Letter from Charles A. Doan, Ohio State University to Michael Heidelberger
In this letter, Doan proposed experiments with dye solutions of egg albumin, a major plasma protein, in an attempt to make
immune reactions visible and to understand their mechanism better. Heidelberger had pioneered the use of dye solutions in
immunochemistry--a red dye bound to albumin or to streptococcus antigen--and had supplied such dyes to Florence R. Sabin at
the Rockefeller Institute for her research on tuberculosis bacteria chemistry and the immune responses to these bacteria.
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1940-01-22 (January 22, 1940)
Doan, Charles A.
Ohio State University
Reproduced with permission of Ohio State University.
Medical Subject Headings (MeSH):
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
At the Rockefeller Institute for Medical Research, 1925-1938
Letter from Michael Heidelberger to Charles A. Doan, Ohio State University (January 30, 1940)
At luncheon in New York at the meeting of the Research Committee of the National Tuberculosis Association, Dr. Sabin told
me that she had discussed with you some of the things which we would like to do in carrying further her observations on the
relationship of phagocytosis of your synthetic azo dye antigen to anti-body formation. I had hesitated to say anything to
you about it because I know how many uses you have for the products of your chemical synthesis and doubtless many demands
for material, just as does Anderson and other biochemists. Dr. Sabin told me, however, that you were interested sufficiently
so that I might feel free to place the matter quite frankly before you for your consideration. I regret that I did not have
the opportunity, after this conversation with her, to talk with you directly, which is what I had hoped might be possible
during the trip to New York.
During this current year we have been interested particularly in attempting to secure further information relative to the
separate or mutual identity of so-called clasmatocytes and monocytes. It has always seemed to me that various pathologic
reactions tend to accentuate the differences in reaction as exemplified by the two morphologic states which formed the original
basis for the separation of these cell types. We have therefore set up a microcinematographic outfit, after having studied
for several years the invitro cultures of these cells from both animal and human sources, and are attempting to accumulate
evidence from a functional and cell motility standpoint, which may throw further light on the subject.
When Dr. Sabin told me of her work with the dye antigen from your laboratory, it seemed to me that there were new possibilities
associated with color microphotography for the accumulation of further proof of her intriguing hypothesis.
She tells me that now you have not only the egg albumin-dye molecules, but also have been able to "mark" a specific
antigen of the stretococcus. Would you think that by comparing and contrasting the degree and specificity of phagocytosis
and the period of time necessary for the breakdown of the synthetic molecule and the appearance of anti-bodies, we might demonstrate
that the monocyte or the clasmatocyte respectively might show a greater efficiency in the handling of one as contrasted with
Dr. Houghton, who has been doing our tissue culture and organ culture work for several years, had his basic training with
Dr. Carrell, and he has been successful for example, in culturing in vitro a human para-thyroid gland removed at operation,
and after cultivating it in the gradually increasing concentrations of the recipient patient's serum with hypopara-thyroid
tetany, has returned it to the surgeon for successful re-implantation with complete functional results, a la Harvey Stone.
In his in vitro cultivations of thyroid tissue, he has been able to demonstrate the elaboration of thyroxin according to Carrell's
Could we not hope to take explants of either spleen or omental milk spots 24 to 72 hours after in vivo inoculation with your
antigen, and determine any specific anti-body formation which might occur thereafter in vitro? Would it not be possible,
also, to introduce the antigen directly into cultures of cells, observe phagocytosis, if and when it occurs, and follow the
anti-body content of the nutrient medium which would be removed from the cultures from time to time? May the material be
There are a number of technical angles to the problem, both from your side and from ours, which it might be desirable to consider
more fully in a personal conference, if you would feel it advisable. I should appreciate your frank reaction to this whole
matter, and I assure you that both Dr. Houghton and myself are quite anxious for your constructive criticism of the general
If the conception does not seem too entirely without sufficient basis for further exploration, and if the work could be facilitated
by our coming and discussing the matter in detail with you before it is carried into actual experimental action, we would
try and arrange to meet your convenience. The utmost conservation of materials would be one of the main considerations.
Anticipating hearing from you, and with best personal regards,