THREE DECADES PROGRESS IN MICROBIOLOGY 



ities of the microbial cell have been badly underrated. It now has 

 become increasingly clear that in the metabolizing cell we are deal- 

 ing with a system of equilibrium reactions in which a continuous inter- 

 play between cell constituents, intermediates and so-called endproducts 

 takes place. 



This newly gained insight strongly contrasts with the current con- 

 ception of the preceding period in which fermentation processes, and 

 catabolism in general, were considered more or less as cascades un- 

 chained by a more or less stable system of catalysts, and in which a 

 suitable substrate via labile intermediates was transformed into a 

 number of stable endproducts fixed for every type of cell. 



It is evident that the introduction of isotopes has brought the study 

 of intermediate metabolism on a level much higher than it had 

 reached before. For it cannot be denied that until recently investi- 

 gators could not go much farther than to demonstrate that a certain 

 type of cell contained enzyme systems which are capable of bringing 

 about some intermediate step-reaction. But this did not imply that 

 under a given set of metabolic conditions this particular step-reaction 

 does indeed take place. As a matter of fact there have been moments 

 that microbiologists have been struggling with a surplus of inter- 

 mediate products ! 



For these reasons it has to be admitted that the drawing up of a 

 scheme for the internal mechanism of a biochemical process on the 

 basis of intermediate products isolated under special conditions has 

 always been afflicted with elements of a speculative character. 



If we contrast this situation with the degree of certainty obtainable 

 by the application of labelled atoms which, if properly examined, 

 give straightforward answers to many questions, it is not too dangerous 

 to predict that in the future studies on the intermediate metabolism 

 will almost completely be based on the use of isotopes. Moreover, it 

 does not seem excluded at all that these studies will alter profoundly 

 several of our current views. 



There are, however, some considerations which tend to moderate 

 these hopeful expectations, and that is in the first place the at present 

 still very restricted availability of many isotopes, more especially of the 

 carbon isotopes. 



In order to apply the radioactive C 11 carbon successfully it is nec- 

 essary to work in the immediate neighbourhood of a powerful cyclo- 



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