Madison 6, Wis.
January 24, 1950.

Dear Kin-

I'm very sorry not to have had some more time (and data) to talk over
the mechanism of UV killing with you. For the past couple of months, I've
been doing some irradiation experizents on heterozygous diploids of E. coli
with some rather peculiar results, and I'd like to compare notes with you.

First of all, no balanced lethal diploids have been found so far, even
among survivors of rather high doses. This would already secs to preclude
recessive lethal mutations as the mechanism of killing. Second, barring
some unforeseon selective effects, heterogenic cells are made effectively
isogenic, ieee, one recovers pure segregant colonies instead of mosaics.

At 10% survival, the a population originally 85% mosaic was converééd to 25%
mosaic, Although not yet formally proven, tk I think thie is not differential
killing.

If these results stand up, they point to a new mechanism of killing,
which may fit the alternatives that you think account for the bulk of UV
effect in Neurospora. The chrmmosome or nucleus would be the unit of inac-
tivation, the mutation being neither "dominant", i.e., effecting the entire
or recessive, i.e., latent in the presence of homologous imaffeeted chromo-
SOMES.

This would show up in your material in much the same way that it does
in coli, nanelyby induced segregations. Do you find anpreciabée increases
in the numbers of homokaryotic conidia after irradiation? THere was a strong
indication of this in N. tetrasperma ascospores hetercuzysous for A/a and for
yellow dwarf, after expesure to X-rays, as I think Esther and I may have
mentioned at some time (also p. 157 of my Heredity review). So far, I haven't
had an opportunity to teat X-ray effects.

A few balanced lethals may be turning up in coli, but they are so rare,
if at all, that they can scarcely account for an appreciable part of the
killing. The "induced segregation" effect is, howver, very striking, and I
would appreciate it if you could tell me your exnerience.

Esther and I very much enjoyed our evening at your home, and we were
refreshed for our trip. If it's not a secret, could we have the recipe for
that chestnut dish that Barkara served? The Whitings were also an unexpec-
ted treat.

vineorel
.

| nn a cree

rs
, Joshua Lederberg

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P.S.-- How'd you like that tricky reasoning of Opatowski's in the last
Genetics? What a fast one.