April 2, 1951

Dear Paul~

Tf you think there is a substantial possibility of winning an AEC fellow
ship, I see no reason why you should not proceed as suggested by NAC. Last
year, if I an not mietaken, the allocated fellowships in biology exccoded
the applicants! It would, of course, be necessary for you to oxplain the
change in your plans. Si.ce the NRC's endtorsenent 4s based upon you earlier
application, it mignt de no harm to write to Lapp concerning there changes,
and asking whether they would influence the NRC appraicnl to AEC. The ma jor
obstacle might be your previous tenure of AEC fellowahip supvort, but this
ds saaething that you obviously oan do nothing abort. The most, sensible ap-
proach, I think, would be to emphadisze that the fellowship would broaden
your truining axl experience in a aew direction. However, I would not be syn~
pathetic to any gross alteration of your project statenent cinply to suit
AEC. ilevertheless, there would be auple opportunity for the appiieution of
Fadiobiclogical techniques, aul perhaps analysis of radiation repponses, in
the study we uave ulrealy discussed, aud if you were duterosted, our projoet
on radiation effecta ou diploid LE. cold might occupy a portion of your time
to this end.

The research prograa I've had in mind would be applicable both cor AEC and

PHS, and of soursexturna on the successful isolation of new crosagable strains
of E. coli. #e have about a dozen now, but this particular routine should also
be continued and expanded under your direction, boti to provide tio wost diversi-
fied waterlal, and to look apecifically for evidence of svocific compatibility
groupe (ueterothallian}. The cultures already isolated prove to be rather diverse
4n such okbracterg as fermentation yeactions; responses to phages and colicina;
and govatie antigens. (The latter, I hope, will be the special interest of another
poswWoctoral applicant}. The differential characters of the fullest set of new
cultures anoull be apecified as fully as possible, and tholr range compared with
the rather confusing taxonomic groupings. Tuen, ac far as possible, the genetic
basle (oligo-, poly-, or extra-genac) of tho overt differencer should be
atuiied, unc these compared with experimentally (4ee. radiation-)} indueed
mutations in the laboratory. For example, the “species” E. cold has beon split
into vordeties "comuamis" and"oanmummicr’, based on sucrose-fermentations Are
all of tiie sucroce-negatives canetically equivalent! “hat are the genetic
factora differentiating them from type positives’ Finally, and the mest interss-
ting f£xem for evolution study, how much genetio differentiutien is concealed
beneath phenotypic similarity! Experimentally, the socuence Lacy ~slac- ——>
Lacy cai sometimes bo shown to result in ‘suppressor’ cutetiona of similar Lac#
phenotype. Is this true of many other phenotypes cheracterietic of 2. coli?
The aimpiest ouaracters +o atudy hore would be fermentation capacities aad
nutritional capacities, the latter particularly since hyzeucrph or anorph
alleles, when unmasked, can be detected for an unlimited number pf lock by
the simple test of (failure of) growth in synthetic minimal medium.

T hope this ia suffloiently detailed for your noeds. Although the detailed
methodology will be novel to you, the general concepts are closely parallel
to those of genetisg investigation of the nature of varictal and specific
differences in such material as Gossypium.

It was not appropriate for me to wake any direct inguiriss about Mra. Levine's
status in Zoology. The department ia legally unable to male most of its conmmit-
ments until the enrollmaant has been established, so that there almoct always
turn out to be more vacancies later than seems apparent at firste I would like
to repeat that I don't know of any worthy students who have been neglected very
long in respect to financial support, but the situation for the tine being is
bound to be very confusing.

Sincerely,

Joshua Lederberg