History of immunology. Paul Ehrlich: The founding of pediatric immunology

Cellular Immunology

Volumn 174, Issue 1, 1996, Pages 1-6

  Silverstein, Arthur M ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RICIN; RICIN ANTIBODY;

ANTIBODY RESPONSE; ARTICLE; HISTORY; IMMUNE RESPONSE; MILK; MOUSE; NEWBORN; NONHUMAN; PASSIVE IMMUNIZATION; PRIORITY JOURNAL;

EID: 0030602156     PISSN: 00088749     EISSN: None     Source Type: Journal    
DOI: 10.1006/cimm.1996.0286     Document Type: Article

References (35)

1. 1. Brambell, F. W. R., "The Transmission of Passive Immunity from Mother to Young." North Holland, Amsterdam, 1970.
2. 2. Hemmings, W. A., Ed., "Maternofoetal Transmission of Immunoglobulins." Cambridge Univ. Press, Cambridge, 1976.
3. 3. Solomon, J. B., "Foetal and Neonatal Immunology." North Holland, Amsterdam, 1971.
4. 4. Loke, Y. W., "Immunology and Immunopathology of the Human Foetal-Maternal Interaction." North Holland, Amsterdam, 1978.
5. 5. Ehrlich, P., "Beiträge zur Theorie und Praxis der histologischen Färbung" [Contributions to the theorie and practice of histologic staining], Doctoral Thesis, University of Leipzig, 1878. This thesis was never published at the time, but was rediscovered 40 years later by Michaelis and included in Himmelweit, F., ed., "The Collected Papers of Paul Ehrlich," London, Pergamon, 1956, pp. 29-64 (hereafter referred to as "Collected Papers"). See also the discussion of the long-term significance of this work in L. Michaelis, Naturwissensch. 7(11), 22, 1919.
6. 5. Ehrlich, P., "Beiträge zur Theorie und Praxis der histologischen Färbung" [Contributions to the theorie and practice of histologic staining], Doctoral Thesis, University of Leipzig, 1878. This thesis was never published at the time, but was rediscovered 40 years later by Michaelis and included in Himmelweit, F., ed., "The Collected Papers of Paul Ehrlich," London, Pergamon, 1956, pp. 29-64 (hereafter referred to as "Collected Papers"). See also the discussion of the long-term significance of this work in L. Michaelis, Naturwissensch. 7(11), 22, 1919.
7. 5. Ehrlich, P., "Beiträge zur Theorie und Praxis der histologischen Färbung" [Contributions to the theorie and practice of histologic staining], Doctoral Thesis, University of Leipzig, 1878. This thesis was never published at the time, but was rediscovered 40 years later by Michaelis and included in Himmelweit, F., ed., "The Collected Papers of Paul Ehrlich," London, Pergamon, 1956, pp. 29-64 (hereafter referred to as "Collected Papers"). See also the discussion of the long-term significance of this work in L. Michaelis, Naturwissensch. 7(11), 22, 1919.
8. 6. Ehrlich, P., Deutsch, med. Wochenschr. 17, 976, 1218, 1891.
9. 7. Ehrlich, P., Klin Jahrb. 6, 299, 1897.
10. 8. Ehrlich, P., Z. Hygiene 12, 183, 1892; "Collected Papers," Vol. II, pp. 31-44.
11. 8. Ehrlich, P., Z. Hygiene 12, 183, 1892; "Collected Papers," Vol. II, pp. 31-44.
12. 9. Ehrlich quotes Arloing, S., "Les Virus," Paris, Alcan, 1891, p. 285): "Quand le père est guéri d'une maladie virulente lorsqu'il paricipe à l'acte de fécondation, il peut encore transmettre une partie de l'immunité dont il jouit. L'ovule mâle, souche de l'élément fécondant, a été dynamiquement modifié à la fin de la maladie du père . . . il apporte dans l'ovule, en y pénétrant, une substance vaccinée, qui se répartira dans toutes les cellules de l'embryon et du foetus." See also Fournier A. (known to contemporaries as le pape des syphiligraphes), "L'Hérédité Syphilitique," Paris, Masson, 1891.
13. 9. Ehrlich quotes Arloing, S., "Les Virus," Paris, Alcan, 1891, p. 285): "Quand le père est guéri d'une maladie virulente lorsqu'il paricipe à l'acte de fécondation, il peut encore transmettre une partie de l'immunité dont il jouit. L'ovule mâle, souche de l'élément fécondant, a été dynamiquement modifié à la fin de la maladie du père . . . il apporte dans l'ovule, en y pénétrant, une substance vaccinée, qui se répartira dans toutes les cellules de l'embryon et du foetus." See also Fournier A. (known to contemporaries as le pape des syphiligraphes), "L'Hérédité Syphilitique," Paris, Masson, 1891.
14. 10. Fournier, E. "Hérédo-syphilis de Seconde Génération," Paris, Rueff, 1905.
15. 11. The "absolute lethal dose" is one that kills all 20 gram mice in 2-4 days. However, more sensitive animals may succumb during this period to as little as 1/4 this amount.
16. 12. Behring, E., and Kitasato, S., Deutsch. med. Wochenschr. 16, 1113, 1890.
17. 13. Ehrlich was not aware that heterologous proteins are cleared from the circulation much more rapidly than homologous ones, due to immune elimination of antigen through the formation of immune complexes. His passive transfer studies employed rabbit anti-ricin in the adult mouse, whereas the newborn mouse received maternal mouse antibodies. Only some 60 years later would this distinction become widely known: Talmage, D. W., Dixon, F. J., Bukantz, S. C., and Dammin, G. J., J. Immunol. 67, 243, 1951; Dixon, F. J., J. Allergy 25, 487, 1954.
18. 13. Ehrlich was not aware that heterologous proteins are cleared from the circulation much more rapidly than homologous ones, due to immune elimination of antigen through the formation of immune complexes. His passive transfer studies employed rabbit anti-ricin in the adult mouse, whereas the newborn mouse received maternal mouse antibodies. Only some 60 years later would this distinction become widely known: Talmage, D. W., Dixon, F. J., Bukantz, S. C., and Dammin, G. J., J. Immunol. 67, 243, 1951; Dixon, F. J., J. Allergy 25, 487, 1954.
19. 14. Ehrlich, P., and Hübener, W., Über die Vererbung der Immunität bei Tetanus, [On the transmission of immunity in tetanus]. Deutsch, med. Wochenschr. 18, 511, 1892; "Collected Papers," Vol. II, pp. 63-71.
20. 14. Ehrlich, P., and Hübener, W., Über die Vererbung der Immunität bei Tetanus, [On the transmission of immunity in tetanus]. Deutsch, med. Wochenschr. 18, 511, 1892; "Collected Papers," Vol. II, pp. 63-71.
21. 15. Brieger, L., and Ehrlich, P. Über die Übertragung von Immunität durch Milch [On the transfer of immunity by milk]. Deutsch. med. Wochenschr. 18, 393, 1892; "Collected Papers," Vol. II, pp. 45-47.
22. 15. Brieger, L., and Ehrlich, P. Über die Übertragung von Immunität durch Milch [On the transfer of immunity by milk]. Deutsch. med. Wochenschr. 18, 393, 1892; "Collected Papers," Vol. II, pp. 45-47.
23. 16. Brieger, L., and Ehrlich, P. Beiträge zur Kenntniss der Milch immunisierte Tiere [Contributions to the knowledge of the milk of immunized animals]. Z. Hyg. 13, 336, 1893; "Collected Papers," Vol. II, pp. 48-55.
24. 16. Brieger, L., and Ehrlich, P. Beiträge zur Kenntniss der Milch immunisierte Tiere [Contributions to the knowledge of the milk of immunized animals]. Z. Hyg. 13, 336, 1893; "Collected Papers," Vol. II, pp. 48-55.
25. 17. 60 years later, an elegant series of experiments by Ita Askonas and coworkers (Biochem. J. 56, 597-601, 1954) would confirm and extend Brieger and Ehrlich's findings, and show that most antibody in rabbit's milk and in goat's colostrum and milk is a transudate from the blood, without degradation and reformation.
26. 18. Ehrlich and Brieger point out in a footnote that Emil Behring had independently reported similar findings in his recently published book "Die Blutserumtherapie," Leipzig, Thieme, 1892, Vol. II, p. 108.
27. 19. Until the advent of preparative electrophoresis, ion exchange columns, and especially of monoclonal antibody technics, several generations of immunologists would utilize this ammonium sulfate approach to the concentration of immunoglobulins.
28. 20. Ehrlich, P., and Wassermann, A. Über die Gewinnung der Diphtherie-Antitoxine aus Blutserum und Milch immunisierter Tiere [On the production of diphtheria antitoxin from the blood and milk of immunized animals]. Z. Hyg. 18, 239; "Collected Papers," Vol. II, pp. 72-79.
29. 20. Ehrlich, P., and Wassermann, A. Über die Gewinnung der Diphtherie-Antitoxine aus Blutserum und Milch immunisierter Tiere [On the production of diphtheria antitoxin from the blood and milk of immunized animals]. Z. Hyg. 18, 239; "Collected Papers," Vol. II, pp. 72-79.
30. 21. In an elegant study of the primary and anamnestic response employing radioiodine-labeled antigens, F. J. Dixon, P. H. Maurer, and M. P. Deichmiller (J. Immunol. 72, 179, 1954) published substantially the same wave-shaped curves illustrating the phases of the immune response that Ehrlich had presented in 1892 (see Figs. 1 and 2), but apparently were unaware of this earlier work.
31. 22. Charrin, A., and Gley, E., Arch. Physiol. 4, 75-82, 1893; idem, Arch. Physiol. 6, 1-6, 1894; Tizzoni, G., and Centanni, E., Riforma Med. Napoli 9, 101-104, 1893; idem, Centralbl. Bakt. Parasit. 13, 81-87, 1893.
32. 22. Charrin, A., and Gley, E., Arch. Physiol. 4, 75-82, 1893; idem, Arch. Physiol. 6, 1-6, 1894; Tizzoni, G., and Centanni, E., Riforma Med. Napoli 9, 101-104, 1893; idem, Centralbl. Bakt. Parasit. 13, 81-87, 1893.
33. 22. Charrin, A., and Gley, E., Arch. Physiol. 4, 75-82, 1893; idem, Arch. Physiol. 6, 1-6, 1894; Tizzoni, G., and Centanni, E., Riforma Med. Napoli 9, 101-104, 1893; idem, Centralbl. Bakt. Parasit. 13, 81-87, 1893.
34. 22. Charrin, A., and Gley, E., Arch. Physiol. 4, 75-82, 1893; idem, Arch. Physiol. 6, 1-6, 1894; Tizzoni, G., and Centanni, E., Riforma Med. Napoli 9, 101-104, 1893; idem, Centralbl. Bakt. Parasit. 13, 81-87, 1893.
35. 23. To illustrate how little remembered was this pediatric work of Ehrlich, I have mentioed elsewhere ("A History of Immunology," New York, Academic Press, 1989, p. xi) that one of the principal reasons for my entry into the history of immunology was receipt in the mid-1970s of a paper to review, written by a young scientist who was unaware that he had repeated work done 80 years earlier by Paul Ehrlich. That work was his study of the origin of passive immunity in the suckling young!