Ribosomes, or the particles of Palade

Early electron microscopy (EM) was troubled by, as George Palade put it, “the perennial and arduous question of artifact versus reality.” Stains and fixatives could precipitate—Keith Porter referred to this as “the coagulating action of the fixative”—and produce structures that were not present in the original sample.

But when Palade noted a particulate component of the cytoplasm, he confirmed its presence using two different fixatives, and described its particular abundance in embryonic, rapidly proliferating, and glandular cells (Palade, 1955). Thus were born the particles of Palade, later known as ribosomes.

Palade saw that the particles were both on the endoplasmic reticulum (ER) and free in the cytoplasm. Although the ER was identified in 1945 (Porter et al., 1945), by 1955 the terms ER, ergastoplasm, and basophilic cytoplasm were still used almost interchangeably—the last in reference to the staining of RNA-rich areas with basic dyes. Palade realized that not all of the ER had bound ribosomes, and thus the basophilic region referred only to what we would now term the rough ER.

This distinction between rough and smooth ER was made even more explicit by Palay and Palade (1955), who found that the so-called Nissl bodies in neurons were none other than clumps of rough ER, which were distinct but connected to sections of “a granular reticulum” or smooth ER. As Palade predicted, the correlation between rough ER and protein synthesis came with later correlative studies using both EM and biochemistry.