Department of Genetics
UW, Madison 6, Wis.
Nov. 12, 1953

Dear Alain:

GREETINGS from Esther and Joshua.

If we do not write to you so very often, please do not feel this means we do
not think of you, as we recall with warm pleasure the "aimabilities" of the time
you spent with us. We have been frightfully busy since mid-Summer, and ae time
passes, it sometimes seems more difficult to start such a letter only because so
many details have accumulated $ijat we want to pages on to you.

I am sorry to learn that your plans at Garches have been disrupted. We do hope
you will have a happy station at Pasteur. And, if we do not reach you again in time,
let us take the présent opportunity to wish you Joyeux Noel, and ask you to pass
the same in due course to Jacques $@RNRRRRRRIR and the Novicks and Jacob and Lwoff
and the Ephrussis as well.

I am starting thie letter at home, and do not recall just when we wrote you last.
We had our share of travelling thia last year:: I enjoy it now less and lesse In
February, as we must have recounted earlier, we spent several weeks in a trip to
Chamblee, Georgia J together with an Englishman, Clive Spicer, who had been a WHO
travelling fellow in our lab) to Edwarde'lab. This helped to solidify a continuing
collaboration in a study of the immunogeneticsa of Salmonella-- we have just had a
paper in the Journal of Immunology on the synthesis of serotypes, and will of courxe
send this tonyou at the aarliest opportunity. You are probably already acqyainted
with the theme of this particular work, namely that the very numerous naturallyoc-
curring serological types of Aalmonella are but diverse combinations of genetic
factors, as can he reconstructed in the laboratory. The biology of transduction
in Salmonella, that phage particles can transport fragments of bacterial nuclei,
is as fascinating as ever, though we cannot claim to have gotten mach more insight
into it. However, a variety of different phages have been found to work in Salmohella
and we also have a very limited but similar system in E. coli. It will be interes
ting #p7f to see how general a function of viruses genetic transduction turns out
to be.

As I said above, we were very busy this summer-- the main reason we declined an
invitation to attend the Cold Spring Harbor Symposium and exhaust ourselves still
further. However, we @id journey to San Francisco, and had an interesting but tiring
drive en route. The occasion was a meeting of the Soc. American Bacteriologists, and
more paspticularly the presentation of a "prize" (if you can imagine such a ridiculous
thing in Science), but despite all this we enjoyed the opportunity of re-visiting old
frienda like Tatum and van Niel at their home grounds. We would have been happy to
have been able to attend the congresses, in spite of the cost in time, but could not
raise the cash for the trip. I had a letter Srom Ephrusei where he seems to have gott
it into hie head that there could have been other reasons for our not coming, but
he forgets that it is possibly even easier for a European scientist to get a subsidy
to visit the US on a brief trip than for any single one of us to the the converse.

As would have been expected, the Salmonella etudy hae been leading us somewhat into
inmunéchemical channels. I do not remember whether I had ever discussed with you the
basic facts of phase-variation from a genetic standpoint. It looks as if pe-ve is
not an ordinary mutation, as had been once supposed, but an "alternating expression
of two genetic potentialities already inhepent in each cell", whatever this means.
That ie, each diphasic Salmonella has factors at each of two loci, but only one of
thtee ie expressed at any time. It turns out that the "specific phase" factors, corre
ponding to alleles at one of these loci are "chemically" distinguishable from the
"group phase" factors, corresponding to the second locus, irrespective of the sero-
logical cross-reactions between them. (E.G., eh behaves as phase-1l, enx as phase-2).
The difference was first described by Sertic & Boulgakov (at the d'“erelae
laboratory) in 1936, but seems to have been overlcoked or discounted since:

simply, ¢he phase-1 (specific phase) bacteria ake ugximtinated not agglutinated

by acriflavine, phase-2 is. Unfortunately, other factors can influence dye-agcluti-
nation of bacteria, but this result seems to be correct with carefu ‘yy controlled
conditions. A Dr. Aleck Bernstein (an !M.D.e, and Dipl. Bact. from England) is here,
officially as a student and Ph.D.-candidate, for a two year fellowship to work this
out. He has been extracting the free flagella, and finds that they behave with
acriflavine like the bacteria. (In thie study we have been finding the Oudin tech-
nique to be especially useful!!) Ne hope tp start some electrophoroe¢tic studies

to verify whether, as we suspect, the difference in reaction with acriflavine is

a reflection of a different ratio of free COOB/NH» in the flagellar protein.
(Formalin-treated bacteria of either phase become agglutinable, in agreevent with
this notion). I am hoping that the chemical studies will give us a slightly better
insight dnto the end-effects of phase-variation at a chemical level, and help to
plan further experiments on the meaning of the semi-irreversible "differentiation"
(in embryological terminology) or narrowing of the initialZ genetic pluripotencies
that seams to he the best description of phase-y¥fAr7%¢tion/ sevaration.

There has been almost now work to correlate the gualitetive receptor analgsis
of Salmnanila in dmrunochemical terms. Weibull (from Tiseline! laboratory)has been
atudying flagella, but from a rather different viewnooint. He visited us hbt long
ago, and we were sorry to learn that he is leaving this etudy to teke up another
ecually interesting-- cytochemical fractionation of bacteria. I did fine a paper
by K. Meyer in the Ann. Inst. Pasteur, 62:282, 1939, on the insezarahbt’ity cf somatic
antigens of Salmonella. Could you help me to find out who this K. Meyer was, and
where he might be lochted at the vrecent time. if possible?(Tre here and initials
areg so ubicuitote as to be confusing).

Esther ia more or less looking over my choulder as I write thir. We recent y
moved to a srall house, aiso et the western outskirts of Madison. We feel much
less cramped than we did et University Heuses (I wieh I cou.4 cay there hae been
a comparable improvement at the lab!)-- have a lovely, secluded sarden-lot which is
refreshing ever with the apvroaching winter (though ve have ‘ad c rewarkably warn
and pleasant eutunn. I should say. Ne show yet!) We have aleo heen reaping a pair
of black kittens, now almost full grown. At the lab, Fether is still preoccupied
with the role of lambda in EB. coli heredity (which seems te hove been the basis of
some recent pronouncements from Lwoff on a new dimension in vetholozy}). The other
people at the lab you probably do not remember. Zinder of covrse gracuated te the
Rockefeller Institute last summer. The two zirls, Phyllis Fried and Ethelyn Lively
have good jobs at Columbia and Illinois. I have two other students now, Larry lMorse
and Helen Byers, and another post-doctoral associate, Tom Yeicon. David Skasr left
recently to a job at Cold Spring Harbor (he Wad been working. curevhot Putilely, on
Be coli immunogenetics. The material then available was, unfortunately, not very
satis&#fctory. More recently, Esther and Bernetein have picked up some crossuble
strains of E. coli O55B4, 011185, ete., which whould be more interesting). Boris
Rotman is another post-doect., officiaaly at the Enzyme Institute, but spending haff
hie time here, and working on the activation of EB. coli lactase. It would appear
that treatment with benzene partially disrupts the ce!! membranes so that RNA lcaks
out, but lactase seems to remain behind, though "activated". The activation could
conceivably start from the inhibition of lactase by the RBA , but this is perhaps
too naive, though being studied carefully, along with severa! ather considerationse.

Personally, I have been relaxing temporarily from the transduction studies to
work on E. coli cytology, especially for the mating procese. This has not yet been
seen directly, but we have fairly substantial evidence for the isolation of single
zygote ce.ls. These cells later split off the full complement of both parents. to-
gether with occasional recombinants (in a limited distribution; 4n concordance i

eek

previous data). These results should disvose oompletely of the ide. (thot

 
sympathetically entertained by many of your colleagues at the Pasteur' ) that

E. coli recombination involves an intact "gene acceptor" cell, and the transport
of small fragments or chromosomes or some unit considerably smaller than the

whole nucleus from a "gene donor". But we are not quite ready to publish the
details, as I am in the midst of single cell isolations in a rather tedious and
long-drawn out way. The cytology unavoidably brings up questions of the micro-
scopic appearance of the nucleus, chromosomes, spindles, etc. There has been a
tremendous amount of nonsense on this subject, and even my brief preliminary
survey has shown numerous possibilities of artefacts. My own opinion is that

the nucleus is typically larger and more vesicular than the usual pictures would
show, and that the "granules" usually represented as chromosomes are simply hyper-
chromatic blosks, possibly segmente of chromosomes. There are, however, some very
suggestive division stages, like metaphase and anaphase, which may be closer tp
realities. I have not seen spindles, but have seen numerous granules that could be
taken for centrioles by an uncrit&cal observer. But the main objective is the
visualization of mating, and we are still perfecting our observational technicues.

I suspect that you have been disturbed at recent political news in this country.
Of course, our papers have the habit of playing up McCarthy's charges/ and then
ignoring the belated responses-~ as for example Secretary Stevens'announcement that
no evidence had been found for reeen$ espionage or loss of documents from Fort
Monmouth, and that the dismissals for “security reasons" did not mean that espionage
had been found. After making a tremémdous fuss, Joe then quietly turned to another
question-- he is now fishing at the General Electric works. I wonder if he will ever
dare to investigate Genera! Motors! But don't over-estimate the importance of
these things. The Bemoerats made a very impressive showing in the recent by-elections
and you can be sure the Republicans are deeply wortied (despite the result in Cali-
fornia). This Truman@White-Brownaal fuss will blow over soon, and is such an
obvious political stunt, nothing will come of it. Velde's pug subpoena was meaning-
less, and he has beem sent to sit in the dunce's chair, you can be sure. All this
business ia talk, to impress weak and confused minds, and I do not see any serious
impairment of our liverties, so long as we fight the intrusions, except in one very
important realm-- visas and passports. But I do not recail that Acheson had any more
enlightened a policy than is being enforced, more noisily, under the McCarrah act.
I am sorry that some people have been afraid to stand up for their cémvictions and
retreated behind the 5th Amendment; the best way, in my opinion, to have fought these
inquisitions would have been candid testimony. As it is, the refusal to testify
cloaks the whole affair (somewhat justifiably) with darkness and suspicion. I wonder
if the Inquisitors will have the nerve to compel testimony by passing legislation
to bypasa the 5th amendment by conferring immunity: I think this would prick their
own ba: loons.

Pogo has recently broken into print again-- we are sénf#ing the jatest edition.

Could I ask a brief favor, namely to receive advertising lists of French scien-
tific books from Masson and other publishers, as we may wish to ofder some.

If you have not already heard it, Quin Luttinger has left Madison to take a
pobition at the Depargment of Physics, University of Michigan, Ann arbor, Mich. I
do not know all of the reasons for his leaving, but he had gotten very deeply involve
with a girl (an undergraduate student and leading actress in the Wisconsin Players),
and I suspect he was afraid he might be obliged to marry her, not for extrinsic
reagona, but owing to the depth of his own attachment, and of this he ia of course

on ieee ct Petes death itselfWe had not seen Quin all Spring ae he had been

a inceton, but curiously enough we met him again at San Francisco
a jrtest achtevment has been the putclase of a tremendous Cadillac corertibie cor
solid black. I am sorry I have not had much occasion to visit with Ackerlmecht ,

or Tucker, and we have scareely s
the campus. Y he oven. Maison Francais. MoShan still haunts