VOL. 12 (1953) GROWTH AND PHAGE PRODUCTION OF B. megatherium IV 47 



resting cell, very few (i ?) active phage particles exist. As the cell starts synthesis, more 

 precursor is synthesized at a rate similar to that of RNA synthesis. The phage reaction 

 also starts and is regulated, at first, only by its own velocity constant, since the substrate 

 (precursor) is present in excess. This is the original rate observed. Since this rate is much 

 higher than that of the formation of the precursor, the precursor will soon be greatly 

 reduced in concentration and the reaction will slow down until the rote of formation 

 of the phage is just equal to the rate of formation of the precursor. This is now a steady 

 state and the reaction can proceed indefinitely. This mechanism may also account for 

 the observation (Weed and Cohen^^) that the first phage liberated from B. coli con- 

 taining i^C pyrimidines contains more of the labelled pyrimidine than does phage 

 liberated later. It predicts that, in a lysogenic culture, phage produced during the lag 

 phase will contain more host C ox P than phage produced during the log phase. 



It may also explain the fact (Krueger and Mundell^^, Northrop^^) that infected 

 sensitive cells in the log phase produce more phage than resting cells. Such infected 

 sensitive cells do not divide, as a rule, but continue to form RNA (Price^''') at nearly 

 the same rate as uninfected cells. If the phage precursor is formed at a rate similar to 

 that of RNA, log cells contain more than resting cells and, in addition, make more, 

 during the phage production period, than do resting cells. 



If the phage precursor is also the precursor of other cell constituents, then destruction 

 of the sensitive cells may be due to the fact that, in these cells, the ratio of phage 

 formation to precursor formation is so high that the concentration of precursor is reduced 

 until it is insufficient to allow the formation of normal cell constituents at the minimum 

 rate required for the life of the cell. In the lysogenic cell, on the other hand, the con- 

 centration of precursor, in the steady state, is high enough to provide the necessary 

 normal cell constituents*. 



Constant compositioit of cells and media during the steady state 



Since bacteria continue to grow indefinitely without change of properties, if supplied 

 with fresh media, it follows that their composition must remain exactly constant and 

 the ratio of any component of the cell or medium to any other component, must also 

 remain constant. 



This condition is strictly fulfilled only if the medium is renewed at a constant rate 

 exactly equal to that required to keep the cell concentration constant. A culture in log 

 growth approximates this condition, but does not fulfil it, for the composition of the 

 medium must change with the change in concentration of the cells. 



Examples of such constant ratios during (approximate) steady state have been 

 observed by many workers. Northrop^^ found that the relative concentration of phage 

 and also of gelatinase, an extracellular enzyme, to the cells was nearly constant during 

 log growth. 



The equations governing this relationship are — = K^Ax where x = concentration of pre- 

 cursor, A = components of the medium (considered to be constant). The transformation of the pre- 



dB dC ... cU- AB dC 



cursor to normal cell constituents is — = A nBx, — = KrCx ... at equilibrium -— = — 1 — — . . . 



dt '^ dt ^ ^ dt dt dt 



and K^Ax — KpB — KqC . . . = o. 



Evidently the addition of a new substance P such that KpP is smaller or of the same order of 



magnitude as K^B or K^C will not have much effect on the various other concentrations. If KpP, 



however, is much larger than the other terms, the value of the other terms must decrease. (C/. also 



Mandelstan^o) . 



References p. 50. y*v\V3^ *-* m / 





