September 26, 1955

Dr. P. D. Skaar
Bio Lab
Cold Spring Harbor, L.I., N.Y.

Near Dave:

Thanks for your letter and the mass of accompanying material. Rather than
wait for a complete digestion (which will take a while, in competition with
other piles of papers on my desk) I thought I had better acknowledge right
away and leave part for later. I ran into Alan in Chicago on Saturday, and
we had a hasty conference. I am relieved to learn of the possibiliity that
strain differences account for the discrepancies in seriation-~ our experience
with j-1895 agreed with yours, and not at all with Jacob's. Are you using
the "Hayes Hfr" that I sent you, or another. If ours is ng.% and you have a
different isclate that is better, would you let us have a copy sc we can try
to reconcile our other results generally.

Are you asking for a W-1895 Lp°? We will send you W~2252, which fits this
prescription. You should also have a better miltiple marker strain to tie in
some of the other loci (at least Alan thought so), so we are also sending W-583
(= Wel v,* Mal,~ Ara™ Xyl™ Gal,"); anticipating your interest in it. I still

think the overall data are compatible with postezygotic losses, and am not even
certain that the blending results have to be exclained differently, though this

ig not implausible (cf. enclosure). Tne following may be a reasohable compromise
also: that the Hfr chromosome is always broken (proximally to Gal-Lp and to Mal-S)
but that the distal fragments do not always penetrate. They do accompany the
proximal sections fregiantly enough to account for the data of TON & JL on post-
zygotic losses; i.e., if there is crossing over with the distal fragment, and
subsejuent loss, one would save markers from the Hfr and eliminate from F- parent.
we had conceded that our evidence showed that losses were often postzygotic, but
cculd not exclude prezygotic losses as well. I had nct wanted to invoke two
distinct mchanisms, but this notiog would not be tec ouch af a strain. On this
basis perhans the effect of blending is not to cause breaks in the chromosome, but
ta reduce the freency with which the Gal fragment is also brought in. From the
diploid data, if these mem are not be be arbitrarily disregarded, I would have to
adhere to the idea that normally the breaks are always at the same site; we haven't
done any comparable experiments with disrupted pairs.

Have you considered whether phage might be playing a special role in your
disruption experiments’? Rather than merely interrupt mating, it haght be breaking
Bp the Hfr chrom gomes. You would then have a transduction of fragments, but via
a conjugal bridge rather than the mature phage particle. Unless you have completed
the comparisens, and find otherwise, this might account for differences between
your results and Jacob's also.

I au happy tc see this burst of tidying-up energy. I will talk to Bill Stone, and
will be happy to send Wilmer wgl5 if he needs it te finish his and.
my
Your vession of’comments on serotype is quite satisfactory (and rather snoothly

stated), thougn + think it quotes my personal convessations rather than prigted
remarks, & better reference might be my paper at the Amherst Growth symposiun, of
which Tracy has a copy (and possibly dtill disagrees), but it hardly mtters.

i an relieved to learn that you have the means to hang on. We dropped our
Detrick connections several years ago, having been fed up with the formalities
of military contracts. I will write to Buzzatti-- but do you think I could honestly
predict un wwakening of your interest in marine biology? Do tell me what I can
or should say in this connection, so I can quotebyou indirectly.

4s to F, I agree this should be published. The empiricism could go to MGB as
effectively as anywhere, but I think you should have more credit for these observa-
tions than the mention in the PNAS paper (which was as emphatic as I could manage,
and which had to be brought out for the purpose of the paper). But not having heard
from you about iv for som time, I thought you had lost interest. This summer, a
new student caue into the lab (Alan Richter) who seemed to be interested particularly
in F, sand just as a starter and for the experience, I suggested he review this
particular problem. He has been running 58-161 through a chemostat, ete., so far
has had no success at all in obtaining F- that way. I have not been able to find
any notes at all on the experiment that Aaron did-— have you any details on that.
Nor can I find any record or trace of the cultures-- any ideas there?

May I suggest the following arrangement: let Alan continue with his experiments:
a) the chemostat, which probably won't work, and b) reinfection trials, on which I
have had some discrepancies. I have also run into some apparently sterile cultures,
and others with greatly mmkasmt enhanced fertility, which deserve some more looking
at. Alan also has some odd resihlts on e/fect of culture age on F status (of Ft);
these may have some bearing on "enhanced fertility’ and sterility, as well as the
odd ratios in some F+ x f+ crosses. This should not taka terribly long, and in any
event cought to be written up in time tc support a collaborative paver with yourself
as the senior author. Meantime, why not record the empirical procedure in MGB.
Rather than my joining you as auttjor on that, 1 would prefer that you merely indicated
that the work had been done at Wisconsin and leave it at that. The purely empirical
aspects are not likely to interest (or be understood/ by)anyone outside the ‘GB
circle, and I would want to see at least eome of the theoretical aspects tried out
before wrapping it up for publication. If you have any notions, independent of
what you started here, you can decide for yourself whether you can integrate them
with the completion here, or reserve them for your own future programs.

What is the B transduction system you were considering- Pl? I will be willing
to bet you, say 2:1, that the auxotrophy, etc., found in S mtation cycles is not
at all allelic with S, or don't you man that?

Yours sinderely,
Hoy

ag
Sositua. Haderber g

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