@
UNIVERSITY of PENNSYLVANIA

PHILADELPHIA 4

The School of Medicene

DEPARTMENT OF PEDIATRICS
1740 Bainbridge Street
Philadelphia 46, Pa.

November 7, 1958

Dr. Joshua Lederberg
Department of Medical Genetics
School of Medicine

The University of Wisconsin
Madison 6, Wisconsin

Dear Josh:

I have been delaying my reply to your last letter so that I would
also be able to congratulate you on the well-deserved recognition which
you have just received.

I have no additional a priori arguments against the view that
antibodies are differentiated on the basis of amino acid sequence.
However the full implication of my argument may not have been clear.
The starting point of our analysis is the recognition tha immunologic
specificity is based on unique constellations of the side chains
(R groups) of amino acid residues. This means that if the antigen is
to play a determinative role in sequence, there must not only be a
mechanism for the instruction of sequence by the antigen. The antigen
must also be able to select a sequence which on subsequent folding of
the polypeptide chain will give rise to the appropriate R group
constellation.

‘A Hsnaoy

Any theory which assigns an elective role to the antigen avoids
the above difficulty, of course. But it seems to me that the present
theories of this kind raise more conceptual problems than they clarify.
Furthermore I believe that the cell transfer experiments, particularly
those involving in vitro incubation of lymph node cells and antigen,
provide evidence against the clonal theory.

With best regards and congratulations also to your wife since
she probably did most of the work.

Sincerely yours,

Parekh

Fred Karush
LRTI,

FK ems