January 15, 1948 Dear Dr. Avery, Since my establishment here at Wisconsin, I have been occupying myself with applying the genetical technique Tatum and I have learned with E. coli to the problem of gene-enzyme relationships in this bacterium. To that end, I have been studying mutations affecting lactase activity, and it may suffice to mention now that a plurality of them have been found, somewhat to my surprise. I would have predicted that all mutations affecting a single enzyme would involve the same gene. The problem: is there indeed but a single enzyme? I am addressing this letter to you to enquire whether you still happen to have a sample of p-nitrophenol-b-galactopyramoside, reported by Goebel and yourself nearly two decades ago (JEM 50, 1929). It occurred to me that this compound, in view of the pH shift in the absorption spectrum of p-nitrophenol, might be a useful chromogenic substrate to assay galactosidase activity. If possible, I would like to test this notion on a small sample (1-2 gms.) before undertaking a large scale preparation. While I would like to ask for this quantity, I could run tests on, say, a tenth that amount. If you can find the bottle, your cooperation would be greatly appreciated. Best regards, Sincerely, Joshua Lederberg Assistant Professor of Genetics