The Lister Institute of Preventive Medicine.

Chairman of the Governing Body :

SIR HENRY H. DALE, O.M., G.B.E.. M.D., F.R.C.P., F.R.S. CHELSEA BRIDGE ROAD,
Hon. Treasurer: LONDON, S.W. 1.
SIR JOHN ANDERSON, P.C., G.C.B., G.C.S.I., G.C.IE., F.R.S.
Director : Telegrams: ‘‘ Bacteriology, Knights. London.”
SIR ALAN DRURY, C.B.E., M.D, F.R.S, Telephone: SLOANE 2181.

eend March 1956.
Professor J.lederberg,
Nepartment of: Genetics,
University of Wisconsin,
Madison,
Wis,, U.S.A.

Dear Josh,

I have not heard anything from you for some time: but
I suspect this may be my fault.

Several bits of news. The first is that I have just
had an invite from Demerec to Z.S.H. for Symposiu » and to
work there for summer; I can't ldave here for more than a
month or so, so don't know if they will want me on those terms,
but I hope so. I feel quite startled at their generosity in
inviting people, fares paid, who don't even have to give a
paper.

For various reasons I am anxicus to get the abortive
transduction paper in before then: and I Have therefore taken
up the tedious task of finishing off MS. I will enclose current
draft with this (or send it separately, as 2nd.Class Air Mail,
to save postage). I inten4 to try and prune a bit further, and
also to be perhaps a bit less dogmatic, in particular to revise
the section comparing your results and mine. Could you glance
through it and see I have said nothing too terrible ? I am
sorry I cannot include photos of pedigree figures, but you
havé had sketches of these before so I hope will be able to
follow O.Ke, and the same in the case of diagrams to illustrated
hypotheses.

When you have looked through, coula you let me know
what you intend to do about publishing your own paper ? I think
I will send mine to the J.gen.Microbiol; in your last letter I
think you spoke of sending yours to something more genetical,
which seems a good idea. If you can let me know I can make the
necessary amendments as to "the accompanying paper" etc. (I have
begun to put in refs. to it as "L.1956" which I suppose will be
O.K. wherever you sen? it).

You asked for mcre detailed comments on your draft.
=D =
I will reserve thse for end of this letter.

Yhen you go through draft, could you please look out for
any places I may have inadvertantly misquoted you ? (or not
mentioned that I got some method from you) # In the discussion
you will see TI have made use of your ideas to clarify my own;
but on the assumption that your paper will soon be available I
have not discussed some of the more general hypotheses which
you consider.

One or two bits of relevant research news. Chris Quad ling
and I have done an experiment which we think rules out Bissetts
theory on distribution of all parental flagella to one daughter
cell in Salmonella etc. The experiment is a very simple one.
He grew up L.T.2 in broth at 37 » mean no. of flagella per cell
c 8, and made about the.same.fhen transfer to 45°: growth
continues at same rate as before, but mean no. of flagella per
cell falls to new steady value of about 0.1 (it varies a bit).
During the change (which begins 1-2 generations after transfer)
the mote moves down from 6 to 1 (or zero, if you include this
Class), and there ts never the bi-modal Aistribution with peaks
at 6 and O predicte- by Bisset's theory. We shall try it on
B. at J.G.M. Symposium in April. (I think I must send him news
of it, as he is apt to explode with slightest stimulus) .This
makes me much happier about identification of mcp with flagellum
(or basal granule). Chris also has fairly good evitence of
correlation of distribution of numbers of Sseony Ain experiments ~~
in which synthesis of mep in a peculiar Stpara CG is halted by
temperature shift (37°39 20°, surprisingly enough). I think when
he has finished there will be little doubt about this identification.

mani, vie et ote J ba. 7

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Madamde Margerie (formerly Hottinguer) and I have been
working away on the ‘segregation! of serological type in SW 666
treated with i lysates: the character scored is time to
sessaticn of translational movement in H serum (x 100 titre);
this is more or less log normally distributed, T am using the
mode to surmarise. "Initials" are irmob. in 5-10" by either
serum. Celis with one mep are immdbilised more slowly, even if
both donor and recipient are b (? diminished chance of entanglement )
Cells which have had one mcp transmitted through many generations
even, wo first: thought, not inmobilised@ at all byganti-serum; but
it now looks as though they are, but with a modal time of over ome
generatiom time: of course this might be result of distal and
of flagellum (only) having i reactivity, from earlier generaticns.

In the course of these experiments we have done tanse Pouce
pedigrees: one E cell at 12th- genepation, and the general picture,
conv ineg, me that situation is 4s in SW 541 with the following
-3=

differences: (1) Fewer E cel!s (usually). (2) Most E cells cease
to be so within a few generations, (3) much smaller probability of
"accidental immobilisation" (4) (probably) fewer mcep produced per
generation. The only thing which you report and T have not seen is
slowing-down'of cell with one mep a bit before, it is "lost".

Tn the same experiments we have come on a peculiar situaticn
which you may have seen too. Viz., the M clones behave very erraticaly
as to proportion of M celis in sub-clones. Experiments so far in
one clone are compatible with loss ang regain, by "mutation", of
ability to make mcep at rates of c 107* per cell per generation, but
in another clone under examination at the moment results so far are
a mess. All of 3 or 4 clones met with since we began to lock for it
have behaved in the same general way. (For all I know it may be
“wiversal in ordinary motile strains, and so account for, for instance,

the usual non-motile minority, and non-Poissoniaby large class of cells
with zero-flagella). It may be releyant to 'flares' and certainly
explains some earlier od4 results in clones.

I have been asked to do a monograph in same series as Bealets,
on transducticn and transformaticn. I would not mind having a go
at it if I could arrange the time. Do you know if anyone in U.S.

is on similar project ? I would like your opinion on whether I should
take this on.

I hear frmvarious rumours that you are going to Melbourne:
I hope this works out, if it is what you want to ao (but I hope you
manage to take in Lonton en route).

Your Papere

Content. The experimental side seems fine, so far as I can judge
without the tables and pedigrees. I feel in a way its a pity you
never (so far as I know) tried SW 541 pedigrees, since I fee? sure
that, with present knowledge, you wou’d at once have got pedigrees
which you would consider capable of disproving my hypothesis if its
wrong; I think we are agreed that results in your paper neither
establish nor disprove it. Apart from this negative one, I have
ne general criticism.

Theoretical. I admire your logical presentation of all possible
alternatives (it has helped me a lot). The hypothesis that mcp =
Cchromonemetal fragments seems less plausible when as now appears,

mop are generated in situations where transduction is not concerned
O of SW 553 )

Your "Suggestion 5". Should you not specify that gene
products do or not 'dilute-out!, and if so, if final level of one
per cell permits synthesis?
-4 =

zermi nol ogy « I still prefer 'unilinear transmission! to catenate,
etc. an? shall I think stick to it. I see no particular reason
why we should use a single set of words if our preferences differ.
(I have use@ toriginal' cell for what you call an ‘4nitial'., T
may change this). Otherwise no comment.

Presentation. I-suspect that a reader unfamiliar with the

materfal might have Considerable trouble in fodlowing your papers: but
the inclusion of tables, pedigrees and figures will help, and the
tidying-up which no doubt has been Aone since the draft I saw.

Anyway its hard for me to judge, the test wehla be to try it on
someone whe has never heard of it before.

This seems to cover all I have to say at the moment.
fiope to hear from you soon.

Yours . 9
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