Georg de Hevesy Nuclear Medicine Pioneer AwardCitation-I 986 Rosalyn S. Yalow and Solomon A. Berson

days, we had assays scheduled and Sol would join in pipetting sample after sample, sometimes timing how long it took to do a rack of test tubes and coming up with schemes to accelerate the number of samples we could handle each hour. On other nights, he would pause to review data. One evening, I had just finished extracting from an islet cell tumor in prepara tion to identify and characterize human proinsulin. The next step was to lypholize, or freeze dry, the tumor extract so as to reduce the volume. As it was 10:00 p.m., I was preparing to freeze the sample and pick up where I left off the next day. Sol walked into my lab and asked what I was doing? I was pleased to be at such a significant step . . . and I think he was pleased . . . but he was surprised that I would stop at that point. So at 10:30 p.m., the two of us assembled vacuum tubing to every aspirator in the lab to create the vacuum necessary to reduce the sample volume. If it had been his sample, I'm convinced he would have worked continuously until human proinsulin was confirmed and the struc ture characterized. L@―@

RosalynS. Yalow,PhD,NobelLaureatein Medicineand Physiology, 1977.

n preparing this tribute to the 1986 Hevesy Nuclear Pioneers my task brought to mind the dilemma of I “Salieri―in “Amadeus―(1 ). I share with Salieri the frustration of explaining to others with words what it rr was like to behold genius; two fellow humans with a inexhaustible capacity for hard work and creativity, with a talent for knowing the right experiment to do, ./ for grasping the significance of the findings, for writing manuscripts with clarity and speed, with a love and excitement for exploring, for creating, for teaching oth ers. As with Mozart, it was wonderful. As a Fellow and Research Associate in “TheLab―in 1968and 1969,Ihaveoftenbeenaskedaboutpersonal reminiscences ofthat time. There are many vivid mem @‘ ories, but several stories capture the intensity and the sense of adventure shared by Drs. Berson and Yalow I- and imparted to those fortunate enough to have worked with them. First there was Dr. Berson (“Sol―)who would come to the Lab at 5 or 6 p.m. after 12 hours at The Mt. Sinai Medical Center. He would first meet A@1 I ‘I with Dr. Yalow to review their new results, plan the Solomon A. Berson, MD in his laboratory at the Veterans next experiment or work on their manuscripts. On some Administration Hospital, Bronx, NY.

Volume28 •Number10 •October1987 1637 My contact with Dr. Yalow (“Roz―)was on a daily including posthumous election to the National Acad basis. Sometimes I would work in her lab and we would emy of Sciences. He received numerous honors from talk continuously while we worked. At other times, I scientific organizations and shared with Dr. Yalow the would work in the lab assigned to me and Roz would first William S. Middleton Award from the Veterans come in every few hours to see how I was doing. One Administration for medical research. He was the author day, I had set up a Sephadex column to separate sub of 231 scientific papers. stances in plasma by molecular weight prior to meas Rosalyn S. Yalow was educated in City uring insulin in each aliquot to determine the fraction and is a graduate of Hunter College. She received her of high molecular proinsulin. Doing this was exciting PhD in Physics from the University oflllinois, returning as it had been done successfully only a few times to New York to teach at Hunter and found additional anywhere. I carefully collected each sample for assay as opportunities in the growing field of medical physics. she watched. “Youknow,― she said, “youcould do In 1972, she became Chiefof The Radioisotope Service twice as many samples in the same time if you had two and later—Director of The Solomon A. Berson Me columns―.By the end ofthe week, the cold room looked morial Lab, Senior Medical Investigator at the Bronx like a forest of Sephadex columns, and test tube rack V.A. and Solomon A. Berson Distinguished Service after test tube rack filled with fractions. In short order, Professor at The Mt. Sinai School of Medicine the titles we assayed and analyzed dozens of samples and dem she now holds. She is a member of many scientific onstrated for the first time that except for patients with societies, is a past President of the Endocrine Society, insulin producing tumors, elevated insulin levels were and has been elected to the National Academy of Sci not due to high levels of proinsulin (2). At that same ences. She is the author of 470 scientific papers. time, she was refining the radioimmunoassay of the GI The early work of Berson and Yalow included mile hormone , and also using Sephadex columns on stone investigations using radioactive tracers for the numerous hormonal peptides, demonstrating large mo determination of plasma volume and protein turnover, lecular weight species of gastrin, ACTH and human and radioiodine in diagnosis and illuminating the . pathophysiology of disease. These observations One of my favorite scientific articles is the “Radioim have been published in prestigious scientific journals, munossay of ACTH in Plasma― (3). This paper is a including The Journal of Clinical Investigation and microcosm of the universe of Berson and Yalow. It Science. This was a remarkable accomplishment for a describes in fine detail the methodologic modifications physicist teaching at Hunter College in New York, who required for an assay ofACTH in plasma at physiologic took a moonlighting job in the Radiosiotope Unit at concentrations, and then goes on page after page to the Bronx Veterans Administration Hospital, and for a confirm the validity of the assay by evaluating plasma physician without training in clinical or laboratory in ACTH levels in numerous physiologic and pathophys vestigation, who in July 1950 accepted a part-time job iologic conditions. In Figure 7 from that publication, in the same Unit while he developed a private practice the ACTH values in patients and laboratory personnel in Internal Medicine on Long Island. When their paper were sampled for up to 24 hours. Two of these subjects on thyroidal and renal iodine clearance appeared less slept for a period some time after midnight, and the than 2 years later in the February 1952 issue of the characteristic nocturnal peak ACTH secretory burst is Journal of Clinical Investigation (3), F.R. Keating, a observed. In the other two subjects, the expected diurnal noted thyroidologist, wrote that their paper was “the variation was not observed. It was noted that the sub most important contribution to the problem of diag jects did not sleep. There are no clues to the identity of nostic tracer procedures which had yet appeared― (4). the subjects but those who know the laboratory would The initial observation of insulin antibodies were suspect that our honorees almost foiled the confirma presented 30 years ago at the Society of Nuclear Medi tion oftheir own experiment through their own zeal. cine meeting in 1956 (5). Not content with the quali Solomon Berson was educated in tative observation of antibodies to insulin, Berson and and received his medical degree from NYU in 1945 Yalow further characterized the interaction and re after initially having been denied admission to any ported that “thebinding of labeled insulin to a fixed medical school for several years. After an Internship at concentration of antibody is a quantitative function of City, he served in The Medical Corps of the the amount of insulin present.―This observation pro U.S. Army. From 1948 to 1950, he was a medical vided the basis for the radioimmunoassay of plasma resident at the Bronx VA Hospital. He was Chief of insulin. that service through 1968 when he became Professor Berson and Yalow would exploit this technique to and Chairman of the Department of Medicine of the explore vast areas of medicine—insulin secretion in Mt. Sinai School of Medicine and the Mt. Sinai Hos health and mellitus, the role of human growth pital. He was also a Senior Medical Investigator at the hormone in metabolism and in patients with short Bronx VA and a member of many scientific societies stature, secretion and biology,

1638 Goldsmith TheJournalof NuclearMedicine ACTH and gastrin physiology and the mystery of how Medicine Pioneer Award to Rosalyn S. Yalow and polypeptide hormones are synthesized. Since Dr. Ber Solomon A. Berson. sons death, Dr. Yalow has continued and extended these investigations. REFERENCES On December 7, 1977 Rosalyn Yalow received the Citation and Gold Medal symbolizing the Nobel Prize 1. Shaffer P. Amadeus. New York: Harper and Row, 1980. in Medicine and Physiology. This award recognized the 2. Berson SA, Yalow RS. Radioimmunoassay of ACTH discovery and development of radioimmunoassay. In in plasma. J Clin Invest 1968; 47:2725. her Nobel Lecture, Dr. Yalow stated “From1950 until 3. Berson SA, Yalow RS, Sorrentino J, et al. The deter his untimely death in 1972, Dr. Solomon Berson was mination of thyroidal and renal plasma 1131—clear joined with me in this scientific adventure and together ance rates as a routine diagnostic test of thyroid dys we gave birth to, and nurtured through its infancy, function. J C/in Invest 1952; 3 1:141. 4. Yalow RS, Solomon A. Berson: The VA years. Mt. radioimmunoassay, a powerful tool for determination Sinai J ofMed 1973; 40:281. of virtually any substance of biologic interest. Would 5. BersonSA,YalowRS, BaumanA, et al. Persistence that he were here to share this moment― (6). That of I 13 1-labeled insulin in the blood of insulin-treated thought is echoed in this presentation. subjects. Northwestern Med 1956; 55:54 1. In recognition of their creativity, intellect, and de 6. Yalow RS. Radioimmunossay: a probe for the fine structure ofbiologic systems. Science 1978; 200:1236. votion to their work which has contributed to world health and scientific achievement directly through their Stan/eyi. Goldsmith, MD own research, and also by making possible the subse Andre Meyer Department quent discoveries of so many other investigators of Physics-Nuclear Medicine throughout the world, The Society ofNuclear Medicine Mount Sinai Medical Center presents the 1986 Georg Charles Dc Hevesy Nuclear New York, New York

VoIume28•Number10•October1987 1639