Abstract
Over a period of almost 30 years, Gomori was one of the most prolific and productive investigators in the emerging field of enzyme histochemistry and was recognized by his peers as a pioneer in developing methods for the histochemical demonstration of hydrolytic enzyme activity, most notably phosphatases, esterases, and lipases. Gomori also made important contributions to diabetes research by developing histological techniques that reliably stained the insulin-secreting B cell of the pancreatic islets of Langerhans. Gomori’s aldehyde fuchsin staining method was standard for pathological and physiological studies on islet B cells in relation to diabetes and obesity until insulin antibodies became widely available for immunohistochemical identification of B cells. Gomori was a founding member of The Histochemical Society in 1950. When the HCS established the Journal of Histochemistry and Cytochemistry in 1953, Gomori served as one of the first Associate Editors. He also served as President of The Histochemical Society.
With the Journal of Histochemistry and Cytochemistry entering its 72nd year of continuous publication, it is befitting to recount the scientific contributions of its founders. The Journal of Histochemistry and Cytochemistry was first published in 1953 by The Histochemical Society, with Ralph Lillie as the inaugural editor-in-chief. Lillie successfully launched the journal with contributions from, and an editorial team of, distinguished pathologists and cell biologists that included George Gomori, who eventually would replace Lillie as editor-in-chief of the Journal.
George Gomori was born in Hungary in 1904 (Fig. 1). He received his MD in 1928 at the University of Budapest, where he held a position that was equivalent to an assistant professor of surgery and pathology. In 1928, he moved to the University of Chicago where he was professor of internal medicine and earned his PhD in pathology.
George Gomori. Image courtesy Special Collections Research Center, University of Chicago Library. Previously published as Fig 4 with permission in Baskin. 1
Over a period of almost 30 years, Gomori was one of the most prolific and productive investigators in the emerging field of enzyme histochemistry and was recognized by his peers as a pioneer in developing methods for the histochemical demonstration of hydrolytic enzyme activity, most notably phosphatases, esterases, and lipases. This was a golden age for enzyme histochemistry and Gomori produced seminal contributions to the newly developing field. However, the histochemical techniques for detecting enzyme activity that he was famous for are no longer in common use and I suspect that few current investigators have ever used them, as most of those techniques have been supplanted by modern methods.
Gomori is best known for adapting biochemical techniques that were used for identifying enzyme activity in tissue homogenates to the in situ localization of enzyme activity in cells visualized by microscopy in tissue slices. His 1939 classical paper on the histochemical demonstration of alkaline phosphatase in kidney marked a seminal milestone in the era of enzyme histochemistry. 2 In 1952, he published one of the first standard texts of histochemistry that was a standard for the theory and practice of using stains for in situ microscopic anatomy and histochemistry, which he defined as a borderline discipline between histology and biochemistry. 3
In addition to his research on enzyme histochemistry, Gomori dabbled in developing and improving histological staining techniques that would reveal different tissue components and cell types based on tinctorial staining reactions, and some of these methods are still use today, such as his trichrome stain for collagen and muscle. Not as well known, however, is that Gomori made important contributions to diabetes research by developing histological techniques that reliably stained pancreatic islet cell types, and the insulin-secreting B cells in particular.
The endocrine cells collectively known as the islets of Langerhans were first described in the human pancreas by Paul Langerhans, a student of the renowned German pathologist, Rudolf Virchow, in his medical thesis at the Berlin Pathological Institute in 1869. Langerhans described the islets as “. . . islands of clear cells” throughout the pancreas, reflecting their transparency in comparison with the pancreatic exocrine parenchyma when viewed in tissue sections by microscopy. The function of these cells was unknown at that time, but in a prescient statement, Langerhans speculated that they might be related to glucose metabolism, as later pathophysiological studies demonstrated that the function these islet cells was definitively associated with glucose metabolism and diabetes mellitus.
By 1900, pathologists had noted that islet morphology and histological staining changed markedly in the pancreases of humans and other mammalian species with diabetes mellitus. Early histological staining techniques that were commonly employed by pathologists during that period, such as hematoxylin and eosin and various trichrome stains, revealed several cell types in the islets based on tinctorial staining properties. The physiological significance of these staining differences was gradually elucidated over several decades by pathophysiological studies on the pancreases of humans and experimental animal models of diabetes mellitus.
An example can be found in the classic paper by Michael Lane, published in the American Journal of Anatomy in 1907. 4 Lane described and illustrated islets with detailed drawings that show guinea pig islets stained with chrome hematoxylin following different fixations. Lane demonstrated that pancreases that had been fixed with 70% ethanol showed violet-stained cells, which we now know are the islet A cells that secrete glucagon, although this function was unknown at that time. The cells that we now know secrete insulin, the islet B cells, were unstained with this technique following alcohol fixation. In contrast, when the pancreases were fixed in formalin, the islet B cells that we now know secrete insulin stained violet with chrome hematoxylin, whereas the A (and other) cells were unstained. Unfortunately for pathophysiologic studies on human islets, Lane’s method was specific for guinea pig islets; the islet B cells of humans and experimental animals stained weakly or not at all.
For the next 30 years, a variety of methods for identifying islet cell types, and the B cells in particular, were developed but they produced poor and irregular results on islets of humans. The ability to reliably stain islet B cells and differentiate them from other islet cell types was of great importance, for physiological and pathophysiological data had identified the B cell as the most likely origin of insulin, which was isolated from islets by Banting and Best in 1921 and used clinically to ameliorate diabetes mellitus in humans. This need set the stage for introduction by Gomori of two staining methods for selective staining of B cells in islets and ushered in the “Gomori Age” of islet pathophysiology in diabetes research.
In 1939, Gomori published a method for differentially staining cell types in pancreatic islets. 5 This was followed in 1941 by his publication of a chromium hematoxylin and phloxine trichrome technique that was paired with the Mallory-Heidenhain Azan stain for differentiating islet A, B, and D cells (later shown to secrete somatostatin), based on staining 70 human pancreases. Notably, the islet B cells of humans stained intensely blue. This was called the “Gomori stain” and was widely used as the standard histological technique for pathophysiological studies in humans and experimental animals in diabetes research. While the method also stained many extrapancreatic cell types such as adenohypophyseal cells, when applied to the islets the method was considered specific for B cells.
In 1950, Gomori published an aldehyde fuchsin staining method for elastic fibers that fortuitously also stained the cytoplasmic granules of islet B cells as well as a variety of other endocrine cells, neurosecretory cells in the neurohypophysis, adenohypophyseal basophils (TSH and gonadotrophs), gastric chief cells, and mast cells. 6 This protocol became known as the Gomori aldehyde fuchsin stain. While the technique was capricious (partly because the fuchsin staining solution had to be “aged”), it did stain islet B cells intensely and in rough proportion, to insulin content, and other islet cell types were unstained. Because this method was favorable for quantitative measurements of B cell mass and changes with diabetes, the Gomori aldehyde fuchsin staining method was standard for pathological and physiological studies on islet B cells in relation to diabetes and obesity for the next 25 years, well into the 1970s 7 when insulin antibodies became widely available for immunohistochemical identification of B cells.
It is interesting and worthwhile to note that although Gomori’s aldehyde fuchsin method was selective for B cells when applied to islets, the method was not believed to be based on staining of insulin per se. Gomori himself did not think so, but he claimed that he was not able to determine the chemical basis for the staining specificity. While the chemical basis for the staining of B cells was unknown, it was thought to be related in part to the disulfide groups of the proinsulin molecule, but there is also evidence in the literature that disputes this. Interest in determining the chemical basis for the Gomori aldehyde fuchsin stain and its use for islet histology was eclipsed by the introduction of immunocytochemical techniques for identifying islet cell types in the 1970s. While antibody-based staining techniques are clearly superior to Gomori’s aldehyde fuchsin method for identifying islet B cells, it is not a stretch to say that islet B cells could already be reliably identified on the basis of their morphology and staining properties with Gomori’s aldehyde fuchsin before the use of immunohistochemical techniques appeared. 1
George Gomori was one of the founding members of The Histochemical Society in 1950. When the HCS established the Journal of Histochemistry and Cytochemistry in 1953, Gomori served as one of the first Associate Editors. He also was elected President of The Histochemical Society in 1956. 8 Unfortunately, he passed away in 1957 at the age of 53 while on leave at the Palo Alto Medical Clinic in California. The Histochemical Society established The George Gomori Award in 1987 to honor Gomori and to recognize outstanding contributions to the field of histochemistry and cytochemistry.
