June 8, 1947. Dr. J. Monod, Service de Nicroblolcgie, Institut Pasteur, Peris,Prance. Tear Jacques! This letter 1s inspired by the publication (at last) of the Cold Spring Harbor Sysposium of last swimmer, which has given me an eprortunity to refrosh my memory concerning certain details dis- cussed by Prof. Lwoff, and I think entre nous on the sand of CSH. They consern the interaction of the galactose -/+ and lactose -/+ mutations, in particular whether they concern allelic changes at the same locus, or interactions of distinct genes. We discussed, last summer, the possibility of a direot attack on ck this nroblem, with recombinational techniques, using mutant strains of K-12. You pointed out at that tine, however, that it wouid be necessary to have a mutablile, or at least. a pair of related Lee- and Lact straing, I showld like to let you know now that I heve such strains and have been using them for some time as ocnvenient genetic markers in linkage studies, Lac- mitants in previously established multiple blochemica? mutant stocks were looked for after treatment with uv and nitrogen tmstaré by plating cells on lactose~EME agar, and looking for white colonies. Two have been found, ont of about 5x104 colonies examined. One of these (in a threonine-leucine-thiamin-less stock)(Y53) 1s typical- ly mutabile and not infrequently throwsoff Lan+ yapillae +; the other, {in & pictin-methionine-less, Tl-resistant stock)(Y87) is likewise Lac~ but to my knowledge dees not revert to Lac+# These mutents are charae terized by their awility to produce acid frem lactose on EWR plates; I have not studied tnem in synthetic medium in any detail. I am planning to use these stocks for studies on mutation (there Seems, for exemple, to te a genetic differential between them) and for the examination of the poss Sibility of physiolcgical differences between independent meversion stocks (in hopes of finding multiple alleles} but I should be delighted to send them to you if you wovld care to use them in relition to this prebiem. Assuming that these and other stocks are 'galactose -', for eaxmple, you could cross a B-M-G-Lac+ with a T-L-B) ~G+Lac- to determine whether, in the prototrovhs, there were any recombinations, of the type G+tL+ or G-L-, I think you should have no difficulty in performing such crosses according to the techniques that have been or are about to be pub- lished; if you would prefer it, I would be willing to isolate a series of prototroph recombinants and send them to you for testing. fhe preliminary work and the determination of the growth rates however is just a bit out of my milieu, and I haven't the time for it. wave Bonner tells me you are expected in the &tetes this summer. Probably I shan't be hers then, but at Wood s Hole; drep up if you have a chance, particularly if you : » are interested in these propositions. Ahyhow let me know whether to cend alone the cultures, Please extend to Prof. Lwoff most sincere regards from br. Tatum ana myselt; we look forawrd to seeing you again, | fours sincerely, 4 — goshua lederberg. ‘ 3 f ; t oF N eo. it oe ces ‘ ere as co - 4 a pe cn Mee } . t