January 16, 1952 Dr. Felix L. Haas Laboratory of Genetics University of Texas Austin, Texas Dear Dr. Haas: This letter is in refcrence to the paper by you and your colleagues, "Wntabions und actagenic agents in oacteria", published in the American Naturalis$, 84: 261-274, 1950, @specially pp. 268-267. I have long been interested in the apparent differance between strain K-12 and strain B with respoct to the phenotypes of Tl-resistant mutanis. In the latter, the "5/1" (i.e. sensitive to T5) is usually associated with a requirement for tryptophane, whereas I have not been able to find this with K-12. In your paper, you repert an asscciaticn between resistance and auxotreph mutations. My older experleace was not in accord with this, and cone of my students has more recently attempted to repeat the experi- ments on a larger scale, using replicasplating for simple and direct tests of auxotrophy among Tl-resistant mutants. “ith the exception of two prolinaless colonies out of a very large number (ca 10/), again no association wae found. Tha two prolineless mitants were readily separable from the Tl-resistance in recombination tests and undoubtedly represented random, spontaneous mutante. Your paper, which mentions this aspect only in passing, did not give experimental details that might permit e closer comparison of our discrepant findings. Were the Saataé colonies from a single plating, and from what sort of mutagenic treatwent, if any? In view of the seeming concordince of their nutritional pequirenents, might you no$ have picked up a clone that was coincidentally auxotrophic and resistant? If your analysis indicates to you that there is indesd a signfficant asaocdation, have you carried out or considered genetic teste? I would appreciate a clarification of the details of this published experiment that might permit the possible dis- crepancy in our findings to be either explained or to be rectified by fur- ther experiments. Yours very sincerely, Joshua Lederberg Associate Professor of Genetics