Commentary
Published:01 May 2003

Cellularversus humoral immunology: a century-long dispute

Arthur M. Silverstein¹

Nature Immunologyvolume 4, pages425–428 (2003)Cite this article

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Historical insight: Immunology's founding fathers argued fiercely about whether Metchnikoff's phagocytes or Ehrlich's antibodies were the most important mediators of immunity. Antibodies won out, but even after lymphocytes re-established cellular immunology, the humoralist-cellularist divide persisted.

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References

Jerne, N.K. Waiting for the end.Cold Spring Harbor Symposium “Antibodies”37, 591–603 (1967).
Google Scholar
Metchnikov, E.Virchows Archiv.96, 177–195 (1884). The founding myth of discovery is described in Metchnikoff, O.,Life of Elie Metchnikoff, 116–117 (Houghton, Mifflin, Boston, 1921).
Google Scholar
Metchnikoff, E.Lectures on the Comparative Pathology of Inflammation (Keegan, Paul, Trench, Trübner, London, 1893). Reprinted by Dover (New York, 1968).
Google Scholar
Metchnikoff, E.Immunity in the Infectious Diseases (Macmillan, New York, 1905). Reprinted by Johnson Reprint Corp. (New York, 1968).
Google Scholar
Behring, E. & Kitasato, S.Deutsch. med. Wochenschr.16, 1113–1114 (1890); Behring, E. & Wernicke, E.Z. Hyg.12, 10–44; 45–57 (1892).
Article Google Scholar
Ehrlich, P.Deutsch. med. Wochenschr.17, 976–979; 1218–1219 (1891).
Article Google Scholar
Pfeiffer, R.Z.Hyg. Infektskr.18, 1–16 (1895). Jules Bordet would later show that both bacteriolysis and hemolysis are due to the action of two substances, humoral antibody and complement;Ann. Inst. Pasteur12, 688–695 (1989).
Google Scholar
Virchow, R.Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre (Hirschwald, Berlin, 1858). English edition:Cellular Pathology (Dover, New York, 1971).
Google Scholar
See also Baxter, A.G.Nature Rev. Immunol.1, 229–232 (2001).
Article CAS Google Scholar
The cellular-humoral debate, including its political aspects, is discussed at greater length in Silverstein, A.M.A History of Immunology, 38–58 (Academic Press, San Diego, 1989).
See Silverstein, A.M.Paul Ehrlich's Receptor Immunology: The Magnificent Obsession, 95–122 (San Diego, Academic Press, 2002).
Book Google Scholar
Ehrlich, P.Klin. Jahrb.6, 299–333 (1897).
Google Scholar
Ehrlich, P.Proc. Roy. Soc. Ser. B66, 424–448 (1900); see also Cambrosio, A., Jacobi, D. & Keating, P. Ehrlich's 'beautiful pictures' and the controversial beginnings of immunological imagery.Isis,84, 662–699 (1993).
Article CAS Google Scholar
Wright, A.E. & Douglas, S.R.Proc. Roy. Soc. Ser. B73, 128–142 (1904). Bernard Shaw would take up Wright's suggestion in his playA Doctor's Dilemma, suggesting that the opsonins “butter the disease germs appetizingly for [the phagocytes].”
Article Google Scholar
For the history of the idea of cell-bound antibodies, see Silverstein, A.M.Nature Immunol.3, 105–108 (2002).
Article CAS Google Scholar
Arrhenius, S.Immunochemistry (Macmillan, New York, 1907).
Google Scholar
Pick, E.P. inHandbuch der pathogenen Mikroorganismen, edn. 2 vol.1 (W. Kolle & A. von Wassermann, eds.) 685–868 (Fischer, Jena, 1912).
Google Scholar
Landsteiner, K. and Lampl, H.Z. Immunitätsforsch.26, 258–276; 293–304 (1917).
CAS Google Scholar
Landsteiner's work in this area is summarized in his classicThe Specificity of Serological Reactions (Dover, New York, 1962). This was a reprint of edn. 2, of 1945; the original German edition was published in 1933.
See the definitive work of its day by Heidelberger's students: Kabat, E.A. & Mayer, M.M.Experimental Immunochemistry (Thomas, Springfield, Illinois, 1948).
Google Scholar
See, for example, Marrack, J.R.The Chemistry of Antigens and Antibodies (HM Stationery Office, London, 1934); Pressman, D.P. & Grossberg, A.The Structural Basis of Antibody Specificity (Benjamin, New York, 1968); Kabat, E.A.Structural Concepts in Immunology and Immunochemistry (Rinehart & Winston, New York, 1968).
Google Scholar
Breinl, F. & Haurowitz, F.Z. Physiol. Chem.192, 45–57 (1930); Pauling, L.J.Am. Chem. Soc.62, 2643–2657 (1940). The comings and goings of Darwinism in immunology are discussed in Silverstein, A.M.Nature Immunol.4, 3–6 (2003).
Article CAS Google Scholar
Murphy, J.B.Monographs of the Rockefeller Institute for Medical Research21 (1926); see also Silverstein, A.M.,Nature Immunol.2, 569–571 (2001).
Google Scholar
Dienes, L.J. Immunol.17, 531–538 (1929); Dienes, L. & Schoenheit, E.W.Am. Rev. Tuberc.20, 92–105 (1929).
Google Scholar
Rivers, T.M. & Schwentker, E.F.J. Exp. Med.61, 689–702 (1935); Kabat, E.A., Wolfe, A. & Bezer, A.E.J. Exp. Med.85, 117–130 (1947);89, 395–398 (1949).
Article CAS PubMed PubMed Central Google Scholar
Landsteiner, K. & Chase, M.W.Proc. Soc. Exp. Biol. Med.49, 688–690 (1942).
Article CAS Google Scholar
Metchnikoff, E.Immunity in the Infectious Diseases, p. 306 (Macmillan, New York, 1905).
Google Scholar
Rich, A.R. & Lewis, M.R. Bull. Johns Hopkins Hosp.50, 115–131 (1932).
Waksman, B.H. & Matoltsy, M.J.J. Immunol.81, 220–234 (1958).
CAS PubMed Google Scholar
Bloom, B.R. & Bennett, B.Science153, 80–82 (1966); David, J.R.Proc. Natl. Acad. Sci. USA56, 72–77 (1966).
Article CAS PubMed Google Scholar
Lurie, M.B.J. Exp. Med.75, 247–268 (1942); Elberg, S.S.Bacteriol. Rev.24, 67–95 (1960). See also Rowley, D.Adv. Immunol.2, 241–264 (1962).
Article CAS PubMed PubMed Central Google Scholar
Mackaness, G.B. & Blanden, R.V.Progr. Allergy11, 89–140 (1967). They were willing to concede that if macrophages do indeed exhibit specificity of action, it is probably due to adherent antibody.
CAS Google Scholar
Granger, G.A. & Weiser, R.S.Science145, 1427–1429 (1964).
Article CAS PubMed Google Scholar
Suter, E. & Ramseier, H.Adv. Immunol.4, 117–173 (1964).
Article CAS Google Scholar
Fishman, M. & Adler, F.L.J. Exp. Med.117, 595–602 (1963); see also Fong, J., Chen, D. & Elberg, S.S.J. Exp. Med.118, 371–386 (1963).
Article CAS PubMed PubMed Central Google Scholar
Askonas, B.A. & Rhodes, J.M.Nature205, 470–474 (1965).
Article CAS PubMed Google Scholar
See, for example, Möller, G. (ed.)Immunol. Rev.40 (1978); Unanue, E.R. & Rosenthal, A.S. (eds.).Macrophage Regulation of Immunity (Academic Press, New York, 1980).
Google Scholar
Zinkernagel, R.M. & Doherty, P.C.J. Exp. Med.141, 1427–1436 (1975); Zinkernagel, R.M. & Doherty, P.C.Adv. Immunol.27, 51–177 (1979).
Article CAS PubMed Google Scholar
This paradigm shift in immunology is discussed at length by Silverstein, A.M.Cell. Immunol.132, 515–531 (1991).
Article CAS PubMed Google Scholar
See Brent, L.A History of Transplantation Immunology (Academic Press, San Diego, 1997).
Google Scholar
Burnet, F.M. & Fenner, F.The Production of Antibodies, edn. 2 (Macmillan, New York, 1949).
Google Scholar
Billingham, R.E., Brent, L. & Medawar, P.B.Nature172, 603–606 (1953).
Article CAS PubMed Google Scholar
For example, Humphrey, J.H. & White, R.G.Immunology for Students of Medicine (Davis, Philadelphia, 1963); Gell, P.G.H. & Coombs, R.R.A. (eds.).Clinical Aspects of Immunology (Blackwell, Oxford, 1963); Mackay, I.R. & Burnet, F.M.Autoimmune Diseases (Thomas, Springfield, IL, 1963).
Google Scholar
Burnet, F.M.Austral. J. Sci.20, 67–69 (1957); Talmage, D.W.Annu. Rev. Med.8, 239–257 (1957).
Google Scholar
See, however, the attempts by Tauber and colleagues to align Metchnikoff more closely to the context of contemporary immunology. Thus: Tauber, A.I.Cell Immunol.139, 505–530 (1992); Tauber, A.I. & Chernyak, L.Metchnikoff and the Origins of Immunology (Oxford University Press, New York, 1991); Tauber, A.I.The Immune Self: Theory or Metaphor? (Cambridge University Press, Cambridge, 1994).
Google Scholar
The most comprehensive summary of these and other modern advances may perhaps be found in Paul, W.E. (ed.).Fundamental Immunology edn. 4 (Lippincott-Raven, Philadelphia, 1999).
Google Scholar
Karush, F.Adv. Immunol.2, 1–40 (1962); Fahey, J.L.Adv. Immunol.2, 41–109 (1962); Edelman, G.M. & Gall, W.E.Ann. Rev. Biochem.38, 415–466 (1969); Poljak, R.J. et al.Proc. Natl. Acad. Sci. USA70, 3305–3310 (1973);71, 1427–1430 (1974).
CAS Google Scholar
Porter, R.R.Brit. Med. Bull.19, 197–201 (1963); Edelman, G.M.Biochemistry9, 3197–3205 (1970); Kunkel, H.G.Harvey Lect.59, 219–242 (1965); Wu, T.T. & Kabat, E.A.J. Exp. Med.132, 211–250 (1970).
Article CAS PubMed Google Scholar
Müller-Eberhard, H.J.Adv. Immunol.8, 1–80 (1968); Mayer, M.M.,Proc. Natl. Acad. Sci. USA69, 2954–2958 (1972).
Article PubMed Google Scholar
Thomas Kuhn defined a paradigm as the set of understandings and assumptions about a field that guide the contemporary design of experiments and interpretation of results,The Structure of Scientific Revolutions 2nd ed. (University of Chicago Press, Chicago, 1970).
Silverstein, A.M.,Nature Immunol.3, 105–108 (2002).
Article CAS Google Scholar
Janeway, C.J. Jr.Immunol. Today13, 11–16 (1992); Medzhitov, R. & Janeway, C.A. Jr.Curr. Opin. Immunol.9, 9 (1997); Janeway, C.A. Jr.Proc. Natl. Acad. Sci. USA98, 7461–7468 (2001).
Article CAS PubMed Google Scholar