose metabolism. This contrasted with the situation in juvenile diabetes, where insulin production by the pancreas was too low to allow proper metabolism of glucose. Yalow and Berson wanted to test the hypothesis about adult-onset diabetes. They used insulin "labeled" with131iodine (that is, they attached, by a chemical reaction, the radioactive isotope of iodine to otherwise normal insulin molecules.) Yalow and Berson injected labeled insulin into diabetic and non-diabetic individuals and measured the rate at which the insulin disappeared.

To their surprise and in contradiction to the liver enzyme hypothesis, they found that the amount of radioactively labeled insulin in the blood of diabetics was higher than that found in the control subjects who had never received insulin injections before. As Yalow and Berson looked into this finding further, they deduced that diabetics were forming antibodies to the animal insulin used to control their disease. These antibodies were binding to radiolabeled insulin, preventing it from entering cells where it was used in sugar metabolism. Individuals who had never taken insulin before did not have these antibodies and so the radiolabeled insulin was consumed more quickly.

Yalow and Berson's proposal that animal insulin could spur antibody formation was not readily accepted by immunologists in the mid1950s. At the time, most immunologists did not believe that antibodies would form to molecules as small as the insulin peptide. Also, the amount of insulin antibodies was too low to be detected by conventional immunological techniques. Yalow and Berson set out to verify these minute levels of insulin antibodies using radiolabeled insulin as their marker. Their original report about insulin antibodies, however, was rejected initially by two journals. Finally, a compromise version was published that omitted "insulin antibody" from the paper's title and included some additional data indicating that an antibody was involved.

The need to detect insulin antibodies at low concentrations led to the development of the radioimmunoassay. The principle behind RIA is that a radiolabeled antigen , such as insulin, will compete with unlabeled antigen for the available binding sites on its specific antibody. As a standard, various mixtures of known amounts of labeled and unlabeled antigen are mixed with antibody. The amounts of radiation detected in each sample correspond to the amount of unlabeled antigen taking up antibody binding sites. In the unknown sample, a known amount of radiolabeled antigen is added and the amount of radioactivity is measured again. The radiation level in the unknown sample is compared to the standard samples; the amount of unlabeled antigen in the unknown sample will be the same as the amount of unlabeled antigen found in the standard sample that yields the same amount of radioactivity. RIA has turned out to be so useful because it can quickly and precisely detect very low concentrations of hormones and other substances in blood or other biological fluids. The principle can also be applied to binding interactions other than that between antigen and antibody, such as between a binding protein or tissue receptor site and an enzyme. In Yalow's Nobel lecture, recorded in Les Prix Nobel 1977, she listed more than 100 biological substanceshormones, drugs, vitamins, enzymes, viruses, non-hormonal proteins, and morethat were being measured using RIA.

In 1968, Yalow became a research professor at the Mt. Sinai School of Medicine, and in 1970, she was made chief of the Nuclear Medicine Service at the VA hospital. Yalow also began to receive a number of prestigious awards in recognition of her role in the development of RIA. In 1976, she was awarded the Albert Lasker Prize for Basic Medical Research. She was the first woman to be honored this laurelan award that often leads to a Nobel Prize. In Yalow's case, this was true, for the very next year, she shared the Nobel Prize in physiology or medicine with Andrew V. Schally and Roger Guillemin for their work on radioimmunoassay. Schally and Guillemin were recognized for their use of RIA to make important discoveries about brain hormones.

Berson had died in 1972, and so did not share in these awards. According to an essay in The Lady Laureates, she remarked that the "tragedy" of winning the Nobel Prize "is that Dr. Berson did not live to share it." Earlier Yalow had paid tribute to her collaborator by asking the VA to name the laboratory, in which the two had worked, the Solomon A. Berson Research Laboratory. She made the request, as quoted in Les Prix Nobel 1977, "so that his name will continue to be on my papers as long as I publish and so that his contributions to our Service will be memorialized."

Yalow has received many other awards, honorary degrees, and lectureships, including the Georg Charles de Henesy Nuclear Medicine Pioneer Award in 1986 and the Scientific Achievement Award of the American Medical Society. In 1978, she hosted a five-part dramatic series on the life of French physical chemist Marie Curie, aired by the Public Broadcasting Service (PBS). In 1980, she became a distinguished professor at the Albert Einstein College of Medicine at Yeshiva University, leaving to become the Solomon A. Berson Distinguished Professor at Large at Mt. Sinai in 1986. She also chaired the Department of Clinical Science at Montefiore Hospital and Medical Center in the early- to mid-1980s.

The fact that Yalow was a trailblazer for women scientists was not lost on her. At a lecture before the Association of American Medical Colleges, as quoted in Lady Laureates, Yalow opined: "We cannot expect that in the foreseeable future women will achieve status in academic medicine in proportion to their numbers. But if we are to start working towards that goal we must believe in ourselves or no one else will believe in us; we must match our aspirations with the guts and determination to succeed; and for those of us who have had the good fortune to move upward, we must feel a personal responsibility to serve as role models and advisors to ease the path for those who come afterwards."

See also Laboratory techniques in immunology; Radioisotopes and their uses in microbiology and immunology

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Yalow, Rosalyn Sussman

Yalow, Rosalyn Sussman


AMERICAN PHYSICIST AND MEDICAL RESEARCHER 1921

Rosalyn Sussman Yalow was awarded the Nobel Prize in physiology or medicine in 1977 for her pioneering work in developing the technique known as radioimmunoassay (RIA), a method first applied to the measurement of concentrations in blood of the hormone insulin. Subsequently the use of RIA was extended to include the detection and quantification of a wide range of substances of biological interest, including other hormones, serum proteins, enzymes, viruses, and tumor antigens.

Born on July 19, 1921, in the Bronx, New York, Rosalyn Sussman studied physics and chemistry at New York's Hunter College, graduating in 1941. She was awarded a Ph.D. in nuclear physics by the University of Illinois in 1945. Two years earlier she had married fellow physics student Aaron Yalow. For a time in the mid-1940s Rosalyn Yalow worked at the Federal Communications Laboratory in New York, but then returned to Hunter College to teach physics. Her work in medical physics began in 1947 at the Veterans Administration (VA) Hospital in the Bronx, which was then in the process of establishing a radioisotope service.

After designing and building much of the equipment she would need to detect and quantify minute amounts of radioactive substances, Yalow devised studies in the early 1950s that used a radioactive isotope of iodine to investigate a number of physiological processes, including the metabolism of proteins. Similar studies monitored changes in insulin levels following the intravenous administration of foreign insulin in both diabetic and non-diabetic patients. The unexpected finding that radiolabeled insulin disappeared more slowly in patients who had received prior insulin injections led Yalow and her colleague Solomon Berson to postulate that the presence of the foreign insulin triggered antibody production. They further concluded that the binding of the radiolabeled insulin to these antibodies caused it to be cleared more slowly from the plasma. Yalow and Berson understood that the binding of labeled insulin to a fixed concentration of antibody depends quantitatively on the amount of insulin present. This led directly to their realization that RIA could be used to measure concentrations of the body's own insulin; insulin levels were not easily determined before the advent of RIA in 1959. Although slow to be adopted by others in the field, the technique was further developed by Yalow and Berson such that it could be used to measure concentrations of substances in body tissues and fluids in even infinitesimal concentrations. RIA is now used to identify hypothyroidism in newborn infants. It is also used in blood bank screening, for cancer detection, for the measurement of neurotransmitters, and in forensic chemistry.

Yalow received many honorary doctorates and awards in addition to her 1977 Nobel Prize (which she shared with Andrew Schally and Robert Guillemin). She was the first woman to receive the Albert Lasker Prize for Basic Medical Research (1976). She has served on several national committees, among them the President's Study Group on Careers for Women. Particularly interested in early science education, she frequently visits junior high and high schools. A strong supporter of nuclear medicine and a defender of nuclear power generation, she works to increase public awareness of the major benefits of these technologies.

see also Insulin; Nuclear Medicine.

Mary R. S. Creese

Bibliography

Biermann, Carol A., and Biermann, Ludwig (1993). "Rosalyn Sussman Yalow (1921 )." In Women in Chemistry and Physics: A Biobibliographic Sourcebook, ed. Louise S. Grinstein, Rose K. Rose, and Miriam H. Rafailovich. Westport, CT: Greenwood Press.

Nathanson, Brina (1997). "Rosalyn Sussman Yalow (1921 )." In Women in the Biological Sciences: A Biobibliographic Sourcebook, ed. by Louise S. Grinstein, Carol A. Biermann, and Rose K. Rose. Westport, CT: Greenwood Press.

Yalow, Rosalyn Sussman (1978). "Rosalyn S. Yalow." In Les Prix Nobel. Stockholm: Nobel Foundation.

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Yalow, Rosalyn

Yalow, Rosalyn (1921– ) US biochemist. In the 1950s, she found that some people who received insulin injections developed antibodies against the hormone. Yalow discovered that insulin, labelled with radioactive iodine, combined with the antibodies; from this she developed radio-immunological tests to detect and measure the amount of insulin present. Yalow shared the 1977 Nobel Prize in physiology or medicine for her development of a method of detecting peptide hormones in the blood. See also antibody

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Yalow, Rosalyn Sussman

Rosalyn Sussman Yalow, 1921–2011, American medical physicist, b. New York City, Ph.D. Univ. of Illinois, 1945. As a researcher at the Bronx Veterans Administration Hospital (from 1947), Yalow and colleague Solomon A. Berson developed a process, called radioimmunoassay, that made it possible to detect mere traces of biological substances in blood and other fluids. Their laboratory used the technique to make a number of discoveries concerning diabetes and insulin as well as other findings. For her work, Yalow was awarded the 1977 Nobel Prize in Physiology or Medicine along with Andrew V. Schally and Roger Guillemin. Yalow also was a professor at Mt. Sinai School of Medicine, New York City, from 1968 until her death.

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