Letter from Michael Heidelberger to William C. Boyd, Boston University
In this letter Heidelberger responded to statements on unsettled issues in immunology made by an unnamed scientist and submitted
to Heidelberger by Boyd, the author of an upcoming textbook on immunology and an occasional critic of Heidelberger's quantitative
theories of antibody-antigen reactions.
Number of Image Pages:
2 (176,415 Bytes)
1940-12-16 (December 16, 1940)
Boyd, William C.
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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 William C. Boyd, Boston University to Michael Heidelberger (December 10, 1940)
Your letter interested me greatly and I certainly envy you your courage in writing a book on immunology - it will surely involve
a prodigious amount of work. I'll be very glad, of course, to look over your antigen-antibody chapter if you care to send
it, but I must warn you that I've already promised to do the sane for another friend who is also writing on Immunochemistry.
As for the comments of your scientist friend, there is little I can add to what I have already written, nor do I think anything
that has happened since has weakened the arguments advanced then (esp. Bact. Revs. Revs. '39,3,49).
"a". The first sentence sums up beautifully prevailing misconceptions regarding specific bacterial agglutination
first, that of antigen-antibody combination as a single, static process, followed by a second aggregative process for which,
I submit, there exist only assumed, but not real, analogies. If "it is generally agreed" that this is the process,
it illustrates all the more clearly the harm wrought by dragging in assumed analogies. If, as stated in the second sentence,
combination is correctly accounted for by the mutual multlivalence theory, as I prefer to call it, separation of specific
antigen-antibody combination into two steps represents an unnecessary complication.
b. I have found no sound evidence in the literature that electrostatic repulsion could cohesive force have anything whatsoever
to do with specific bacterial agglutination. I know of no useful prediction as to the process baaed on these two, to me an
entirely gratuitous assumptions, whereas, making use of the principles already referred to (also J. Esp. Med 37, 65, 885)
one can readily predict, when a little information is available, whether or not agglutination will take place.
1. I do not question the experimental facts cited, merely their interpretation. The agglutination of a sensitized, salt-free
suspension may be better predicted on the basis of the neutralization of well-known Coulomb force effects than by the introduction
of a special and vague concept such as "cohesive force."
2. It seems to me that Mudd and Jeffe's old experiments (J. Gene Physiol 35, 18, 599) as well as our own above referred
to, showed that electrophoresis measurements and "potential" would be of influence only in the venue that too large
Coulomb forces might impede the completion of specific aggregation.
c. The apparently arbitrary separation of specific agglutination from other agglutinations is a convenience because antigen-antibody
interaction supplies a clue as to mechanism that is lacking in the other types. I believe that as the factors promoting particulation
in other systems come to be as well understood as those responsible for bacterial agglutination these other systems will show
real analogies in place of those which now have to be assumed. One can visualize hydrogen-bonding or other secondary valence
forces as connecting links. I still feel that the shifting of emphasis in agglutination from demonstrated chemical interaction
of "generally agreed" multivalent components to the assumed physical analogies has impeded the understanding of the
process, and still is, according to your friend's comments.
I think we are likely to have a very stimulating conference in March. In a few days I hope to be able to send out a tentative
Looking forward to seeing you them, if not before, and with greetings to Dr. Hooker,