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NATIONAL RESEARCH COUNCIL
CANADA

PROJECT

CHALK RIVER. ONT

November 2nd, 1948,

Dr. Joshua Lederberg,
Department of Genetics,

The University of Wisconsin,
Modison 6, Wisconsin.

Dear Joshua,

Thank you for your letter and for the extremely
interesting information concerning the diploid Kl2 and its possible
use for determining the delay between segregation and phenotypic
expressions

I should like very much to see the experiment done,
particularly as the delay appears to be absent in the case of
mutation to streptomycin resistance. Thus, the magnitude of the
delay is apparently a function of the partioular mutation, and from
a comparison of various delays one might gain some idea of the degree
of permanence of the systems or structures altered by the mutation.

As streptomycin resistance is an easy character to
work with, I would suggest that it be added along with V," and Vigre
(Streptomycin resistant mutants will grow in any concentration of ©
streptomycin up to and including 4000 units per ec; 52 units per cc.
is adequate to inhibit the growth of all susceptible bacteria. The
simple resistant and resistant-dependent (sr and sd) forms arise at
very similar mutation rates, approximately 10-10,” ana are selected
by plating large populations with liquid agar containing 64 or 128
units per cc.) I can put this character on any of your haploid
strains, here, if you like.

I am not quite clear as to the degree of accuracy
with which one can compare the rising proportions of resistant
segregants with the declining proportions of heterozygous diploids,
in a culture; or whether the diploids are mono- or polymucleate. In
the latter case I assume that individuals containing a mixture of
diploid and haploid muclii, or more than one type of haploid nucleus,
would give rise to mosaic or sectored colonies on EMB agar, and that
Dr. Joshua Lederberg ~ 2 Nov. 2/48.

there would be no error from this source. In any case the
experiment should give an accurate comparison of the times of
appearance of phenotypic phage resistant, and streptomagin resistant,
segregants, and if what I suspect is correct these wilfJ/differ by
from two to three generations,

I shall be extremely glad to have your reactions to
the use of the additional mutant locus, and any further details.

Again many thanks for having suggested these materials and for your
generous offer to attempt to build up stocks.

Sincerely,

Howard B, Newcombe

HBNsar