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If the rules of etiquette would indicate the lady should be addressed first, and because I shall later show Rosalyn Yalow invited Solomon Berson to work with her in the laboratory, why do I call this The Berson and Yalow Saga and why was their laboratory referred to as The Berson and Yalow Laboratory?
Roz Yalow was born in New York City in 1921 of a German mother and East Side New York father. She grew up as a very bright, willful, very motivated, and determined child and attended public schools. On entering high school, she was much engrossed in mathematics, but in high school she was exposed to a very enthusiastic chemistry teacher, Mr. Mondzak, who temporarily diverted her interests to chemistry. Subsequently, she came under the tutelage of Professors Herbert Otis, Duane Roller, and Jerry Zacharias, who swayed her interests to physics. After reading Eve Curies book on her mother, Marie Curie, and attending a seminar by Enrico Fermi in 1939, her interests in radioisotopes blossomed. She was graduated from Hunter College, magna cum laude and Phi Beta Kappa (1).1
Although it was a foregone conclusion that women did not fare well in the scientific arena, particularly in physics, nor were they welcome in graduate teaching positions, due to her persistence or the dearth of males in graduate schools in World War II, she was admitted to the graduate program in physics at The University of Illinois in 1941, on a scholarship. Roz Yalow was the only woman on the faculty of 400 at The College of Engineering. She received a M.S. degree in Nuclear Physics in 1943 and a Ph.D. in January 1945.
While at The University of Illinois, she met her future husband, whom she married in 1943. He was in the same program and also on scholarship. He subsequently became Professor of Physics at Cooper Union College.
Back in New York, in 1945, Dr. Yalow obtained a teaching position at Hunter College. Because she did not feel it was sufficiently challenging for a full-time career, she volunteered to work in the laboratory of Dr. Edith Quimby at the College of Physicians and Surgeons of Columbia University, to learn the medical applications of radioisotopes. Through Dr. Quimby, she met Dr. G. Failla, one of the foremost physicists in the country. He introduced her to Dr. Bernard Roswit, Chief of Radiotherapy at the Bronx VA Hospital, who hired her as a part-time consultant to equip and develop the Radioisotope Service. In January 1950, she resigned from the faculty of Hunter College and went to work at the Bronx VA Hospital full time.
In the spring of 1950, Dr. Yalow realized she needed an associate with a clinical background in medicine, but was unable to find someone to meet her standards. She consulted Dr. Bernard Straus, Chief of Medicine at the Bronx VA Hospital. He introduced her to Dr. Solomon Berson, whom he described "as the brightest physician I have ever trained." Although Dr. Berson had already committed himself to a position in the VA Hospital in Bedford, Massachusetts, he had a long interview with Dr. Yalow, during which they challenged each other with mathematical problems. Later, commenting on the interview, she stated, "After half an hour, I knew he was the smartest person I had ever met." He must have been equally impressed by her, because he resigned his prior commitment and joined Dr. Yalow at the Bronx VA Hospital (1).
Solomon Berson was born in New York City in 1918. His father was a Russian immigrant who had studied chemical engineering at Columbia University, but subsequently applied his knowledge to the business of dying furs. Early in life it was observed that Sol was very bright, an excellent mathematician, an accomplished violinist, a master bridge player, and an expert chess player. After being graduated from the City College of New York in 1938, and being rejected by many medical schools, he entered New York University and earned a M.S. degree and a fellowship to teach anatomy in the Dental School. In 1941 he was admitted to New York University School of Medicine, from which he graduated AOA in 1945. He interned at Boston City Hospital from 1945 to 1946, then joined the Army as a Medical Officer from 1946 to 1948. Subsequently, for 2 yr, he served as a resident in medicine at the Bronx VA Hospital, following which he joined Roz Yalow in the Radioisotope Laboratory. The first year he also moonlighted in the private practice of medicine, which he enjoyed very much. However, due to the demands of the research work in which he had become involved, he discontinued the part-time practice (2).
It was generally known in their laboratory that Berson and Yalow liked to work by themselves, sometimes even to the point of washing their own glassware. They had a large joint office, to which the office door was always closed. They liked to do their own thinking and have their own discussions in private. They were both very diligent and devoted to their work, to the point that the time of the day or night was not permitted to interrupt an experiment or project on which they were working. This self-discipline was carried over to their limitation of the number of their research fellows, usually two at a time for a year or two, followed by a similar period without any, after which they would take on one or two more for a few years. The explanation given for this was that much though they enjoyed teaching, the time it detracted from their research was more than they wanted to forgo.
It is not clear how the idea of the RIA and tagging of insulin was conceived. Bauman and Rothschild stated that Bauman approached Sol Berson and suggested that the laboratory tag insulin and they study its behavior. As Bauman informed me, he approached Berson and said, "Hey Sol, why not tag some insulin and see where the body handles it? Sols answer to me because he was involved in other work at the time was, Im too busy. The second time I approached him, he said he was still too busy, but that didnt discourage me. The third time I said, Sol, I called him Boss at the time, what about insulin? Finally, he called out to Kitty, who was our chemist, and said, Kitty, tag some insulin!" When I later discussed this matter with Jesse Roth, his opinion was that Berson and Yalow had become disenchanted with their work on albumin, because their work had been scooped by Ken Sterling, so decided to look for another pure protein. The possibility exists that since Yalows husband was a diabetic and insulin was another pure protein, she was emotionally influenced to undertake the study of tagged insulin. Shimon Glick, another of their fellows, who was in the laboratory at the same time as Jesse Roth, attributed the stimulus for this study to Dr. I. Arthur Mirsky.1
When this question was presented to Dr. Yalow, and I asked her if it initially was thought of by one or the other, she replied, "We spoke to each other about it, it was a possibility." However, in an article entitled "Remembrances in Endocrinology" in 1991 (3), she stated, "It was a serendipitous discovery in that it was fallout into what might be considered an unrelated study. Prompted by the suggestion of Dr. I. Arthur Mirsky that maturity onset diabetes might not be due to an absolute deficiency of insulin secretion, but rather is abnormally rapid degradation by an enzyme, which Dr. Mirsky called insulinase, Dr. Solomon A. Berson and I attempted to study the metabolism of I-131 after iv administration to diabetic and nondiabetic subjects. We observed a slower rate of disappearance of the I-131 insulin from the plasma of the subjects who had been treated with insulin whether or not they were diabetic. We postulated that the slower disappearance was a consequence of the binding of labeled insulin to antibodies that had developed in response to administration of foreign proteins, i.e. animal insulin. We used a variety of physicochemical systems, including among others, paper electrophoresis, ultracentrifugal analysis and salting out methods to prove that the protein that bound insulin in the plasma of insulin treated subjects had the characteristics of an antibody, an IgG immunoglobulin."1
The earliest application of the RIA was to tag red blood cells, electrolytes, iodine, and albumin, to study blood volume, red blood cell survival, bone and muscle metabolism, and thyroid function among many other metabolic processes. Arthur Bauman and Marcus Rothschild were the first to test the RIA clinically, followed a few years later by Enoch Gordis, Shimon Glick, and Jesse Roth.
Arthur Bauman, whether because he was given the assignment or because he convinced Berson to have insulin tagged, undertook its administration to about six patients and observed that at the end of 24 h, there was still 24% of the insulin remaining in the blood stream, when according to all calculations, there should have been none. Berson then took over the problem and, after much painstaking investigation, concluded it was due to the presence of insulin antibodies in the blood stream. This conclusion was arrived at when they realized that of the patients they were studying, in whom the tagged insulin persisted, were psychiatric patients who had been given insulin to create hypoglycemic shock. The previously administered insulin stimulated the body to the production of antibodies. Hence, they concluded that an insulin-binding globulin or insulin-binding antibodies retained the insulin in the blood stream. The rest of the story is well known to anyone who has had an interest in RIA or Berson and Yalow. Their first article was rejected both by Science and The Journal of Clinical Investigation, because the reviewers and editors were unable to comprehend that so small a molecule as insulin could stimulate the production of antibodies in the human. By removing the term "insulin binding antibody" from the title, they appeased the editors and reviewers of this epoch-making report, which was finally accepted by The Journal of Clinical Investigation in 1955 and published in February 1956. Subsequent to the work mentioned, Bauman worked on tagged iodine in the study of thyroid space and other thyroid problems. He eventually left Berson and Yalow to go into private practice, specializing in endocrinology and nuclear medicine.
Rothschild also worked with Bauman on the original tagged insulin studies, as well as on serum albumin, blood volume studies, and other tagged elements. He had been invited by Sol Berson to continue to do research in the laboratory, but after much contemplation replied, "Sol, Im so thrilled, but I cant do this. If I was to work with you or for you, Id always be doing the things that you wanted done, because I cant outthink you, I cant compete with you and I would never know whether I can ever do anything on my own." Rothschild then moved from the Bronx VA Hospital to the VA hospital in Manhattan, with Bersons help. There, he continued to work in the fields of cardiac physiology and nuclear medicine, using radioactive sodium and potassium to study the exchange of salts across the pulmonary membrane. Fortunately, while there, he was able to work with another Nobel Laureate, Andrea Cournand. He subsequently became head of his own Nuclear Medicine Laboratory in the VA, associated with New York University. Most recently, and up to the time of his retirement, he became involved in the study of alcoholism and also the effects of alcohol on the liver. He subsequently became editor of the journals Heptology, The Journal of Alcoholism, and Seminars on Liver Disease.1
In 1963, Berson and Yalow approached Gerald Aurbach and John Potts to develop the first RIA for PTH, the report of which was published that year. On their own, Berson and Yalow later discovered the heterogeneity of circulating PTH, an important, clinically relevant finding.
In approximately 1960, Melvin Grumbach suggested to Berson and Yalow that they should look into the possibility of developing an RIA for GH. This challenge was assigned to Roth and Glick. They undertook the project of developing a RIA for GH in the summer of 1961, and their efforts were realized by 1963. One finding that stimulated the progress of their investigations was the realization that insulin hypoglycemia caused a significant increase in the secretion of GH. Subsequently, Glick and Roth published several noteworthy articles on the subject and presented their work on the development of the RIA for GH at the national meeting of The American Society of Clinical Investigation. It met with such great acclaim that Glick received a standing ovation at the termination of his presentation. Subsequently, they were invited to speak at many meetings and received many job offers.1
When Glick left Berson and Yalow, he became Associate Director of the Division of Endocrinology and Metabolism at Maimonides Hospital in New York and, for the next 3 yr, Chief of Endocrinology at Coney Island Hospital, a city hospital. He subsequently was named Chief of Medicine. Unfortunately, because of inadequate financing and other reasons, the medical care at Coney Island Hospital was very poor. Glick got together with Gary Thompson, who subsequently became Chief of Medicine at Harlem Hospital and later Associate Dean at Columbia, and organized the Chiefs of Services of the New York Municipal Hospitals into an organization called The Society of Urban Physicians. Their objective was to improve medical care in the New York City hospitals. In 1974, Glick moved to Israel, became the first Chairman of the Department of Medicine in a new medical school, and ultimately was named Dean of the Faculty of Medical Sciences of the Ben Gurion University of the Negev. He has also been editor of many journals and on editorial boards of many others. In between all of his other responsibilities at the medical school in Israel, he was a visiting scientist at the National Institutes of Health (NIH) in 19831984.1
After the GH project had been accomplished, and because Jesse Roth was at the point where Vietnam was a cloud on the horizon, Sol Berson encouraged him to go to the NIH to continue his research. Berson feared that if Roth went into the military service, he would never get back into research, which would have been a great loss to medical science. He, therefore, contacted a friend at the NIH who assisted Roth to get into the Clinical Endocrinology Branch in 1963.1
There were several projects pending on GH RIAs when Roth and Glick left the Bronx VA Hospital. This work was completed and published subsequently. In the next few years, at the NIH, they perfected a RIA for vasopressin, then spread out and with the help of M. J. Peterson, Gary Robertson and others, and developed assays for ACTH, FSH, adrenal hormones, insulin, and proinsulin with its various components.
In 1963, Roth began to work with Ira Pastan on the first studies on receptors, which were continued with Robert Lefkowitz over a period of the next 6 or 7 yr. His most important work was the 1970 reports on "The Radioreceptor Assay of ACTH."
Among Roths other accomplishments, in conjunction with Glick, was the discovery that in acromegalics there was nonsupressibility of GH secretion, following the administration of glucose. In association with these diagnostic studies, he also accumulated a sufficiently large series of cases of acromegaly to probe that irradiation following surgery was the most efficacious form of therapy. In another study of Mexican Americans and Pima Indians in the southwest, he observed a greater incidence of obesity and diabetes in these ethnic groups.
There were other fellows whose careers were influenced by Berson and Yalow, who worked in the laboratory part time, nights, or in addition to medical residencies at the hospital. Enoch Gordis became Director of the National Institute on Alcohol Abuse and Alcoholism. He had been a fellow in the year 1958 to 1959.
Sheldon Rothenberg worked in the laboratory nights and weekends while completing his medical residency at the Bronx VA Hospital. He developed the first assays on vitamin B-12 and folate. Because he worked wholly on his own, neither the names of Berson nor Yalow are coauthors. He became Professor of Medicine and Chief of Oncology and Hematology at State University of New York Health Science Center in Brooklyn, New York.
Sidney Schreiber was interested in cardiac physiology and worked with Rothschild on albumin metabolism. Together, they developed the Nuclear Medicine Service at the Manhattan VA Hospital.
Stanley Goldsmith became Chief of Nuclear Medicine at Mount Sinai Hospital in New York.
John Walsh worked on gastrin while in their laboratory and later became a world authority on gastrointestinal hormones. He also helped develop the first assay on a virus, the assay for hepatitis B virus.
Dr. Eugene Strauss worked with Dr. Yalow a few years after Bersons death and wrote an excellent biography on her life. He subsequently became Chief of the Division of Digestive Diseases of the Department of Medicine State University of New York Health Sciences Center in Brooklyn.
One of the most recent of the great achievers of their fellows and associates is a second-generation physician and scientist, William A. Bauman. Between 1979 and 1982, he was a fellow in endocrinology at the Bronx VA Hospital and at Montefiore Medical Center, subsequent to which he became Physician/Research Associate at the Solomon A. Berson Research Laboratory, Associate Professor of Medicine at the Albert Einstein College of Medicine, and Professor of Medicine and Rehabilitation Medicine at Mount Sinai School of Medicine. His most significant studies were the use of RIA of insulin in the differential diagnosis of malingering, factitious administration and criminal use of insulin to cause hypoglycemia, and innovative and extensive studies of endocrine changes in paraplegics, in many cases using healthy twins as controls.1
Although there were many other excellent scientists whose lives and work were influenced by Berson and Yalow, I have only mentioned those whose work was directly associated with them.
An admirable characteristic of Berson and Yalow is that they always welcomed visiting scientists to their laboratory and were never reluctant to teach them their methods or to help them use the RIA technique to identity additional proteins for their own particular research use (1).
With all respect to their disciples, I think recognition of the achievements of Berson and Yalow by the scientific community is worthy of reiteration. Berson was a member of the National Academy of Sciences and Professor of Medicine and Chairman of the Department of Medicine at Mount Sinai School of Medicine. As mentioned earlier, Dr. Bernard Straus once said of Dr. Berson, "He is the brightest physician I have ever trained." In interviewing Dr. Shimon Glick on his relationship with the Berson and Yalow laboratory, he said, "When we [meaning he and Roth] first began to work with Berson and Yalow, we quickly developed an inferiority complex because Berson was so smart it was beyond comprehension. He was a real renaissance man; higher mathematics for him was like ABC. He would go away on a vacation and take four or five books on higher mathematics that he hadnt read before. He was violinist, a connoisseur of the arts, and a phenomenal chess player. I mean, he was just an unbelievable guy." In Dr. Yalows biographical summary at The Nobel Prize Awards Ceremony, she said, "Sols leaving the laboratory in 1968 to assume the Chairmanship of the Department of Medicine at Mount Sinai School of Medicine and his premature death four years later were a great loss to investigative medicine. At my request, the laboratory which we shared has been designated The Solomon A. Berson Research Laboratory so 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." Dr. Rolf Luft in his notifying Dr. Yalow of her award, and in reference to Dr. Berson, explained that it was explicitly noted in the will of Alfred Nobel that the prize was not to be awarded posthumously, unless the person to whom it had been awarded died between the time of notification and its bestowal (1).
Dr. Yalows accomplishments were culminated by the award of The Nobel Prize. In addition to having been elected to the National Academy of Sciences, she is also a member of the American Academy of Arts and Sciences. She has received more than 50 awards, including The Albert Lasker Award, The Gairdner Foundation Award, The Lilly and Banting Awards of the American Diabetes Association, the first Veterans Administration William S. Middleton Award for Medical Research, The G. van Hevesy Nuclear Medicine Pioneer Award, and The Fred Conrad Koch Award of The Endocrine Society, of which she was the first female President.
Among Yalows personality characteristics were her firm belief that a woman could do a good job in her chosen profession and still be an attentive mother. She was also an ardent campaigner for equal rights for women and was most adamant that person be recognized for their accomplishments, and not for their gender.1
Having read this article, I dont think any further discussion is indicated to explain to the reader the title of the partnership of Berson and Yalow.
Acknowledgments
I express my appreciation to Susan Koppi and Lenne Miller, of The Endocrine Society staff, for editorial assistance in the preparation of the manuscript.
Footnotes
A.F. is Staff Consultant of The Endocrine Society History Project.
1 Bauman, A., W. Bauman, S. Glick, J. Roth, M. Rothschild, and R. Yalow, personal communication.
Received March 28, 2001.
Accepted March 22, 2002.
References
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