DEC 15 1969

WASHINGTON (es UNIVERSITY
et

SCHOOL OF MEDICINE
ST. LOUIS, MISSOURI 63110

DEPARTMENT OF PSYCHIATRY
4989 BARNES HOSPITAL PLAZA
SUITE 4105

SAINT LOUIS, MISSOURI 63110

December 1, 1969

Professor Joshua Lederberg
Department of Genetics

Stanford University Medical Center
Stanford, California 94305

Dear Professor Lederberg:

Thank you for your letter of November 10 and the copy of your excellent
commentary entitled "The big fuss over MSG." I was particularly pleased to
read your commentary because it focuses on aspects of MSG research which go
beyond the current controversy over MSG as a food additive.

I do not have a literature check list of analogous effects of other
amino acids and, in fact, I do not know of anyone who has loaded infant animals
with individual amino acids and then carefully examined the central nervous
system for acute neurotoxicity. In the course of my own studies I have ad-
ministered a good sampling of amino acids in massive oral doses by feeding
tube to 10 day old mice (glycine, leucine, methionine, phenylalanine, lysine,
arginine, serine, alanine, proline, aspartic acid and glutamic acid) and have
found that of these amino acids only glutamic and aspartic acid are capable of
inducing neuronal necrosis in the hypothalamus. The lesion induced by aspartate
is identical to the one associated with glutamate treatment. Interestingly
enough, glutamine, the amide form of glutamate induces only a tiny lesion
when given in massive doses (probably by conversion locally to glutamate).
GABA, even at doses which are both massive and lethal induces no hypothalamic
changes, An additional compound, sodium glutarate, which is structurally
identical to glutamate, except for having no amino group, is also unable to
produce the hypothalamic lesion at massive doses. We have some additional
studies under way at present in hopes of further clarifying these intriguing
questions of specificity and mechanism of action.

Enclosed are some reprints of my published work on glutamate and the
developing central nervous system.

Sincerely,
phe W Bheeg,
John W. Olney, M.D.

JWO:hme