38 MICROSOMAL PARTICLES 



one — the light microscope — did not have enough resolving power, and the other 

 — the electron microscope, introduced in biological research at the time of the 

 discovery of the microsomes — could provide the necessary resolution but pre- 

 paratory techniques for the electron microscopy of biological specimens were 

 still inadequate. As a result the microsomes remained until recently a cyto- 

 chemical concept only, without a known structural counterpart in the organiza- 

 tion of the intact cell. Many cytologists and cytochemists even doubted that 

 these small bodies were derived from a pre-existing cell structure and were 

 inclined to consider them artifacts due to cytoplasmic clumping or mitochon- 

 drial fragmentation [23] during the homogenization of the tissue. 



Because of their characteristically high content of RNA, the microsomes were 

 rather early correlated with the so-called "basophil substance" of the cytoplasm. 

 Although the correlation was based on circumstantial evidence obtained on a 

 limited number of cell types [7, 24], it was soon assumed to be generally valid, 

 and consequently the microsomes and the basophil cytoplasm began to be re- 

 garded as equivalent terms in two different technical vocabularies. An apparent 

 convergence was thus effected between two lines of cytochemical research: an 

 old line exemplified by the work of Brachet's (cf. [25]) and Cassperson's (cf. 

 [26]) groups and aiming at the localization of nucleic acids in situ, and a new 

 line based on cell-fractionation procedures. The correlation appeared to be 

 further strengthened when the large body of circumstantial evidence accumu- 

 lated by Brachet and Cassperson on the role of RNA in protein synthesis 

 received full and repeated support from experiments showing that the micro- 

 somes were the most active cell fraction in the incorporation of labeled amino 

 acids into proteins. 



The lack of morphological information, the concentration of the work on 

 liver, and the equation of the microsomes with the basophil substance of the 

 cytoplasm had some unfavorable consequences on the development of general 

 ideas in the field. It was assumed, for instance, without enough evidence, that 

 entities similar or identical to Claude's microsomes existed in all cells, bacterial 

 cells included, and it was also believed that the chemical composition of liver 

 microsomes was representative for microsomes in general. As we shall see, both 

 assumptions are now in need of revision. 



THE ENDOPLASMIC RETICULUM 



I shall turn now to another development, in a different field, which from the 

 beginning seemed to have some connection with our main problem. A few 

 years after the discovery of the microsomes, and again in conjunction with work 

 done on Rous sarcomata, Porter, Claude, and Fullam \27] and Claude, Porter, 

 and Pickels [28] succeeded in obtaining electron micrographs of thinly spread 

 cells (avian fibroblasts) maintained in tissue culture. Below the limit of reso- 

 lution of the light microscope and well within the range of calculated micro- 

 somal sizes, they found a "lace-like" network of slightly higher density than the 



