Yamary 23, 1948.
Dr. 8.C.Rittenbderg,
The University of Southern California,
University Park
los Angeles 7, California.
Dear Dr. Rittenberg,

Thank you for writing me about your plans with Salmonella. It
turns out that we are interested now in very auch the same problea,
but there is no reason why we should not turn this common interest
into sutual aduwatage rather than mtual embarrassment. Long before
I had any indication of success in my coli recombination experiments,
Iwas very mich struck by the patterns of the diagnostic serological
formilae in the Salmonella group. To mp they implied very clearly that
_ Rew types were generated, at least in part, by genetic recombination.

My incidental study of the nutrition of the Salmonella group was moti-~
vated by this inference, as I hoped to find among existing types material
with which to do recombination experiments on a nutritional basis. Por

a variety of reasons, no critical test was possible with the "natural"
material. Having just become securely re-established at Wisconsin, I

am turning my attention to this problem again.

The more work éhat can be focussed on the group, the more surely the
problem will be solved. It is my feeling, however, that the first few
attempts will surely be unsuccessful, for there is every reason to expeat
strain specificities in the recombination reaction. In coli, as you know,
Knl2 is the only one among three strains tested which "paid-off", I woukd
suggest that we both continue this study according to our own lights, and
keep each other well-informed as to developments.
&.C .Rittenberg -~2-

As to the genetic control of antigenic structure, I think that the existing
data allow as definite a conclusion as will ever be possible without the aid of
recombination factorial analysis. The flagellar antigens are certainly determined
by some hereditary unit distinct from the antigens themselves, in view of the
eongancy of potantialities in the course of phase variation, and because the
specificity of subseguent flagellar production is supposed to be afm unaffected
by treatments (e.g. phenol agar) which suppress the phenotypic manifestation
of that capacity. However, 1 am at a loses to provide any simple, hypothetical
explanation of phase variation that takes all the facts into account. It is the
genetical basis of phase variation that I hope can be studied adequately if re-
combinational techniques can be devised.

I should be very interested to see some work done on antigenic variation
and inheritance in E. coli K-12. If that sort of prohlem should come within your
fancy, or that of one of your students, I shall be glad to send you any strains
you would need.

Youra sincerely,

Joshua Lederberg
Ageistant Professor of Genetics