August 1, 1952

Biclogical Laboratory
Long Island Biological Association
Cold Spring Harbor, L.I.,; NoY.

Dear Mr. Hartman:
Thank you for your letter of July 29.

Coneerning the bicchemistry of divers resistant mtants, I have been in
correspondence with Dr. Colwell for some time. She is having some difficulty
in reproducing her published experiments, but this seens to be a matter of
the purity of the reagent, a point not previously emphasized. I am looking
forward to a aatisfactory confirmation of her experiments (which, prim facie,
might still very well represent a selection of mutants. Quanones seem to
behave very much like penicillin in the seiection of auxotrophs in minkmal
medius).

Our experiments with stgeptonycin-rosistanee included en examination of
the Merck strain of Ei coli. They had lost their deseribed non-serobic 3*
matant, and neither they nor I have been able to repeat the experinent, aven
starting with their culture. I do not doubt that there mey be biochemical
differences among S’ mutanta, and it would certainly be worthwhile to study
such mutants before they are exposed to streptomycin. Whether an s™ mitant 4s
resistant to streptomycin in a non-streptogycin environnent is a nearly meta~
physical question, The mutant character can only be defined operationally,
namely that 1OO% of the mitant calls survive when they ave exposed to SU,
whereas aliost all non—imtant cells fail to develop. I do not doubt there may
be physiological adjustments to the presence of SM when an S° cell is exposed
to it, but there 1s no evidence that such exposure induces specifde genetic changes.

;< would be vary much interested to receive further dedails of the Cu/induced

aemall colony variants, and Dr. DeLamater's new techniques. E. coli certainly
dis very near the limit of useful microscopical techniques.

Sincerely,
Joshua Lederberg