4 SUBCELLULAR PARTICLES 



of the transplantable liver tumor (fig. i), they are smaller and less numerous. 

 The striking difference in nucleus to cytoplasm ratio is evident, as is the large 

 number of lipid droplets in the tumor cell. In favorable material, phase contrast 

 microscopy can reveal the presence of structures at times considered artifacts by 

 some. Thus, the CJolgi apparatus can readily be seen in these transplantable liver 

 tumor cells (29) and the endoplasmic reticulum was seen by Fawcett and Ito ( 1 1 ) 

 in guinea pig spermatocytes. 



Naturally, such purely morphological observations, together with the resolution 

 limitation of light microscopy, leave much room for speculation. The observations 

 do not tell us what really happens when the mitochondria move up to the nuclear 

 membrane, or what the nature and fate of the pinocytosis vacuoles are. 



ELECTRON MICROSCOPY 



The limitation of resolution may be overcome, to a great degree, by electron 

 microscopy. 



Elsewhere in this volume (38) we see new examples of the power of electron 

 microscopy from Dr. Palade, the man to whom not only biochemistry but all of 

 biology and medicine owes so great a debt. I am confident that he. Dr. Keith Porter 

 and other electron microscopists will promptly agree that our dependence upon 

 osmium fixation leaves some important questions unanswered for the moment; 

 for example, that not too much chemical meaning can yet be attached to detailed 

 appearance and precise measurements of membranes in electron micrographs. 

 From the work of Fernandez-Moran and Finean ( 12), of Birbeck and Mercer (4), 

 of Peachey (41 ), and of Ito and Fawcett (18), it is apparent that the double mem- 

 branes seen in osmium-fixed sections may result from films of very different 

 biochemical substances. 



Yet electron microscopy of thin sections has helped answer many questions of 

 biochemical cytology. Perhaps more important, it has raised many other questions 

 which could not even be phrased without this new look into the near-molecular 

 level within the cell. 



To cite a few examples, it is now possible to assert categorically that organelles 

 like the mitochondria of liver survive homogenization and centrifugation quite 

 handsomely, and to indicate the kinds of changes which occur in other sub- 

 cellular particles. 



Figure 3 is chosen because it is sometimes said that mitochondria isolated from 

 liver homogenates in unfortified sucrose solutions do not show good preservation 

 of fine structure. Sections like this show that such is not the case. Mitochondrial 

 fine structure is excellently preserved in this pellet obtained from a 0.88 m sucrose 

 homogenate. The figure also demonstrates how readily contamination by micro- 

 somes may be identified. Since microsomes arise largely through fragmentation 

 of ergastoplasm, the ribonucleoprotein granules of Palade (37) and endoplasmic 



