134 TEMPORAL ORGANIZATION IN CELLS 



will be sufficiently definite to expose the whole theory to the crucial test of 

 success or failure, and so settle its future. 



The problem of controlling 6 without changing any of the microscopic 

 quantities such as rates of macromolecular synthesis, pool sizes, mean levels of 

 molecular and macromolecular species, etc., would seem to be a rather difficult 

 one. Certainly it involves a different experimental design from that normally 

 used to change the state of a cell, which involves exposing it to a different 

 environment for a period of time and then observing any changes which occur 

 with respect to a known set of variables. Such procedures always change the 

 microscopic parameters of the cell and so they usually involve changes in 

 many variables, only a few of which are measured. What we would like to be 

 able to do is to change the level of oscillatory activity of a cell, its talandic energy 

 level, without changing its microscopic state as measured by steady state 

 values of molecular and macromolecular species. In terms of Figs. 3 and 4, 

 we would like to move the trajectories either further from, or closer to, the 

 steady state values, without altering these steady state quantities. One way of 

 doing this might be to disturb the system briefly and periodically so that the 

 trajectories are pushed either towards or away from the steady state values, but 

 the disturbances must then be transient ones which do not alter permanently 

 the microscopic parameters. 



Consider, then, a population of microorganisms with well-defined rhythmic 

 behaviour such as luminescence in Gonyaulaxpolyedra or mating in Paramecium, 

 growing very slowly on a limited nitrogen supply and under constant environ- 

 mental conditions with respect to light and temperature, i.e. there are to be no 

 exogenous diurnal periodicities. For Gonyaulax this means constant dim 

 fight, since the only energy source available to this organism comes through 

 photosynthetic activity (Sweeney and Hastings, 1957). The synthetic activity of 

 these organisms would then presumably be limited by the sizes of the precursor 

 pools for mRNA and protein synthesis, these being small due to the limited 

 amount of nitrogen available so that the cells are near steady state conditions. 

 Suppose now the culture is given a small pulse of amino acids. This should 

 stimulate protein synthesis temporarily, but it is important that the pulse be 

 small enough so that the amino acids are used up in say half an hour, after 

 which time the pool sizes will revert to their original levels limited by nitrogen 

 availability. The eff'ect of such a pulse is to cause a transient shift in the oscil- 

 lating trajectories of the different protein species. A transient increase in the 

 rate of protein synthesis is to be expected in two accounts. The first is the 

 increased size of the amino acid pool. The second is the inductive effect which 

 amino acids appear to have on mRNA synthesis (Stent and Brenner, 1961). 

 Therefore both these controlling parameters of protein syntheis should be 

 increased temporarily. 



Now the direction in which such a disturbance will shift an oscillating 

 trajectory, whether towards or away from the steady state value, will depend 

 upon what part of the trajectory the system is on when the disturbance begins. 

 If it is on that part of the trajectory which lies below the steady state, then the 

 stimulus will shift the system "up" towards it, thus decreasing the amplitude 



