ROLE OF NUCLEIC ACIDS 67 



Obviously, these facts are irrelevant to the existence of a connexion be- 

 tween RNA synthesis and protein formation. They are a mere reflexion of 

 the general requirements of cells for growth or for any type of synthesis. 

 In the same way, the fact that a population of growing bacteria usually 

 make protein and nucleic acid simultaneously does not imply that the 

 mechanism of protein synthesis is such that one type of macromolecule 

 cannot be made without the other being made at the same time. 



More significant are the attempts made at dissociating the two processes, 

 e.g. by varying growth-rate, by using inhibitors or by causing specifically 

 the synthesis of a protein. Let us consider briefly a few typical data. 



Spiegelman and Kamen (1947) showed that the phosphorus of yeast 

 RNA is renewed very slowly in actively respiring yeast which is deprived of 

 nitrogen source. If ammonium salts are added, proteins are synthesized, 

 the uptake of radioactive phosphate is increased in all phosphorus com- 

 pounds of the cell, but much more so in RNA than in any other cellular 

 constituent, as if the synthesis of RNA was indeed connected with protein 

 synthesis. Abrams et al. (1949) made similar observations for the incorpora- 

 tion of precursors into RNA purines; however, it was later found that 

 X-rays markedly reduce this RNA metabolism without inhibiting protein 

 synthesis (Abrams, 1951). Grenson (1952) studied incorporation of phos- 

 phate into various types of animal tissues which have in common a high 

 rate of protein synthesis, but which differ physiologically. She found no 

 simple or uniform correlation between phosphorus incorporation into RNA 

 and the production of protein. Similar observations were made for RNA 

 synthesis during synthesis and secretion of amylase by pigeon liver pan- 

 creas (Hokin and Hokin, 1953, 1954, 1956), or during the period of recovery 

 after starvation in muscle or liver (Laird et al., 1955 ; Zak and Gutmann, 

 1960). In continuous cultures of a flagellate, a simple correlation was 

 clearly observed between RNA synthesis and protein formation when the 

 organisms were growing at a constant rate. However, strong disharmonies 

 appeared as soon as the rate of growth was abruptly changed by a sudden 

 modification of the medium composition. A net loss of RNA for instance 

 could even be observed at times when protein synthesis was stimulated 

 (Jeener, 1952). Price (1952) and more recently Magasanik et al. (1959), 

 Peabody and Hurwitz (1960) observed comparable phenomena with 

 bacteria: if the substance serving as carbon source is replaced by another 

 one to which the organism is not adapted, growth slows down very much 

 while the bacteria make enzymes which will metabolize the new carbon 

 source. RNA synthesis is very much depressed during this period. 



Direct comparison of RNA fonnation and protein synthesis thus led to 

 conflicting results for many years: a rather convincing correlation was 

 found in certain systems but it failed to appear in crucial cases. The syn- 

 thesis of protein and of RNA may very often occur simultaneously, but 



