evil December 5, 1955 Dear Aaron-— I hac some second thoughts about lactase which I sibourkxoos had not clarified during our discussion. If you accept the existence of a "y-system" in Lac+ strains, it seems to me you are going to have compkications in evaluating any of your other experiments without measurement and control of the intracellular inducer concentration. Now I think we are agreed that there is some system for accumulating TMG which is more active in induced than in noninduced cells. But why not then use Lac, , which according to Monod differs in the lack of any concentrating ability (presumably even in cells induces with TMG and othar substrates)? I believe it is correct that TMQ (as well as MG and BuG) will induce Lac,. If you can still find the maintenance of “duplicons" at threshold levels of TMQ, you have prima facie evidence against the neces— sary role of the y system in the perpetuation of the high ard low states of the cells, a point which would be subject to direct test with isotopically labelled inducers. The main trouble my be that higher ooneentrathons of in- ducers my be necessary, but this is not so serious a trouble, since you would avert the other problem of a unique intracellular level. If this works out, you can also use tim lactose as a non-inducing subssrate (14 the presence of threshold TMG) as a colony—indicating score for the two states. I think you have as suitable Lac.” stocks as I could give you. By the way, 1 forgot what you told me about the r-equivalent of a cup of coffees. Could you also give ms r-yield of atations (have you published this?) and the references to the pharmacodynamles of caffédie? (as well as the pH-gradient-elewtrophoresis technique? It was a swell visit; we ottght to mix more often.