618 J. M. REINER 
how systems comprising various interacting mechanisms will evolve with time, 
and how rates of reaction will depend on the various factors involved. The material 
I shall present here is a modest attempt to illustrate this point, and to present 
frankly the difficulties and limitations as well as the valuable features of the mathe- 
matical treatment. 
PROTEIN SYNTHESIS: A SIMPLE MODEL 
Let us consider what we know or have fairly good reason to suppose true about the 
mechanisms of protein synthesis. Proteins are formed from amino acids; and these 
may enter the cell from without, or be formed inside the cell from simpler precursors, 
which eventually enter from without. Both free amino acids and precursors enter 
by some device more complex than simple diffusion; one commonly speaks of active 
transport. Numerous schemes of active transport have been proposed, some concrete 
and some vague. The one that seems to me to be most satisfying will be presented at 
this Conference by Dr. Roy BritTEN, to whom I am indebted for the privilege of 
reading his manuscript in advance of presentation. However, for the sake of mathe- 
matical simplicity, I shall consider here chiefly a somewhat simpler scheme, the so- 
called permease of COHEN AND Monop!. The essence of this mechanism is the assump- 
tion that the rate of transport of a compound from outside to inside of the cell is 
formally the same as the rate of an enzymatic mechanism; the intermediate com- 
plex discharges the substance in question into the cell interior in its free form*.**. 
Inside the cell, amino acid precursor is converted to free amino acid; we simplify 
the complexities of this sort of process by writing it as a single reaction. 
Amino acid, whether of endogenous or exogenous origin, is activated, according 
to the scheme resulting from the work of HOAGLAND ef al.?, with the help of ATP; 
each type of amino acid is acted upon by a specific enzyme, and its activated form 
is a compound with a specific RNA, usually present in solution in the cell sap, 
of relatively low molecular weight?, and commonly referred Ito as S-RNA (S for 
soluble). 
We must now speculate a little. The work of HOAGLAND cited above? suggests 
that protein synthesis from activated amino acids commonly occurs in submicro- 
scopic particles (microsomes, ribosomes) rich in RNA of substantial molecular 
weight (about 0.6 x ro® and the dimer of this type*)***. The current notion, un- 
supported by any real evidence but in accord with generally held views as to how 
the genetic control of protein specificity is mediated, is that the ribosomal RNA 
(or some specific fraction of it®.®) acts as a template to determine the specific poly- 
peptide sequences that are synthesized. 
The term template is somewhat vague. What is essential to the idea is that a large 
* The permease mechanism treats the rate of exit as a diffusion /eak. The possibility of a mecha- 
nism of active outward transport (evitase) might be considered. In this paper we neglect outward 
movement for the sake of simplicity, and because this seems unlikely to be significant in the pre- 
sence of active utilization for synthesis. 
** The relation also resembles a Langmuir adsorption isotherm. The formal properties do not 
permit the inference that an enzymatic or an adsorption mechanism is at work. For further dis- 
cussion of this problem, see ref. 15. 
*** The case for synthesis in ribosomes rests substantially on evidence for energy-requiring 
incorporation of labelled amino acids. No really good evidence for net protein synthesis in purified 
ribosomal systems is yet available. 
References p. 632 
