SOUTH MANCHESTER HOSPITAL MANAGEMENT COMMITTEE

Secretary:

AH. Foams, Pcie, FUR, CHRISTIE HOSPITAL & HOLT RADIUM INSTITUTE,
Telephone No. : WITHINGTON,
DiDsbury 2431 MANCHESTER, 20.

CYTOGENETICS LABORATORY
16th June, 1958,

Prof. Joshua Lederberg,

Walter & Hliza Hall Institute of Medical Research,
MELBOURNE,

Australia.

Dear Prof. Lederberg,

I was fascinated by your letter in Nature of May 17th, both by the
techniques and the interpretation, I am not a microbiologist nor a serologist,
but as a geneticist I have tried to follow your work, The idea of production
of antibody being limited to one kind per cell reminds me of some work of Beale's
in Paramecium. As I remember it was antigen production which was limited to one
at a time of a number of alternatives, the specific antigen varying with temperature.

However, the novelty of the phenomenon you describe, behoves us to search
widely for possible explanations. It is for this reason that I am emboldened to
suggest two alternative explanations which come to mind.

1). All cells producing antibody produce both kinds but the specific groups are
attached to a non-specific "antibody organelle" which might however be a
generic "Salmonella antibody". This organelle is used up by 10 bacteria of
one species so that it is no longer available for the second species, the
antibodies for which have been smothered by the antigens of the first.

2). The second hypothesis has been suggested to me by my colleague Muldal. The
maximum amount of antibody per cell is finite and less than equivalent to the
antigens of 20 bacteria. Production of the two antibodies is independent so
that only a small minority of the cells will produce all of one kind. The
rest will produce a mixture, but such a mixture will not be sufficient to deal
with the antigens of 10 bacteria of one kind. Such cells would be excluded
from your analysis because "If even one organism in the droplet remained
motile, this was recorded as %no inhibition! ",

Both hypothesis are open to testing.
1). By using fewer bacteria per droplet - say 3. This wuld increase the
proportion with complete inhibition. But if the hypothesis is correct some

of these should have enough antibody organelle left to immobilize a further
3 bacteria of the second species.

P.T.0.
-?2.

2). Use 10 bacteria but test all single cells which immobilize some of the
first species with 10 of the second species. These should contain varying
amounts of the second antibody, according to the total antibody production
“per cell.

I hope you will feel that this letter has been constructive.

Yours sincerely,

platen —

, 7 / A.J.Bateman.
0S Pebawe, feat neti on sooo spo eal, oehnel
ome, ate aAm Chey prepatiin; of wdebeleng as ix A frets -

wil the ricrntes of otltr iin the abroe ((-e ‘) toler ne
puntes of ella im the ey dnb, yy the bali yrerintiak i Tobe 4
hm caOlS, AY & were small the prpontiin of webihit, rye
ood} bo ced mtorr of ob «= the drys ils acticad

;,
Age .

v4