Science
Radioimmunoassays lead three to Nobel Prize Development of sensitive radioimmunoassay methods enabled scientists to find the peptide hormones that control much body chemistry "The beauty of this field, unlike many others, is that we're really just beginning, and the work is almost still in its infancy." So says a colleague of Dr. Andrew S. Schally, one of this year's three recipients of the Nobel Prize in Medicine & Physi ology. The prize was granted for work on radioimmunoassays (RIA's) and on pep tide hormones—two areas that have en joyed profound growth since the early 1950's. Joining Schally, who is senior investi gator at the Veterans Administration Hospital in New Orleans, are Dr. Roger Guillemin of Salk Institute in San Diego and Dr. Rosalyn S. Yalow, director of the Solomon A. Berson Research Laboratory of the Veterans Administration Hospital, Bronx, Ν.Ύ. All three scientists are ac tively studying peptide hormones—and, in particular, a group of such molecules that play kingpin roles controlling phys iology and behavior. This year's Nobel Prize was split asymmetrically, a gesture that reflects how this research has developed. Yalow, who is the first woman and the first nu clear physicist to have won the Albert Lasker Basic Medical Research Award
Rosalyn Yalow 36
C&ENNov. 7, 1977
(1976), was awarded a half share of the Nobel Prize. She was cited for "develop ment of radioimmunoassays of peptide hormones." Schally and Guillemin, who share the remainder of the prize, were cited for "their discoveries concerning peptide hormone production of the brain." Their work would have been "al most impossible" without RIA's, says a colleague active in the field. Thus, Yalow's contribution of a pow erful analytical technique gave birth to a whole area of research and made possible the discovery and description of a host of compounds that exert potent control over body functions. The impact of RIA's also goes beyond basic research, as they are used in clinical assays. The RIA takes advantage of the sensi tivity and selectivity of antibody-antigen interactions. Typically, to develop an RIA, one first must purify an antigen—for example, a particular peptide hormone. Next, specific antibodies to this antigen are raised, usually by injecting the antigen (or a derivative) into an animal such as a goat or rabbit. Also, a stock of radioactively labeled antigen is made. Together, these two ingredients make up a "kit" that when calibrated becomes the basis for an assay. Tissue samples, or samples from purified extracts, are added back to this kit, and the degree to which a sample competes with the labeled antigen for the antibody is a direct measure of that sam ple's antigenic content. The earliest RIA's developed out of insulin studies in the 1950's by Yalow and the late Solomon A. Berson. They intro duced radioactive iodine labels into the
Roger Guillemin
insulin peptide to monitor its action in diabetics. During these studies, they also noted that insulin-treated diabetics carry antibodies to this hormone—an obser vation controversial enough to keep their paper from passing peer review in Science. Ironically, this observation is a cornerstone of RIA's, which depend on the ability of "natural" molecules such as insulin or other hormones to elicit anti body production. Yalow's attentions now are turned, in part, to another set of seemingly out-ofplace molecules. They include several peptide hormones that are known to exert specific and profound effects in a partic ular organ, but have since been found in organs that carry out completely different functions. For example, Yalow and her colleagues find the peptide hormone cholecystokinin in the cerebral cortex of pigs. Ordinarily, this molecule—along with another shorter peptide derived from cholecystokinin's final (carboxy-terminal) eight amino acids—is found in the gut where it exerts potent physiological ef fects. The role of either peptide in brain tissues is unknown, though they might control sensations such as hunger and satiety. It is just such probing into the where abouts and origins of particular molecules that brought Guillemin and Schally to look at the pituitary gland. This gland secretes an assortment of hormones that control diverse body functions such as growth (growth hormone), stress (adrenocorticotropin), and reproduction (leutinizing hormone and follicle stimulating hormone).
Andrew Schally
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