Letter from William C. Boyd, Boston University to Michael Heidelberger
In this letter and its appendix Boyd, who had on several occasions disagreed with Heidelberger's quantitative theories
of antibody-antigen reactions, asked him to respond to statements on unsettled issues in immunology made by an unnamed scientist
as a way of clarifying Heidelberger's own position on these matters.
Number of Image Pages:
2 (160,534 Bytes)
1940-12-10 (December 10, 1940)
Boyd, William C.
Courtesy of Michael Heidelberger.
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Medical Subject Headings (MeSH):
Allergy and Immunology
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Letter from Michael Heidelberger to William C. Boyd, Boston University (December 16, 1940)
I am engaged in writing a book on immunology. That means, of course, that there will be a chapter on antibody-antigen re-actions
and that means of course that I must discuss the lattice theory, so ably championed by yourself, among others (including Pauling).
It is my wish to be as fair as possible in this discussion (though I do not say I shall not be polemical). Therefore it is
quite important for me to understand your point of view as fully 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 do 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
your opinion of each statement, whether you agree with it, and in case you do not, a brief statement (or reference to a page
of your writings where such reasons are offered) of your reasons for disagreeing with the statement. If you are willing to
do this it will be of considerable assistance to me, although you of course realize that anything you say to Hooker and Boyd
is likely to be used against you.
When my chapter on antibody-antigen 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 symposium on immunochemistry before the N.Y. Acad. Sci., which
you so kindly invited us to. We are carrying out some quantitative studies on horse-antihem-ocyanin which I feel will be
worth reporting. (Also some experiments designed to test the lattice theory).
William C. Boyd
a. I think it is generally agreed that the agglutination reaction consists of two steps; one, combination of antibody with
bacteria and, two, agglutination of the sensitized suspension. The combination between antibody and bacteria is, I think,
correctly accounted for by the Marrack-Heidelberger lattice theory.
b. The agglutination of the sensitized cells is, I believe, accounted for by a combination of an electrostatic repulsion and
cohesive force. I do not believe the lattice theory has any bearing on this stage whatever. There are a number of experimental
facts which confirm this statement of which I believe the following, two are the most important.
1. As Bordet and others, including Northrop- and deKruif have shown the combination between antigen and antibody can be completely
separated from agglutination by causing the combination to take place in the absence of salt. This step fits in with the lattice
theory. The agglutination of this sensitized suspension, upon the addition of electrolytes, can now be predicted by measurements
of the electro-kinetic potential and of the cohesive force.
2. Further confirmation of the fact that the agglutination is determined by the potential is offered by the agglutination
of non-sensitized bacteria and by the agglutination of bacteria with normal serum or by other proteins. All these various
types of agglutination, not only of bacteria but probably of all suspensions, may be predicted by electrophoresis measurements,
whereas the lattice theory can obviously apply only to specific agglutination.
c. So far as I know the separation of specific agglutination from all the many other known agglutination is purely arbitrary
as it is extremely unlikely that an entirely different mechanism is involved in specific bacterial agglutination.