June 27, 1960

Dr. Ruth Sager
Department of Zoology
Columbia University
New York 27, New York

Dear Ruth:

| have been meaning to answer your letter of May 20 for some time,
having carried It along with me on a couple of plane trips. 1! mistaid
my notes and will start over again.

To answer your specific questions: 1) we have not succeeded In
separating the phase controlling element from the Hp locus. However,
we do not have a particularly sensitive technique for doing this. !
suppose one might look for translocations of the controller to some locus
which controls sugar fermentation and thereby establish a highly mutable
fermenting clone. But it might then be rather difficult to establish
that this was the origin of the Instability.

lino and | did spend some time In looking for environmental control
of phase variation but did not succeed In establishing any definite one.
! agree with your formulation In heading 3. | suspect we were driving
at more or less the same point In paragraph 4.1 of our 1956 paper. It
Is not easy to be sure!

if nucleic Information can be repressed by the output from a cyto-
plasmic feedback cycle, It seems to me that there fs very little In the
universe that could not be explained. Do your non-chromosomal determinants
really fall to fit such a scheme?

Yours as ever,

Joshua Lederberg
Professor and Executive
Deaprtment of Genetics