September 15, 1951.

Dr. P. R. Edwards,
Communicable Disease Center,
Public Health Service,

Box 185, Chamblee, Ga.

Dear Dr. Edwards:

Our investigations on the possibility of genetic recombination
in Salmonella, especially S. typhimurium, have finally begun to bear
some fruit, in a rather surprising way. Mr. N. Zinder, who has been
working on this problem in my laboratory as the subject of a doctoral
thesis, originally set out to duplicate the methodology originally
developed for Escherichia coli by Tatum and myself. However, he has
recently discovered a system which resembles, in most of its details,
the transformation of pneumococcal types much more closely than the
"sexual" system of E. coli.

Expeeure of cultures of any one of many strains of S. typhimuriun
to low concentrations of penicillin or to certain weak bacteriophages
results in the elaboration of an "agent" which we call "PA" that seems
to be capable of tranamitting inherited traite from one bacterium to
another. This agent is separated from the bacterial cells by filtration
through sintered glass or by heat-sterilization. The traits which have
so far been studied include a considerable variety of nutritional require-
ments (i.e., the transfer is from a wild type to a nutritional mutant),
fermentation differences, and resistance to streptomycin (1.¢e., transfer
from a resistant mutant to a normal sensitive). This system differs from
the E. coli not only in passing through a bacterlal-filter, but also in
the fact that here only a single trait 1s tranamitted at one tims, whereas
E. coli shows definite evidence of linkage. As a starting point for sero-
logical studied, we have noted that FA preparations from S, typhimurium
are active on S. typhi, transmitting at any one time either the ability
to ferment arabinose or rhamaose, streptomycin-resistance, or growth on
minimal medium (tryptophane-independence). It has also been noted that FA
is absorbed by cells of a variety of serotypes sharing in eomnon the XII
somatic antigen. We are now anxious to set up experiments to test the
possibility, mentioned 4n your own writings, of transfer of antigenic
specificities. For this purpose, we would be greatly obliged to receive
a rather large set of authentic type cultures, as enumerated in the attached
list. Our first trials will be dvoted to the replacement of the d antigen
of S. typhi by the 1.;1,2,3 complex of 3, typhimrium. We have some immuni-
zations in progress, but if you could also apare a few ml of d-serun, we
would appreciate it very much.

Sincereky yours,

Joshua Lederberg,
Associate Professor of Gen.