Letter from Otto Bier, Instituto Biologico (Brazil) to Michael Heidelberger
Otto Bier recounted in this letter his return to Brazil from a year in Heidelberger's laboratory, where he had studied
complement, a complex, essential component of host defense mechanisms against invading organisms. At the time, the term referred
to the heat-sensitive factors in serum that trigger cytolysis, the dissolution of antibody-coated cells. Today, complement
refers to a functionally related system of at least twenty different serum proteins that play a key role not just in cytolysis,
but in other immune responses, including phagocytosis, the engulfing of foreign matter by immune cells, and anaphylaxis, a
form of hypersensitivity reaction to a specific antigen with often life-threatening consequences. Heidelberger was one of
the founders of the study of complement by showing that it was a group of chemical substances related to one another through
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1942-05-26 (May 26, 1942)
Instituto Biologico (Brazil)
Reproduced with permission of the Instituto Biologico, Avenida Conselheiro Rodrigues Alves
Medical Subject Headings (MeSH):
Complement System Proteins
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Ever since I arrived, I have had the desire to write you, but the letter was postponed in order that you might receive news
not only about myself, but also about my work.
As you probably have heard, I came back by boat and after a rather exciting 30 days trip I finally arrived in Rio. Unfortunately,
part of my baggage which had been shipped ahead on another steamer, since I at first had thought of returning by plane, has
been lost, but it is better the baggage than myself, although the sharks don't think the same way.
After my arrival, I spent almost one whole month to adapt my laboratory to good conditions of work, as I wanted to continue
the researches along the same lines as in your laboratory. I therefore had to teach my negro how to wash the glasses and to
take care of the pipettes according to Mary's technique; the Micro-Kjeldahl also had to be readjusted and so on. Now the
conditions are satisfactory (except rubber caps and good Pyrex test tubes we cannot get here) and I have made some quantitative
titrations of complement in beef serum.
The results I have obtained so far are summarized below.
1) [Chart = "Pneumo III System: SIII 1 mg in 25 ml. saline; Serum B-69 1 to 5."]
This experiment gave ca. 0.165 mg N for 5 ml. of beef complement, a value of the same order of that obtained for guinea-pig
complement. In this experiment I have used beef serum from the same day of bleeding, but having observed that after 24 hours
in the ice-box a large precipitate was found, I decided to use the complement after centrifuging off that precipitate, in
order to avoid the high values obtained for the blanks.
2) [Chart = "Also, Pneumo III System: SIII 1 mg/25 ml saline; Serum 1 to 6."]
C' in 5 cc. of beef complement : 0,146.
3) In a third experiment, by using the egg albumin system, values of the same
order hive been obtained and the dilution effect (with 4 and 8 ml. portions
of complement) has been verified.
Titrations of C'1 (according to Hegedus, beef serum has 1600 units of C'l, 100 C'3 and no 2 and 4) in the original
complement and in the C'Supernatant gave the following result (by using 0,l of the reagent 234, a mixture of 9 parts of
Endpiece l/10 + 1 part of guinea-pig serum heated 15 minutes at 56 degrees C):
C'l in original beef complement - 500 units
C'1 in C' Supernatant - 0 (not anti-complementary).
I think these results are significant and should like to have your critic about the same, as well as suggestions for further
work. I also would be very grateful if you could send me by airmail some 40 ml. of Pneumo III Serum, in order that I would
not have to interrupt the work while waiting for the rabbits I am immunizing now.
I always remember the pleasant stay at your laboratory and the friendly spirit of everybody - Treffer's politeness, Manfred's
frank collaboration at any time (except at the time of the seminar . . . ), the agreeable neighborliness of Mrs. McPherson,
the sweetness of Mary and the teaching qualities of Soo Hoo, particularly at the Chinese restaurants! Please give to all my
I hope you and Mrs. Heidelberger are well and that you will soon be able to visit us in Brazil, where she will certainly find
some new lamps for her collection.
With kindest regards to you and Mrs. Heidelberger,