UNIVERSITY OF CALIFORNIA

DEPARTMENT OF PHYSIOLOGY
SCHOOL OF MEDICINE
BERKELEY 4, CALIFORNIA

October 7, 1955

Professor Joshua Lederberg
University of Wisconsin
Department of Genetics
Madison 6, Wisconsin

Dear Dr. Lederberg:
Thank you very much for your interesting letter of September 26th.

Replica plating is a technique with which I was unfamiliar until, in
a conversation held after my letter to you was mailed, Ed Adelberg suggested it
as a good way of doing the sort of experiment that I had in mind. I+ is
eertainly an elegant method!

I very much appreciate your invitation to spend a month at Madison
and believe that it might be arranged~-but not until sometime in the latter
half of the calendar year 1956. Unfortunately I must at the present time
support myself almost entirely through the clinical practice of medicine; one
of my grants pays me indirectly for one day a week, but the rest of the time
I spend in the lab is on my own. I have used up all my leave and then some for
the calendar year July, 1955, through June, 1956. But I can no doubt arrange
to be away a month of the following calendar year; and I should like very much
indeed to get some experience with the methodology of bacterial genetics.

_ 3 In the meantime I will investigate the possibility of doing here the
LAC + Vi experiment that you suggest. Quite possibly Ed Adelberg would be

interested in collaborating on it. I am pretty busy and may not find it practical
to divert the time involved, but I will write you again when I have worked on
the matter a bit.

I agree that the question of the relative primitiveness of intra- vs.
intercellular sexuality will not be answered by the discovery of the former in
"vegetatively" reproducing bacteria. Actually I am interested in such phenomena
more from the standpoint of a further understanding of bacterial nuclear behavior
as such. The fragmentability of the genetic systems of those relatively few
bacteria that have been studied and the displaceability of genetic material,
presumably in "chromosomes", by (2) subchromosomal blocks of one or more genetic
determinants (as with transforming principles and virally transduced material
and as in the "coitus interruptus" phenomenon of Blie Wollman and his collaborator)
mystify and intrigue me. Are there genetic messengers that communicate in an
analogous way between nuclear bodies within the cell. And are their “crossing
over" processes between these messengers and the homologous parts of the bacterial
chromosomes such as occur between different related phages infecting a single
cell? Are the virulent phages merely such messengers escaped from the more
typical controls of the cell? And are they thus gene products having arisen
originally in evolution as part of a “sexual” mechanism, but having developed a
Professor Joshua Lederberg -~2- October 7, 1955

certain degree of autonomous phylogeny? I dare say these questions are as
tantalizing to you as to me, and quite probably you have more evolved ideas
about them than I.

I shall have to give the terminology “parasexual" vs. "sexual" some
thought. Actually I do not use the former term in my review on the origin of
sexuality, but consider all phenomena in both categories as part of the broad
spectrum of “sexuality”. (Incidentally, I think that "parasexuality” in fungi
is probably a secondarily derived mechanism in evolution, but I'm not sure. At
the moment I'm toying with the idea of exploring the minute flagellates for
comparable mechanisms. Chrornlina pusilla, a marine chrysomonad, is a wee critter
of 1.5-2: in diameter, which grows to populations of 1 x 10° in liquid media.

So far, however, it has not been reared axenically (i.e., by itself) and has
refused to colonize on agar surfaces).

Very sincerely yours,

Wars. Mayheng

Ellsworth C. Dougherty

ECD: jd