April 6, 1952

Dear Rothfels:

One of my stulents accidentally ran into leucine-inhibition story
again, as mentioned in the ms. of your paper to Genetics on the Lag-Vy-L-T
linkage. I haven't done much more about it, but we did find that K-12
itself (also 580161) is inhibited by leveine. In liquid minimal mediun
aubetantial inhibition is seen at 100 ug/ml, but was noticeable at less.
As you noted, the inhibition ie relieved by amino acids. I do not know
whether this has any very direct bearing on L, , except that we are
probably running inteqquantitative modifiers, rather than a sharp serre-
gation. Your interpretation of the origin of vi eeems more reasonable
than ever. If we are dealing with an amino acid balance, it seems quite
likely that an increased response to leusine qua growth factor would be
accompanied by an increased sensitivity to it qua aeae antagonist. Con-
celwably, it might be worth while to clarify this possibility in a foot-
note; Orow tells me this could be done. Otherwise, the whole matter may
well be buried, which might be just as well also.

Some aspects of K-12 sex are very active aguin. “e're collaborating
with Cavalli on this. The enclosure gives part of the story. More
recently it looks as if F+ x Fe orosses involve either a relative sexuality
situation, or phenotypic variability in a so-ealled f+ oulture. The whole
T-L- line, starting from 679-660, is F-. The perturbed segregathon behavior
of filial T-L- stocks is a consequence of their being F+, which throws out
this evidence for chromosomal aberration. The Mal-S elimination seens to
be a regular feature, and ite direction is likely determined by the polarity
of the parents with respect to F. The segment from the F+ parent (relative
or absolute) ie the one which 4s cast out. I shouldn't be surprised 4f this
segnent is a whole chromosome or chromosare arm (if there is any residual
atructural heterozygosity, 1t amounts to the same thing), and the whole story
looka more and more like Sefara coprophila. Hayes! experiments (Nature, Jan '52)
fit in very well, though not those partioular interpretations, which he
seers to be revising drastically himself. Just now, I'm looking again at
Cavalli's old Hfr strains, with very promising results.

Sincerely,

Joshua Lederberg

PS~ 5-161