2. SYSTEM AND ENVIRONMENT 13 



find that the analysis which we are attempting in the present work is grossly 

 inadequate to the task in hand, and that no reasonable or useful dynamic 

 separation can be made between the metabolic and the epigenetic systems of 

 single cells. Then a distinctly more complicated procedure must be adopted. 



The Epigenetic system 



In the epigenetic system, the major activities are considered to be the bio- 

 synthesis, diffusion, and interaction of macromolecules. The time required 

 for the synthesis of a single protein molecule in bacteria has been estimated at 

 about 5 sec (McQuillen, Roberts, and Britten, 1959) and appears to be a 

 matter of a few minutes in higher organisms (Loftfield and Eigner, 1958). 

 On the basis of crude estimates RNA synthesis requires about 1 sec in bacteria 

 and perhaps 1 min in higher organisms. 



Some idea of the relaxation time of the epigenetic system in bacteria is 

 given by the observation that there is a 4 min time lag before the synthesis of 

 j8-galactosidase begins after adding a jS-galactoside to a culture of Escherichia 

 coli, and similar time lags occur during the induction of other enzymes 

 (Pardee, 1962). In the cells of higher organisms, the lag is considerably longer. 

 Thus Feigelson and Greengard (1962) have shown that there is a 2 h time lag 

 before tryptophane pyrrolase synthesis begins in rat liver following intravenous 

 injection of tryptophane. The series of studies made by these investigators is 

 particularly relevant to the present discussion, for they have obtained a clear- 

 cut experimental distinction between two levels of response in liver cells, one 

 metabolic and the other epigenetic, using our terminology. The first response of 

 the enzyme system to tryptophane is an activation of the apoenzyme whereby 

 apotryptophane pyrrolase becomes saturated with respect to its iron protopor- 

 phyrin cofactor. This is a characteristic "metabolic" response which involves 

 no macromolecular synthesis, and a "small" injection of tryptophane might 

 demonstrate that the process has a relaxation time of a very few minutes, as we 

 have assumed for the metabolic system. However, an "epigenetic" response 

 is first observed some 2 h or so following an injection of substrate, a response 

 which Feigelson and Greengard have clearly demonstrated to involve de novo 

 synthesis of enzyme and hence, presumably, of the informationally homo- 

 logous messenger RNA. These responses are separated in time in a rather 

 striking manner, and it is only after a metabolic steady state has been reached 

 that the epigenetic response becomes evident (Greengard and Feigelson, 1961). 

 The relaxation time of the epigenetic system in liver cells must therefore be 

 of the order of 2 h. Thus we may suggest that the epigenetic system of cells 

 may have relaxation times in the range lO^-lO^ sec (about 1| min to 3 h), the 

 time varying according to the cell type, whether bacterial, protozoon, liver, 

 muscle, etc. 



Now as we have observed earlier, the epigenetic system can be regarded as 

 part of the environment of the metabolic system of single cells providing that 

 the relaxation times of the two systems are sufficiently different. Our estimates 

 suggest that generally this will be the case, and that macromolecular concen- 

 trations can be regarded as unchanging or slowly changing parameters during 



