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zr, Eewis Chargaff

Cell Cheaistry Laboratory
Stluntia University

630 Wort 163th Street

tiew York 32, h, Y,

Tear Zrwing

Thank you for your note, Just a day ago, the issue cf Neture in
question arrived in Madison ana I had a crance to reed your article,
witch of course interested me very auch indeed.

I nave nothing more to tell you that would be eerectally relevant
to the technical prodleme of that work; however, T nave a paper in

_Preee tn the Cournal of Basteriolcgy, which ill be coming out very

Siortiy, which gives some more details on the process cf reversion ant
on the relationship between protcplasts and Leform growth of dacteria.

Alsc ‘included in that text Le acme inention of our swn unsuccessful
and otherwise unsucceasful attempts dt achieving transduction of genetic
markers to protoplast recipients, I your om successful results can bs
remularized you will, of course, have furnished extremely important tool
for genetic research and one tiiat I would be rost anxious to be able to
exploit at the earliest cpportunity, It was. as I az mire you ure aware,
thie possibility which motivated my own civersion te the general problem
uf the technology of protcplasts in EB. coli, You will not be surprised
if I approach accomplishments along these lines with a sertain sense of
hypercriticitsm perhars based in part by ry owm inaoility to fulfill ny
initial expectation of the utility cf protoplasts for sich purposes,

The more 80 as we have conducted experinents identical designs to your
own and have run only into red herring along the way,

I wonder if it would be posstble for you to-alley some of. my wa
sxepticisne with a more detauilea account of the other eleven experiuents
which were not presented in full in your prelininary note, together with
the further information which I am sure you have accumulated. To verify
that a chemical agent nas indeed irducad a genetic change 1s one of the
tricclest problems ir bacterial genetice. ana very much the more so under
the handicap of two cf the conditions in your experiments; namely, the
very high background of spontaneous reversions already present ir your
untreated cultures, ani the long interval of growth of tre treated popu-
lation, the latver leaving oren many posaitilities of undetected selective
growth, The very nature of spontaneous mutation, its predictable unpre-
dictalility, and the exaggeration of this oy the clonal distribution
Page 2 - December 13, 1957

which tenda to defy simple statistical analysis confound the problem
even more, It would however help me to get a conetructive prospective
on your experiment if you could give me the figurea on the other rung,
i am partioularly anxious to knew if any of these experiments the
treated cultures actually showed a smaller number of reversions than
the untreated ones,

If these problema of inference can be dealt with in a system
Which geems to ve inherently irregular in ita yielding of positive
results, the next urgent question thet I would ask is whether the
phenomenon conforms to the definition of e genetic transduction (see
for exauple my article in the American Soientist last year), & crucial
test for this purpose would be a comparison of the effectiveness of DNA
extracted from the wild type and from the same rutart respectively,

May I also inquire whether you have had comparable results with
any other mutants aa recipient, and indeed whether any others have
been triedt JI em enclosing « copy of the paper referred to above,

With all best wishes,

Yeura sincerely,

Joshua Lederberg
Professor of Medical Genetics

JLJew

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