Biological Laboratory
Cold Spring Harbor, N.Y.
September 21, 1955
Dr. J. Lederberg
Department of Genetics
University of Wisconsin,
Madison, Wisconsin

Dear Josh,
I was disappointed in not being able to see you and isther at East Lansing.

I am enclosing a rough equivalent of what was presented there; you are
already familiar with most of it. With regard to this piece of work: Alan
is repeating some of the experiments at Purdue. when these are completed a
paper should be in order. We anticipate doing at least two further things: 1)
kanetics of DNA transfer during mixed growth as correlated with the kinetics of
gene transfer and 2) experiments wherein the hot parent is removed by phage
lysis, the initially cold parent cleaned up, extracted, and the various fractions
analysed for radioactivity (RNA, protein, etc.). Beyond these, I think that
radioautography of isolated exconjugants is the next logical step, and feasible.
This we hope you will do. Levinthal was through yesterday and showed mild,
unprompted interest in this kind of thing. According to him, the Pasteur group
is interested in trying kinetic studies of p32 transfer similar to those we
project.

After hearing of Wollmann and Jacob's interrupted conjugation experiments
we were in a position to test them immediately using the interruption procedure
we had been employing in the p32 experiments. I'm also enclosing an abstract
of the talk I gave at the phage meetings regarding this experiment. The
inverted sequence is ofcourse immediately suggestive of an inversion. 1 intend
to establish more firmly the conclusion that the difference in the two
experiments is a function of the strain used, which is critical. So far, we have
used our procedure on Hayes! Hfr (lysogenic), but the frequency of recombination
was appreciably lower than in crosses using W1895 derivatives so that the
data were not very extensive. I understand that.crosses involving non-lysogenic
Hayes' Hfr are more Sfertile", so that this may be in order. I think that after
elucidation cf this point, we will submit this data as a Note to J.Bact. There
‘are a number of suggestive things brought out by the experiments that should
be followed, except for the fact that they parallel so closely the things you
are studging in your pedigrees. These deal mainly with the heterogeneity of
recombinant clones, xxax e.g. most clones which contain L4 also contain Lac/,
but frequently not in the same cells. The system differs from the one you are
studying in that it does not involve two different strains, but otherwise is a
erude but quick equivalent.

Besides finishing up the preceding two units of work and a few others
(K12xB crosses, mutability), my work next year is planned tc concentrate on the
following two points: 1) The long-postponed demongtration that Ff can be
converted to F- by growth at low cell conéentrathons 2) comparative study of .
sex. recomb. and transduction of a large series of streptomycin res. and dep. od S
strains that Demerec has available with the idea of showing that the S locus

is complex (a la Salmonella loci).
nN

With regard to the"F-disinfection": Although the finding is on record
(Nelson and Lederberg), I believe a short note on the empirical procedure is
still in order. I specify the empirical procedure because we don't know how
soon it willbe understood and also because I think you felt it would be hast
to keep the note a strictly VYisconsin contribution. The advisability of a
short note is borne out, I think, by the fact that Clowes (who is here now) and
Rowley were unable to repeat the results because they didn't understand exactly
how they were done,

I am enclosing a summary of data on attempts to disinfect other strains
than 58-141. In answer to your question of some time ago, I have no record of
any difficulty in reinfecting converted F- cells. My attempts involved limited
experiments on 58-1461 —all successful; and on W1895 F~ -all unsuccessful. Two
difficulties that may have confused you were :"F-duction of W1177 by growth with
58-141 rather than K-12, ant secondary F-disinfection of reinfected derived F-.

quiets this was just as difficult as the primary disinfection had been in spite of the

fact that the cells were now initially motile. That is, it still took several
passages on motag.

f will be able, in the near future, to do a few further experiments to
complete this story. But, at present, I don't know the extent of your additional
data, i.e. exactly what hasn't been done. Perhaps, if your experiments now
dwarf the little I did on the subject, you could write the note as senior author.
On the other hand, possibly some of your data on the subject you would prefer
to include in a subsequent publication. At any rate, could you let me know what
needs to be done, or what has been done (so that I can decide what needs to be done).
I hope you now have an idea of the information I can provide at this time.

With regard to the cattle serum story. Possibly you could straighten me out
on this. I couldn't talk to Wilmer and Bill Stone simultaenously at Lansing,
and when I talked to each of them, he seemed to assume that the other was not
at all interested altho he was. There are two problems really, not very closely
related; the crossreaction between cattle A and WG15 and the non-inmune(?) bodies
in cattle serum which agglut. coli. Wilmer was in on the former while I was
there; Bill provided the twin sera for the latter but was not otherwise involved.
I would think that Wilmer and I should finish and write up the former, and that,
since there are other things that could be done, Bill could hepbp finish up the
latter, Would this arrangement run counter to any discussions you have had with .
either of them? Wilmer indicated a willingness to prepare some new anti-WGL5
serum to confirm the cross-reaction. If the arrangement as given above seems
appropriate could you send him a culture of WG15% I will instruct him further
on its use,

I sent Sonneborn a manuscript of my thesis for publication purposes, In it
I made the following statement: "If antiserum does not induce transfromations
by removing inhibitors, the flux-equilibrium model is not invalidated, in toto.
As Lederberg has pointed out (Cell.gen.and hered.symb.) such a system of mitual
inhibitions is sufficiently flexible to account for any fallible self-perpetuating
mechanism." ts this an acceptable interpretation of your comments on serotype.?

Thank you for mentioning my name to Scripps Institution. I wrote to
Buzzatti that 1 was interested in being considered and that I would ask you to
write a letter of recommendation. It would go to: Dr. A.A.Buzzatti-Traverso,
Seripps Oceanography Institution, La Jolla, Cal, -At the moment, my source of
income for hext year is guaranteed but indeterminate as to source. The Camp
Detrick grant was discontinued (how did you fare? I'm told that Braun wasn't
awarded a grant). We have applied for an NSF grant.

Best regards to the lab.
Sincerely,

” DAwe