PALADE 39 



rest of the cytoplasm. Porter, continuing the study of this structure in cultured 

 material, arrived at the conclusion that it consisted of vesicles and tubules 

 interconnected in a continuous network. Since the network was restricted to 

 the inner or endoplasmic region of the cytoplasm, he proposed the name endo- 

 plasmic reticulum for the entire structure [29, 30]. The discovery of this net- 

 work provided a likely candidate for the role of microsomal precursor within 

 the intact cell, and indeed both Claude [31] and Porter [30] speculated that 

 the microsomes might represent derivatives of the endoplasmic reticulum, but 

 the assumption could not be verified at the time because the electron microscopy 

 of cells and tissues was still in infancy. The examination of a liver cell, for 

 instance, was a difficult and uncertain project; in fact, the first attempt [32] 

 to identity "microsomes" in electron micrographs of sectioned hepatic cells 

 yielded misleading results. 5 



In the early 1950's, however, a succession of technical improvements covering 

 the whole series of preparative steps [33, 34] but affecting primarily microtomy 

 [35, 36] made possible the examination of thin sections of practically all cell 

 types in the electron microscope. With this spectacular breaking through the 

 barriers of technical difficulties, the search for the intracellular equivalents of 

 the microsomes finally became possible. But most electron microscopists en- 

 gaged at that time in the study of the fine structure of the cell were not directly 

 interested in the microsome problem; they were rather attracted by a related 

 question: namely that of the structural substrate of cytoplasmic basophilia. 

 Apparently it did not matter, because, as already mentioned, the two problems 

 were expected to have a common solution. In the newly opened realm of fine 

 cellular organization the microscopists found an unsuspected and, at the begin- 

 ning, puzzling abundance of structures. After a few years spent in deciphering 

 these findings and in arguing about various interpretations, 6 it became clear 

 that the ground substance of the cytoplasm contained an extensive system of 

 spaces, described as vesicles, tubules, and cisternae 7 (figs. 1 and 2), limited by 

 a thin membrane (~ 7 m/*) and interconnected in a more or less continuous 

 network. 



It was soon realized that the so-called ground substance of the cytoplasm was 

 divided into two distinct phases by the existence of this internal membrane 

 system: one represented by the content of the interconnected vesicles, the 

 other by the surrounding cytoplasmic matrix. It was also observed that small, 

 dense particles, ~ 15 m/x in diameter, appeared to be attached to the membrane 

 (on the surface facing the cytoplasmic matrix) in certain parts of the reticulum 

 (fig. 2) while other parts remained free. In addition, it was found that similar 

 particles occurred apparently freely scattered throughout the cytoplasmic matrix 



r ' Masses of glycogen were apparently taken for microsomes. 



6 Representative samples of the various interpretations advanced can be found in refer- 

 ences 37 to 39. 



7 The term designates flat, shallow vesicles which measure only 50 to 70 m(i in depth 

 but reach into microns in the other two directions. 



