October 10, 1951.

Dr. H. P. Treffers,

Dept. Medical Microblology
Yale University

New Haven, Connecticut.

Dear Pete:

Earlier this summer, I wrote to you asking permission to quote your
private communication on the behavior towards streptomycin of strain
58-278 which we were using in connection with a demonstration of indi-
rect selection of adaptive mtante by replica plating. Ben Rubin told
me later that you spent the summer in California and may not have promptly
gotten my letter, nor been able to attend to it. I hope you hold no ob-
jection to this quotation, but I will be glad to delete it from our ms.
when J. Bact. beturns proof,if you should wish it.

Last summer, before the CSH symposium in June, I used replica plating
to analyse segregations of crosses involving em-standard sensitive x an
resistant from standard sensitive (8° x S™), and noticed then that some
recombinants gave 4 rather fuzzy response compared to the clear cut dif-
ference between the parents. After seeing 58-278 1a this system, it occurred
to me that our "standard" Ss’ might actually be S” Ms+. Dr. David Skaar
just recently joined our lab. staff, and at my suggestion he looked into
the matter further. In at least one cross, he has extracted S° ise+ (i.e.,

type like 58-278) in a high proportion of segregants from an 3° Ms- x
S land we thought Ms-]. He obtained the same result, less surprisingly
from 8° Ms~ x S* iis+ [1.6., 58-278 3°]. The experiments support the hypo-
thesis that Ms is a locus distinct from S and mo@ifying the observed
mutability of the latter, (exactly as you proposed almost two years ago).
They algo may support the thesis that spontaneous mitation of standard
8° to 8S 1s a two-step affair: first Ms— to MB+ , and then S® to ST as
accelerated by the latter.

Your earlier letter mentioned that you were continuing your investiga-
tion of 58-278, and we hesitate to go any further into the whole problem
before consulting with you. The experiments were initiated as a pedagogic
exercise for Dr. Skaar, but with the investment of some further effort it
might be possible to confirm the two-step picture of ticks mtation, to
s™, If you have contemplated a similar anaygsis yourself, or if you can
suggest a feasible division of labor, please let us know in either case.

Sincerely,

Jeshua Lederberg