October 25, 1949.

Dr @ E, L a Tatum,

Dept. Blology,

Stanford University,
California.

Dear Fad:

Iwill try to get W-757 and W-760 out again, and to you, as soon
as possible. thanks very mach.

Ag far as recent advances in genetics go, things are decidedly luke-
warm in this lab. The heterozygous diploids are probably old-hat by
now, but maybe it would help to mention that Zelle has done innumerable
singie cell isclations on them, which just about clinch the notion
of a sexual stage. The point is that, except for Mal, and a touple of
nearby loci, the heterozygous cells split off , usuatiy, either of
the parental combinations of characters. There is some crossing-over,
but the parental combinations are much more frequent. The parental
groupings of factors ure therefore intucts: together, in the same cell.
T still don't have the whole story_on the "elimination mechanism" which
causes the haplogenicity cf Mal, S™, ete.., in the diploids. Cavalli's
Hfr strains have pretty well blown up, at Teast for our purposes—~ the
recombination frequency is undoubtedly higher, but not high enough to
pick recombinanta without selection (conscious or otherwise!) Esther is
doing some work on lambda now, to try to explain why we can recover a
substant&éal proportion of lambda-negative prototrophs in crosses of
lamida~positive and lambda—negative parents. It may be that the zygote
becomes disinfected, asd in the diploid condition may be more difficult
to be made lysogenic. This would explain the cropping up of plaques in
previously unblemished cultures of Salmonella when they are crossed and
the prototrophs examined.

Lately, two recombinging strains (+ K-12) have been found-~ at least
they are very likely. One ia in Salmonella coli 1; the other ia another
Ey coli strain, from chiskens. The situation is confused by the fact that
reversed prototrophs can be selected from good double mtants(!) in some
cases. I don't understand thisphenomenon at all, unless we happen to be
hitting a common suppressor mutation (e.g. for threonine and histidine),
But we also have reassortment of unselected markers which make it almosh
certainly recombination. So sex is not an isolated phenomenon,

I also spent some time to clean up the use of drug-resistance to select
recombinants. The parents have to be grwwn together for a few hoursa’
but otherwise the results are quite straightforward. Streptomycin (100 u/ml)

x azide (M/500), in nutrient agar, have worked best so far, although the

Az™ mitation is frequent enough to cause a little trouble. Resistance, together
with unselected markers, may be a method of choice for organisms with a
finicky nutrition, ar which don't readily give mutants,

Miss Ethelyn Lively has been getting along well in a cytological study
of diploids vs. haploids. There are some definite peculiarities, whose sig-
nificamce re diploidy is not yet clear.

We were very glad to see the linkage data on Neurospora published from
your group and Beadle's. But why the dickens isn't someone studying, croseing-
over? Or is someone?

With best regards,

Sincerely, :

Joshua Lederberg