July 18, 1947.

Dear Newcombe-

Thanks for the information in your letter just received.

I wish it were possible for me to visit the GSH lab. again,
but I just don't see how I can manage it. My wife and I are beaving
for Woods Hole on the first of August for a vacation, and to
write, Meanwhile, I have a lot of things to clean up here, and
I just can't find the time. Could I simply reverse your invita-
tion?

From the tone of your letter more than anything else I gather
that you are strongly impressed with the possibility that irradia-
tion, in addition to inducing changes at the Vy locus to a resis-
tant allel, may also induce mtations to allels which although
Sensitive are characterized by high(er) rates of mutation to a
resistant state. I must say that I have been led to the same notions
On KaxKa general considerations, as well as bi my studies on stable
and unstable Lac- mutants. On the wasis of the efficacy of radiation
in inducing reverse-mutation in Drosophila, Muller was led to the
conclusion that absorbed energy could somehow be "canalizeda" to
the critical part of the gene that mst be restored. My wife has
been working on induced reversions in Neurepora, and I think that
it would be unwise to categorize any reversion necessarily as a
precise restoration of the original configuration, but rather that
there may be 4 number of "wild-type" configurations. It should be
possible to distinguish some of these by differences in mutability.

This would be,to me, a somewhat more satisfactory interpretation of
a delayed effect of a radiution than one where the absorted energy
is somehbw merely stored by a "non-genic" molecule.

It should be a veryg simple matter to determine the genetic (
identity of spontaneous,zero-point, and end-point mutants. However,
it should be pointed out that in K-12 there are at least three
differemt genes mutation of which leads to resistance to Tl. They
are however phenotypically distinguishable. There may be others
which are not which would complicate the story. At any rate it
should certainly be dome.

I am enclosing a not very good photograph that you may be interested
to see: merely the phenotypes of the 4 combinations of Lac +/- and
Vv, 7/S . From an cross heterozygous for these factors, all 4 types
are obtained as you baAve of course heard.

Hoping that you will be able to drop in up here,

Witn best resardsy

Yours sincerely, q