Letter from Michael Heidelberger to Max Delbruck, California Institute of Technology
In this letter, Heidelberger commented on a mathematical theory for calculating the rate, or velocity, of antigen-antibody
reactions proposed by the biophysicist Max Delbruck. Heidelberger pointed out that such a theory would have to account for
the different stages and other complexities of antibody-antigen reactions.
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1938-03-28 (March 28, 1938)
California Institute of Technology. Kerckhoff Laboratories of Biology
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Medical Subject Headings (MeSH):
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Letter from Max Delbruck, California Institute of Technology to Michael Heidelberger (March 16, 1938)
I wish I could attend the seminar you and Dr. Pauling are planning to run, although I fear my physical background would not
Under separate cover I am sending copies of the reprints which we still have, including the precipitin theory. I should be
glad to have you return this one when you have finished it. I am also sending the derivation of the three-stage equation,
although it does not have to be used in practice.
I am very glad that you are both interested in serological specificity and its mechanisms and hope you will emerge with something
more satisfactory than our makeshift. I think your theory of reaction velocity a plausible one, and some actual diffusion
constants will be published very shortly by Kabat and Pedersen in "Science", so that you may be able to use them.
I do not know, though, how you will be able to distinguish between the primary union of multivalent antigen and multivalent
antibody and the subsequent unions which build up the large aggregates which ultimately separate. I imagine the velocity
must decrease greatly as the aggregate increases in size. Can you provide for a constantly diminishing collision rate? Also,
in the precipitin reaction between pneumococcus polysaccharides and potent antisera visible reaction takes place almost instantly
except at high dilutions and in the cold, so that there is no obvious difference between the large horse and small rabbit
antibody molecules. It is also known that the velocity of precipitation is greatly influenced by the pH, so that all of these
effects must be taken into account in a completely satisfactory theory.
Velocity of combination has been discussed by ( ), and by Hooker and Boyd (J. Bact: 36, 31, 69, 37, 33, 70; J. Gen.
Physiol: 35, 19, 373; J. Immunol: 37, 33, 337), but velocity of particulation was actually measured. Eagle has also published
some data which could be explained on almost any theory (J. Immunol. 50, 18, 395).
Our theories have been attacked by Malkiel and Boyd (J. Exp. Med. 37, 66, 383), apparently as a result of a complete misapprehension
as to the range covered by our antibody excess equation, and by Booker and Boyd (J. Immunol: 37,33,337 ), partly because they
failed to note that the conditions of the experiment criticized eliminated the alternative they suggest, and partly on the
basis of their own experiments, the technique and subject matter of which are, I believe, open to some objection.
Wishing you all success, and looking forward eagerly to the result of your deliberations,