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The Time Dimension
By Charles During the early part of this century, current views on cell biology could be summarized in three words: 1) “specificity,” that is, each cell type has a unique function, which is often to produce a given substance and, conversely, each function is carried out by a specialized cell type; 2) “alternance” of activity and rest,that is, each period of functional activity of the cell is followed by a period during which the activity ceases; and 3) “stability” of the cell make-up, that is, the cell is an unchanging, permanent structure, that makes use of food as energy-providing fuel to carry out its function. In 1927, soon after I entered medical school in Lille, France. the cell properties associated with these threepostulates were repeatedly emphasized by our teachers. Yet in the course of my career,especiallywith the advent of radioautography(alsocalledautoradiography),resultswere obtained that led me time and again toquestiontheir validity. Cell specificity was put into question by results obtained in 1933 when I was a research student at the University of Paris under the guidance of Antoine Giroud, a pioneerin the histochemistry revival of the 1930s. My task was to devise a silver nitrate staining method for the histochemical localization of ascorbic acid (vitamin C). The method was successfully worked out. However, under the influence of the current views on cell specificity, we expected to stain a cell specialized in handling ascorbic acid, perhaps the fibroblast of the periodontal ligament holdingthe teeth, which are known to loosen and eventually fall out in cases of vitamin C deficiency. Instead, a wide variety of cells, particularly a number of endocrine cells, were stained for ascorbic acid (1). Moreover, the postulate that each cell type makes a unique product seems to be valid for some cells, such Philippe


Cell Biology
rected toward the follicle lumen, but would all becomecuboidal when secretory material is resorbed from the lumen for release outside the follicle and would all shift to a flattened form when secretory activity stops. The 1281 available in Paris at the time proved to be too weak to test this theory by ra-


as the beta cells of pancreatic islets producing insulin, but is too restrictive for others; thus, thyroid cells release twohormones, as described below, and pancreatic acinar cells secrete more than 20 enzymes. In addition, besides specific products, cells bring forth accessory ones. For instance, the odontoblasts of growing teeth are known to be specialized in producing dentinal collagen (2), but they also secrete some glycoprotein (2) and phosphoprotein (3). In conclusion, the “specificity” postulate can be retained, butwith qualificatiotis that limit its impact. The allernance of cell function was examined later, when investigating the entry of radioiodine into the thyroid gland. Previously, however, 2 years were spent at Yale University where I observed that while maternal behavior is under hormonal influence in mice, it can be elicited by the continued presence of newborn pups, probably through central nervousmechanisms (4). The work on radioiodine was started in 1937, when I went back to Paris to become a biologist in the Physics Laboratory of Frederic Joliot who, with his wife, Irene Curie, had first produced artificial radioactive substances. It was then possible to prepare radioiodine 128!, whose halflife is 25 rain. When injected into rats and guinea pigs, this iodine appeared in the thyroid glandwithin minutes (5). I also hoped to use radioautography to examine whether thyroid cells collected iodine in a manner consistent with the then current alternance postulate. The thyroid gland is composed of numerous sac-like follicles lined by a layerof uniform cellswhose shape, however, differs in different follicles, and at the time was assumed to change according to the secretory state. Thus,...