CARNEGIE INSTITUTION OF WASHINGTON DEPARTMENT OF GENETICS COLD SPRING HARBOR, LONG ISLAND. N. Y. April 18, 1950 Dr. Joshua Lederberg Department of Genetics University of Wisconsin fadison, Wisconsin Dear Joshua: Thank vou very much for your prompt and informative answer to my query. I agree that it would be preferable to work out the suppressor story on K¥12, if possible, and your suggested drug-resistance experiment would indeed be an elegant approach. I don't think it's altogether impossible to get somewhere with a nonsexual strain, however. The experiment I have in mind is to subject a histidine-serine/glycineless "reversion" to the penicillin procedure, screening for histidineless and serine-glycineless mutants separately. If a suppressor is involved, reverse mutation of the Suppressor should release the two original requirements as a unit, and a fraction of the histidineless mutants obtained should also require serine/glycine, and vice versa. Wild type B/r would be used as a control. Negative results would prove nothing, of course, but it seems to me that positive results would establish the suppressor beyond reasonable doubt. I would appreciate your sending me the K-12 mutanty requiring histidine and serine/glycine, If it gives proto- trophs on minimal, or if another K-12 diauxotroph turns up that does so, I think someone ought to do your drug-resistance experiment. If not, I will go ahead with B/r. Thanks again, and best regards to Esther. Yours sincerely, Evelyn M. “Witkin