WALTER REED ARMY INSTITUTE OF RESEARCH
WALTER REED ARMY MEDICAL CENTER
WASHINGTON 12. D.C.

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IN REPLY REFER TO: &; 4 October 1956

Germfree Research Unit

Dr. Joshua Lederberg
Dept. of Genetics
College of Agriculture
University of Wisconsin
Madison 6, Wisconsin

Dear Dr. Lederberg:

Thank you for your letter of September 27th and the copy of your
note on protoplasts. I was very interested in the observations on the
formation of protoplasts in the presence of penicillin and your inter-
pretation of these results with respect to the action of penicillin. I
agree with you that they tie in very nicely with my observations ---
especially in view of our findings of last fall and winter. Jack
Strominger and I arrived at the same conclusions you have last
January (quite independently) and at that time decided to publish
jointly. Because Jack was just setting up shop in St. Louis and I
have had a hectic year working with germ-free animals, we are
only now writing up this work. Of course, both Strominger and I
presented this work at the 130th ACS meeting and Strominger is dis-
cussing it again this month for the Pharmacology Society.

In essence, we found that cell walls contained the same amino
acids and the same new amino sugar (and in the same proportions)
as were present in the uridine derivative. On the basis of this and
the published work on cell wall composition, it was proposed that
penicillin interfered with cell wall formation and that one result of
this was the interruption of a transferase reaction in which ordinarily
the amino sugar-peptide was incorporated as a unit into cell wall.
It was also pointed out that this interference with a synthesis which
is essential to bacteria but not to animals could explain the selective
toxicity of penicillin.

Iam sending Jack a draft of our manuscript and after he works
it over, I will send youa copy. This should be in less than two weeks.
I think it would be worthwhile to refer to each others publication in
press as each strengthens and complements the other so beautifully.
You ask about a UDP-- diaminopimelic acid complex.
Relatively few organisms accumulate UDP-derivatives, and I have
not studied appropriate organism with this in mind. You realize
the UDP-derivative that has been studied contains three residues
which may be unique to bacterial cell walls and for this reason one
more unique compound does not add greatly to the argument.

I'm afraid I have no suggestions for quick tests of UDP enzymes
beyond those Kalckar would suggest. I consider your interpretation
of f -forms as protoplastzas correct and that this simple but remark-
able observation has far-reaching implications not only in your genettic
work but in many other fields as well.

Sincerely,

Sod

JAMES T. PARK