October 23, 1958

Or. Fred Karush
Chitdrens Hospital
1740 Bainbridge Street
Philade!phia 46, Pa.

Dear Fred:

1 was Just delighted to get that last reprint from you entitled ''Stuetura!
and Energetic Aspects cf Antibody Hapten Interactions". That experiment with
urea is one 1 was proposing to Harold Deutsch Just the other day and neither
of us had been aware that you had already done it. The result you got was
what | would have considered in advance to be strong confirmatury avidence
that antibody sequence does depend on just such structural factors as sequence
of amino acids. If I can reconstruct your reasoning your main argument against
sequence is tne lack of a plausible mechanism for instruction of sequence by
an antigen. Of course t agree with you wholeheartedly on this point and in
fact this argument underlies my agreement with the conception that the antigen
must have an elective or retrospective role in determining antibody specificity.
Of course the structural factor would by no means whatsoever minimize the -gle
of disulfide linkages in holding the protein together and determining its
essential shape but | would consider that the possible configurations that
disulfide linkages could establish would depend on sequence considerations.

Now what {| would like to press you for an answer on is whetner there are
any other compelling arguments against the differentiatton of antibodies or
the basis of amino acid sequence.

With best reqards.

Yours sincerely,

Joshua Lederberg
Professor of Medical Genetics

JL/jp