STANFORD UNIVERSITY

  MEDICAL CENTER
PALO ALTO, CALIFORNIA

DEPARTMENT OF GENETICS
JcEool of ilfedxine

August 28, 1961

DAwnport I-,?oo
Cables STANMED

Dr. Peter Sneath
bdical Rosearch Council
National Inrtltute for Hedtcal Research
The Ridgeway, Hill HI11
London, N.W. 7, England

Dear Peter:

   This reply to your letter of 9 3une 1s probably far too late to be
consquentia! for the paper on eplsomes, but ln any case, my cammnts would
be mainly for your interest, and would hardly be likely to evoke a strenuous
effort at a revision though you may wlrh to uso your own judgment about
this.

   Let me answer anothor potnt flrst of all, that XV2 is now doubtless
much bettor to find In Jscob~s system than was the )c2 of our earlier work, and
since so much genetic work has been done with the Parls strains, I belleva
that 1 would recamend that you use thaa for any further devolopnents,  In our
own early work we did not have the analytical techntques by which we might
have distlngulshed different variants of the V2 phenetype.

   Hay I note also that the address of our doparttnent is in the medical
school at Palo brto, not _ ,riford, Callfornla.

To the paper --                                  o

   As Jacob will now acknowledge, the term eplscme was rather remarkably
rntfclprted by Thaapson.  The refarmce to this Is o ppehdod.

   Page me, 1ysogenIc bacteriophage, line six - the antecedent for "this"
might be clsrlfled.

Page two, other eplsomes, 1 Ine one - `Vcmwr?' or "tnferred"?

   Page three, distribution of bacterial o p1sornes. second paragraph, line
two - Is it really a dofinltlw characteristic of epismes that they are
infectlous? or that they can be removed by ecrldine? Perhaps I am Interpreting
the term "tomnon" too strfngmtly.

   Page four, second paragraph, RNA episaaes - I don't see the hnpllcatlon
that epismer can also contain RNA since Ztnder's phage has by no means been
proven to be o pisanlc.  This is, of course, an interesting posslblllty,


2

Dr. Peter Sneath

August 28, 1961

  The nusbor of episclaes per ceil, line two - %na episcaee in the celli' -
perhaps in the nucleus or chromosome, but the cell mey contain several of
these.

  Page five - Adsiberg has soma more recent evidence on phosphorous
starved F+ cells, that they 8re resdily disinfected by the contagion of F;
from which he concludes that under these cond1tiono there is one F particle
per cell.  He believes that there may also be a more definite regulation in
the segregation of the determinants.  There is also an interesting note on
this point in a recent issue of the Canadian dourn of Senetlcs and
Cytology, I believe by dames.

  Effective episomes on the cell, llno four - i do not accept that
Heecacaro and Colombo had demmstrated a surfece antigen characteristic of
male cells.  They had shown that such cells were more agglutinable by colt
entisera.  They did, of course, themselves, make the claim which I would
here c<mtost, and which has, of course, been fully substanti8ted by the
Orskovs.

   Psge SIX - I was interested in your remerk about the metebolism of F+
end F- cells.  Caval'tl has mentioned something CQ the affect that one of
his students hed found It different during mating and I will have to ask
him more about this.

  Page six, peragraph four - It might be worth noting that the Bharkeran's
F factor also seems to be a cinogen.
might be able to eleborrte on it.   if the point is not clear, Rruce

  Page eight, second paregraph -
is this good syntex?        *`In et 1 three ceses end unlike bacteriophegJ'-

  Page ten, Richter - I think his paper is now in press in Genetics1
Research.  Third peragreph, 1 ine one - "clessi~`, please! think of a better
cliche than thet.

  Page eleven, seccrrd line from bottom - anal P ous.  last 1 Ine - is this
datun correct?, I .o., do capitsl I and~cepital e  reinforce one another?

   Page t h i rteen ,  second pe reg reph - the sme point is perhaps even more
encient, see for example, my review in "Physiological Reviews", October, 1952,
end, among others
lecture (Science, , 8 reference to a peper by Green which I eppend. Hy Nobel
        19%) is also preoccupied with the same issues, and I in!
tether surprised, frankly, thet you had overlooked this discussion.  I would


3

Dr. Peter Sneath

August 28, 1961

agree in ploclng special emphasis on the modification of surface properties
by smm of the episunes.  We might considgr the fol lowing gradation - that
in bacteriophsges 8 complete envelope is formed around the genetic materi81;
that the colicinogens engender a fairly general modificrtion of the cell
wall lending it toxic properties (on this point see Cerbal and Barry);
while the F particle generates a specific, end I'm inclined to think a local
Rallfication of the cell wall.  in fact, one could explain the fact that
the point of attachment of the F particle on the chromosome is the last
to be transmtttod in ~ju~ation,  if this chratmsmally fixed F were in
fact anchored to the wall,  it is hard, in fact, for me to think of any
alternative end plrrusible explanation for the polarity of chraaoscme
transfer.  if this paper is Intended to be a balanced historical review,
as I suspect it wit! be taken:as, you might ask yourself whether the
apt same concept was not, infact, fully laid out in Esther's 1953 paper on
lysogenicfty, that it wes then subsequently attacfcod by Wolman 8nd Jacob
as a aisinterpratatfm of sexual polarity, and than was only finally
ragulsrizod with the rec&descence of the term episcme.  I rely entirely
on your own sense of propr'l'ety in dealing with this question; If the review
is not intended to establish the historical development of the subject,
you might be content wtth the present format of the menuscript.

  Other work Is going well - the laboratory is now almost completely
converted to work on bac?lftiz ~:1hti1ls.  We have bmm very plea4 to have
another one of your canyratriots to rseintain our 1-g tradition, 8nd Walter
Bodmer, frcm CsRIbridge is naw busily working on the kinetics of fnrctlvation
of transforming DNA by nucleases.  No asked me sm8 questions reCaMty about
penicif1inaso, and this moves me to ask you whether you have considered any.
tangible work on the genetics of penicillinase in the transformable strairts
of B. subtllfs.  Very likely we hsve discussed this before, but the detafls
o sc8pe my memory at the present time, and while I do not think we would in
any case lslrke 8ny hesty moves in that direction, 1 would be interested to
know what your inclinations or results heva been atong these lines.

  Mel Frrrdkin (an erstwhile graduate on pars-mutation in corn under Brenk)
has also been working here and in a perhaps not very brilliant exprlment
has shown that competent cells lose their caprcity to take up DNA (while
retaining their vfabi\fty) upon treatment with periodate.  it's not clear that
this shows us any more about the atechanism of competence than it doas of
conjugation in E. colt, but m are following this up. A perhaps mom impor-
tant, though by no means as ret table a  finding, is that under sane conditions
perlodate will also inactivate the DNA for which there seems to be no good
chemical excuse, but this might still be a fluke, elthough we are reminded of
McCarty's studies on the fnactivatlm of DNA by other oxidizing agents many
yerrs ago.

With fond regards to Joan and yourself

Yours sincerely,

Joshua Ledwfmrg