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04

April 18, 1974

Professor Hans L. Kornberg
Department of Biochemistry
University of Leicester
University Road

Leicester LE1 7RH

ENGLAND

Dear Dr. Kornberg,

Thank you for your letter of April 5th. How curious that you
should have unearthed those remarks about chloroacetate just now.
I say this because within the last month I had also reminded myself
of those ancient observations, reread those remarks, and looked around
a bit to see if anyone else had done any more work on those types than
I had done. The answer is generally negative. I never did do the
comprehensive study that I had planned, partly because the strains
in which these -utants occurred became less interesting for some
other reasons irrelevant to the present purpose. I think there is
some passing mention of these mutants in one or another later symposium
volume but I cannot put my hands upon it and I do not think it would
add any significant information.

It is apparent that some or all of these mutants are deficient
in the socalled formic hydrogen lyase reaction, and I certainly think
it would be rewarding today to see if they can be related to the set
of chlorate rekistant mutants which embrace a whole set of defects connected
with the embedding of the wall bound cytochrome system. I have, however,
not pursuit this myself nor am I likely to do so and it would please me
very much to learn that you were able to shed some additional light on
these curious beasts.

May I call your attention also to Penfold's observations on mutants
resistant to ethylene chlorohydrin which he reported to be incapable of
fermenting glycerol. I recently had some suspicion that these might be
tied up to C-AMP activation defects but can offer no particular evidence
in support of that speculation. I do not recall having confirmed his
claimed observation in fact.

It would be intriguing to know the mechanism of resistance that these
mutants display with the considerable likelihood that they will prove to
be permease specific effects perhaps entailing a wider range of dysfunctions
in the cell membrane.

I have not been able to find any further literature on chloroacetate
and would be intrigued if you could eventually share news of your findings.
T am curious to know in fact how you happened to stumble on this point in
my 1947 paper, particularly if you were in fact looking for light on this
Professor Hans L. Kornberg ~2- 4/18/74

particular question.

Let me apologize for having led you to a fruitless search for
the "elsewhere" with the hope that it did not detain you too long
before your writing me,

Bincerely yours,

Joshua Lederberg
Professor of Genetics

JL/rr