STANFORD UNIVERSITY
MEDICAL CENTER
PALO ALTO, CALIFORNIA

DEPARTMENT OF BIOCHEMISTRY February 8, 1961 DAvenport 1-1200

School of Medicine

Dr. Joshua Lederberg
Department of Genetics
Stanford University
school of Medicine
Palio Alto, California

Dear Josh:

The following are comments on Herman Eisen's
manuscript:

1. The title is confusing. Since microsomal
antibody activity exists before the experiment begins,
and the authors are showing a solubilization of this
activity, I would suggest as title, "The Solubilization
of Microsomal Antibody Activity by the Specific Interaction
Between Lymph Node Microsomes and a Crystallizable Fraction
of Gamma Globulin".

2. I don't think the word "subunit" should be used
since there is no evidence that gamma globulin is actually
composed of the three Porter fractions as real biologically
relevant units. Suppose, for example, as has been suggested
by Edelman, Y-globulin is made up of 3 chains and the papain
cleaves these chains vertically into | -) units, each containing
portions of the 3 chains. The word "subunit” has a special
sense and will be essential later on when a clear under-
standing | of synthesis is accomplished. I therefore would
suggest "fraction" which is more precise.

3. The experiments on "Passive cutaneous anaphylaxis
reaction of microsomal antibody", page 8, don't seem to lead
to any conclusion. If there is one, it would well be stated.
It is not clear whether the position is that the animal's
normal Y~globulin liberates microsomal antibody to give a
cutaneous reaction, or if microsomes per se are capable of
entering into the reaction. This should be clarified.

The major change that I would suggest is in the dis-
cussion. The experiments with ribosomes are suddenly intro-
duced. These experiments are critical to understanding of
the phenomena. Antibody is shown to be linked to ribosomes.
Page 2,
Dr. Lederberg
Feb. 8, 1961

If it were true that fraction III liberates antibody
activity by virtue of an exchange reaction and then one
should expect the same reaction for the ribosomes to
which Y-globulin is linked. Unless, of course, some
other hypotheses are introduced, It is not clear why

this very simple experiment wasn't performed or mentioned.

One other interpretation might be mentioned. Suppose
that we picture microsomes as a bag in which (a) antibody
floats free, and (b) antibody is linked to ribosomes. The
free antibody is that antibody which is on the way towards
being secreted. The mechanism of Y-globulin - fraction III
liberation would be part of the mechanism of secretion.

The raising of this point is because of the findings of
Brambell et al. that Y-globulin will pass the egg sac men-
branes as will fraction III, whereas fractions I and II do
not.

Lastly, some statement concerning the possibility of
a chemical interaction between fraction III and the material
involved in microsomal antibody activity should be brought
UD.

Please put this into English.

Best,

le
yy
Mel Cohn

MC ims
enc.