YALE UNIVERSITY OSBORN BOTANICAL LABORATORY NEW HAVEN, CONNECTICUT Novcanber 6, 1946. DeE'r i501: ;lim's the Genius? (That is Leeyvi's description; I heard it pit? my own ears this su er ;bct ds ~lo~e.) Bonnei just let me see zL cosy of your rnzmAscript, t.m reztciing it nas&jst like being at Cold aping htrbour, iiea?ink one line of Pvidence after snotller until one Is almost compelied to s:3y:bt,o,, IT11 believe 3nything yolj say, It i2 yuitc tiirilling, f-nytking new? There is only one polhlht which is not mite clear to me, snc; tliat is the deteil Qf the postul; ted mechznism of substrFte-enzyme interEIctions, particularly betv:?.esn different syst-ms. Vmt, jcan$~xf do yor, propose is tile mekenism by -irizich tLe formztion of' t second enzym depletes tLe first ; why skoula trip 2rk;sence of ExogenoLs 3? af,"ect this process if the substrates are sim1,iy conipting on instable enzyme aolecules? Khy &re tLe enzyincz less uri&t~b&k i11 tk pr sence of hzide? All of trese que.tions are bLsed on titis con- ception of thp role of subst,i-cte: tht the precursor sufiers rancAom reversible chxges, o ccasionally poducing enzymetick liy syec6;ic mo.ecules, End tkt tiieze& zre stsbilized by the prebence of tiie substrate. :!ocever, it is dif'ficE:lt :or ne to se~ thtl role of a ,on6 ?nother Siwhe3ical mutant6 ~~rhich is Lrlus kre crosseci, in the yrcsence mi sbsence of lactose. iny sug:,c. tiom? Sincerely,