CABLE ADDRESS "RESEARCH"

IN YOUR REPLY PLEASE QUOTE

FILE NO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

NATIONAL RESEARCH COUNCIL

           CANADA

ATOMIC  ENERGY  PROJECT

CHALK RIVER. ONT

May 4, 1946.

Dr. Joshua Lederberg,
Department of Genetics,
The University of Wisconsin,
College of Agriculture,
Madison 6, Wisconsin.

Dear Lederberg:

         hlany thanks for your letter and your comments concerning
the sectored colony technique.

         My interest in this is due to the difficulty of inter-
preting some of the data on "delayed phenotypic expression" as due to
recessiveness of the mutation and the presence of the two or four
nuclei.

        As you suggest, the data on induced mutation could be
explained along these lines, but one usually irradiates resting nuclei,
and the cytological evidence for the presence of more than one nuclei
is from actively dividing cells.  On the other hand the data on
spontaneous mutation in growing cultures indicates a delay in pheno-
typic expression of two or three cell generations in addition to any
arising frolp the presence of more than one nucleus.  [That i-unless
one assumes some such peculiar behavior of these nuclei as for example
a nearly regular exchange of places of the inner two of a row of four).

         From the Robinow pictures one would expect a mutation
in a four-nucleate cell to give rise to one phenotypic mutant two
generations later,  and that thereafter the number of descended mutants
.would double with each successive generation.  The spontaneous data
fail to fit this expectation since the number more than doubles with
each of the first three or four divisions, and three generations after
the appearance of a single phenotypic mutant the number present is,
not eight, but something like six times this number.

         It is still possible that the average number of nuclei
in resting bacteria is only slightly more than one and that the delayed
effect of irradiation is due to some phenomenon which is active in
producing the observed effect in spontaneous mutants. Thus, your
sector technique may be useful in providing a missing piece of
information, provided one can make quantitative allolmnce for the chance
of induced inviability in the nuclei of treated cells.


Dr. Joshua Lederberg,

4.5.48

        Again many thanks for your letter.  I am interested
in your remarks on the plateau and decline in the U.V. response curve.
Kelner has some unpublished U.V. and X-ray dose effect curves from
actinomycetes showing plateaux,and U.V. induced phage resistance
bears a similar relationship to dose. I am doubtful however whether
it is a matter of differential sensitivity of the mutant since one
would occasionally expect an upward swing in the curve instead of the
plateau, as for example in your material, if you irradiated the mutant
and scored back mutants.

Tith all best wishes,

Sincerely,
      /

H. B. Newcombe.

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