{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:52:36Z","timestamp":1790819556662,"version":"4.1.0"},"reference-count":137,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Med. Hist."],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>This paper analyses how research on antibiotic resistance has been a driving force in the development of new antibiotics. Drug resistance, while being a problem for physicians and patients, offers attractive perspectives for those who research and develop new medicines. It imposes limits on the usability of older medicines and simultaneously modifies pathologies in a way that opens markets for new treatments. Studying resistance can thus be an important part of developing and marketing antibiotics.<\/jats:p><jats:p>The chosen example is that of the German pharmaceutical company Bayer. Before World War Two, Bayer had pioneered the development of anti-infective chemotherapy, sulpha drugs in particular, but had missed the boat when it came to fungal antibiotics. Exacerbated by the effects of war, Bayer\u2019s world market presence, which had been considerable prior to the war, had plummeted. In this critical situation, the company opted for a development strategy that tried to capitalise on the problems created by the use of first-generation antibiotics. Part and parcel of this strategy was monitoring what can be called the structural change of infectious disease. In practice, this meant to focus on pathologies resulting from resistance and hospital infections. In addition, Bayer also focused on lifestyle pathologies such as athlete\u2019s foot. This paper will follow drug development and marketing at Bayer from 1945 to about 1980. In this period, Bayer managed to regain some of its previous standing in markets but could not escape from the overall crisis of anti-infective drug development from the 1970s on.<\/jats:p>","DOI":"10.1017\/mdh.2016.2","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T12:31:21Z","timestamp":1457958681000},"page":"155-180","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":37,"title":["Re-Inventing Infectious Disease: Antibiotic Resistance and Drug Development at the Bayer Company 1945\u201380"],"prefix":"10.1017","volume":"60","author":[{"given":"Christoph","family":"Gradmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"S0025727316000028_r58","unstructured":"Bunge to Hansen, 2.11.1960, BAL, 367\/626."},{"key":"S0025727316000028_r27","unstructured":"Charles-Edward Emory Winslow, The Conquest of Epidemic Disease: A Chapter in the History of Ideas (Princeton, NJ: Princeton University Press, 1987 (1967))."},{"key":"S0025727316000028_r18","unstructured":"Gradmann 2011, op. cit. (note 17)."},{"key":"S0025727316000028_r119","unstructured":"Dalhoff, op. cit. (note 75), 100."},{"key":"S0025727316000028_r39","unstructured":"That company was Schenley. It took Bayer almost 30 years before substantial turnover could be achieved in the US market. Ibid., 318\u201319. Cf. Kleedehn, op. cit. (note 31), 152\u20133."},{"key":"S0025727316000028_r117","unstructured":"Work had started in 1981. On ciprofloxacin: Dalhoff, op. cit. (note 75), 92\u20136."},{"key":"S0025727316000028_r115","unstructured":"BAL, 323\/150."},{"key":"S0025727316000028_r51","unstructured":"Arthur Daemmrich, Pharmacopolitics: Drug Regulation in the United States and Germany (Chapel Hill, NC: University of North Carolina Press, 2004), 77\u20138."},{"key":"S0025727316000028_r110","unstructured":"Research committee [Forschungskommittee] 1974, BAL 323\/87."},{"key":"S0025727316000028_r49","unstructured":"Christoph Gradmann, \u2018Sensitive Matters. The World Health Organisation and Antibiotics Resistance Testing, 1945\u201375\u2019, Social History of Medicine, 26, (2013), 555\u201374. Cf. Kathryn Hillier, \u2018Babies and Bacteria: Phage Typing, Bacteriologists, and the Birth of Infection Control\u2019, Bulletin of the History of Medicine, 80, (2006), 733\u201361."},{"key":"S0025727316000028_r10","unstructured":"Author\u2019s transcription from http:\/\/www.youtube.com\/watch?v=uZt6q2uwM2g. Cf. Centers for Disease Control and Prevention (CDC) (ed.) Antibiotic Resistance Threats in the United States, 2013 (CDC, 2013)."},{"key":"S0025727316000028_r103","unstructured":"Greenwood, op. cit. (note 8), 358."},{"key":"S0025727316000028_r97","unstructured":"Bartmann, op. cit. (note 21), 320."},{"key":"S0025727316000028_r36","unstructured":"Wimmer, op. cit. (note 14). According to Redeker, op. cit. (note 34), 90, a patent was registered in 1943."},{"key":"S0025727316000028_r120","unstructured":"Viviane Quirke and Jean-Paul Gaudilli\u00e8re, \u2018The Era of Biomedicine: Science, Medicine, and Public Health in Britain and France after the Second World War\u2019, Medical History, 52, (2008), 441\u201352, here 451."},{"key":"S0025727316000028_r94","unstructured":"State of the art report [Statusbericht] for 1973, AK \u00df-lactam-Antibiotika, BAL 323\/99. Cf. Baum, op. cit. (note 22): 263\u20136 on Bayer\u2019s new antibiotics in the 1970s."},{"key":"S0025727316000028_r91","unstructured":"Bud, op. cit. (note 3), 116\u201339."},{"key":"S0025727316000028_r78","unstructured":"Baum, op. cit. (note 22), 131\u20133; H.G. Lazell, From Pills to Penicillin: The Beecham Story: A Personal Account (London: Heinemann, 1975), 177\u20139."},{"key":"S0025727316000028_r76","unstructured":"Jean-Paul Gaudilli\u00e8re and Ulrike Thoms, \u2018Introduction\u2019, in J.-P. Gaudilli\u00e8re and U Thoms (eds), Research for Sales: The Development of Scientific Marketing in the 20th Century Pharmaceutical Industry (London: Pickering and Chatto, forthcoming), 1\u201317. I thank the authors for sharing their unpublished work with me."},{"key":"S0025727316000028_r102","unstructured":"Baum, op. cit. (note 22), 253."},{"key":"S0025727316000028_r89","unstructured":"Flurin Condrau and Robert Kirk, \u2018Negotiating Hospital Infections: The Debate between Ecological Balance and Eradication Strategies in British Hospitals, 1947\u201369\u2019, Dynamis, 31, (2011), 385\u2013405; Ayliffe and English, op. cit. (note 1)."},{"key":"S0025727316000028_r92","unstructured":"Memorandum on resistance determination, Walter, 30.9.1960, BAL, 372\/27."},{"key":"S0025727316000028_r86","unstructured":"Dalhoff, op. cit. (note 26) for an overview. The brand names with years of marketing and effective substances are: Stapenor (1962) Oxacillin; Resitopen (1972) Carbenicillin $+$ Oxacillin; Microcillin (1973) Carbenicillin; Securopen (1977) Azlocillin; Baypen (1977) Mezlocillin. Azlocillin and Mezlocillin were own developments."},{"key":"S0025727316000028_r101","unstructured":"Greenwood, op. cit. (note 8), 345\u201392. Aya Homei and Michael Worboys, Pathologies of Progress: Fungal Disease in Britain and the United States, 1850\u20132000 (Basingstoke: Palgrave, 2013)."},{"key":"S0025727316000028_r57","unstructured":"BAL, 363\/101, of 5.11.62."},{"key":"S0025727316000028_r112","unstructured":"BAL 323\/156, Department research [Ressort Forschung], minutes of a meeting held 10.1.77 (of 14.1.77)."},{"key":"S0025727316000028_r79","unstructured":"Bud, op. cit. (note 3), 75\u201396; Greenwood, op. cit. (note 8), 122\u20136."},{"key":"S0025727316000028_r75","unstructured":"BAL, 363\/101; Baum, op. cit. (note 22): 253. Plans to employ a mycologist go back to 1961. Once hired, Metzger was sent on the customary training tour (Marget and Liebermeister, which were collaborating clinicians; Chabbert, a researcher at the Institut Pasteur). A short biography of Metzger is to be found in Axel A.H. Dalhoff, \u2018Discovery and Development of Anti-infectives at Bayer: A Personal View. Part III. Fluorquinolones\u2019, Sim News, 58, (2008), 89\u2013105."},{"key":"S0025727316000028_r69","unstructured":"Podolsky, op. cit. (note 61)."},{"key":"S0025727316000028_r111","unstructured":"Research committee [Forschungskommittee] 1976, BAL 323\/87."},{"key":"S0025727316000028_r68","unstructured":"Bud, op. cit. (note 3), 116\u201339; Greenwood, op. cit. (note 8); E.M. Tansey (ed.) Post Penicillin Antibiotics: from Acceptance to Resistance. A Witness Seminar, held at the Wellcome Institute for the History of Medicine, London, 12 May 1998 (London: Wellcome Trust, 2000)."},{"key":"S0025727316000028_r65","unstructured":"Memorandum on the meeting of the \u201cworking group [Arbeitsgruppe] chemotherapeutics: antibiotics, sulphonamides, tubculostatics\u201d, 5.11.1962, BAL, 363\/101."},{"key":"S0025727316000028_r88","unstructured":"Undated memorandum, Bayer archives, BAL, 372\/28. Judging from its positioning in the archive it should be from the mid-1960s."},{"key":"S0025727316000028_r84","unstructured":"Walter\u2019s memorandum on the introduction of Bayer 5393 [propicillin]. 12.12.1961, BAL, 363\/101. The memorandum is reporting a discussion in Walter\u2019s team on the marketing of the antibiotic and was addressed to employees in pharmaceutical marketing and development."},{"key":"S0025727316000028_r63","unstructured":"Domagk, Annual report [Jahresbericht] 1953, BAL, 103\/11.2, p.\u00a023."},{"key":"S0025727316000028_r62","unstructured":"Domagk to Kreutzer, 10.3.1951, BAL, 372\/016."},{"key":"S0025727316000028_r83","unstructured":"Dalhoff, op. cit. (note 26), 10."},{"key":"S0025727316000028_r56","unstructured":"From Orthomycin advert of 1955, BAL 166\/8."},{"key":"S0025727316000028_r53","unstructured":"Barry, op. cit. (note 33), 194\u20138. Redeker, op. cit. (note 34), 180\u201397 points to the affirmative character of Domagk\u2019s and his collaborators\u2019 statements."},{"key":"S0025727316000028_r73","unstructured":"BAL 316\/3.82 and 316\/3.85 where the delivery of suspected resistant samples is documented. While in the early 1950 we see lots of spontaneous delivery with requests for determination of strains, the laboratory showed little interest in such activity after about 1955 and instead relied on collaboration with established partners."},{"key":"S0025727316000028_r55","unstructured":"Ibid., 1957."},{"key":"#cr-split#-S0025727316000028_r40.1","doi-asserted-by":"crossref","unstructured":"42. Mauro Capocci, '??\"A Chain is Gonna Come\". Building a Penicillin Production Plant in Post-war Italy', Dynamis, 31, (2011), 343-62","DOI":"10.4321\/S0211-95362011000200005"},{"key":"#cr-split#-S0025727316000028_r40.2","doi-asserted-by":"crossref","unstructured":"43. Maria Jes??s Santemases, 'Screening Antibiotics: Industrial Research by CEPA and Merck in the 1950s', Dynamis, 31, (2011), 407-27.","DOI":"10.4321\/S0211-95362011000200008"},{"key":"S0025727316000028_r116","unstructured":"Charles H. Stuart-Harris and David M. Harris (eds), The Control of Antibiotic-resistant Bacteria, (London; New York: Academic Press, 1982); John Mann, The Elusive Magic Bullet: The search for the Perfect Drug (Oxford: Oxford University Press, 1999); J. Parascandola (ed.) The History of Antibiotics: Symposium, (Madison, WI: American Institute of the History of Pharmacy, 1980). Greenwood, op. cit. (note 8), 262\u20133. Rang, op. cit. (note 9), 16\u201317; Spellberg et al., op. cit. (note 9)."},{"key":"S0025727316000028_r122","doi-asserted-by":"crossref","unstructured":"Louis Galambos and Jane Eliot Sewell, Networks of Innovation: Vaccine Development at Merck, Sharp and Dohme, and Mulford, 1895\u20131995 (Cambridge: Cambridge University Press, 1996), 241\u20133 have emphasised a similar pattern in their study of Merck, Sharp & Dome\u2019s vaccine business.","DOI":"10.1017\/CBO9780511629518"},{"key":"S0025727316000028_r50","unstructured":"BAL, 316\/3.82."},{"key":"S0025727316000028_r105","unstructured":"Bartmann, op. cit. (note 21), 350 mentions that Adalat and Canesten in 1975 created three times as much turnover than ten other newly marketed preparations in those years."},{"key":"S0025727316000028_r2","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1050"},{"key":"S0025727316000028_r19","unstructured":"Horst Bernd D\u00fcnschede, Tropenmedizinische Forschung bei Bayer (D\u00fcsseldorf: Trilsch, 1971). Bayer Leverkusen Tropenabteilung, Die Chemotherapie der Schlafkrankheit (Leverkusen: Bayer, 1938)."},{"key":"S0025727316000028_r74","unstructured":"Minutes of a meeting 5.11.62 of the working group [Arbeitsgruppe] on antibiotics, sulphonamides and tuberculostatics, BAL, 372\/29, 4: \u2018For preparations that are traded already it is impossible to employ excellent testers\u2019."},{"key":"S0025727316000028_r52","unstructured":"Ludwig Heilmeyer, \u2018Vorl\u00e4ufiger Bericht \u00fcber Isonikotins\u00e4urehydrazid (Rimifon, Neoteben) auf Grund experimenteller und klinischer Untersuchungen\u2019, Deutsche medizinische Wochenschrift, 94, (1952), 1303\u20138."},{"key":"S0025727316000028_r38","unstructured":"Bartmann, op. cit. (note 21), 301\u201329."},{"key":"S0025727316000028_r87","unstructured":"Cf. letter by Walter to Bunge, 20.7.1960 (BAL, 372\/27) where he states, on the example of the new antibiotic chloramphenicol, his opinion that any new antibiotic would be devalued by resistant bacteria over time."},{"key":"S0025727316000028_r21","unstructured":"Wilhelm Bartmann, Zwischen Tradition und Fortschritt. Aus der Geschichte der Pharmabereiche von Bayer, Hoechst und Schering von 1935\u201375 (Stuttgart: Steiner, 2003), 106\u201312. Cf. John E. Lesch, \u2018Chemistry and biomedicine in an industrial setting: the invention of the sulfa drugs\u2019, in S.H. Mauskopf (ed.), Chemical Sciences in the Modern World (Philadelphia, PA, University of Pennsylvania Press, 1993), 158\u2013215."},{"key":"S0025727316000028_r108","unstructured":"Research commission [Forschungskomission] pharma, minutes of the meeting 7.10.1977, 21.10.1977. BAL, 323\/86. Cf. Research commission [Forschungskomission] pharma, minutes of the meeting 1.2.1974 (8.2.74), \u2018Target of Bayer\u2019s research is to find new \u00df-lactam antibiotics, which combine the advantages of currently traded products (effectiveness in small quantities and concurrent low toxicity) but do not possess their disadvantages (limited antibacterial spectrum, sensitivity to pencillinase, triggering allergies, swift discharge, sometime a necessity to apply by drips)\u2019."},{"key":"S0025727316000028_r32","doi-asserted-by":"crossref","unstructured":"Ekkehard Grundmann, Gerhard Domagk \u2013 der erste Sieger \u00fcber die Infektionskrankheiten (M\u00fcnster: Lit, 2001).","DOI":"10.1007\/s002920100469"},{"key":"S0025727316000028_r45","unstructured":"On this and the following, see Barry, op. cit. (note 33): 192\u2013202. Cf. Redeker, op. cit. (note 34), 123."},{"key":"S0025727316000028_r106","unstructured":"BAL, 327\/87."},{"key":"#cr-split#-S0025727316000028_r5.1","unstructured":"58. William C. Summers, 'Microbial drug resistance: a historical perspective', in R.G. Wax et??al. (eds), Bacterial Resistance to Antimicrobials (Boca Raton, FL: CRC Press, 2008), 1-9"},{"key":"#cr-split#-S0025727316000028_r5.2","unstructured":"59. Frank Ryan, The Forgotten Plague: How the Battle Against Tuberculosis Was Won - and Lost (Boston: Little, Brown, 1993)"},{"key":"#cr-split#-S0025727316000028_r5.3","doi-asserted-by":"crossref","unstructured":"60. Claudia Eberhardt-Metzger and Renate Ries, Verkannt und heimt??kisch - Die ungebrochene Macht der Seuchen (Basel: Birkh??user, 1996)","DOI":"10.1007\/978-3-0348-6025-3"},{"key":"#cr-split#-S0025727316000028_r5.4","unstructured":"61. H. Schadewaldt (ed.) Die R??ckkehr der Seuchen (K??ln: vgs, 1994)."},{"key":"S0025727316000028_r34","unstructured":"Domagk, unpublished memories, quoted in Dietrich Redeker, Zur Entwicklungsgeschichte der Tuberkulostatika und Antituberkulotika (Stuttgart: Deutscher Apotheker Verlag, 1990), 100."},{"key":"S0025727316000028_r113","unstructured":"Cf. Bartmann, op. cit. (note 21), 363."},{"key":"S0025727316000028_r43","unstructured":"Ibid., 98, 104, Barry, op. cit. (note 33), 49."},{"key":"S0025727316000028_r71","unstructured":"Ludwig Heilmeyer and Albert Michael Walter, Antibiotika-Fibel. Indikation und Anwendung der Chemotherapeutika und Antibiotika (Stuttgart: Thieme, 1954). In later editions, he co-authored the book with his co-researchers at Bayer: Albert Michael Walter et\u00a0al., Antibiotika-Fibel. Antibiotika und Chemotherapie (Stuttgart: Thieme, 1969)."},{"key":"S0025727316000028_r31","unstructured":"Bartmann, op. cit. (note 21), 301\u20133. Cf. Patrick Kleedehn, Die R\u00fcckkehr auf den Weltmarkt. Die Internationalisierung der Bayer AG Leverkusen nach dem Zweiten Weltkrieg bis zum Jahre 1961 (Stuttgart: Franz Steiner Verlag, 2007), 151\u201363."},{"key":"S0025727316000028_r107","unstructured":"Daemmrich, op. cit. (note 51), 55."},{"key":"S0025727316000028_r104","unstructured":"Baum, op. cit. (note 22): 356. The numbers are in millions of Deutsche Mark."},{"key":"S0025727316000028_r121","unstructured":"Braun, op. cit. (note 26), 140."},{"key":"S0025727316000028_r98","unstructured":"Ibid., 339."},{"key":"S0025727316000028_r61","doi-asserted-by":"publisher","DOI":"10.1093\/jhmas\/jrq003"},{"key":"S0025727316000028_r24","first-page":"27","volume-title":"Bakterien in Krieg und Frieden: eine Geschichte der medizinischen Bakteriologie in Deutschland 1890\u2013933","author":"Berger","year":"2009"},{"key":"S0025727316000028_r42","unstructured":"Redeker, op. cit. (note 34), 93."},{"key":"#cr-split#-S0025727316000028_r3.1","unstructured":"72. L.A. Reyolds and E.M. Tansey (eds), Superbugs and Superdrugs: A History of MRSA, (London: Wellcome Trust Centre for the History of Medicine at UCL 2008)"},{"key":"#cr-split#-S0025727316000028_r3.2","unstructured":"73. Robert Bud, Penicillin: Triumph and Tragedy (Oxford: Oxford University Press, 2007)"},{"key":"#cr-split#-S0025727316000028_r3.3","doi-asserted-by":"crossref","unstructured":"74. Nicholas B. King, 'The Scale Politics of Emerging Diseases', Osiris, 19, (2004), 62-76","DOI":"10.1086\/649394"},{"key":"#cr-split#-S0025727316000028_r3.4","doi-asserted-by":"crossref","unstructured":"75. David Satcher, 'Emerging Infections: Getting Ahead of the Curve', Emerging Infectious Diseases, 1, (1995), 6","DOI":"10.3201\/eid0101.950101"},{"key":"#cr-split#-S0025727316000028_r3.5","unstructured":"76. Joshua Lederberg, Robert E. Shope and Stanley C. Oaks (eds), Emerging Infections. Microbial Threats to Health in the United States (Washington, DC: National Academic Press, 1992)."},{"key":"S0025727316000028_r30","unstructured":"Bud, op. cit. (note 3): 23\u201353."},{"key":"S0025727316000028_r99","doi-asserted-by":"crossref","unstructured":"John T. MacFarlane and Michael Worboys, \u2018The Changing Management of Acute Bronchitis in Britain, 1940\u201370: The Impact of Antibiotics\u2019, Medical History, 52, (2008), 47\u201372.","DOI":"10.1017\/S0025727300000156"},{"key":"S0025727316000028_r80","unstructured":"Bud, op. cit. (note 3), 116\u201339."},{"key":"S0025727316000028_r4","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-1348(01)00012-0"},{"key":"S0025727316000028_r93","unstructured":"Quoted in Redeker, op. cit. (note 34), 100."},{"key":"S0025727316000028_r114","doi-asserted-by":"crossref","unstructured":"BAL, 372\/87, Letter Bartmann to Bunge, 29.8.1968.","DOI":"10.1086\/aaa.8.3_4.1557173"},{"key":"S0025727316000028_r60","doi-asserted-by":"crossref","unstructured":"Ulrike Lindner, Gesundheitspolitik in der Nachkriegszeit: Grossbritannien und die Bundesrepublik Deutschland im Vergleich (M\u00fcnchen R. Oldenbourg 2004), 127\u201359. Cf. Smith, op. cit. (note 33).","DOI":"10.1524\/9783486707588"},{"key":"S0025727316000028_r6","first-page":"1940","volume-title":"The Natural History of Infectious Disease","author":"Burnet","year":"1953"},{"key":"S0025727316000028_r7","first-page":"78","volume-title":"Wird Kassandra heiser? Die Geschichte falscher \u00d6koalarme","author":"H\u00fcnem\u00f6rder","year":"2004"},{"key":"#cr-split#-S0025727316000028_r20.1","unstructured":"83. John E. Lesch, The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine (Oxford: Oxford University Press, 2007)"},{"key":"#cr-split#-S0025727316000028_r20.2","unstructured":"84. Cf. Axel A.H. Dalhoff, 'Discovery and Development of Anti-infectives at Bayer: A Personal View. Part I: Antiparasitics, Sulfonamides, and Antitubercular drugs', Sim News, 57, (2007), 135-50, here 135-42."},{"key":"S0025727316000028_r54","unstructured":"BAL 103\/11.2. Annual report [Jahresbericht] for 1958."},{"key":"S0025727316000028_r13","volume-title":"Die I.G. Farbenindustrie AG: Wirtschaft, Technik und Politik 1904\u201345","author":"Plumpe","year":"1990"},{"key":"S0025727316000028_r37","unstructured":"Domagk, quoted in Redeker, op. cit. (note 34), 100."},{"key":"S0025727316000028_r8","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780199534845.001.0001","volume-title":"Antimicrobial Drugs. Chronicle of a Twentieth Century Triumph","author":"Greenwood","year":"2008"},{"key":"S0025727316000028_r95","unstructured":"Ibid."},{"key":"#cr-split#-S0025727316000028_r15.1","unstructured":"88. Lutz Sauerteig, 'Ethische Richtlinien, Patientenrechte und ??rztliches Verhalten bei der Arzneimittelerprobung 1892-31', Medizinhistorisches Journal, 35, (2000), 303-34"},{"key":"#cr-split#-S0025727316000028_r15.2","doi-asserted-by":"crossref","unstructured":"89. Axel C??sar H??ntelmann, Paul Ehrlich: Leben, Forschung, ??konomien, Netzwerke (G??ttingen: Wallstein, 2011).","DOI":"10.5771\/9783835321205"},{"key":"S0025727316000028_r48","unstructured":"Archive of the Bayer AG, Leverkusen (BAL), 316\/3."},{"key":"S0025727316000028_r16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.56021\/9780801893131","volume-title":"Laboratory Disease: Robert Koch\u2019s Medical Bacteriology","author":"Gradmann","year":"2009"},{"key":"#cr-split#-S0025727316000028_r17.1","doi-asserted-by":"crossref","unstructured":"91. Christoph Gradmann, 'Magic Bullets and Moving Targets: Antibiotic Resistance and Experimental Chemotherapy 1900-40', Dynamis, 31, (2011), 305-21. Cf. Ehrlich's side chain theory: Cay-R??diger Pr??ll, Andreas-Holger Maehle and Robert Francis Halliwell, A Short History of the Drug Receptor Concept (Basingstoke: Palgrave, 2009)","DOI":"10.4321\/S0211-95362011000200003"},{"key":"#cr-split#-S0025727316000028_r17.2","doi-asserted-by":"crossref","unstructured":"92. John Parascandola, 'The Theoretical Basis of Paul Ehrlich's Chemotherapy', Journal for the History of Medicine and Allied Sciences, 36, (1981), 19-43","DOI":"10.1093\/jhmas\/XXXVI.1.19"},{"key":"#cr-split#-S0025727316000028_r17.3","unstructured":"93. Arthur Silverstein, Paul Ehrlich's Receptor Immunology: The Magnificent Obsession (San Diego, CA: Academic Press, 2003)."},{"key":"S0025727316000028_r47","unstructured":"Redeker, op. cit. (note 34), 104."},{"key":"S0025727316000028_r100","unstructured":"Greene, op. cit. (note 96)."},{"key":"#cr-split#-S0025727316000028_r23.1","doi-asserted-by":"crossref","unstructured":"96. Jean-Paul Gaudilli??re and Ulrike Thoms, 'Pharmaceutical Firms and the Construction of Drug Markets: from Branding to Scientific Marketing', History and Technology, 29, (2013), 105-15","DOI":"10.1080\/07341512.2013.828867"},{"key":"#cr-split#-S0025727316000028_r23.2","doi-asserted-by":"crossref","unstructured":"97. Ulrike Thoms, 'Standardizing Selling. Pharmaceutical marketing, the Pharmaceutical Company and the Marketing Expert (1900-80)', History and Technology, 29, (2013), 169-87.","DOI":"10.1080\/07341512.2013.827015"},{"key":"S0025727316000028_r81","unstructured":"Kassler Post No. 230\/Vol.80, 1.9.1962, \u2018Sieg \u00fcber die Resistenz der Bakterien\u2018, in BAL, 363\/101. The substances were Binotal (ampicillin), Stapenor (oxacillin) and Baycillin (propicillin). Cf. Dalhoff, op. cit. (note 26): 13. Cf. BAL, 363\/101, 1.6.1962, Walter\u2019s memorandum on the coordinated introduction of the three medicines."},{"key":"S0025727316000028_r59","unstructured":"Bartmann, op. cit. (note 21), 320."},{"key":"#cr-split#-S0025727316000028_r26.1","unstructured":"100. Dalhoff 2007, op. cit. (note 20)"},{"key":"#cr-split#-S0025727316000028_r26.2","unstructured":"101. Axel A.H. Dalhoff, 'Discovery and Development of Anti-infectives at Bayer: A Personal View. Part II: ??-lactam antibiotics', Sim News, 58, (2008), 6-18"},{"key":"#cr-split#-S0025727316000028_r26.3","unstructured":"102. Cf. Heiko Braun, 'Von der Vertriebs- und \"Propagandapolitik\" zum Pharmamarketing? Eine Marketinggeschichte des deutschen Pharmabereichs der Farbenfrabriken Bayer AG 1957-71' (Unpublished M.A. thesis: University of Bonn, 2009)."},{"key":"S0025727316000028_r72","doi-asserted-by":"crossref","unstructured":"Domagk, Jahresbericht f\u00fcr 1958, BAL, 103\/11.2.","DOI":"10.1111\/j.0954-6820.1958.tb19083.x"},{"key":"S0025727316000028_r29","doi-asserted-by":"publisher","DOI":"10.1086\/649418"},{"key":"S0025727316000028_r35","unstructured":"Background: Dalhoff, op. cit. (note 20), 143\u20134; Redeker, op. cit. (note 34), 84\u2013104."},{"key":"S0025727316000028_r96","unstructured":"Jeremy Greene, Prescribing by Numbers: Drugs and the Definition of Disease (Baltimore, MD: Johns Hopkins University Press, 2007)."},{"key":"S0025727316000028_r44","unstructured":"Kolmer, op. cit. (note 28): 54\u20136, H.W. Florey et\u00a0al. Antibiotics: A Survey of Penicillin, Streptomycin, and other Antimicrobial Substances from Fungi, Actinomycetes, Bacteria, and Plants (Oxford: Oxford University Press, 1949), 1365\u2013400."},{"key":"S0025727316000028_r77","unstructured":"Ilana L\u00f6wy, Between Bench and Bedside: Science, Healing and Interleukin-2 in a Cancer Ward (Cambridge, MA; London: Harvard University Press, 1996); Alberto Cambrosio and Peter Keating, Biomedical Platforms. Realigning the Normal and the Pathological in Late-Twentieth-Century Medicine (Cambridge, MA: MIT Press, 2003), 50."},{"key":"S0025727316000028_r41","unstructured":"Redeker, op. cit. (note 34), 91, Dalhoff, op. cit. (note 20), 144, 146."},{"key":"S0025727316000028_r9","unstructured":"Ibid.: 262\/3; Humphrey P. Rang, \u2018The development of the pharmaceutical industry\u2019, in H.P. Rang (ed.), Drug Discovery and Development: Technology in Transition (London: Churchill Livingstone, 2005), 3\u201318, here 16\/7; Brad Spellberg et al., \u2018Trends in Antimicrobial Drug Development: Implications for the Future\u2019, Clinical Infectious Diseases, 38, (2004), 1279\u201386. Cf. Maryn McKenna\u2019s blog on the empty pipeline: http:\/\/www.superbugtheblog.com\/2009\/11\/antibiotics-eu-pipeline-is-empty-too.html. See Maryn McKenna, Suberbug: The Fatal Menace of MRSA (New York: Free Press, 2010), ch. 12 on the end of antibiotics."},{"key":"S0025727316000028_r109","doi-asserted-by":"crossref","unstructured":"Greenwood, op. cit. (note 8), 187\/8. Cf. Linda Bryder, Flurin Condrau and Michael Worboys, \u2018Tuberculosis and its histories: then and now\u2019, in F Condrau and M Worboys (eds), Tuberculosis Then and Now: Perspectives on the History of an Infectious Disease, (Montreal: McGill-Queens University Press, 2010), 3\u201323.","DOI":"10.1515\/9780773577046-001"},{"key":"S0025727316000028_r90","unstructured":"State of the art report [Statusbericht] for 1980, working group immune defence, BAL, 323\/104, of 28.1.1981."},{"key":"S0025727316000028_r82","unstructured":"Bartmann, op. cit. (note 21), 309."},{"key":"S0025727316000028_r25","unstructured":"Parascandola, op. cit. (note 17); Pr\u00fcll, Maehle and Halliwell, op. cit. (note 17)."},{"key":"S0025727316000028_r22","volume-title":"Geschichte der Pharma nach dem Zweiten Weltkrieg","author":"Baum","year":"1983"},{"key":"S0025727316000028_r85","unstructured":"BAL, 363\/101. Memorandum on the meeting of the \u2018working group [Arbeitsgruppe] chemotherapeutics: antibiotics, sulphonamides, tubculostatics\u2019, 5.11.1962. It reports on very good sales of Baycillin, while Stapenor is doing less well. Binotal only became marketed from 1.11.1961."},{"key":"S0025727316000028_r70","unstructured":"Albert Michael Walter, \u2018Experimentelle Grundlagen und klinische Erfahrungen zur Antibiotika-Resistenz der Bakterien und der Resistenzverz\u00f6gerung durch eine Kombinationstherapie\u2019, Habilitation: University of Freiburg, 1957."},{"key":"S0025727316000028_r64","unstructured":"Domagk to Bunge, 10.11.1958, BAL, 372\/24."},{"key":"S0025727316000028_r11","first-page":"17","volume-title":"Harmonizing Drugs. Standards in 20th-Century Pharmaceutical History","author":"Bonah","year":"2009"},{"key":"S0025727316000028_r66","unstructured":"Annual Report 1958 of pharmaceutical sales department [Jahresbericht f\u00fcr 1958 der Pharmazeutischen Verkaufsabteilung], BAL, 103\/11.2. Cf. Bartmann, op. cit. (note 21), 321."},{"key":"S0025727316000028_r12","unstructured":"Eberhardt-Metzger and Ries, op. cit. (note 5); Schadewaldt, op. cit. (note 5); Ryan, op. cit. (note 5)."},{"key":"S0025727316000028_r1","unstructured":"Daniel E. Koshland, \u2018The Microbial Wars\u2019, Science, 257, (1992), 1021. A scholarly monograph on the history of hospital infections Graham A.J. Ayliffe and Mary P. English, Hospital Infection From Miasmas to MRSA (Cambridge: Cambridge University Press, 2003), 134\u201370 seems to confirm the lines of development presented by Koshland: it describes a substantial improvement in relation to hospital infections occurring in the early twentieth century which was threatened by consequences of widespread antibiotic use after World War Two."},{"key":"S0025727316000028_r118","unstructured":"Quotes from an advertising poster campaign for Ciprofloxacin, BAL, 166\/8."},{"key":"S0025727316000028_r28","unstructured":"Bud, op. cit. (note 3): 116\u20138; Lesch, op. cit. (note 20); For a contemporary account see John A. Kolmer, Penicillin Therapy. Including Streptomycin, Tyrothricin And Other Antibiotic Therapy 2nd ed. (New York; London: Appleton-Century, 1947 (1945)): 54\u201356."},{"key":"S0025727316000028_r33","unstructured":"Francis Barrymore Smith, The Retreat of Tuberculosis 1850\u2013950 (London: Croom Helm, 1987). For a contemporary account see V.C. Barry, The Chemotherapy of Tuberculosis (London: Butterworth, 1964). Cf. George Weisz and Jesse Olszynko-Gryn, \u2018The Theory of Epidemiologic Transition: The Origin of a Citation Classic\u2019, Journal for the History of Medicine and Allied Sciences, 65, (2009), 287\u2013326."},{"key":"S0025727316000028_r46","doi-asserted-by":"crossref","unstructured":"H. Dennig and H. Hangleiter, \u2018Der heutige Stand der Chemotherapie bakterieller Erkrankungen und der Infektionskrankheiten\u2019, Deutsche medizinische Wochenschrift, 76, (1951), 647\u20139; 680\u20132: here 647.","DOI":"10.1055\/s-0028-1116770"},{"key":"S0025727316000028_r14","doi-asserted-by":"crossref","DOI":"10.3790\/978-3-428-48051-7","volume-title":"\u2018Wir haben fast immer was Neues\u2019: Gesundheitswesen und Innovation der Pharma-Industrie in Deutschland 1880\u2013935","author":"Wimmer","year":"1994"},{"key":"S0025727316000028_r67","unstructured":"Hillier, op. cit. (note 49)."}],"container-title":["Medical History"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0025727316000028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T19:39:07Z","timestamp":1748806747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0025727316000028\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,14]]},"references-count":137,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["S0025727316000028"],"URL":"https:\/\/doi.org\/10.1017\/mdh.2016.2","relation":{},"ISSN":["0025-7273","2048-8343"],"issn-type":[{"value":"0025-7273","type":"print"},{"value":"2048-8343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,14]]},"assertion":[{"value":"\u00a9 The Author 2016. 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