The designing of anti-diphtheria serotherapy at the Institut Pasteur (1888-1900): the role of a supranational network of microbiologists Gabriel Gachelin Rehseis, UMR 7596 CNRS-Université Paris VII. Paris. [email protected] Dynamis Fecha de recepción: 28 de julio de 2006 [0211-9536] 2007; 27: 45-62 Fecha de aceptación: 22 de enero de 2007 SUMMARY: 1.—Introduction. 2.—Shuttling of research on diphtheria between France and Germany. 3.—The designing of French standards and norms in accordance with German ones. 4.—The rapid decline of strong anti-German feelings at the Institut Pasteur. ABSTRACT: The development of anti-diphtheria serotherapy at the Institut Pasteur immedia- tely follows the crisis known as the Pasteur-Koch debate. Research on diphtheria in Paris is indicative of the importance granted by Pasteurian scientists to Koch’s school criticisms. After 1887, relations between French and German bacteriologists become more relaxed. A scientific and social network develops between them. It later extends to other fields of research at the Institut Pasteur, particularly therapeutic chemistry. The evolution of Franco-German relations at the Institut Pasteur is placed in the general framework of the way French universities con- sidered German science. PALABRAS CLAVE: Difteria, seroterapia, relaciones franco-alemanas, red científica, Roux, von Behring. KEYWORDS: diphtheria, serotherapy, Franco-German relations, scientific network, Roux, von Behring. 1. Introduction A violent debate between Louis Pasteur (1822-1895) and Robert Koch (1843- 1910) broke out in 1881 on the issue of the vaccination against anthrax soon after the International Congress of Medicine in London held in August of that year. It became openly aggressive after the IV International Congress for Hygiene and Demography (Geneva, September 1882). Koch’s and Loeffler’s criticisms, not to say indictment, were actually directed against the entire 46 Gabriel Gachelin Dynamis 2007; 27: 45-62 methodological approach of Pasteur to microbes, microbial diseases and induction of a refractory condition and in fine to the validity of the results. The Koch-Pasteur debate, the differences in procedures in Pasteur’s and Koch’s laboratories, have been studied extensively elsewhere, and will not be examined once more 1. The main methodological questions raised by Koch in his 1882 paper 2 as summarized in 1883 by distant observers 3, were: claim of the priority of discovery; questioning of the purity of the bacteria used to prepare the vaccine; questioning of the existence of «general laws» of attenuation; abusive generalization of the results of some experiments; abusive publicity given to the anthrax vaccine; strong doubts concerning the efficacy and reproducibility of the vaccine and the secrecy kept on preparation protocols. Several non-scientific reasons are very likely to have boosted the bitterness of the dispute. They are certainly rooted in Koch’s and Pasteur’s strong respectively anti-French and anti-German feelings 4, and also in the economic interests involved in the success or failure of vaccination of cattle against anthrax 5. The important point for us lies in the fact that the Pasteur-Koch debate was the first critical discussion of the definitions and methods to be used to identify microbes, prove their role in causing diseases and combating 1. SALOMON-BAYET, Claire. Pasteur et la revolution pasteurienne, Paris, Payot, 1998; CARTER, K. Codell. The rise of causal concepts of disease: case histories, Burlington, Ashgate, 2003; GEISON, Gerald. The private science of Louis Pasteur, Princeton, Princeton University Press, 1995; GRADMANN, Christoph. Krankheit im Labor. Robert Koch und die medizinische Bakteriologie, Göttingen, Wallstein Verlag, 2005; MOULIN, Anne-Marie. Le dernier langage de la médecine: histoire de l‘immunologie, de Pasteur au Sida, Paris, PUF, 1991; BROCK, T. D. Robert Koch: a life in medicine and bacteriology, Washington, ASM Press, 1998; CARTER, K.C. The Koch-Pasteur dispute on establishing the cause of anthrax. Bull. Hist. Med., 1988, 62, 42-57. A recent English version of the main papers by Koch and by Pasteur dealing with the dispute over anthrax can be downloaded from www.foundersof science.net 2. Translated in CARTER, K. C. Essays of Robert Koch, New York, Greenwood Press, 1987. 3. Dr Robert Koch latest estimate of Pasteur’s methods and discoveries and the present position of the general inoculation problem. Editorial. Boston Medical and Surgical Journal, 1883, 108 (3), January 18. The answer of Pasteur to Koch is published in the same journal, ( 9, March 1). 4. For a discussion of the context by a close witness, on the Pasteur side, of the Koch-Pasteur dispute, see METCHNIKOFF, Elya. Trois fondateurs de la médecine moderne Lister, Pasteur et Koch, Paris, Felix Alcan, 1933. 5. Anthrax, or charbon in French, is an infectious disease caused by a sporulating bacterium, Bacillus anthracis. The disease exists in animals and humans. In the absence of vaccination, the death toll of the disease is about 10% among cattle. This explains in part why discussions about the efficacy of the vaccine were dominated by economics: to be useful, vaccination of cattle had to decrease animals’ death toll to below 1-2%. The designing of anti-diphtheria serotherapy at the Institut Pasteur (1888-1900) 47 Dynamis 2007; 27: 45-62 the latter. Actually, and whatever the response of Pasteur himself to Koch could have been 6, criticisms of Pasteur’s methods were not ignored by French microbiologists, although their work, including vaccination against rabies in 1885, somehow continued along their former methodological scheme. In that respect, the development of research on diphtheria in France after 1888 illustrates a movement away from the criticized Pasteur’s methods. The work on diphtheria at the Institut Pasteur indeed appears to have developed in a manner indicating an underlying will to avoid the kind of criticisms raised against the anti-anthrax and anti-rabies vaccines. Actually, it also served the introduction of a culture of the norm and of quantification at the Institut Pasteur, in a scientific context which very rapidly lost most of its initial hostile feeling and instead has to be placed in the context of a kind of race between French and German scientists 7. The aim of the present paper is thus to examine, by studying the diphtheria case, the influence German microbiology had on scientific procedures and attitudes at the Institut Pasteur. 2. Shuttling of research on diphtheria between France and Germany Diphtheria is an illness affecting the upper respiratory tract, the noso- graphy of which is described and the disease named (diphtérite) in 1826 by the French physician P. Bretonneau 8. Diphtheria is characterized by sore throat, fever, and the progressive development, on the tonsils and the pharynx, of membranes adherent to mucosa, which in the most severe cases, leads to the obstruction of airways and suffocation. Diphtheria is a highly contagious disease spread by infected individuals, and is associated with epidemic outbreaks. During the 1888-1894 period, diphtheria was 6. PASTEUR, Louis. La vaccination contre le charbon. La Revue Scientifique, 20 janvier 1883. 7. WEINDLING, Paul. From medical research to clinical practice: serum therapy for diphtheria in the 1890s. In: PICKSTONE John V. (Ed.), Medical innovations in historical perspective, New York, St Martin’s Press, 1992, pp. 72-83; and WEINDLING, P. Scientific elites and laboratory organisation in fin de siècle Paris and Berlin. The Pasteur Institute and Robert Koch Institute for Infectious Diseases compared. In: A. Cunningham and P. Williams (Eds.), The laboratory revolution in medicine, Cambridge, Cambridge University Press, 1992, pp. 170-188. 8. BRETONNEAU, Pierre-Fidèle. Des inflammations spéciales du tissu muqueux, et en particulier de la diphtérite, ou inflammation pelliculaire, connue sous le nom de croup, d’angine maligne, d’an- gine gangréneuse, etc, Paris, Crevot , 1826 (available on line at the Bibliothèque Nationale de France). 48 Gabriel Gachelin Dynamis 2007; 27: 45-62 responsible for an average annual death toll of 6-7 per 10,000 persons in Europe 9. Mortality could reach 80 % in children under 10. Consequently, the disease and particularly the suffocating form of diphtheria often obser- ved in children (named the «croup») inspired much fear among parents. As for rabies, diphtheria was not only a deadly disease; it was also a highly significant social target for researchers 10. Before the introduction of specific antidiphtheria serotherapy in 1894, treatment of diphtheria chiefly consisted of the disinfection of the throat in attempts to kill bacteria and dislodge membranes. One of the first effective treatments, introduced in the 1880s was the insertion of tubes into the throat through the membranes, to prevent victims from suffocating. In the most severe cases, tracheotomy was performed 11. That therapeutic strategy, associated with hygienic procedures and disinfection, was in use in 1890 12. The same procedures later remain in use as adjuvant to serotherapy 13. The causative agent of diphtheria is Corynebacterium diphtheriae (Klebs-Loeffler bacillus), a bacillus first identified in 1883 by E. Klebs (1834-1912) in throat lesions of patients and grown in vitro by F. Loeffler (1852-1915) in 1884, two German bacteriologists. The first period of active research on diphtheria at the Institut Pasteur (1888-1889) corresponds to the demonstration by E. Roux (1853-1933) that the Klebs-Loeffler bacillus is the genuine and only cause of diphtheria 14 (thus meeting the require- ment of «one bacterial species-one disease» and that of purity of bacterial strains emphasized by Koch). Major scientific breakthroughs are made in Germany at the same moment: the bacteria responsible for two major hu- man infectious diseases, diphtheria and tetanus, are proved to act through the soluble toxins they release in infected organisms. E.von Behring (1854- 9. WEISSENFELD, J. Die Veränderungen der Sterblichkeit an Diphterie und Schralach, Centralblatt für allgemeine Gesundheitspflege, 1900, p. 318, cité dans la revue des journaux par RENAUD, F.