My dear Hayes:

I appreciate your courtesy in consulting me about your paper at
the next SGM session. I was.about to say that it was not really necessary,
but I So not want to deprive myself of any opporti&nity of hearing from
you. Of course you may quote our findings at length- and the experiments
thems@ives, if you wish. I should mention that Cavalli is joined with
Mrs. Lederberg and myself in a collaboration on this particular work, but
I think any one of us can speak for the others. If I have managed to
make myself clear about them, our interpretations are also available to
you. +ransduction is, I think, a useful word for infective types of

enetic transmission. It is largely intended to supplant "transformation"
as in pneumoccecus) which I find mishbading.

I am not sure just what you mean by "confirming by genetic meandsthe
relevance of streptomycin in the sexual process itself." From your experiments,
it would be a good guess that streptomycin (on S% cells) does not inhibit
cells from continuing with their F+ functions, but does inhibit them as
F-. This can be cohfirmed, in part, by the definite (but very low)yields
of %&S? F+ x TL- S° E+ [by transduction] on smminimal agar. The whole situation
may be more gomplex than either you cr I hase imagined. The very low yield of
this last cross leads ae to wonder whether wa don't have a system of relative
potency, in which the lower partner, evennin an F+ x F+, behaves as a relative
F~. I'd rather not be qucted on this yet, but it looks as if this picture
may yet work. Your suggestion(restated){ that an F+ culture may show pheno~
typic variation so that scme celis will behave nomantarily as F~ is equally
sound (and perhaps supported by the effect cf aeration in impressing such a
bshavicr on 58-161), but it does not seem to fit so well. I am so much in
the middle of thoughts and experiments on these points that I can't give you
avery stable picture of the status of our speculations until they themsblves
settle down. Tc change the subject, we have been trying to cross sm-inacti-
vated 58-161, washed te remove surplus sm, on to W-677, so far unsuccessfully.
Have you tried this? The residual sm is not enough to inhibit the growth of
added prctotrophs, and we have the check of the occurrence of $° prototrophs
from 58-161 s* x 677 S?. If this is really so, it makes a good argument
for real zygotic fusion, for it means that the s* "gamete" carries snough
sm cr sm-inhibited cytoplasm to inhibit further development of an s*, but not
a st, "ob" game te . It might also weakaa the whole experiment, for one could
argue that SY cells are apparently sterilized only because of the persistence
of the antibiotic. I would welcome your criticism of this point. I trust
you will agree that the extruded-gamete concept is only one of several hypotheses,
and note that your second letter to Nature abandons the proposal of the first
that the gamete is lambda. Unfortunately ( as I gloomily thought to myself) this
hgpcthesis has been uncritically accepted, pebhaps almost to the point of
distortion, by various people (especially in Paris). Their feeling seems to
be that your experiment conclusively throws out sexuality as an explana-
tion of recvumbination in K-12. For ay part, this is either quibbling or
nonsense, but if I may have showa some signs of annoyance, please believe
that they were nct directed at you. If, as I believe, you stand with sie
on this issue, 1 hope you will take pains to express yourself in such a
way that this kind of misunderstanding will be less likely tbonarise.

Cavalli has mentioned your wish to publish more fully in JG¥, and I
applaud the suggestion of a concomitant publication. Although I shall
very much enjoy hearing from you @EN#é¥X¥, it may be more convenient
for ypu to deal directly with Cavalli on this matter, as he will probably
bear the main burden of writing, as senior author.
  

my work on the compatibility story, this point of view must be rejected. Just what
it does mean , I am perhaps too chary of suggesting. A physiological differentiation
of gametes is certain; whether there is a corresponding morphological differentiation
(including your suggestion of the extrusion) is unsettled. I do not personally care
for the terms "gene donor" and gene acceptor, because thef carry a connotation of a
transductive process. On the other hand, it now appears that the peculiar linkage
behavior of filial stocks can be related to their polarity with resnect to F+. There
is a good deal of evidence that, following fertilization, there is an elimination

of a chromosomal segment carrying the Mal and S, but none of the other factors so a
far recognized. This elimination also perturbs the segregation of other factors, s

as Lac, V,, etc. I1t would be possible to interpret this on the basis of a defective
gamete, but I think it more likely from the regularity of this behavior, and from
the constitution of persistent diploids, that the (relatively) F+ parent contributes
a full genome, but that this genome later suffers the elimination of tne Jal-S
segment. [I have a chapter in Genetics in the 20th Century, MacMillan, 1951, that
goes over some of the background on this. Ne now better understand what determines

the direction of elimination." ; _
I can see no possibility that the F+ agent is itseif the gamete, nor can
it be lambda.
Perhaps I misunderstoof your letter to Nature on the SM crosses: do you
‘Suggest that atr raptouycin induces the extragion of the gamete to the cell surface?
If this wera the case, S$” 58-161 should be more fertile than non-treated. Is this
Yew igge not have missed n&ticing that we are a
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Sincerely,

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