Letter from A. M. Pappenheimer, Jr., University of Pennsylvania School of Medicine to Michael Heidelberger
In this exchange of letters Heidelberger and Pappenheimer discussed hypotheses and evidence regarding the location of the
sites at which antibody molecules (later shown to be Y-shaped) bind to antigens. One hypothesis, proposed by the preeminent
physical chemist Linus Pauling and discussed in this letter, held that these binding sites were located at the ends of a symmetrical
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1940-10-23 (October 23, 1940)
Pappenheimer, A. M. Jr
University of Pennsylvania. School of Medicine
Reproduced with permission of John R. Pappenheimer.
Medical Subject Headings (MeSH):
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Letter from Michael Heidelberger to A. M. Pappenheimer, Jr., University of Pennsylvania School of Medicine (October 31, 1940)
I wonder if you would be so kind as to send J.W. Williams of the Department of Chemistry, University of Wisconsin, a reprint
of your Bast. Rev. 3 49 (1S39) article and also a reprint of your paper with Kendall on quantitative precipitin reaction with
pneumococcus polysaccharides. They are continuing the digestion studies which I recently spoke to you about and wish to analyze
their preparations quantitatively for antibody content and A/S ratio. I expect to do some of this for them but they wish
to try it themselves.
I read Linus Paulings' recent paper with great interest. It seems to me, however, that a number of his assumptions are
invalidated by some of our recent work along with Pope's etc. In particular, we can state definitely that the reactive
sites are not on the ends of the molecule in either diphtheria antitoxin or pneumococcus antibody, at least not on both ends.
Moreover, in the case of antitoxin the reacting sites are less susceptible to heat denaturation than are other localities.
I am becoming most enthusiastic about the enzyme method of locating the position of reactive groups on different kinds of
antibody molecules. There are a number of other little things about the Pauling theory that I wonder about. For example,
he states that antigen containing weak groups will be a good one whereas one containing many strong groups will be poor.
If this is the case, why is diphtheria toxin an excellent antigen in the horse and a very poor one in the rabbit whereas the
reverse appears to be the case with egg albumin?
I am taking the liberty of sending your copies of two manuscripts dealing with peptic digestion of antibodies. The one on
antitoxin was presented last June at the Colloid Symposium and is in press in J. Phys, Chem. The other is a progress report
of my summer's work sent to Williams a few weeks ago. It contains a crude picture of the structure of horse pneumococcus
antibody as I see it. Will you please return the manuscripts when you are through with them.
Probably my criticisms of the Pauling theory are but a few in-consequential details. I would like to know what you think.
I thought I might write him since he evidently knew nothing of the enzyme work.
Parenthetically, the recent paper by Fell, Coghill and Stern in J. Immunol. is my idea of complete confusion. Except in one
case I do not think more than 8% antibody was present, in any of their preparations.