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Localization and Integration of Cellular Function^*

( National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md.)

Despite several areas of confusion and doubt, mostly attributable to defective methods, the cytochemical data presented here permit us to arrive at certain general conclusions that are difficult to refute. Thus, it is obvious that, from a biochemical standpoint, the cell is not simply a bag of enzymes arranged in a haphazard fashion and dependent only on the laws of diffusion for their integrated function. Nor is the cell biochemically only a nucleus or, as some schools of thought would apparently have it, a collection of mitochondria. It is, on the other hand, a complicated mosaic of structural units that are endowed with specific biochemical properties. Furthermore, although some degree of functional autonomy may be indicated in the case of certain elements, the mitochondria in particular, there is reason to believe that in no single instance is this autonomy complete but rather that the structural units are mutually dependent on one another in their contribution to the metabolism of the cell. The data would also appear to have some bearing on differentiation, or at least that aspect of differentiation involving the strategic intracellular location of these specifically endowed structures so that their individual activities can be integrated efficiently in the over-all function of a tissue. In heart muscle, for example, the relationship of the mitochondrion to the myofibril (36, 84) is an ideal arrangement for the resynthesis of ATP degraded during muscular activity. In view of the experi nents of Bartley and Davies (4) on the secretory activity of kidney mitochondria, the polar distribution of these structures in the tubular cells of the kidney would seem to be another example. These are not new ideas. For many years, the cytologist has had them in mind. Now, however, there are concrete biochemical data to back them.

In a consideration of the future of cytochemistry, the important questions are what, specifically and incontrovertibly, is the function of each type of cell structure, and, to be less academic and more practical, what happens to these structures in cellular dysfunction. It is reasonable to predict, for example, that cytochemical investigations will eventually play an important role in the understanding of carcinogenesis. Although some cell fractionation studies have been concerned with unraveling the carcinogenic process, the cytochemical information available in that field is much less complete than that available for the normal cell. There is still a great deal to be done before the problem of cancer can be discussed intelligently from the cytochemical standpoint.

^* Presented April 10, 1953, to the American Association for Cancer Research as part of a symposium entitled "The Morphology and Activities of Living Cells and Cellular Components."

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