Sensitive matters: The world health organisation and antibiotic resistance testing, 1945-1975

Social History of Medicine

Volumn 26, Issue 3, 2013, Pages 555-574

  Gradmann, Christoph ^a  

^a UNIVERSITY OF OSLO   (Norway)

Author keywords

antibiotic resistance; clinical microbiology; Hans Ericsson; John Sherris; World Health Organisation

Indexed keywords

EID: 84881089749     PISSN: 0951631X     EISSN: 14774666     Source Type: Journal    
DOI: 10.1093/shm/hkt018     Document Type: Article

References (157)

1. Robert Bud, The Uses of Life. A history of biotechnology (Cambridge: Cambridge University Press 1993);
2. Paul Rabinow, Making PCR: A story of biotechnology (Chicago: University of Chicago Press 1996);
3. cf. Jean Paul Gaudillière, 'New Wine in Old Bottles? The Biotechnology Problem in the History of Molecular Biology', Studies in History and Philosophy of Biological and Biomedical Sciences 2009, 40, 20-8.
4. For introductions to that history see William C. Summers, 'Microbial Drug Resistance: A Historical Perspective', in Richard G. Wax, Kim Lewis, Abigail A. Salyers and Harry Taber (eds), Bacterial Resistance to Antimicrobials (Boca Raton: CRC Press 2008), 1-9;
5. Jørund Straand, Christoph Gradmann, Morton Lindbæk, and Gunnar Skov Simonsen, 'Antibiotic Development and Resistance', in Kris Heggenhougen and Stella Quah (eds), International Encyclopaedia of Public Health (San Diego: Academic Press 2008, 200-11);
6. 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, Wellcome Witnesses to Twentienth-century Medicine (London: Wellcome Trust Centre for the History of Medicine at UCL 2000);
7. L. A. Reynolds and E. M. Tansey (eds), Superbugs and Superdrugs: A History of MRSA. Vol. 32, Wellcome Witnesses to Twentieth-century Medicine (London: Wellcome Trust Centre for the History of Medicine at UCL 2008).
8. On antibiotics in general see Robert Bud, Penicillin: Triumph and Tragedy (Oxford: Oxford University Press 2007).
9. An introduction to the history of antibiotics use in clinical medicine is offered by Scott H. Podolsky, 'Antibiotics and the Social History of the Controlled Clinical Trial', Journal for the History of Medicine and Allied Sciences 2010, 65, 327-67.
10. On the history of standardisation in biology and medicine Christian Bonah, Christophe Masutti, Anne Rasmussen and Jonathan Simon (eds), Harmonizing Drugs: Standards in 20th-Century Pharmaceutical History (Paris: Editions Glyphe 2009).
11. Graham A. J. Ayliffe and Mary P. English, Hospital Infection From Miasmas to MRSA (Cambridge: Cambridge University Press 2003);
12. Flurin Condrau and Robert Kirk, 'Negotiating Hospital Infections: The Debate between Ecological Balance and Eradication Strategies in British Hospitals, 1947-1969', Dynamis, 2011, 31, 385-405.
13. Stuart B. Levy, The Antibiotic Paradox. How Miracle Drugs are Destroying the Miracle (New York; London: Plenum Press 1992), 80.
14. Antibiotic resistance as a clinical phenomenon entered the stage during the Second World War: John E. Lesch, The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine (Oxford: Oxford University Press 2007).
15. On MRSA see Maryn McKenna, Suberbug: The fatal menace of MRSA (New York: Free Press 2010).
16. On nineteenth-century medical bacteriology and common infectious disease Silvia Berger, Bakterien in Krieg und Frieden: eine Geschichte der medizinischen Bakteriologie in Deutschland 1890-1933 (Göttingen: Wallstein 2009).
17. Charles-Edward Emory Winslow, The Conquest of Epidemic Disease: A Chapter in the History of Ideas (Princeton, NJ: Princeton Universty Press 1987 (1967)).
18. Nicholas B. King, 'The Scale Politics of Emerging Diseases', Osiris 2004, 19, 62-76;
19. 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).
20. On the changing notions of infectious causality see Christoph Gradmann, 'Alles eine Frage der Methode. Zur Historizität der Kochschen Postulate 1840-2000', Medizinhistorisches Journal, 2008, 43, 121-48.
21. On evolutionary biology and infection studies see Piere-Olivier Méthot, 'Research traditions and evolutionary explanations in medicine', Theoretical Medicine and Bioethics, 2011, 32, 75-90, 84.
22. On multi drug resistant tuberculosis see David S. Barnes, 'Targeting Patient Zero', in Flurin Condrau and Michael Worboys (eds), Tuberculosis Then and Now: Perspectives on the History of an Infectious Disease (Montreal: McGill-Queens University Press 2010), 49-71.
23. Richard P. Wenzel, Stalking Microbes. A Relentless Pursuit of Infection Control (Bloomington/Indiana: Authorhouse 2005).
24. The author is a leading practitioner in the field of hospital infections and has published an instructive popular text on the issue.
25. Hans Schlossberger, 'Chemotherapie der Infektionskrankheiten', in Wilhelm Kolle, Rudolf Kraus and Paul Uhlenhuth (eds), Handbuch der pathogenen Mikroorganismen (Jena; Berlin; Wien: Gustav Fischer; Urban und Schwarzenberg 1930), 551-730.
26. Christoph Gradmann, 'Magic Bullets and Moving Targets: Antibiotic Resistance and Experimental Chemotherapy 1900-1940', Dynamis, 2011, 31, 305-21 on antibiotic resistance in experimental pharmacology. On bacterial genetics
27. Thomas D. Brock, The Emergence of Bacterial Genetics (Cold Spring Harbour: Cold Spring Harbour Laboratory Press 1990);
28. Angela N. H. Creager, 'Adaption or Selection? Old issues and new stakes in the postwar debates over bacterial drug resitance', Studies in History and Philosophy of Biological and Biomedical Sciences, 2007, 38, 159-90.
29. The earliest clinical reports seem to be linked to the mass application of sulpha drugs against STDs Lesch, The First Miracle Drugs.
30. Alexander Flemings famous observation of the inhibition of bacterial growth by penicillin mould in 1928 is often referred to as a susceptibility test.
31. Lesch, The First Miracle Drugs.
32. Expert Commitee on Antibiotics, Report of the First Session, World Health Organisation. Technical Report Series World Health Organisation, 26, Geneva, 1950.
33. The extensive literature on the history of the WHO may be accessed through Yves Beigbeder, The World Health Organization (The Hague: Nijhoff 1998);
34. Lee Kelley, Historical Dictionary of the World Health Organisation (Lanham, MD: Scarecrow Press 1998);
35. Amy L. Staples, The Birth of Development: How The World Bank, Food and Agriculture Organization, and World Health Organization changed the world, 1945-1965 (Kent, OH: Kent State University Press 2006).
36. WHO Archive, Geneva, Switzerland, T9/87/7.
37. Georg Henneberg, 'Antibiotische Stoffe', Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene, 1950, 155, 76-99, 83-4.
38. Henneberg's paper was an address delivered to the Vereinigung Deutscher Hygieniker und Mikrobiologen' in 1949. Cf. Tansey, Post Penicillin Antibiotics, 13-14. It should be noted that resistant tuberculosis develops in patients rather than being spread within populations.
39. George Gee Jackson and Maxwell Finland, 'Comparison of methods for determining sensitivity of bacteria to antibiotics in vitro', Archives of Internal Medicine, 1951, 88, 446-60, 447.
40. Bud, Penicilin, 116-19.
41. Perrin H. Long, 'Bacterial Resistance as a Factor in Antibiotic Therapy', Bulletin of the New York Academy of Medicine, 1952, 28, 809-16, 811.
42. Gunnar Näfström (Chief HLS) to Selman Waksman, 6 March 1957, WHO Archive, A10/136/3. With only one meeting so far it had not exactly been bustling with activity.
43. World Health Organization, The Second Ten Years of the World Health Organization 1958-1967 (Geneva: World Health Organization 1968), 47-50. Health Laboratory Methods was created as a branch of the Division for Therapeutic Substances.
44. See the organisational chart in Kelley, Historical Dictionary, appendix.
45. Ayliffe, Hospital Infection;
46. Condrau and Kirk, 'Negotiating Hospital Infections'.
47. Donald C. Grove and William A. Randall, Assay Methods of Antibiotics. A Laboratory Manual (New York: Medical Enzyclopedia, Inc. 1955).
48. Historically, sensitivity to a specific antibiotic needed to be determined before resistance was considered a relevant factor.
49. In that sense Alexander Flemings observation of 1928 that the presence of a Penicillium mould inhibits growth of Staphylococcus aureus could be called a susceptibility test
50. Laura J. V. Piddock, 'Techniques used for the Determination of Antimicrobial Resistance and Sensitivity in Bacteria', Journal of Applied Bacteriology, 1990, 68, 307-18, 307.
51. Kathryn Hillier, 'Babies and Bacteria: Phage Typing, Bacteriologists, and the Birth of Infection Control', Bulletin of the History of Medicine, 2006, 80, 733-61. For a contemporary overview on staphylococcal infections
52. Wilhelm Meyer, Die Staphylokokkenerkrankungen des Menschen (Leipzig: J.A.Barth 1962).
53. Henry F. Chambers and Frank R. Leo, 'Waves of Resistance: Staphylococcus aureus in the antibiotic era', Nature Reviews/Microbiology, 2009, 7, 629-41.
54. Hillier, 'Babies and Bacteria'.
55. On the history of phage typing see William C. Summers, Félix d'Herelle and the Origins of Molecular Biology (New Haven, CT; London: Yale University Press 1999).
56. WHO Archive, HLM 33, 'Functions of Hospital Laboratories-Research' by Dr Hans Ericsson, Stockholm, 7 October 1958.
57. Arnold Branch, D. H. Starkey and Edna E. Power, 'The International Situation with Regard to the Use of Discs for Antibiotic Sensitivity Tests', Antibiotics Annual, 1959, 1958-59, 833-5.
58. Ericsson, Functions of Hospital Laboratories.
59. Expert Committee on Health Laboratory Methods, Hospital Laboratory Services. Second Report of the Expert Committee on Health Laboratory Methods, World Health Organisation. Technical Report Series World Health Organisation, 161, Geneva, 1959, 28.
60. On the League of Nations Health Organisation and biological standardisation see Iris Borowy, Coming to Terms with World Health. The League of Nations Health Organisation 1921-1946 (Frankfurt am Main: Lang 2009), 154-9;
61. Pauline M. H. Mazumdar, 'The State, The Serum Institutes and the League of Nations', in Christoph Gradmann and Jonathan Simon (eds), Evaluating and Standardizing Therapeutic Agents 1890-1950 (Houndmills: Palgrave Macmillan, 2010), 118-38.
62. Expert Commitee on Antibiotics, Standardization of Methods for Conducting Microbic Sensititity Tests. Second Report of the Expert Comittee on Antibiotics, World Health Organisation. Technical Report Series World Health Organisation, 210, Geneva, 1961.
63. From the files at the WHO it becomes clear that Ericsson was the driving force. It was he who had most of the correspondence with Geneva throughout the ICS period. (A 10/370/3; A10/181/3.) Also it was Ericsson who had been working on hospital laboratories for WHO before.
64. This division of labour was confirmed in a conversation by the author with John Sherris in December 2011. On Sherris' career
65. Alexander J McAdam, 'John C. Sherris, M.D.', Journal of Clinical Microbiology, 2012, 50, 3416-17.
66. There are few accounts written by those who have be witnesses to that very history
67. Arthur L. Barry, 'Standardisation of Antimicrobial Susceptibility Testing', Clinics in Laboratory Medicine, 1989, 9, 203-19;
68. J. A. Poupard, S. F. Rittenhouse and L. R. Walsh, 'The evolution of antimicrobial susceptibility testing methods', Advances in Experimental Medicine and Biology, 1994, 349, 3-14;
69. Fred C. Tenover, 'Antimicrobial Susceptibility Testing Methods for Bacterial Pathogens', in Douglas L. Mayers (eds), Antimicrobial Drug Resistence. Clinical end Epidemiological Aspects (Totowa, NJ: Humana Press 2009), 1151-59;
70. Philip F. Wheat, 'History and Development of Antimicrobial Susceptibility Testing Methodology', Journal of Antimicrobial Chemotherapy, 2001, 48, 1-4. Piddock, Techniques provides some very interesting insight.
71. For a contemporary manual see Grove and Randall, Assay Methods.
72. Expert Commitee on Antibiotics, Standardization of Methods, 12 where that recommendation is made. Yet for virtues of its precision, the more laborious diffusion technique was recommended in surveys and research. Cf. Piddock, Techniques, 308.
73. D. C. Morley, 'A Simple Method of Testing the Sensitivity of Wound Bacteria to Penicillin and Sulphatiazole by the Use of Impregnated Blotted Paper Discs', The Journal of Pathology and Bacteriology, 1945, 57, 379-82 presented a method to do so in 1945.
74. In the paper, precursors from about 1943 are mentioned. According to Arthur L. Barry, 'Standardisation of Antimicrobial Susceptibility Testing', Clinics in Laboratory Medicine, 1989, 9, 203-19, 206 it was in 1945 that that instead of moist ones, dried discs came into use. These could be stored and transported.
75. See Branch, International Situation for a contemporary overview. 39J.
76. C. Gould and J.H. Bowie, 'The determination of bacterial sensitivity to antibiotics', Edinburgh Medical Journal, 1952, 59, 178-199 cited in Piddock, Technique, 307.
77. Robert V. Hoffman, George Gee Jackson and Mary P. Turner, 'Reliability of Antibiotic Sensitivity Tests as Determined by a Survey Study', Journal of Laboratory and Clinical Medicine, 1958, 51, 873-82, 879.
78. Branch, International Situation.
79. Expert Commitee on Antibiotics, Standardization of Methods, 4.
80. Grant supporting letters WHO Archive (A10/181/3).
81. From these letters it also becomes clear that it was Ericsson who was organising that work. At any rate it was his institute that received the funding.
82. Expert Commitee on Antibiotics, Standardization of Methods, 4.
83. Hans M. Ericsson and John C. Sherris, Antibiotic Sensitivity Testing. Report of an International Collaborative Study (Copenhagen: Munksgaard 1971).
84. Judging from conversations I had with elder practitioners it is indeed quite legendary amongst them.
85. See John C. Sherris, The Epidemiology of Drug Resistance In American Hospital Association (ed.) Intertational Congress on Nosocomial Infections, (Chicago: American Hospital Association 1971), 50-60.
86. Also WHO archive A10/370/3, consultant report of 23 June 71, where it is stated as a plain fact that there are 'various susceptibility testing procedures that would be controlled by manufacturers and national authorities'.
87. Ericsson and Sherris, Antibiotic Sensitivity Testing, 9-10, where a list of the conferences can be found.
88. The network was entirely comprised of elite institutions, after all. Cf. the list of collaborating institutions on the closing pages of Ericsson and Sherris, Antibiotic Sensitivity Testing.
89. A. W. Bauer, W. M. M. Kirby, J. C. Sherris and M. Turck, 'Antibiotic Susceptibility Testing by a Standardised Single Disc Method', The American Journal of Clinical Pathology, 1965, 45, 493-96.
90. Ericsson and Sherris, Antibiotic Sensitivity Testing, 64-5.
91. From a group of 70 clinical laboratories, surveyed in Branch International Situation in 1958, 47 thought that reading the degree resistance of a strain from the size of the inhibition zone was impossible.
92. Barry, Standardisation, 206.
93. Memorandum Sherris to Ericsson, 8 November 1965, a copy of which was given to the author by John Sherris.
94. Ericsson and Sherris, Antibiotic Sensitivity Testing, 80.
95. Beigbeder, World Health Organization; Kelley, Historical Dictionary.
96. On WHO and Biological Standardisation in the 1960s
97. WHO, The Second Ten Years, 237-43. On the Committee for Biological Standardisation see A. S. Outschoorn, 'The Biological Standardization Programme of the World Health Organization', Journal of Biological Standardization, 1973, 1, 203-13;
98. P. Sizaret, 'Evolution of Activities in International Biological Standardisation since the Early Days of the Health Organisation of the League of Nations', Bulletin of the World Health Organization, 1988, 66, 1-6.
99. Anne Kveim H. Lie, 'Producing Standards, Producing the Nordic Region. Antibiotic susceptibility testing from 1950-1970', Science in Context, in print.
100. On this andthe following Cf.AnnaYusof, 'Some important contributions tomedical microbiology made by companies financially supporting the publication of this special issue of APMIS', Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 2007, 115, 680-5;
101. ToreMidtvedt, 'Norsk helsevesen sett fra Stockholm', Tidsskrift for Den norske legeforening, 2000, 120, 2047-9;
102. Göran Kronvall, 'Commentary', Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 2007, 115, 619-20
103. Siri Jensen, Anne Kveim Lie, Knut Eirik Eiassen, Morten Lindbæk and Christoph Gradmann, 'Erindringer om resistens-et aktørseminar om antibiotikaresistensens historie i Norge', Michael. Publication Series of the Norwegian Medical Society, 2012, 9, 5-79.
104. Liebermeister (München) to DGHM, Ausschuss zur Vereinheitlichung der Technik der Resistenzbestimmungen der Deutschen Gesellschaft für Hygiene und Mikrobiologie, Hannover, Germany, 17 September 1963.
105. Liebermeister was the comitee's secretary. Translated by the author.
106. Ericsson an Bartmann, 30 May 1972, Archives of the Bayer Company, Leverkusen, Germany (hereafter Bayer Archive), 372/66. The text is in clumsy German, which it has been attempted to mimic in the translation.
107. World Health Organization, The Third Ten Years of the World Health Organization: 1968-1977 (Genva: World Health Organization 1978), 249.
108. Outschoorn, Biological Standardization;
109. Sizaret, Evolution.
110. On the history of biological standardisation in League of Nations Health Organisation, see Mazumdar, State.
111. Sizaret, Evolution.
112. It is mentioned in Ericsson's letter to Candau, 4 May 1970 (A10/136/2) where he refuses to further commit himself to membership in the WHO's antibiotics committee before the ICS report had been scrutinized. It also mentioned in a draft letter by Outschoorn (undated, but certainly written soon after the meeting), A 10/370/30.
113. A consultant's report delivered in 23 June 1971 quotes from it. This later report challenged Ericsson's proposals of compulsory standards and instead proposed to have standards handled by local authorities.
114. On Balows: Gary V. Doern, 'Membership-Albert Balows Obituary', Microbe. The News Magazine of the American Society for Microbiology, 2007, 2, 42-3.
115. Balows to Outschoorn, 16 March 1972, WHO archive, A10/370/3.
116. Balows, Consultant report of 15 March 1972 'In Vitro Antimicrobial Sensitivity Testing', p. 2, WHO archive A10/370/3.
117. Ballows, Status Report on In Vitro Antibiotic Sensitivity (Susceptibility) Testing, 1 March 1974, WHO Archive, A10/370/3.
118. On Garrod and Waterworth see Tansey, Post Penicillin Antibiotcs, 22.
119. Garrod to Outschhoorn, 3 December 1970, WHO Archives, A10/370/3.
120. Garrod's consultants report to WHO of 3 March 1972, WHO Archiv A10/370/3.
121. Minutes of the meeting of 'Ausschuss ...' DGHM Archive.
122. Commission for Food and Drugs, quoted in US Supreme Court decision of 28 April 1969 (1969 Lexis 3274 at 〈www.lexisnexis.com〉).
123. Barry, Standardization, 208.
124. Barry, Standardization, 211. Cf Tenover, Susceptibility Testing, 1152. These standards have been reviewed and expanded ever since (Barry, Standardization, 214).
125. Balows to Outschoorn, 26 January 1972, WHO archive, A10/370/3.
126. Barry, Standardization, 211 for a description of the composition of NCCLS that seems to include professions, government agencies and industry.
127. Chief, BS to Torloni, Schering corporation, 30 March 1972, WHO Archiv, A10/370/10.
128. Anon, 'Antibiotic Sensitivity Testing', British Medical Journal, 1971, 5759, 416.
129. It should be noted that the anonymous author was also quite critical of Ericsson's and Sherris' work in the sense that they had failed to propose the simple method that had also been part of their original mandate.
130. Finland to Bartmann, 13 May 1971, Bayer Archive 372/66. On Finland's work on antibiotics see Podolsky, 'Antbiotics'.
131. The plan is frequently mentioned in letters and consultant reports from about June 1971.
132. BS tried to convince various laboratories to host such a library. Contacts were most promising and intensive with the Institute Pasteur (Y. A. Chabbert), which, however, ultimately refused to embark on the mission in November 1971 (A10/370/3).
133. From the available information it seems that the project was not completed.
134. WHO Archive, A10/370/3.
135. As late as 13 November 1969, WHO confirmed in a letter to Ericsson that the report of the ICS was 'likely to be a candidate for publication in the Bulletin [of the WHO]'. Memorandum Chief TP, WHO archive, A10/183/3a.
136. Ericsson and Sherris, Antibiotic Sensitivity Testing, 82-7. Given that both Ericsson and Sherris had received grants from Geneva for 10 years, this was not an entirely accurate description of the WHO's role.
137. In 1965 Ericsson had gladly accepted another period of five years (Ericsson to Candau 30 August 1965, WHO archive, A10/136/3).
138. In 1970 he refused to accept another nomination as long as his work was scrutinised (Ericsson to Candau 4 May 1970).
139. Ericsson to Bernhard, 12 August 1970, WHO Archives A10/136/3.
140. Piddock, Techniques.
141. On further developments and in passing on the introduction of PCR technology from the 1990s
142. Harold Richardson, 'Blurring the boundaries', Chemistry & Industry, 1999, 627-30;
143. Fred C. Tenover, 'Bauer and Kirby meet Watson and Crick, Antimicrobial Susceptibility Testing in the Molecular Area', ASM News, 1992, 58, 669-72.
144. Podolsky, Antibiotics.
145. David Demortian, 'From drug crises to regulatory change: The mediation of expertise', Health, Risk and Society, 2008, 10, 37-51;
146. David Vogel, 'The Gobalization of Pharmaceutical Regulation', Governance, 1998, 11, 1-22.
147. Cf. On the history of drug regulation Jean-Paul Gaudillière and Volker Hess (eds), Ways of Regulating Drugs in the 19th and 20th Centuries, (Houndmills: Palgrave 2012).
148. Bud, Penicillin, 192-212.
149. Thomas F. O'Brien and Ralph S. Kent, 'Computer-Generated Plots of Results of Antimicrobial-Susceptibility Tests', Journal of the American Medical Association, 1969, 210, 84-92.
150. I thank Thomas O'Brien (Boston) for this autobiographical detail (personal communication).
151. See also 〈www.who.int/drugresistance/whonetsoftware/en/index. html〉.
152. Cf. Bud, Penicillin, 278).
153. Lie, Producing Standards;
154. Kronvall, Commentary.
155. Ericsson to Bartmann, 30 May 1972, Bayer Archive, 372/66. Translated by the author.
156. Yusof, Contributions.
157. Memoradum, Chief BST, 21 October 1975, WHO archive, A10/136/3.