FUNCTIONAL CHANGES IN STRUCTURE 65 



achieved by turthcr observations because the strLielural modulations inxohed were 

 too subtle tor the resolving power ol the light microscope and because correlated 

 morphological and biochemical studies, like the one Heideiihain had carried 

 through, had to be shitted inside the cell. I'or a long time such an operation was 

 impossible and, as a result, the intracellular part ot the secretory process inevitably 

 became a matter of speculation rather than a topic of factual research. 



At present, however, we can take advantage of the higher resolving power of 

 the electron microscope in the hope that, at the diinensional level it explores, some 

 structural modulations will be distinct enough for clear interpretation. Of course 

 the electron inicroscope has its own liinitations. Many structural changes, and 

 probably the most significant ones, remain beyond its present resolving power, 

 but what has been gained over the light microscope is already impressive. It can 

 be said, without exaggeration, that the instrument can become an important and 

 efficient tool for research in general and special cell physiology, just because it can 

 be used to analyze naturally occurring or experimentally induced structural modu- 

 lations. If, in addition, cell fractionation procedures are concurrently used, com- 

 plementary information can be obtained aliout the chemistry and the biochemical 

 activity of the cell components studied. Finally, if the structural changes, chemical 

 constitution, and biochemical activity of the various cell components are followed 

 in time during a significant period of the activity of the gland, and if the results 

 are integrated, one may hope to find answers to such questions as: where are the 

 digestive enzymes produced inside the cell and how are they handled therein 

 before release? Prompted by such hopes. Dr. Philip Siekevitz and I decided to 

 undertake such a project which, as can be seen, combines new techniques with 

 old and simple experimental approaches (36-39). It is, one could say, a collabora- 

 tion over almost a century between Rudolf Heidenhain, Philip Siekevitz, and 

 myself. 



I have chosen three examples, taken from our study of the secretory cycle of the 

 pancreatic exocrine cell, to illustrate the type of information that can be obtained 

 at present by electron microscopy, either alone or in combination with cell frac- 

 tionation procedures. 



Association of Mitochondria With Lipid Inclusions in Fasting Animals. 

 Under normal conditions the exocrine cells of the pancreas are poorly syn- 

 chronized: some of them have completed the storage of new zymogen granules, 

 while others are still at the beginning of this operation. We tried various means 

 to bring in step the cell population of the gland, and the best we found was to 

 starve our experimental animals, the guinea pigs, for 48 hours. At the end of this 

 period, all the exocrine cells were loaded with zymogen granules and at the follow- 

 ing food intake most of them simultaneously discharged their secretory products. 

 In addition to a relatively good synchronization of the acinar cells, the fasting 

 has yielded an interesting byproduct which will be presented as a first example 

 of structural modulation. 



