Tissue Fraction-past and Present

THIS IS NOT a review. It is an essay, conceived in the first place as a tribute to one of the founders of modern biology. Accordingly, it dwells over the past and considers tissue fracfionation mainly in its historical perspective. It does take a brief look at the present state of the art, mainly in order to give some sort of idea of what has been accomplished in the last 25 years thanks to the development of tissue fractionafion. This survery is restricted to liver, the original object of the method. The bibliography is mainly historical, but includes references to a few recent reviews and research papers, through which much of the remaining literature can easily be traced back. It is exactly 25 years since Albert Claude published in The Journal of Experimental Medicine two consecutive papers under the common title "Fractionation of Mam-malian Liver Cells by Differential Centrifugation" (49, 50). He was summarizing in them the results of a long effort that started in 1937 with an attempt to isolate the Rous sarcoma virus by high-speed centrifugation (44), led to the discovery of micro-somes (45), and came to its final fruition in the concept of enzyme distribution studies (48) which, under the impulse of Claude's pupils, George Hogeboom, Walter Schneider, and George Palade, was to renovate biology. Indeed, we may well ask on the occasion of this anniversary what would be the present state of cell biology without cell fractionation. Even had the development of electron microscopy proceeded unchanged, what else would we have to contemplate today but a rich atlas of beautiful and tantalizing images, through which our imagination would be forever weaving the elusive threads of hypothetical mechanisms? Molecular biology itself might have followed a very different course without Claude's contribution. It is sometimes forgotten by enthusiastic historians of Escherichia coli and phage biology how much the adventure that culminated in the unravelling of the mechanism of protein synthesis and in the deciphering of the genetic code owes 20 D