Letter from Felix Haurowitz to Michael Heidelberger
In asking Heidelberger for help in responding to the comments of a reviewer and in ushering the paper under review towards
publication, Haurowitz acknowledged the central role Heidelberger played in the field of immunochemistry during the 1930s
The main point is however the assertion of the referee that it is unnecessary to resort to the "subterfuge" of azoproteins.
Why? I have read very attentively the papers of your laboratory, quoted by the referee, and other papers of this series,
but I really have no idea, what the referee means. Is there any other possibility of determining anti-globulins? The referee
might have in mind your paper on thyroglobulin, where you have shown that all of the added antigen is precipitated as long
as antibody is in excess, and that antibody can be calculated simply by subtraction of added antigen from total precipitate.
But in other papers, on azo-obalbumin, azo-serumalbumin, azo-streptoprotein, you have found that such a calculation is not
valid, because a part only of the added antigen is precipitated. Now, there is one thing, which I could not understand, and
which might have led the referee to the believe that such a simple calculation is possible in general; that is your similar
assumption in other and even in your last papers (e.g. J. Am. Chem. Soc. 67, 585, 1945). In all of these papers you assume
that all of the added antigen is precipitated. I have not been able to find any prove for this your opinion and I fear that
I must have overlooked some important paper. In an older paper (J. exp. Med. 62, 697, 1935) you mention some of your reasons,
among them the uniformity of ovalbumin. Since that time it has been proved that crystalline ovalbumin is not uniform; it
is very well understandable, therefore, that a part might remain dissolved. My own experiments have led me to the opinion
that not all of the added antigen is precipitated by antibody, even if the latter is in excess. Accordingly I see no other
way to determine antibodies than by using labeled antigens, for instance azo-proteins, as shown in my paper. If I am mistaken,
please correct me. - The last sentence of the referee's comment is quite incomprehensible to me. If you could guess,
what modification is meant, please explain it to me.
Number of Image Pages:
2 (279,255 Bytes)
1948-02-10 (February 10, 1948)
Reproduced with permission of Alice Haurowitz Sievert.
Medical Subject Headings (MeSH):
Allergy and Immunology
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Letter from Michael Heidelberger to Felix Haurowitz (February 16, 1948)
Under the same cover I am sending you a copy of a short typescript returned to my by the "Archives of Biochemistry"
and a copy of the referee's unfavourable comment. I am applying to you, because the referee bases his opinion on your
work and because I am not able to understand what the referee means. I should be very much indebted to you for your authoritative
interpretation of your own work.
I will admit, first of all, that I am blamed quite correctly for not having quoted you paper on serum albumin. I shall certainly
correct this mistake. In the same paper you had shown, that anti-ovalbumin is not precipitated by azo-obalbumin, so that
you could not recommend your method as a method for the determination of antibodies. You attributed, at that time, precipitation
or non-precipitation by azo-proteins to a property of the respective protein. Later I have shown that the main factor is
the amount of azo-groups per protein molecule (J. Immun. 40, 392 (Table II) and that azo-obalbumin is precipitated by azo-obalbumin
(ibid. 43, 333, Table 2). Therefore I am proposing now to determine antibodies against proteins by precipitation with azo-proteins
poor in azo-goups. I believe that this idea is worth of a publication, and I think that 2 pages of a typescript are not exaggerated
for the treatment of this problem.
I am very sorry that my letter will cause you much work. But please, do answer to me. The matter is of the utmost importance
to me for two reasons. One of them is, that a similar thing happened two years ago with a paper sent to the J. Am. Chem.
Soc. This paper also was returned to me with reference to your work. If this practice continues, the editors must get the
impression that I am sending to them worthless papers. You can imagine that this will have tragic consequences for me in
The second reason for my applying to you directly is, however, the fact that both referees seem to assume that I disregard
intentionally your results. This is particularly painful for me, because among all my American colleagues it has been just
you who helped me most during the war time. Please believe me that it is far from me to disregard anything of your work.
It is hardly possible to quote all pertinent papers in a short experimental paper. But I am very willing to send you my papers
before submitting them to an editor, to prevent the omission of any important contribution of you laboratory. -
I would be very grateful to you, dear Professor Heidelberger, if you could help me in this matter by explaining to me the
meaning of the comment of the referee, by informing me, what modification might have been wanted (last sentence of comment)
and by explaining to me also the reason for your assumption, that all of the added antigen is precipitated, although you have
proved the contrary in at east three antigens. I think that no differences can arise, if these questions are elucidated
and I hope that you will be so kind as to help me to elucidate them.
Since common mail to Turkey takes 6 to 10 weeks, please use airmail for your answer. Neither the paper, nor the comment are
required by me, since I have copies of both. With my kindest regards and best thanks.