December 13, 1964

Dr. Avram Goldstein
Department of Pharmacology
Harvard Medical School
Boston 15, Mass.

Dear Avram:

Thank you for your invitation to the panel dissussion at the Pharmacology
Society. Much as I would like to visit San Francisco again, howewr, I
was not plaming to attend the Feder&tion meetings, and could not conveniently
arrange to do so now.

I appreciate your interest inngenetic traneduction, and wish I could sug-
gest an alternative speaker. However, I am not sure what you have in mind
as the connection between this topic and the biochemical basis of acquired(?)
resis tance.

May I ask a question that perhaps implies a suggestion? Is anything known
of the basis of acquired resistance to drugs as seen in mammals? I would like
to learn more about the entire topic, but have been frustrated by my inability
to find any substantial literature to back up the textbooks! generalizations
about it, 1.e., the statement that tolerance may develop to any of a number
of drugs. I rebliza that the problem with opiates and barbitugates is as ob-
scure as it is pressing. Do you know of any work on tolerance to any other
agent that offers any hint of the mechaniams that may be operating? (Cf.

Mohanty, Nature 7/24/54).

Yours sincerely,

Joshua Lederberg
Professor of Genetics