The Historical Role of Animal Experiments in the Development of Diphtheria Prophylaxis
Abstract
In several respects the experimental work carried out over the decades to find a specific and reliable way of treating and preventing diphtheria determined the use of laboratory animals in the quality control of biological products in general. On the one hand, diphtheria was one of the first diseases where experimental animal research laid the foundation for combatting this disease (1, 2). On the other hand, many common routine procedures such as the determination of the efficacy of a vaccine and the use of a standard vaccine arose from diphtheria research. Before discussing the current method of vaccine production and control, attention will therefore be paid to the history of diphtheria prophylaxis and in particular to the significance of the animal experiment in this.
Keywords
Diphtheria Toxin Diphtheria Toxoid Potency Testing Corynebacterium Diphtheriae Potency AssayPreview
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References
- 1.Turner, J.: Reckoning with the beast. The Johns Hopkins University Press, Baltimore (1980), p. 115, ISBN 0-8018-2399-4.Google Scholar
- 2.Prigge, R.: Diphtherie-Schutzimpfungen mit hochactiven Impfstof. (Diphtheria vaccination with highly active vaccines.) Ergebnisse der Hygiene, (1939), 22, 1–63.Google Scholar
- 3.Ramshorst, J.D. van and Ehrengut, E.: Diphtherieschutzimpfung (Diphtheria vaccination, in the book entitled Handbuch der Schutzimpfungen (Vaccination Manual) by Herrlich, A., (1965), p. 394, Springer Verlag, Berlin.Google Scholar
- 4.Parish, H.J.: A history of immunization. E and S Livingstone Ltd., Edinburgh/London, 1965.Google Scholar
- 5.Guye.: Ned. Tijdschrift v. Geneeskunde (1889), II, 13, p.435.Google Scholar
- 6.Hoogendoorn, D.: Statistisch onderzoek naar de uitkomsten der inentingen tegen difterie. (Statistical examination of the results of diphtheria vaccination.) Ned. Tijdschr. Geneeskd. (1949), 93, III, 37, 3153–3162.PubMedGoogle Scholar
- 7.Kwantes, W.: Diphtheria in Europe, J. Hyg. Camb. (1984), 93, 433–437.PubMedCrossRefGoogle Scholar
- 8.Loeffler, M.: Untersuchung über die Bedeutung der Microorganismen für die Entstehung der Diphtherie beim Menschen, bei der Taube and beim Kalbe. (The role of microorganisms in the causation of diphtheria in man, pigeons and calves.) Mitteilungen aus den Kaiserl. Gesundheitsamte, Vol. II, (1884), p. 421.Google Scholar
- 9.Roux, E. and Yersin, A.: Contribution à l’etude de la diphtherie. (Contribution to the study of diphtheria). Annales de l’Institut Pasteur, (1888), 2, 12, 629–661.Google Scholar
- 10.Behring, E. von and Wernicke: Uber Immunisierung und Heilung von Versuchstieren bei der Diphtherie. (Immunisation and cure of experimental animals with respect to diphtheria.) Zeitschrift für Hygiene, (1892), 12, 10–44.CrossRefGoogle Scholar
- 11.Behring, E. von and Kitasato: Uber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Tieren. (Production of diphtheria immunity and tetanus immunity in animals.) Deutsche Medizinische Wochenschrift, (1890), 49, 113.Google Scholar
- 12.Wernicke: Ein experimenteller beitrag zur kenntnis des Löffler-schen Diphtheriebacillus und zur “Blutserumtherapie”. (Experimental work on Loeffler’s dipththeria bacillus and blood serum therapy.) Archiv. für Hygiene, (1893), XVIII, 193–250.Google Scholar
- 13.Fokker: Ned. Tijdschr. Geneesk., (1891), I, 1, p. 19.Google Scholar
- 14.Ehrlich, P. and Wassermann, A.: Uber die Gewinnung der Diphtherie-Antitoxine aus Blutserum und Milch immunisierter Tiere. (Preparation of diphtheria from the serum and milk of immunized animals.) Zeitschr. für Hygiene, (1894), 18, 239–251.CrossRefGoogle Scholar
- 15.Roux, M.E. and Martin, M.L.: Contribution á l’etude de la Diphtherie. (Contribution to the study of diphtheria.) Annales de l’Institut Pasteur, (1894), 8, 9, 609.Google Scholar
- 16.Strauss, M.: De serum-therapie der Diphtherie. (Serum therapy of diphtheria.) Ned. Tijdschr. Geneesk. (1899), I, 6, 197–209.Google Scholar
- 17.Bierens de Haan, J.C.: De uitkomsten der serumbehandeling van diptherie aan het Leidsche ziekenhuis van 1894–1899. (Results of diphtheria serum treatment in the Leiden Hospital, 1894-99.) Ned. Tijdschr. Geneeskd. (1899), II, 289–297.Google Scholar
- 18.Virchow, R.: An address on the value of pathological experiments, The British Medical Journal, (1881), 198–204.Google Scholar
- 19.Anonymus: Klinische und therapeutische Mitteilungen. (Clinical and therapeutic communications.) Wiener Klinische Wochenschrift, (1895), 10, 190.Google Scholar
- 20.Babes, V.: Bull, Acad. Med. (Paris), (1895), 34, 216.Google Scholar
- 21.Smith, T.: Active immunity produced by so-called balanced or neutral mixtures of diphtheria toxin and antitoxin. J. Exp. Med. (1909), 102, 1288–1289.Google Scholar
- 22.Behring, E. von: Uber ein neues Diphtherieschutzmittel. (A new anti-diphtheria agent.) Deutsche Medizinische Wochenschrift, (1913), 39, 19, 873–876.CrossRefGoogle Scholar
- 23.Otto, R. and Blumenthal, G.: Weitere tierexperimentelle Beitrage zur aktiven Immunisierung gegen Diphtherie. (Further animal experiments concerning active immunization against diphtheria.) Zeitsch. für Hygiene, (1930), 111, 380.CrossRefGoogle Scholar
- 24.Wilson, G.S.: The Hazards of Immunization, The Athlone Press (1969).Google Scholar
- 25.Ramon, G.: Sur le pouvoir floculant et sur les propriétés immunisantes d’une diphtherique rendue anatoxique (anatoxine). (Flocculating activity and immunizing properties of a diphtheria anatoxin.) C.R. Acad. Sci. (1923), 177, 1338–1342.Google Scholar
- 26.Ehrlich, P.: Klin. Jahrbuch (1898), 6, 299.Google Scholar
- 27.Salkowski, E.: Uber die Wirkung der Antiseptica auf Toxine. (Effect of antiseptics on toxins.) Berl. Klin. Wschr. (1898), 35, 545–549.Google Scholar
- 28.Löwenstein, E. and Eisler, R. von: über den Einfluss des Formaldehyd auf Blutserum. (Effect of formaldehyde on blood serum.) Zentralb. für Bakt. Origin. (1912), 261–281.Google Scholar
- 29.Glenny, A.T. and Hopkins, B.E.: Diphtheria toxoid as an immunizing agent. Brit. J. Exp. Pathol. (1923), 4, 283–288.Google Scholar
- 30.Glenny, A.T. and Südmersen: Notes on the production of immunity to diphtheria toxin. J. of Hyg. (1921), 20, 184.Google Scholar
- 31.Lévy, F.M.: The fiftieth anniversary of diphtheria and tetanus immunization. Preventive Medicine,, (1975), 4, 226–237.PubMedCrossRefGoogle Scholar
- 32.Ramon, G.: Sur la production de l’antitoxine diphterique. (Production of diphtheria antitoxin.) C.R., Acad. Sci. (Paris). (1925), 93, 506.Google Scholar
- 33.Günther, O.: Antagonism and synergy of antigens. Bull. Wld. Hlth. Org. (1955), 13, 479–489.Google Scholar
- 34.Glenny, A.T.: J. Path. Bact. (1926), 29, 38.Google Scholar
- 35.Holt, L.B. and Bousfeld, G.: Brit. Med. J. (1949), 1, 695.PubMedCrossRefGoogle Scholar
- 36.Schmidt, S. and Hansen: Uber die Reinigung und konzentrierung von Diphtherie-toxin und Diphtherie-anatoxin mit besonderem Hinblick auf die aktive Immunisierung von Menschen. (Purification and concentration of diphtheria toxin and anatoxin with special reference to active immunization in man.) Biochem. Z. (1930), 228, 263.Google Scholar
- 37.Farago, F.: Uber das Schicksal und die Wirksamkeit des Anatoxin Präzipitatdepots im Organismus. (Fate and activity of the anatoxin precipitate depot in the body.) Zeitschr. Immun. Forsch. (1935), 86, 191–204.Google Scholar
- 38.Roux, M.E., Martin, M.L. and Chaillou, P.: Trois cents cas de diphterie par le serum antidiphthérique. (300 Cases of diphtheria caused by anti-diphtheria serum.) Annales de l’Institut Pasteur, (1894), VIII, 9, 640–667.Google Scholar
- 39.Ehrlich, P.: Die Wehrtbemessung des Diphtherieheilserums und deren theoretische Grundlage. (Assessing the potency of the diphtheria serum and its theoretical foundations) Klin. Jahrbuch, (1897), Vol. VI, 299.Google Scholar
- 40.Marx: Experimentelle Untersuchungen über die Beziehung zwischen den Gehalt an Immunitätseinheiten und dem schützenden und heilenden Werth der Diphtherieheilsera. (Experimental investigation of the connection between the level of immunity units and the protective and therapeutic activity of diphtheria sera.) Zeitschr. für Hygiene, (1901), 38, 372–285.CrossRefGoogle Scholar
- 41.Madsen, Th.: Uber Messung der Stärke des antidiphtherischen Serums. (Determination of the activity of anti-diphtheria serum.) Zeitschr. für Hygiene, (1897), 24, 425–443.CrossRefGoogle Scholar
- 42.Dreyer, G. and Madsen, Th.: Uber Immunisierung mit den Toxonen des Diphtheriegiftes. (Immunization with the toxoids of the diphtheria toxin.) Zeitschr. für Hygiene, (1901), 37, 250–267.CrossRefGoogle Scholar
- 43.Prausnitz, C.: III Die Standardisierung von Heilseren, serologischen Reaktionen und Impfstoffen. (Standardizing antitoxins, serological reactions and vaccines. Part III.) Ergebnisse der Immunitätsforschung, (1929), 10, 271–332.Google Scholar
- 44.Krause, R. and Backer, S.: Zbl. Bakt., I Abt. Ref. Suppl. (1913), 57, 106.Google Scholar
- 45.Ramon, G.: La floculation dans les mélanges de toxine et de serum antidiphtérique. (Flocculation in mixtures of antidiphtheria serum and toxin.) Annales de 1’Institut Pasteur, (1923), 37, 12, 1001–1011.Google Scholar
- 46.Glenny, A.T. and Barr, M.: Alum-toxoid precipitates as antigens. Journ. of Path., (1931), 34, 118–119.Google Scholar
- 47.Prigge, R.: Experimentelle Untersuchungen über die Wirksamkeit von Diphtherie Impfstoffen. (Experimental investigations of the activity of diphtheria vaccines.) Deutsch. Med. Wochenschr., (1937), 39, 1478–1482.CrossRefGoogle Scholar
- 48.Madsen, Th. and Schmidt, S.: Seasonal variation in the susceptibility of laboratory animals to diphtheria toxin. Acta Soc. Medic Fenn. Duodecim, Ser. A. 15, (1932); 15.Google Scholar
- 49.Prigge, R.: Theorie und Methodik der Antigenmessung. (Theory and method of antigen determination.) Zeitschr. für Hygiene, (1937), 119, 186–192.CrossRefGoogle Scholar
- 50.Greenberg, L.: International standardization of diphtheria toxoids. Bull. Wld. Hlth. Org., (1953), 9, 829–836.Google Scholar
- 51.World Health Organization, Expert Committee on Biological Standardization. (1952), Wld. Hlth. Org. Tech. Rep. Ser., 56, 4, 5.Google Scholar
- 52.Bonin, O.: Einige Grundlagen der Prüfung von Biologische Produkten. (Basis of testing biological products.) In the book entitled Handbuch der Schutzimpfungen (Vaccination Manual). Herrlich, A., (1965), p. 53, Springer Verlag, Berlin.Google Scholar
- 53.Trevan, J.W.: The error of determination of toxicity. Proc. Roy. Soc. (London), (1927), 101B, 483–514.Google Scholar
- 54.Trevan, J.W.: A statistical note on the testing of antidysentry sera. Journ. of Path., (1929), Vol. 32, 127–135.CrossRefGoogle Scholar
- 55.Vorschriften für die Staatl, Prüfung der Impfstoffe zur aktiven Schutzimpfung gegen Diphtherie. (Instructions for the official testing of vaccines intended for active immunization against diphtheria.) Issued by the German Ministry of Internal Affairs, Ministerialbl. f.d. Innere Verwaltung (1935), 52, p. 1525.Google Scholar
- 56.Noordam, A.L. et al.: De nieuwe diphtherie-entstof, PT. (The new diphtheria vaccine called PT.) Ned. Tijdschr. Geneesk. (1949), 93, 48, 4014–1419.Google Scholar
- 57.Bonebakker, A. et al.: Vaccinatie tegen infectieziekten. (Vaccination against infectious diseases.) Stafleu’s Wetenschappelijke Uitgeversmaatschappij N.V., Leiden (1965).Google Scholar
- 58.W.H.O.-Technical Report Series 638 (1979).Google Scholar
- 59.Hardegree, M.C.: WHO Ad Hoc Meeting: Potency testing of toxoids, Geneva, Dec. 12–14, 1983.Google Scholar
- 60.Knight, P.A.: A consideration of some methods by which the cost of potency assays for diphtheria and tetanus vaccines might be reduced. Develop. Biol. Standard. (1978), 41, 67–72.Google Scholar
- 61.European Pharmacopoeia, (Suppl. Vol. III (1977)).Google Scholar
- 62.Kreeftenberg, J.G. et al.: A mouse model to estimate the potency of the diphtheria component in combined vaccines, Symposium IABS, April 1985, London. Develop. Biol. Standard (1986), 64, 21–24.Google Scholar
- 63.Kreeftenberg, J.G. et al.: An investigation of a mouse model to estimate the potency of the diphtheria component in vaccines. Journ. Biol. Standard. (1985), 13, 229–234.CrossRefGoogle Scholar
- 64.W.H.O.-Technical Report Series 760 (1987).Google Scholar
- 65.Kreeftenberg, J.G.: Report of an informal meeting about alternative methods for the potency control of the diphtheria and tetanus components in vaccines, Bilthoven, December 1985. Develop. Biol. Standard. (1986), 65, 261–266.Google Scholar
- 66.Abreo, C.B. and Stainer, D.W.: A tissue culture assay for diphtheria toxicity testing. Symposium IABS, April 1985, London. Develop. Biol. Standard. (1986), 64, 33–37.Google Scholar