Published online by Cambridge University Press: 17 May 2012
1 Behring is here quoting Goethe's Faust: “Blut ist ein ganz besonderer Saft.” Emil Behring and Shibasaburo Kitasato, ‘Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren’, Deutsch. med. Wochenschr., 1890, 16 (49): pp. 1113–14, on p. 1113. Behring was at this time well aware of the specificity of the anti-bacterial activity of blood, as well as its apparent unpredic-tability; Emil Behring, and F Nissen, ‘Ueber bacterienfeindliche Eigenschaften verschiedener Blutserumarten. Ein Beitrag zur Immunitätsfrage’, Zeitschrift für Hygiene, 1890, 8: 412–33, on p. 431.
2 W D Foster, A history of medical bacteriology and immunology, London, Heinemann, 1970, and more recently, and with more contextual sensitivity, Arthur M Silverstein, A history of immunology, San Diego, Academic Press, 1989.
3 Written fifty years after the events, Bulloch's history is the first to make use of this debate to mark the transfer from bacteriology to immunology. William Bulloch, The history of bacteriology, London, Oxford University Press, 1938, particularly ch. 11.
4 Emil Roux and Alexandre Yersin, ‘Contribution à l'étude de la diphthérie’, Annales de l'Institut Pasteur 1888, 2(12): 629–61.
5 Behring and Kitasato, op. cit., note 1 above.
6 Ibid., and Emil Behring, ‘Untersuchungen über das Zustandekommen der Diphtherie-Immunität bei Thieren’, Deutsch. med. Wochenschr., 1890, 16 (50): 1145–8.
7 Starting in 1871, the Germans annexed Alsace, which while being a great blow to French national pride also constituted a significant motivation for the scientific work of first Pasteur and later Roux.
8 For a detailed and yet reflective intellectual biography of Koch, see Christoph Gradmann, Krankheit im Labor: Robert Koch und die medizinische Bakteriologie, Göttingen, Wallstein, 2005. There are a number of biographies of Pasteur that analyse his approach to microbiological research. The most challenging is Gerald L Geison, The private science of Louis Pasteur, Princeton University Press, 1995, but other detailed presentations include Patrice Debré, Louis Pasteur, Paris, Flammarion, 1994.
9 Andrew Mendelsohn, Cultures of bacteriology: formation and transformation of a science in France and Germany, 1870–1914, PhD thesis, Princeton University, 1996, pp. 299–309. Here, Mendelsohn argues that Roux's use of solid media, combined with the skills brought to Paris from Germany by Yersin, contributed to a re-alignment starting in 1885. Their research on the virulence of germs progressively adopted the use of antiseptics described in the present paper. See pp. 313–35.
10 For a comparison of the structure and functioning of Koch's Institute for Hygiene and the Pasteur Institute, see Paul Weindling, ‘Scientific elites and laboratory organisation in fin de siècle Paris and Berlin’, in Andrew Cunningham and Perry Williams (eds), The laboratory revolution in medicine, Cambridge University Press, 1992, pp. 170–88.
11 For this story about Roux, see Mary Cressac, Le Docteur Roux mon oncle, Paris, L'Arche, 1950. While others, like Edmond Nocard, may have volunteered to serve during the Franco-Prussian war, there were no military career doctors working for the Pasteur Institute at this time.
12 “Es kommt dabei wenig darauf an, ob wir bei den letztgenannten Heilwirkungen, die mit dem Blut immunisirter anderer Thiere erzielt werden können, die Bacterien direkt beeinflussen, oder ob wir die krankmachenden Wirkungen ihrer Stoffwechsel-producte paralysiren. Ich glaube ein Recht zu haben, beides als eine Desinfection im lebenden Organismus zu bezeichnen.” Emil Behring, ‘Ueber Desinfection am lebenden Organismus’, Deutsch. med. Wochenschr., 1891, 17(52): 1393–97, on p.1393.
13 Today, Poznan in Poland.
14 Behring Archive, Marburg; 08-04/T-II/ 1071, from 22 December 1881.
15 Emil Behring, ‘Ueber Jodoform und Jodoformwirkung’, Deutsch. med. Wochenschr., 1882, 8 (11): 146–8.
16 “Die Einwirkung auf septische Substansten ist in folgender Weise zu erklären. Bei der Fäulniss wie bei allen lebhaften Zersetzungsprocessen enstehen oder sind vorhanden oxydirende chemische Körper, die, wie man sich durch mikroskopische Betrachtung überzeugen kann, aus Jodoform Jod entwickeln; das Jod in statu nascendi ist aber nachweislich im Stande, fäulnissfähige Substanzen in fäulnissunfähige zu verwandeln und in faulenden Substanzen die Fäulniss zu sistiren.” Ibid., p. 147.
17 Emil Behring, ‘Ueber Jodoformintoxication’, Deutsch. med. Wochenschr., 1882, 8 (20): 278–9, and 8(21): 297–298.
18 Emil Behring, ‘Die Bedeutung des Jodoforms in der antiseptischen Wundbehandlung’, Deutsch. med. Wochenschr., 1882,8 (23): 321–3, and 1882, 8 (24): 336–337.
19 J Mikulicz, ‘Zur Jodoformbehandlung’, Centralblatt für Chirurgie, 1882, p. 1.
20 Iodoform—CHI3—is the homologue of chloroform—CHCl3—with the chlorine replaced by iodine.
21 Kurzwelly, ‘Das Jodoform. Eine Monographie mit Rücksicht auf Chemie, Physiologie, Pharmacie und Therapie, von Dr. J. Righini; aus dem Italienischen übertragen von Dr E. Janssens’, Schmidt's Jahrbücher der in- und ausländischen gesammten Medicin, 1864, 121: 25–31.
22 W Watson Cheyne, ‘On a new method of arresting gonorrhoea’, Br. med. J., 24 July 1880, ii: 124–5.
23 Kurzwelly, op. cit., note 21 above, p. 29.
24 Ibid., p. 31.
25 Joseph Lister, ‘An address on the antiseptic system of treatment in surgery’, Br. med. J., 18 July 1868, ii: pp. 53–6, on p. 53.
26 Joseph Lister, ‘On a new method of treating compound fracture, abscesses, &c.’, Lancet, 16 March 1867, i: 326.
27 Anthony S Travis, The rainbow makers: the origins of the synthetic dyestuffs industry in western Europe, Bethlehem, Lehigh University Press, 1993.
28 For more on industrial chemical pollution during this period, see the relevant contributions in Ernst Homburg, Anthony S Travis, and Harm G Schröter (eds), The chemical industry in Europe, 1850–1914: industrial growth, pollution and professionalization, Berlin, Springer, 1998.
29 The Deutsche Militärärtzliche Zeitschrift was published between 1872 and 1912. The early issues were edited by Dr Leuthold, Oberstabarzt at the Invalidenhause in Berlin.
30 Although in Silesia, Winzig—now part of Poland and known as Wińsko—was a few hundred kilometres south of Posen.
31 Emil Behring, ‘Ueber Jodoformvergiftung und ihre Behandlung’, Deutsch. med. Wochenschr., 1884, 10 (5): 68–70.
32 A small town about 50 miles south of Posen, Bojanowo is today in Poland.
33 H Zeiss and R Bieling, Behring: Gestalt und Werk, Berlin, B Schultz, 1940, p. 39.
34 The loss of the relevant Prussian military documents makes it impossible to confirm this hypothesis concerning the aims of the military command in this case.
35 “Wenig Sicheres ist von der innern Wirkung des Jodoform bekannt.” Carl Binz, ‘Ueber Jodoform und über Jodsäure’, Archiv für experimentelle Pathologie und Pharmakologie, 1878, 8: 309.
36 In 1877, Carl Möller defended a dissertation at the Rheinischen Friedrich-Wilhelms-Universität in Bonn, half of which was dedicated to iodoform. Carl Möller, Pharmakologische Untersuchungen über Jodoform und Jodsäure, MD thesis, Rheinischen Friedrich-Wilhelms-Universität, 1877.
37 Behring Archive, Marburg, 08-04/T-II/1083.
38 Emil Behring, ‘Der antiseptische Wert der Silberlösungen und Behandlung von Milzbrand mit Silberlösungen’, Deutsch. med. Wochenschr., 1887, 13 (37, 38): 805–7, 830–4.
39 Pentamethylendiamine, or 1,5-diaminopentane had become increasingly identified with the chemical principle thought to be responsible for the putrefaction of dead bodies, cadaverine.
40 Oscar Kniffler, Jodoform zur inneren Anwendung, MD thesis, Rheinische Friedrich-Wilhelms-Universität, 1889, p. 33.
41 Behring was transferred to Robert Koch's Institute in Berlin in July 1889.
42 It is interesting to note that in January 1890, Behring was taking a course in hygiene at the Robert Koch Institute, in which Oscar Boer taught a section on the action of disinfectants on bacteria, 08-04/T-II/1086, ‘Bericht über einen Kursus im Institut von Robert Koch’.
43 Emil Behring, ‘Ueber Desinfection, Desinfectionsmittel und Desinfections-methoden’, Zeitschrift für Hygiene, 1890, 9: 395–478.
44 “Das Jodtrichlorid ist nicht das einzige Mittel, mit welchem man gute Heilresultate bei der Diphtherie der Meerschweinchen erzielen kann ; auch Naphthylamin und unter den Metallsalzen namentlich das Goldnatriumchlorid erwiesen sich wirksam; indessen waren bis jetzt die Erfolge mit dem Jodtrichlorid die besten.” Ibid., p. 464.
45 This competition around the diphtheria antitoxin is well analysed in Paul Weindling, ‘From medical research to clinical practice: serum therapy for diphtheria in the 1890s’, in John Pickstone (ed.), Medical innovations in historical perspective, New York, St Martin's Press, 1992, pp. 72–83. For more on the history of tuberculin as a treatment, see Christoph Gradmann, ‘Redemption, danger and risk: the history of anti-bacterial chemotherapy and the transformation of tuberculin’, in Thomas Schlich and Ulrich Tröhler (eds), The risks of medical innovation: risk perception and assessment in historical context, London, Routledge, 2005, pp. 53–70.
46 The nine methods retained by Behring in his subsequent account of the period were the following: sterilizing the bacteria at high temperature, pretreating the culture with iodine trichloride, using the bodily fluids of sick animals to induce immunity in others, using chemical agents to cure infected animals, using hydrogen peroxide (a disinfectant) as a prophylactic, employing attenuated bacteria culture followed by a full strength one, using pre-treated toxin, trying incremental doses of toxin, and feeding the animals with the toxin. See Emil Behring, Die Geschichte der Diphtherie. Mit besondere Berücksichtigung der Immunitätslehre, Leipzig, Georg Thieme, 1893, p. 148.
47 Georg Cornet, ‘Ueber das Verhalten der Tuberkelbacillen im thierischen Organismus unter dem Einfluss entwickelungshemmender Stoffe’, Zeitschrift für Hygiene, 1889, 5: 100–1, cited in Gradmann, op. cit., note 8 above, p. 138.
48 Oscar Boer, ‘Ueber die Behandlung diphtherieinfizierter Meerschweinchen mit chemischen Präparaten’, Zeitschrift für Hygiene und Infektionskrankheiten, 1892, 11: 154–64. “Experimental” disease was the term used to describe human disease induced in an animal usually by the inoculation of a bacterial culture.
49 Erika Schulte, Der Anteil Erich Wernickes an der Entwicklung des Diphtherieantitoxins, MD thesis, Berlin, 2000.