ee Jamary 14, 1953

ae
Dear Dr. Cohn:

Your letter of December 1 was a tall order! I have been waiting for
the xnm supplementary message you promised, but have been able to recover
my equilibrium somewhat meanwhile— enough to remind you about it. We
do not have anything like the detailed physiological analysis of our
mutants that would be needed to fill your specifications. I will do the
best I can, but many of the stocks have to be repurified, checked, and
put in some sort of order as wellaas, so far as possible, a uniform geno-
typic background so that the results will refer to known fac $ors.

To go over some of the types in your requisition: Lac,- is the only

thing even approaching a clearcut glucose-negative we have found (whether

by isolations on glucose, lactose, or maltose). The point of block is some
what mysterious (Mike had someone working on it). The genetics of Cst+
(constitutive Lac+) 1s still rather obscure; if it can be done, and when I

can get to concentrate on it, I'll try to get the Cst+ Gal- combination by
crossings. K-12 ferments melibiose poorly enough from the point of view of
scoring on indicator agar that we've never gone after melibiose-negative
mutants. We have some arabinose—negatives that have not been closely studied
genetically, but you can have these anyhow. All Ara- have been Gal+, and vice
versa. Of course, Ara— Gal- recombinants are not too difficult to get. [I assume
you refer to l-arabinose]. The Lac- series is what I had in mind grom the be-
ginning. If you can let me know what you already have, and perhaps know, about
this set, I will work up the others and send them on.

I have to admit that we have hardly begun the genetic analysis (not to men-
tion physiology) of the fermentation mutants other than Lac-. The whole linkage
system has had to be put into some sort of order before we could do a detailed
analysis that would be meaningful. I think, howeverg that there are enough
Lac- @ypes, and enough genetic information on them to justify an immknogenetic
study in your hands.

I hope you will always keep in migd the necessity of a close watch over tke
genotypic purity of the straihs. Lac -, for example, is always under considerable

selective disadvantage as compared with a variety of reversions and suppressors
that accumulate in almosh any stock not closely watched. It would be unfortunate
to be embarrassed by the difficulties that beset Mitchell et al. with trypto-
phane desmolase in Neurospora.

t ure/ sincerely,

/ Joshua Lederberg