Oo a oy October 7, 1948

Dr, Luigi Cavalli .

Department of Genetics — -
Whittingehame Lodge :

4 storey's Way

Cambridge, Zngland

Dear Dr, Cavalli:

I wes most pleased to receive your letter and to hear of your plans
for setting up a laboratory for genetic research on bacteria, I will of
course assist you in any way that I can, and correspond with you on any
detail, Under separate cover, I am sending reprints of some of our publi-
cations,

I was especially pleased to note your interest in problems of crossing=-
over and would be inclined to agree that B, coli would provide very suitable
material, However, there are certain obvious limitations, especially that
among the recombinants, only those which are "prototrophic" are detectable,
so that one is restricted to the segregation of “indifferent" characters
(sugar fermentations; phage resistance, etc) within the particular class -
of prototronhs, This limitation is not too serious, however, and an exten-
sion along the, lines, and beyond, of my paper in Genetics, November 1947,
would be quite fruitful, If Dr. Fisher has not already shown this to you,
you might be interested. to see an elaboration of the procedure for estina-
ting “absolute” distances which is incorporated in a letter to him dated
May 18, 1948, which accompanied a reprint of my paper in Genetics,

Fortunately, additional stocks are now available which provide an
abundance of linked fermentation markers, I am sending you 52-1601, a
foundation biotin; methionine-less stock, and %=533. The latter was
derived by a series of steps from %+53 (mentioned in the paper) and in
addition to the threonine, leucine, thiamin-less and Lactose» of 153, carries
4 additional fermentation markers (Maltose-; galactose-; arabinose-; xylose-)
as well as Ty". I have not yet mapped these factors, except that Maly- is
closely linked to BM, and the others somewhat more loosely, but I think
that because of the ease of scoring prototrophs for sugar fermentations and
phage resistance they will be very suitable for crossover studies, One in-~

novation may be suggested: using a synthetic EMB-sugar medium for scoring
for fermentation,. This disposes of any confusion that might. arise from
contamination of the prototrophs with adjacent parental cells, It is also
-very feasible to conduct the platings for obtaining prototrophs by spread=
ing on a synthetic =MB, and thus secure an immediate classffication of the
prototrophs with respect to the sugar used, This will be especially useful
in testing the rarer classes,

BR b eA LSSaare ey

 

“SSAC SRR
‘

PAS tr taaS,

 
Page 2--October 7, 1948 - Luigi Cavallt

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I might add that a new development has arisen that may simplify the
problem immensely, Whereas the prototrophs, typically, may be reasoned
to be haploid and fully reduced, stocka have been found yielding prota
trophs upon crossing that are not fully reduced, and appvear to be diploid
heterozygotes, since they later segregate out to give all recombination
classes, However, (a) the segregation is not random, but strongly biased
for various factors, and (b) I have good evidence that some loci are repre-
sented once, not twice, suggesting that this alteration of the life cycle
in these stocks is associated with heteroploldy, or a deficiency on one
of the chromatids of the heterozygotes for a region near the Mal locus,
The problem is not yet worked out, but the situation has already been
useful since recombinants can be secured from the heterozygotes without.
nutritional selection, and even the elusive multiple-requirement types
can be recovered.

“The cultures are readily neintained by monthly or quarterly transfer
on nutrient agar slopes, The phage should of course be refrigerated, ‘and
may be cultivated on 58-1 61.

With my best wishes, and regards to ‘Dr, Mather and Dr, Fisher,
Yours sincerely,

Joshua Lederberg
Asst, Prof, of Genetiog

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