Ookober 12, 1956

Dr. P. Mitehell

Dept. Zoology
University of Edinburgh
Scotland

Dear Dr. Mitchell:
Thak you for your note and letter of the 5th,

I realize that my "finiings" as recorded in the note you saw have been
almost if not entirely enticipated by other workers, though haps not all
the details fitted so coherently as they did in the E. coli/penieillin/sucrose
trials. This may be partly due to the greater fregility of the protoplaste
in E. coli: thay can be prapared in fair yield ( 1-10%) from Proteus even in
dilute mdia. I have hoped to rectify any possible impression of uniqueness,
and also to clarify the implicit hypothesis of penicillin action, by the accom
panying "pos teeript'.

Your interesting note offered certain obscurities to my own reading, perhaps
because I am not as familiar as I should be with your previously published work.
(I would appreciate receiving whatever reprints you can spare on this count!)

The mlonate-arabinose combination is such a weird mixture it surely was not
devised ad hoc, but I don't understand what the specific functions of the com
ponents are intended to be. I also am not olear as to your meaning for "autolysis"
which connotes, to ma, the dissolution of tlesue or cellular structure after
death.

Dr. Park tellea ma he has reached identical conclusions as to the mechanism
of penicillin action and the role of the accumlated Uridine-diphosphate conju-
gates from his chemical studies.

Doubtless the min reason these issues were not appreciated sooner was the
aura of mysticiem that has surrounded the studies of "L-forms"; I am sure you
will sympathise with my task of reading and reinterpreting that literature! We
hawe however succeeding in the further propagation of EB. coli protoplasts as
L-form colonies in penicillin-containing agar (not broth!) and this opens the
door to what I hope will be more exact studies of the genetic and physiological
significance of these mysterious elements. Unfortunately, our experiments with
mixtures of marked strains ao far do not encourage the hope for new genetically
interesting developments with the L forms. The mechanism of prolifera$ion of
L-forms is another issue? at least one process superficially resembling budding
(from a small perhaps granular protuberance) has been obseryfed; so far segmentation
of a “large body’ has not been, in my omn mterfal.

Yours sineerely,

P.S. Dr. Zinder has a note in preas accompan mine -
in the PNAS, on lysozyme effects on E, coli, rae will ‘Joshua Lederberg

be ste his separa the d Professor of Genetic
canta” fraguity rom the subsequent sphering of we venennee
4

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