DEPT. OF BIOCHEMISTRY
WILLIAM C. Bow& PH. D.

  ASSOCIATE PROFESSOR

BOSTON UNIVERSITY
&ZHOOL OF MEDICINE
80 L. CONCORD STREET
    808TON. NA8S.

Dec. 10, 1940

Dear Dr. Heidelberger:

            I am engaged in writing a book on immunology. That
means, of coume, that there will be a chapter on antibody-antigen re-
actionsns And that means or course that I must discuss the lattice theory,
so ably champixxec? by yourself, among others(including Pauling).

  It is my wish to be aa fair as possible in this discussion (though

I do not say I shall not be polemicalj. Therefore it is quite important
for me to understand your point of view as fu&ly as I can* I am therefore
sending to you copies of a number of statements made, not by Hooker or
myself, but by another well known scientist, whose name I cfo not feel
justified in using , which state his opinion of the relative places of
the lattice theory and the older Bordet theory. I should like to ask
of YCU your opinion of each statement, whether you agree with it, and in
cace you do not, a brief statement(or reference to a page of your writings8
where such reasons are offered) of your reason5 for W disagreeing
with the statement. If you are willing to do this it will be of con-
siderable assistance to me, although you of course realize that a&thing
you say to Hooker and Boyd is likely to be used against you*

  When my chapter on antibody-ahigen reactions has been revised into
a presentable state, I should like to ask you to read it, if you would
be willing to spare the time. That would enable you to protest against
any (unconsciously, I assure you) unfair treatment of your opinions.

  Hooker and I look forward to seeing you this spring at the s;,mposium
on imraunocheaistry be?ore the N*Y. Acad. Sci., which you so !:indly invit xd
us to. We are carrying out some van?itative studies on horse-actihem-
ocyanin which I feel will be worth reporting. (Al50 some experiments
desig,ned to test the l?ttico theory).

Sincerely,


copy

          a.  I think it is Zen&rally agreed that the a;glJtination
reaction consists of two steps; one, ccmbination of ant<bod$ with
bacteria and, two, agzl:2tinati-n of the sensitized susoensionl
The combination between antibody and bacteria is, I think,
oorrectly acco;-nted for by the Yarrack- "eidelberger lattice theory.

       b.   The agglutination of the sensitized cells is, I believe,
accounted for by a combination of an Electrostatic rdpulsion and
oobesive foroe.  I do not believe the lattice theory has any
bearin:, on this stage whatever.  There are a mcrber of experimental
facts which confirm this statement of which I bel;.eve the followin,, twq fire
the most important.

       1.  As ForBet and others, including "Jorthrnp- aad deKr,,if
have shown the combination between antigen and antibody can be
completely separated from agglutination by causing the oombina+inn
to take place in the absence of salt. This step fits in with the
lattioe theory.  The agglutination of this sensitized suspensionk
upon the addition of electrolytes, can now be predicted by
measI,rements of the electro-kinetic Totential and ?f the cohesive
force.

       2.   Further confirmation of the fact that the
az;lutination is determined by the potential is offered by the
agglutination of non-sensitized bacteria and by the agglutination of haoteria
with normal serum or by other proteins.  Cl! these various types
of agglutine-tion, not only of bacteria ?xlt probably of all
suspensions, may be predicted by electrcnhoresis measurements,
whereas the lattice theory can obviously apply only to specific

            Y
agglutination,

          0*  So far as I know the separation of specific a;;lutination
from a&l the many other known azglutinations is purely arbitrary as
it is extremely unlikely that an entirely different mechanism is
involved in specific bacterial ag;PAinationo