Rosalyn Yalow transformed clinical medicine through the development of extremely sensitive methods of measuring concentrations of hormones.
Professor Rosalyn Yalow, who has died aged 89, transformed clinical medicine through the development of new and extremely sensitive methods of measuring concentrations of hormones, and other biologically active molecules, in the body. These techniques are known collectively as radioimmunoassay, or RIA. For this, and for her later development of such techniques in a wide spectrum of investigations, she won the Nobel prize for medicine and physiology in 1977.
The possibility of radioimmunoassay techniques, able to detect any substance down to a few parts in a hundred billion, first emerged in the early 1950s, as a theoretical offshoot of the experimental use of radio iodine in the investigation of human thyroid function and disease. Early work carried out by Yalow and Solomon Berson, at the Bronx Veterans Administration hospital (now the James J Peters Veterans Affairs Medical Centre), in New York, involved following a minute dose of injected iodine-131 during its concentration in the thyroid gland and during metabolism.
Such investigations had never before been possible. However, this method depended on the patient being given a radioactive substance; and its sensitivity was limited. Nevertheless, Yalow used the method experimentally to determine or confirm several basic factors, such as the volume of the body's blood compartments, the distribution and movement of serum components, and the volume of the space between cells.
This was new science – yet to Yalow, an aspiring nuclear physicist with rapidly growing expertise in physiology and medicine, and Berson, a medical clinician whose mathematics and physics eventually attained professorial level, it was not good enough. They sought an investigative method of far greater sensitivity, easier to handle in the laboratory and more acceptable to patients.
Theoretically, this could be done by exploiting the natural immune process, in which the body sees every protein as an "antigen", to which it responds by producing a specific "antibody". In the laboratory, the extent to which a small sample inhibits a particular antigen indicates the level of antibody in that sample. In turn, this can indicate the extent to which that antigen (which can range from natural hormones to drugs, chemicals, or almost any substance) is present in the sample. In the mid-1950s Yalow and Berson discovered that the blood sera of all patients who had been treated with insulin contained specific antibodies to insulin. Unfortunately, the prevailing wisdom at that time was that insulin was too small a molecule to produce an antibody, and when Yalow and Berson tried to publish their findings, their carefully constructed paper was rejected in 1955 by the US Journal of Clinical Investigation, while the cautious research journal Science asked them to refer to specific "immunoglobulins" rather than insulin "antibodies".
Yalow and Berson knew that they were right. They saw that specific antibodies were the key to techniques which could have huge value in endocrinology and other aspects of clinical medicine. They were infuriated that their years of investigation could be so casually rejected. This episode embittered Yalow for the rest of her life, but its immediate effect was to stimulate an increase in the scope and precision of her research to produce results which, in the end, nobody could refute.
Over 10 years, Yalow refined the radioactive and biochemical procedures into practical clinical methods, demonstrating on the way that – as had been suggested by the earlier results – many late-onset diabetics have a high blood-sugar level because their immune system renders them insensitive to the presence of their own insulin.
With Berson, Yalow extended the scope of RIA into the measurement of growth hormone, gastrin, parathyroid and a wide spectrum of other hormones and serum constituents which, with their individual triggering and controlling proteins, could for the first time be measured accurately from extremely small samples. By the end of this period of research, the technique and basis of RIA was being used in thousands of laboratories throughout the world, providing a platform for a revolution in clinical medicine.
In 1972, when their triumph was widely recognised and the world expected them to receive a fully justified Nobel prize, Berson died from a heart attack, at the age of only 53. Although Berson had already left to extend his own clinical studies, Yalow was shattered. The world believed that Berson, who generally presented their joint work at conferences, had led the research. Yalow realised that if her huge contribution were to be recognised, she would have to prove herself all over again. She embarked upon this task with awesome determination.
Naming her laboratory at the Bronx VA after Berson, and working with Eugene Straus, a young postgraduate physician, she opened up new areas of research in gastric hormones. She demonstrated that the same hormones exist in many different forms, that some have quite separate roles in different parts of the body and that one of these (cholecystokinin) controls appetite and hence obesity. She then pioneered the use of RIA in the detection of drugs, enzymes, and viral and bacterial antigens, eventually opening the way to the investigation of any substance of biological interest.
In 1976 Yalow won the coveted Lasker Medical Research award, which turned out to be the harbinger of her Nobel prize. When her Nobel dissertation was printed in Science, the medical world was embarrassed to find that she had included the text of the letter from the Journal of Clinical Investigation which, 22 years earlier, had rejected Yalow and Berson's discovery and identification of insulin antibodies.
Yalow worked on in her laboratory until 1987, holding professorships in New York at the Mount Sinai School of Medicine and at the Albert Einstein College of Medicine. She was, she said, glad to close the laboratory because "research is becoming grotesquely over-regulated and inhibited". She then embarked on a lecturing campaign aimed at encouraging the entry of women into science. As always she was aggressive, uncompromising and highly focused. These were the qualities that took her to the top in a man's world. "Women have to be better at it than men," she declared. Some described her as "excoriating and vitriolic" but, in reality, this was the stuff of adversity and of brilliant science.
Apart from a few years of postgraduate study at the University of Illinois, Yalow always lived and worked in New York. She was born Rosalyn Sussman of immigrant parents in the south Bronx. A child throughout the depression, angered by poverty and disease, she decided when she was 13 that she would study medicine and become a research scientist. She won a scholarship to Hunter College (a women's college now part of the City University of New York). Legend has it that, to keep his students attentive, her physics professor once declared he would make two mistakes in a long calculation. When he had finished, he asked if anyone had spotted them. "Yes," said Rosalyn, "but which two did you make deliberately? You made three!" To his dismay, she was right.
In spite of her brilliance, she found that being a woman, Jewish and poor made it almost impossible for her to study medicine. Her family could not afford fees and she craved absolute independence. She majored in nuclear physics, and decided to marry and have children as well as becoming a scientist. She knew the difficulties, yet was determined to overcome them.
In 1941, with many male physicists entering the armed services, she was offered an assistantship at the University of Illinois. There she met her future husband, Aaron Yalow (also a nuclear physicist), took a master's degree, realised that techniques of radioisotope tracers being used in plant biology might have much wider application, and took her doctorate under the great Maurice Goldhaber (later director of the Brookhaven National Laboratory).
When the Bronx VA hospital decided to set up a radioisotope laboratory in 1947, Goldhaber said that Yalow should organise and run it. She jumped at the opportunity to pioneer the science of medical physics and, over three decades, transformed the world of clinical medicine. While doing this she had two children and a full family life that fulfilled what she called the "earth mother" component of womanhood. As a scientist she was a tiger, a warrior. "The only difference between men and women in science is that the women have the babies," she said in later life. "This makes it more difficult for women in science, but should not be seen as a barrier, for it is merely another challenge to be overcome."
Her husband died in 1992. Yalow is survived by their son Benjamin and daughter Elanna, and two grandchildren.
• Rosalyn Sussman Yalow, scientist, born 19 July 1921; died 30 May 2011
The possibility of radioimmunoassay techniques, able to detect any substance down to a few parts in a hundred billion, first emerged in the early 1950s, as a theoretical offshoot of the experimental use of radio iodine in the investigation of human thyroid function and disease. Early work carried out by Yalow and Solomon Berson, at the Bronx Veterans Administration hospital (now the James J Peters Veterans Affairs Medical Centre), in New York, involved following a minute dose of injected iodine-131 during its concentration in the thyroid gland and during metabolism.
Such investigations had never before been possible. However, this method depended on the patient being given a radioactive substance; and its sensitivity was limited. Nevertheless, Yalow used the method experimentally to determine or confirm several basic factors, such as the volume of the body's blood compartments, the distribution and movement of serum components, and the volume of the space between cells.
This was new science – yet to Yalow, an aspiring nuclear physicist with rapidly growing expertise in physiology and medicine, and Berson, a medical clinician whose mathematics and physics eventually attained professorial level, it was not good enough. They sought an investigative method of far greater sensitivity, easier to handle in the laboratory and more acceptable to patients.
Theoretically, this could be done by exploiting the natural immune process, in which the body sees every protein as an "antigen", to which it responds by producing a specific "antibody". In the laboratory, the extent to which a small sample inhibits a particular antigen indicates the level of antibody in that sample. In turn, this can indicate the extent to which that antigen (which can range from natural hormones to drugs, chemicals, or almost any substance) is present in the sample. In the mid-1950s Yalow and Berson discovered that the blood sera of all patients who had been treated with insulin contained specific antibodies to insulin. Unfortunately, the prevailing wisdom at that time was that insulin was too small a molecule to produce an antibody, and when Yalow and Berson tried to publish their findings, their carefully constructed paper was rejected in 1955 by the US Journal of Clinical Investigation, while the cautious research journal Science asked them to refer to specific "immunoglobulins" rather than insulin "antibodies".
Yalow and Berson knew that they were right. They saw that specific antibodies were the key to techniques which could have huge value in endocrinology and other aspects of clinical medicine. They were infuriated that their years of investigation could be so casually rejected. This episode embittered Yalow for the rest of her life, but its immediate effect was to stimulate an increase in the scope and precision of her research to produce results which, in the end, nobody could refute.
Over 10 years, Yalow refined the radioactive and biochemical procedures into practical clinical methods, demonstrating on the way that – as had been suggested by the earlier results – many late-onset diabetics have a high blood-sugar level because their immune system renders them insensitive to the presence of their own insulin.
With Berson, Yalow extended the scope of RIA into the measurement of growth hormone, gastrin, parathyroid and a wide spectrum of other hormones and serum constituents which, with their individual triggering and controlling proteins, could for the first time be measured accurately from extremely small samples. By the end of this period of research, the technique and basis of RIA was being used in thousands of laboratories throughout the world, providing a platform for a revolution in clinical medicine.
In 1972, when their triumph was widely recognised and the world expected them to receive a fully justified Nobel prize, Berson died from a heart attack, at the age of only 53. Although Berson had already left to extend his own clinical studies, Yalow was shattered. The world believed that Berson, who generally presented their joint work at conferences, had led the research. Yalow realised that if her huge contribution were to be recognised, she would have to prove herself all over again. She embarked upon this task with awesome determination.
Naming her laboratory at the Bronx VA after Berson, and working with Eugene Straus, a young postgraduate physician, she opened up new areas of research in gastric hormones. She demonstrated that the same hormones exist in many different forms, that some have quite separate roles in different parts of the body and that one of these (cholecystokinin) controls appetite and hence obesity. She then pioneered the use of RIA in the detection of drugs, enzymes, and viral and bacterial antigens, eventually opening the way to the investigation of any substance of biological interest.
In 1976 Yalow won the coveted Lasker Medical Research award, which turned out to be the harbinger of her Nobel prize. When her Nobel dissertation was printed in Science, the medical world was embarrassed to find that she had included the text of the letter from the Journal of Clinical Investigation which, 22 years earlier, had rejected Yalow and Berson's discovery and identification of insulin antibodies.
Yalow worked on in her laboratory until 1987, holding professorships in New York at the Mount Sinai School of Medicine and at the Albert Einstein College of Medicine. She was, she said, glad to close the laboratory because "research is becoming grotesquely over-regulated and inhibited". She then embarked on a lecturing campaign aimed at encouraging the entry of women into science. As always she was aggressive, uncompromising and highly focused. These were the qualities that took her to the top in a man's world. "Women have to be better at it than men," she declared. Some described her as "excoriating and vitriolic" but, in reality, this was the stuff of adversity and of brilliant science.
Apart from a few years of postgraduate study at the University of Illinois, Yalow always lived and worked in New York. She was born Rosalyn Sussman of immigrant parents in the south Bronx. A child throughout the depression, angered by poverty and disease, she decided when she was 13 that she would study medicine and become a research scientist. She won a scholarship to Hunter College (a women's college now part of the City University of New York). Legend has it that, to keep his students attentive, her physics professor once declared he would make two mistakes in a long calculation. When he had finished, he asked if anyone had spotted them. "Yes," said Rosalyn, "but which two did you make deliberately? You made three!" To his dismay, she was right.
In spite of her brilliance, she found that being a woman, Jewish and poor made it almost impossible for her to study medicine. Her family could not afford fees and she craved absolute independence. She majored in nuclear physics, and decided to marry and have children as well as becoming a scientist. She knew the difficulties, yet was determined to overcome them.
In 1941, with many male physicists entering the armed services, she was offered an assistantship at the University of Illinois. There she met her future husband, Aaron Yalow (also a nuclear physicist), took a master's degree, realised that techniques of radioisotope tracers being used in plant biology might have much wider application, and took her doctorate under the great Maurice Goldhaber (later director of the Brookhaven National Laboratory).
When the Bronx VA hospital decided to set up a radioisotope laboratory in 1947, Goldhaber said that Yalow should organise and run it. She jumped at the opportunity to pioneer the science of medical physics and, over three decades, transformed the world of clinical medicine. While doing this she had two children and a full family life that fulfilled what she called the "earth mother" component of womanhood. As a scientist she was a tiger, a warrior. "The only difference between men and women in science is that the women have the babies," she said in later life. "This makes it more difficult for women in science, but should not be seen as a barrier, for it is merely another challenge to be overcome."
Her husband died in 1992. Yalow is survived by their son Benjamin and daughter Elanna, and two grandchildren.
• Rosalyn Sussman Yalow, scientist, born 19 July 1921; died 30 May 2011
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