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The Lister Institute of Preventive Medicine.

Chairman of the Governing Body :

Sir Henry H. DALE, 0.M., G.B.E., M.D., F.R.C.P., F.R.S. CHELSEA BRIDGE ROAD,

Hon. Treasurer : LONDON, S.W.1.

THE Rr. HON, VISCOUNT WAVERLEY, P.C., G.C.B.,

PROFESSOR A. A. MILES, C.B.E., M.D., F.R.C.P.

G.C.S.1L, G.C.LE., F.R.S.
Telegrams : ‘' Bacteriology, Knights, London.”
Telephone : SLOane 2181.

Director :

6th.April 1955.

Professor J.lLederberg,
Department of Genetics,
University of Wisconsin,
Madison,

Wis, U.S.A.

Dear Josh,

Many thanks for your letters of March 5 and 30,
T am glad to hear that Wright has done so well.

I am sorry to find we still don't see eye to eye
on interpretation. As far as I am concerned, my notion of
two classes of non-replicating particles is, I fesl, reasonably
established by my “large pedigree" experiments, which otherwise
seem inexplicable. Your new experiments appear to cast some
doubt on the attribution of trails (on standard motility medium
with SW 541) to the "gene-bearing" cell, since they sugrest that

a@ cell with a m.cep only may initiate a trail (on diluted medtu-
with SW 553). owever, if you still consider the particulate

nature and non-reproductive character,as "amply settled” (your
letter of Jan.26) then the SW 541 trails on standard medium
cannot be attributed to meCepe-bearing cells, since count of
colonies compared with maximum number of generations possible

in period of incubation demands phenotypig lag in loss of motility
of more than 1 generation. On my. theory the probability of
moving through medium is a function of numberof MeC ep, with a
probability of zero (or near it) for mono-particulate celly
inferred from absence of macro-branching; one would expect

& priori, and your experiments on spontaneous “deep! in SW 553
{and ours on the same phenomenon in SW 545 and other strains),
indicate, I think, that the probability of not getting stuck

is also a function of gelatin-agar concentration. On this
Interpretation the 2 trails on standard medium shown tn your table
would be nearly certainly trails produced by gene-hearers, and

it would remain to decide what proportion, 1f anyof the trails
which daveloped on softer medium only grew from cells with 1 crime
MeCep_ only. As you incubated 8 hours at 37°, a count of more
than, say 50 colonies in a trail would disprove its origin from a
meC ep cell. A critical test of my interpretation of your data
might ‘be possible in the case of your platings of clones which
you s&y on occasion give as many as 7 trails. On my interpretation
no more than 1] of these grew from a gene-bearer, the rest should
-2.

therefore each contain fewer colonies than Mo. of generation times
at 37°, (How many colonies (about) do you mean by "a well-
developed trail", in this context ?). Ina fluid medium a mone-
particulate cell ought to produce a trail, though it might be marked
by diffusion of non-motiles. So far, all your evidence seems to me
compatible with the hypothesis; I shall of course be much
qdisconcertes Jf youcome up with something which Jisproves it, but
on the whole I feel fairly confident (even willing to het). Have
you ever tried a macro-pedigree on 541 ? It may be that it is
easier to re-isolate the E cell late in this strain. This ts T
agres the hard way, but verhaps more informative.

As to publication, for a joint preliminary account P.N.A.S. 1s
agrescable to me, though T weuld have thought Nature just as suitable
“hy should papers in Nature be more 44scursive ? Or is this a mis-
type for less? What Will be more difficult will be +o Aect4e on
content. “e are, I take it, agres* on the mono-=mep, concept, and
we have good evidence for its occurrence in 3 situaticns, viz. in
abortive clones, in clone of sib of transformed cells and in clone
Produced by sponta motile in 0 strains like 545 and 553. 2. here
is working on a probable 4th.type, viz. result of distritution out
after transfer to environment in which mop not formed. As we don't
yet agree on what happens in abortive transduction T Suppose the
sib of transformed cell case may be clearest. If the pre liminary
paper is devoted mainly tec the mcno=m¢p case, and hedges on

abortives", then I suppose it might be necessary to bring in the
spont. motiles, in which case we should join Quadling as a co-author
I think, for as I mentioned earlier, he has done quite a bit on this
here, (as part of his thesis work). Fowever, maybe I should wait
and see your promised draft (and get on with the missing section,
and re-write, of my own). As to main paper, the difficulties of
getting our opinions (and protocols) acress to each other seems to
be substantial, so perhaps we shall have tg do them separately;~ my
only ebjection to this is that its a pity to have two when one could
have sufficed, (especially if they ccme to afferent conclusions),
However, this may he resolved by events. (A day or two of 44scussion
might have done it, ‘ut not possible T fear).

I intend to have a bat at>the inhibition of tratls in 543
by anti-serum for donor's H antigen, transferred to micro=manipe

ee?

From earlier er» periments T am pretty sure th is a genuine
effect, seen only [for sure) in 543. Have head some trouble »4ith
cross-reacticns in sera, so am now in midst of making, and cross-
absorbing, some of my own for a change.

An unexpected thing we also mean tc lcok into is trails from
T™ 2 in presence of anti-i and anti-1,2 after treatment with a
particular lysate of a donor Thich is bee, - As you know it does
not normally happen, but we have had quite definite tratils on several
36

occasions, so must now try and find what is the relevant variable.

My T 1 ~-utants are not Boing well, too many phenomene but
none of any obvious general interest. Marjorie Krauss, from
N.¥,U., will, if all g0es weil, spend some time here jn sumer.

We are thinking of looking for abortive transformations (a propos
capsule) in Pn.

I have consulted Race about Proc .Roy .Soc.eBe No difficulty
in getting in, he says, but variable delay, 6 months or more.

As to terminology, I wonder if we really need to coin
&@ new word ? Jennings after all got by without one. I talked
to Sonneborne when he was here a week or two ba&k (he gave 3 «+:
excellent lectures) who thought"uni-linear transmission” was 0.K.,
but not*u-l inheritance", since the latter in biology is too much
associated with the tdea of things which ere replicated. A good
point I think, He was T fpund prepared to be convinced by my
pedigrees (but of course T had not any of your ? discrepant data
to present). Paper-to Genetical Soc. went over quite well,
discussion at end showed that at least some of audience followed
the paper OK. Pollock (no geneticist he) pointed out resemblance
of my non-replicating gene” to his penicillin-sensitive site or
of what not, since, @#f one considers whole culture, each determines
M4 linear synthesis of something, pen-ase or MeC ope, during subsequent
~ exponential growth.

Yours sincerely,

3 Derry lr 3 5p

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