April 1, 1951.

Dear Paul-

I was,pf course, sorry to learn of the disappointing outaane of
your NRC application. However, this might have been due tn vart to
your sugested program which tne connittee conceivably sight have
raviewod with some hesitancy.

If tnere is any reasonable possibility of euccess, by all meuns
follow up with the AEC application. It might be well to emphasize
the function of your fellowship in familiarizing yousmeif with the
methodology of microbial genetics, rather than the specific vaive of
the Tessaron project. However, we have recautly undertaken a very email
oontract with AEC to study the effects of radiations on (heterozygous
diploid) bacteria, ami there would be sone oppurtunity fer coliabore-
tion on thie programe On the other hand, I would prefer thet you not
38 tied to this project, which I a: planning to kaco on a small scale
for the time being.

Your last letter also asked fer soe discussion of your project
Ou gtrain reiationehivs. I have not hastened to answer in order to
&ive 1% sone thought, and alse becuuse the May 1 deadline ie stiil
sane time off. The baeis of the plan is the isolation of « dozen or
sO new strains (#0 far, stiil cowing inj} of E~. coli which can be inter-
ergssed with Lele, and possibly with each other. These cultures show
a considerabie range of overt phenotypic differences, inoluding reaction
%6 bacteriouuuges and eolicins, production of these agenis, fermentation
of certuin carbohydrates (espaofally lactose and sucrose), nhtritiohal
status, und finally serological structure. Another fellow is planning
to analyse the gserological differences, which are quite marked: each
of the first 10 has a dietinct somatic antigen, and sone are new additions
to the long list of Ee cold somatic antigens. I would recomend e project
base upon the cataloguing of the overt characteristics of the crosnable
atrains, comparing their mge with that of the taxonomic description of
Ge coli; ietornuining the genetic bases of the differences (e.g. are the
different sucrose-negative types the same, single-gene ~<utation?), and
finally exmxmingx looking for cryptic genetic differences as reflected
by the occurrence of new characteristics fron crosses of -arents which are
superficlaliy alike in respect to « given character. The laat might be
of some importance in indicating the extent of latent genetic varkability
which recombination can expose. Finally, the gene differences detected
in the new isolates should be correlated with the experimentally produced
mutathones in the laboratory (6.2. lactove-negative "paracolion” with par-~
ticular Lao- mutatione in strain K-12).

Let me know if you need some more inforsationse Part of the program
should also include an extension, and preferably an expansion, of the routine
of finding new crossable strains, especially designed to detect compathbility
groupe if possible. Enclosed is a letter of endorsement which you may
need for your AEC a>plication.

Joshua Lederberg