February 16, 1973

Dr. Olen Kewgq

Department of Microbiology
University of Washington
Seattle, Washingoon 98105

Dear Dr. Kew,

I have your phone message about neolactose. This was discussed in
the 1951 Cold Spring Harbor Symposium and again in the volume "Genetics
in the 20th Century" edited by L.C. Dunn. I discussed the possible
significance of constitutive mutants in a debate with Jacques Monod which
appears in the discussion of "Enzymes, Units of Biological Structure and
Function" edited by 0.H. Gabh@er, Academic Press 1956. At that time the
Pasteur group believed that the inducer functioned as a kind of template
that played an instructive role in enzyme specificity; they tried to
counter the implications of the constitutive mutation by postulating
that this behavior was the consequence of the synthesis of an internal
inducer. My counter-argument against that was that lactase constitutive
cells were not induced with respect to the galactose pathway as would
be the case with every then known galactoside. Not long after that the
PaJaMo experiment experiment broke through all our intellectual blinders
and repressors were born.

You asked why I did not refer to this any further? I guess I have to
ask why some of my contemporaries, who are well aware of this work, did
not undertake that discussion. I felt I had certainly fulfilled my
responsibility in bringing the facts on to fhe table. I would have pursued
the issue further if I had gone more deeply into the structure of beta-
galactosidase, so as to be able to verify the identity of the enzyme
produced in the constitutive compared to the induced cells. Other matters ~~
especially the working out of tranadeduction and the application of this
technique to the immunogenetics of Satmonella -- preoccupied me more during
this period.

Kenneth Schaffner of the Department of Philosophy, University of
Pittsburgh, has written a very perceptive history of this area of
scientific discovery. He may still not get hadwe sent his manuscript to
the journal and I suspect he would be interested in any comment you
wished to add to his account.

Sincerely yours,

Joshua Lederberg
Professor of Genetics

JL/rr

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