Paul Ehrlich's passion: The origins of his receptor immunology

Cellular Immunology

Volumn 194, Issue 2, 1999, Pages 213-221

  Silverstein, Arthur M ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

ABRIN; RICIN;

ANTIBODY PRODUCTION; ARTICLE; AUTOIMMUNITY; CELL INTERACTION; CELL SURVIVAL; CROSS REACTION; IMMUNE RESPONSE; IMMUNOLOGY; PRIORITY JOURNAL; RECEPTOR BINDING; RECEPTOR UPREGULATION; STEREOCHEMISTRY;

SANGUISORBA;

EID: 0033563719     PISSN: 00088749     EISSN: None     Source Type: Journal    
DOI: 10.1006/cimm.1999.1505     Document Type: Article

References (67)

1. Michaelis L. Paul Ehrlich: Eine Darstellung seines wissenschaftlichen Wirkens. 1914;Gustav Fischer, Jena. p. 25.
2. Ehrlich, P., Das Sauerstoffbedürfnis des Organismus, Eine Farbenanalytische Studie, Hirschwald, Berlin, 1885. Reprinted in "Collected Papers of Paul Ehrlich", Pergamon, Oxford, 1956, Vol. I, pp. 364-432; English translation pp. 433-496. These volumes will henceforth be referred to as "Collected Papers".
3. Ehrlich, P., Das Sauerstoffbedürfnis des Organismus, Eine Farbenanalytische Studie, Hirschwald, Berlin, 1885. Reprinted in "Collected Papers of Paul Ehrlich", Pergamon, Oxford, 1956, Vol. I, pp. 364-432; English translation pp. 433-496. These volumes will henceforth be referred to as "Collected Papers".
4. Ehrlich, P., Das Sauerstoffbedürfnis des Organismus, Eine Farbenanalytische Studie, Hirschwald, Berlin, 1885. Reprinted in "Collected Papers of Paul Ehrlich", Pergamon, Oxford, 1956, Vol. I, pp. 364-432; English translation pp. 433-496. These volumes will henceforth be referred to as "Collected Papers".
5. Michaelis L. Naturwissenschaften. 7:1919;165.
6. Ehrlich P. Beiträge zur Theorie und Praxis der histologische Färbung. June 17, 1878;University of Leipzig. p. 29-64.
7. Bull. Hist. Med. 48:1974;199.
8. From Ehrlich's autobiographical notes included in a letter to his friend Christian Herter, quoted, in, Marquardt, M, Paul Ehrlich, Schuman, New York, 1957, p, 15.
9. The Franco-Prussian War had just seen the defeat of France, with the reversion to German hands of Alsace with its famous University at Strasbourg. (Louis Pasteur had been a professor here years before.) The enforced resignation of French professors opened up many faculty positions for German academics.
10. Ehrlich P. Arch. Mikroscop. Anat. 13:1877;263-228.
11. Coons A. H., Leduc E. H., Connally J. M. J. Exp. Med. 102:1955;49.
12. See note 4. Ehrlich apparently chose Leipzig for his thesis defense because Cohnheim and Weigert, with whom he had done much of his staining research, had recently moved to the University there from Breslau.
13. Silverstein A. M. Cell. Immunol. 67:1982;396.
14. Michaelis, note 3, p, 168.
15. Eckmann M.-L. Die Doktorarbeit Paul Ehrlichs und ihre Bedeutung für die Geschichte der histologischen Färbung. 1959;University of Hamburg. p. 26.
16. Ehrlich believed that these cells play a role in nutrition and chose the name from an old High German word, mesten, to feed or fatten. It is related to the English word, meat.
17. In his book "Hematology: The Blossoming of a Science" (Lea & Febiger, Philadelphia, 1985, p. 25), Maxwell Wintrobe says that "the simple investigation that Paul Ehrlich conducted...had consequences far more important than he dreamed. A new era in the history of hematology was initiated". Elsewhere in the book, Wintrobe named Ehrlich as the "father" of modern hematology. It is significant that in Wintrobe's "Blood Pure and Eloquent," (McGraw-Hill, New York, 1980), Ehrlich's name appears more frequently cited in the name index than that of any other individual.
18. In his book "Hematology: The Blossoming of a Science" (Lea & Febiger, Philadelphia, 1985, p. 25), Maxwell Wintrobe says that "the simple investigation that Paul Ehrlich conducted...had consequences far more important than he dreamed. A new era in the history of hematology was initiated". Elsewhere in the book, Wintrobe named Ehrlich as the "father" of modern hematology. It is significant that in Wintrobe's "Blood Pure and Eloquent," (McGraw-Hill, New York, 1980), Ehrlich's name appears more frequently cited in the name index than that of any other individual.
19. Ehrlich P. Deutsch. Med. Wochenschr. 8:1882;21-353.
20. Ehrlich P. Z. Klin. Med. 5:1882;285-629.
21. Ehrlich P. Deutsch. Med. Wochenschr. 12:1886;49-508.
22. Ehrlich, note 2.
23. Pflügers Arch. Ges. Physiol. Mensch. Tier. 10:1875;251.
24. Metchnikoff I. Virchows Archiv. 96:1884;177.
25. Koch R. Berlin Klin. Wochenschr. 19:1882;221.
26. Ehrlich P. Deutsch. Med. Wochenschr. 8:1882;269-313.
27. Marquardt, note 6, p, 28.
28. Ehrlich P. Deutsch. Med. Wochenschr. 16:1890;717-566.
29. Ehrlich, P., Proceedings of the VII International Congress of Hygiene and Demography, London, Vol. 2, 1891, p. 211; Collected Papers, Vol. I, pp. 13-20.
30. Ehrlich, P., Proceedings of the VII International Congress of Hygiene and Demography, London, Vol. 2, 1891, p. 211; Collected Papers, Vol. I, pp. 13-20.
31. Ehrlich's studies of the immunology of plant toxins is discussed at length in several chapters in the "Ehrlich Festschrift:" Th. Madsen, Method and quantitative principles in dealing with problems of immunity, pp. 151-158; H. Aronson, The constitution of toxins, pp. 166-190; and H. Ritz, Plant toxins, pp. 200-208.
32. Ehrlich's studies of the immunology of plant toxins is discussed at length in several chapters in the "Ehrlich Festschrift:" Th. Madsen, Method and quantitative principles in dealing with problems of immunity, pp. 151-158; H. Aronson, The constitution of toxins, pp. 166-190; and H. Ritz, Plant toxins, pp. 200-208.
33. Ehrlich's studies of the immunology of plant toxins is discussed at length in several chapters in the "Ehrlich Festschrift:" Th. Madsen, Method and quantitative principles in dealing with problems of immunity, pp. 151-158; H. Aronson, The constitution of toxins, pp. 166-190; and H. Ritz, Plant toxins, pp. 200-208.
34. Roux E., Yersin A. Ann. Inst. Pasteur. 2:1888;629.
35. Behring E., Kitasato S. Deutsch. Med. Wochenschr. 16:1890;1113.
36. Ehrlich P. Deutsch. Med. Wochenschr. 17:1891;976.
37. Ehrlich P. Deutsch. Med. Wochenschr. 17:1891;1218.
38. Ehrlich, always alert for clinical correlates, would say "The most noteworthy finding that surprised me most is the sudden - I might say critical - appearance of immunity on the sixth day. One automatically is led to the speculation that the critical fall of the fevers in so many diseases, as in pneumonia and measles, which frequently occurs at the end of the first week, is attributable to a similar event, the critical onset of immunity, (Ehrlich's italics),", Collected Papers, Vol, II, p, 25.
39. Münch. Med. Wochenschr. 40:1893;449.
40. Ehrlich P. Fortschr. Medizin. 15:1897;41.
41. Silverstein A. M. Cell. Immunol. 174:1996;1.
42. Ehrlich P. Z. Hygiene. 12:1892;183-144.
43. Biochem. J. 56:1954;597-601.
44. See, for example, Brambell, F. W. R., The Transmission of Passive Immunity from Mother to Young, North Holland, Amsterdam, 1970; Hemmings, W. A., ed., "Maternofoetal Transmission of Immunoglobulins," Cambridge Univ. Press, Cambridge, 1976.
45. See, for example, Brambell, F. W. R., The Transmission of Passive Immunity from Mother to Young, North Holland, Amsterdam, 1970; Hemmings, W. A., ed., "Maternofoetal Transmission of Immunoglobulins," Cambridge Univ. Press, Cambridge, 1976.
46. Ehrlich P., Hübener W. Deutsch. Med. Wochenschr. 18:1892;511-571.
47. Brieger L., Ehrlich P. Deutsch. Med. Wochenschr. 18:1892;393-347.
48. Brieger L., Ehrlich P. Z. Hygiene. 13:1893;336-355.
49. Behring, Kitasato, Behring E., Wernicke E. Deutsch. Med. Wochenschr. 12:1892;10.
50. Ehrlich P., Kossel H., Wassermann A. Deutsch. Med. Wochenschr. 20:1894;353-360.
51. Ehrlich E. Klin. Jahrbuch. 6:1897;299-125.
52. J. Hist. Med. Allied Sci. 35:1980;397.
53. Madsen, note 27, p, 155.
54. Ehrlich literally pictured these molecules in cartoon form to illustrate his ideas. See, for example, Cambrosio, A, Jacobs, D, and, Keating, P, Image et controverse scientifique dans les premières théories immunologiques, in, Usages de l'Image au XIXe Siècle, Créaphis, Paris, 1991.
55. Jules Bordet would contest both the theory and the names that Ehrlich employed (see, A. M. Silverstein, History of Immunology, Academic Press, New York, 1989, pp, 193, - 197, ). Bordet believed in a physical adsorption theory of antigen-antibody-complement interactions; he called Ehrlich's, Ambozeptor, a, substance sensibilisatrice, and Ehrlich's, Komplement, by the more neutral term, alexine.
56. Ehrlich, note 44.
57. Jerne N. K. Proc. Natl. Acad. Sci. USA. 41:1955;849.
58. Burnet, F. M, Austral. J. Sci. 20, 67, 1957; see also Burnet's, The Clonal Selection Theory of Antibody Formation, Cambridge Univ. Press, London, 1959.
59. Burnet, F. M, Austral. J. Sci. 20, 67, 1957; see also Burnet's, The Clonal Selection Theory of Antibody Formation, Cambridge Univ. Press, London, 1959.
60. Ehrlich was not alone among scientists who had decided that they had "solved" the outstanding problems in their disciplines. Many others would do it in other fields of science, and in immunology, Burnet and Jerne would declare "the end" in the 1960s. At an international symposium on "Molecular and Cellular Aspects of Antibody Formation" held in Prague, Czechoslovakia, in 1964, attended by this author, Burnet implied that his clonal selection theory had carried the day and substantially solved the outstanding problems in immunology. Jerne's "Summary: Waiting for the end" (, in, "Antibodies", Cold Spring Harbor Symp. on Quant. Biol, 32, 601, 1967) made this conclusion somewhat more explicitly. Finally, Jerne made it official in his tribute to Burnet, The complete solution of immunology, Austral. Ann. Med, 4, 347, 1969. For a general discussion of the phenomenon of the declaration of "The End of..." see A. M. Silverstein, History of Science, 37, 1, 1999.
61. Ehrlich was not alone among scientists who had decided that they had "solved" the outstanding problems in their disciplines. Many others would do it in other fields of science, and in immunology, Burnet and Jerne would declare "the end" in the 1960s. At an international symposium on "Molecular and Cellular Aspects of Antibody Formation" held in Prague, Czechoslovakia, in 1964, attended by this author, Burnet implied that his clonal selection theory had carried the day and substantially solved the outstanding problems in immunology. Jerne's "Summary: Waiting for the end" (, in, "Antibodies", Cold Spring Harbor Symp. on Quant. Biol, 32, 601, 1967) made this conclusion somewhat more explicitly. Finally, Jerne made it official in his tribute to Burnet, The complete solution of immunology, Austral. Ann. Med, 4, 347, 1969. For a general discussion of the phenomenon of the declaration of "The End of..." see A. M. Silverstein, History of Science, 37, 1, 1999.
62. Ehrlich was not alone among scientists who had decided that they had "solved" the outstanding problems in their disciplines. Many others would do it in other fields of science, and in immunology, Burnet and Jerne would declare "the end" in the 1960s. At an international symposium on "Molecular and Cellular Aspects of Antibody Formation" held in Prague, Czechoslovakia, in 1964, attended by this author, Burnet implied that his clonal selection theory had carried the day and substantially solved the outstanding problems in immunology. Jerne's "Summary: Waiting for the end" (, in, "Antibodies", Cold Spring Harbor Symp. on Quant. Biol, 32, 601, 1967) made this conclusion somewhat more explicitly. Finally, Jerne made it official in his tribute to Burnet, The complete solution of immunology, Austral. Ann. Med, 4, 347, 1969. For a general discussion of the phenomenon of the declaration of "The End of..." see A. M. Silverstein, History of Science, 37, 1, 1999.
63. Bordet J. Ann. Inst. Pasteur. 12:1898;688.
64. Ehrlich P., Morgenroth J. Berlin Klin. Wochenschr. 36:1899;6.
65. Ehrlich's studies on experimental oncology are summarized in chapters by V. Czerny and H. Apolant in the Ehrlich Festschrift, pp. 355-378. The term "Ehrlich ascites tumor" still survives from this period.
66. A summary of this theory may be found in Georg Schöne's chapter in the Ehrlich Festschrift, pp. 379-408.
67. In their discussion of the origins of receptor theory in pharmacology, Parascandola and Jasensky (note 5) conclude that Ehrlich thought initially that his receptor theory did not apply to drug action, but finally concluded that most drugs had a haptophore group in addition to a toxophore group.