Accepted Article
Received Date: 03-Jan-2014 Accepted Date: 13-Jan-2014 Article Type: Invited Editorial
Microbe discovery: lessons from the past
Drancourt M1*
1
Aix Marseille Université, URMITE, UMR63, CNRS 7278, IRD 198, Inserm 1095, 13005
Marseille, France.
*
Corresponding author: Michel Drancourt, Unité de Recherche sur les Maladies Infectieuses
et Tropicales Emergentes, Faculté de Médecine, 27, Boulevard Jean Moulin, Marseille cedex 5- France. Tel: 33 4 91 32 43 75. Fax: 33 4 91 38 77 72. Email: [email protected]
Just a little more than 2,000 bacterial species have been cultured at least once from clinical specimens, and more species undoubtfully remain to be cultured. The same denombrement remains to be done for viruses and microeukaryotes in human microbiota [1]. Culturing a microbe remains the graal in microbiology, as the cultured microbe is an unsurpassed starting point of knowledge, opening the doors to fully understand and eventually manipulate the microbe, including prevention of colonization and disease through vaccination and treatment. Accordingly, pathogens have been among the very first microbes to be cultured and in this This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/1469-0691.12533 This article is protected by copyright. All rights reserved.
Accepted Article
thematic issue of Clinical Microbiology and Infections, we are telling the story of the discovery of four such big killers, illustrating the sometimes tortuous way of microbial discovery. C. Thèves and collaborators report on the discovery of smallpox [2] whereas E. Cambau [3], D. Lippi [4] and T. Butler [5] report on the discovery of Mycobacterium tuberculosis, Vibrio cholerae and Yersinia pestis, respectively.
The four stories tell us lessons on which to base our research in clinical microbiology. In any case, the initial discovery of the pathogen did arrive from nowhere, but in fact grew upon a previous corpus of knowledge mixing popular, empirical and scientific knowledge. In particular, these four quite different infectious diseases had been recognized for centuries as specific entities by populations and doctors, through any specific array of epidemiology and clinics, such as epidemic, deadly lymph node (buboe) in the case of plague [5]. Paleomicrobiology, a retrospective history of microbes and the diseases they caused [6], now allows to appreciate this aspect as smallpox virus [7], M. tuberculosis [8] as well as Y. pestis [9] have been detected in ancient suitable specimens, being respectively the skin, bones and the dental pulp. V. cholerae has not been yet detected in ancient specimens, because the suitable material (probably intestinal content in mummy or frozen corpses of cholera victims) is rare and none had the opportunity to test it.
Discovering a new pathogen often relied on the development and use of a new technology. Microscopy, more precisely microscopy improvement, contributed to the discovery of M. tuberculosis by Robert Koch in 1882 as he invented a new staining method [3]; and the use of new electron microscopy was decisive in the case of smallpox [2]. Interestingly, in 1854, both John Snow in London and Filippo Paccini in Florence also used optic microscopy as part as their investigation of cholera epidemics, but failed to go further in culturing V. cholerae, finally isolated by R. Koch thirty years later [4]. Indeed, the implementation of solid culture medium instead of broth, previously developed in Louis Pasteur's laboratory was a decisive step for initial isolation of M. tuberculosis and V. cholerae by R. Koch [3,4]. As for plague also, use of an ambiant temperature instead of 37°C This article is protected by copyright. All rights reserved.
Accepted Article
contributed to success by Alexandre Yersin in 1894, in addition to culturing diseased lymph node instead of blood [5]. Eventhough two major pathogens, i.e. Treponema pallidum and Mycobacterium leprae, remain to be cultured in axenic medium as they have been propagated only in animals. Nowadays, the discovery of microbes has moved towards organisms in complex microbiota, including by-passing organisms, resident organisms and opportunistic pathogens. Bacterial culturomics, using diversification of culture media and culture conditions (atmosphere, temperature of incubation), now yields hundreds of colonies per culture plate, to be identified [10]. This rebirth of culture is then made possible by a new technology for rapid identification of such huge amount of colonies, by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry [11]. Therefore, more and more organisms do share their discovery in common, being cultured in the same laboratory from the very same specimen, instead of the singular history of their predecessors.
Also, the four histories reported in this thematic issue, teach us not to fall into some pitfalls of scientific communication in microbiology, the last and not least step of microbe discovery. The dispute over who was the very first inventor of Y. pestis, after the controversial 1894's paper by Shibasaburo Kitasato in the Lancet, is well known [5,12]. Rush in publication before getting pure culture of the new microbe, mixing his own data with those of another doctor led S. Kitasato to publish inaccurate data, and finally ternished the glory of the discover of Clostridium tetani. Influence of Kitasato's reputation over neutral review of the data by the Lancet, also had a negative role in this history [13]. Ignoring and underreporting previously published data is another pitfall when dealing with microbe discovery. Even Nobel-prized R. Koch failed to mention contributive previous works by Jean Antoine Villemin [14], who in 1865 established the transmissibility of tuberculosis, in his very first paper on M. tuberculosis [15]; R. Koch finally acknowledged this contribution in his second paper, published two years later in 1884 [16]. Likewise, R. Koch clearly missed previous work by F. Paccini, regarding the discovery of V. cholerae [4].
This article is protected by copyright. All rights reserved.
Accepted Article
In conclusion, the four microbe discovery stories here reported, are a source of lessons for microbiologists fishing for new microbes. Using new laboratory tools, not mentioning new conceptual ones, is a source of discovery. Fair report of unique discovery, using modern standards of species definition and modern tools to communicate, is a source of perenity.
References
1. Lagier JC, Armougom F, Million M, Hugon P, Pagnier I, Robert C, Bittar F, Fournous G, Gimenez G, Maraninchi M, Trape JF, Koonin EV, La Scola B, Raoult D.Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect. 2012;18:1185-93. 2. Thèves C, Biagini P, Crubézy E. The re-discovery of smallpox. Clin Microbiol Infect 2014 (in press). 3. Cambau E, Drancourt M. Steps towards the discovery of m. tuberculosis by R. Koch, 1882. Clin Microbiol Infect 2014 (in press). 4. Lippi D. The greatest steps towards the discovery of Vibrio cholerae. Clin Microbiol Infect 2014 (in press). 5. Butler T. Plague history: discoveries of the causative bacterium, transmission by rodent flea bites, effective antimicrobial therapies, fluctuations in incidence, diagnostic tests, vaccines, virulence plasmids, and cause of ancient epidemics. Clin Microbiol Infect 2014 (in-press). 6. Drancourt M, Raoult D. Palaeomicrobiology: current issues and perspectives. Nat Rev Microbiol. 2005;3:23-35. 7. Biagini P, Thèves C, Balaresque P, Géraut A, Cannet C, Keyser C, Nikolaeva D, Gérard P, Duchesne S, Orlando L, Willerslev E, Alekseev AN, de Micco P, Ludes B, Crubézy E. Variola virus in a 300-year-old Siberian mummy. N Engl J Med. This article is protected by copyright. All rights reserved.
Accepted Article
2012;367:2057-9. 8. Donoghue HD. Insights into ancient leprosy and tuberculosis using metagenomics. Trends Microbiol. 2013; 21:448-50. 9. Raoult D, Mouffok N, Bitam I, Piarroux R, Drancourt M. Plague: history and contemporary analysis. J Infect. 2013;66:18-26. 10. Lagier JC, Million M, Hugon P, Armougom F, Raoult D. Human gut microbiota: repertoire and variations. Front Cell Infect Microbiol. 2012;2:136. 11. Seng P, Rolain JM, Fournier PE, La Scola B, Drancourt M, Raoult D. MALDI-TOFmass spectrometry applications in clinical microbiology. Future Microbiol. 2010;5:1733-54. 12. Solomon T. Hong Kong, 1894: the role of James A Lowson in the controversial discovery of the plague bacillus. Lancet. 1997;350:59-62. 13. Kitasato S. The bacillus of bubonic plague. Lancet 1894; ii: 428–30. 14. Villemin, JA. Études sur la tuberculose : preuves rationnelles et expérimentales de sa spécificité et de son inoculabilité. Paris : J.-B. Baillière, 1868. 15. Koch R. Die Äetiologie der Tuberkulose. Berliner klinische Wochenschrift 1882; 15: 221-30. 16. Koch R. Die aetiologie der tuberculose. Mittheilungen aus dem Kaiserlichen Gesundheitsamt 1884; 2; 1-88.
This article is protected by copyright. All rights reserved.
Received Date: 03-Jan-2014 Accepted Date: 13-Jan-2014 Article Type: Invited Editorial
Microbe discovery: lessons from the past
Drancourt M1*
1
Aix Marseille Université, URMITE, UMR63, CNRS 7278, IRD 198, Inserm 1095, 13005
Marseille, France.
*
Corresponding author: Michel Drancourt, Unité de Recherche sur les Maladies Infectieuses
et Tropicales Emergentes, Faculté de Médecine, 27, Boulevard Jean Moulin, Marseille cedex 5- France. Tel: 33 4 91 32 43 75. Fax: 33 4 91 38 77 72. Email: [email protected]
Just a little more than 2,000 bacterial species have been cultured at least once from clinical specimens, and more species undoubtfully remain to be cultured. The same denombrement remains to be done for viruses and microeukaryotes in human microbiota [1]. Culturing a microbe remains the graal in microbiology, as the cultured microbe is an unsurpassed starting point of knowledge, opening the doors to fully understand and eventually manipulate the microbe, including prevention of colonization and disease through vaccination and treatment. Accordingly, pathogens have been among the very first microbes to be cultured and in this This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/1469-0691.12533 This article is protected by copyright. All rights reserved.
Accepted Article
thematic issue of Clinical Microbiology and Infections, we are telling the story of the discovery of four such big killers, illustrating the sometimes tortuous way of microbial discovery. C. Thèves and collaborators report on the discovery of smallpox [2] whereas E. Cambau [3], D. Lippi [4] and T. Butler [5] report on the discovery of Mycobacterium tuberculosis, Vibrio cholerae and Yersinia pestis, respectively.
The four stories tell us lessons on which to base our research in clinical microbiology. In any case, the initial discovery of the pathogen did arrive from nowhere, but in fact grew upon a previous corpus of knowledge mixing popular, empirical and scientific knowledge. In particular, these four quite different infectious diseases had been recognized for centuries as specific entities by populations and doctors, through any specific array of epidemiology and clinics, such as epidemic, deadly lymph node (buboe) in the case of plague [5]. Paleomicrobiology, a retrospective history of microbes and the diseases they caused [6], now allows to appreciate this aspect as smallpox virus [7], M. tuberculosis [8] as well as Y. pestis [9] have been detected in ancient suitable specimens, being respectively the skin, bones and the dental pulp. V. cholerae has not been yet detected in ancient specimens, because the suitable material (probably intestinal content in mummy or frozen corpses of cholera victims) is rare and none had the opportunity to test it.
Discovering a new pathogen often relied on the development and use of a new technology. Microscopy, more precisely microscopy improvement, contributed to the discovery of M. tuberculosis by Robert Koch in 1882 as he invented a new staining method [3]; and the use of new electron microscopy was decisive in the case of smallpox [2]. Interestingly, in 1854, both John Snow in London and Filippo Paccini in Florence also used optic microscopy as part as their investigation of cholera epidemics, but failed to go further in culturing V. cholerae, finally isolated by R. Koch thirty years later [4]. Indeed, the implementation of solid culture medium instead of broth, previously developed in Louis Pasteur's laboratory was a decisive step for initial isolation of M. tuberculosis and V. cholerae by R. Koch [3,4]. As for plague also, use of an ambiant temperature instead of 37°C This article is protected by copyright. All rights reserved.
Accepted Article
contributed to success by Alexandre Yersin in 1894, in addition to culturing diseased lymph node instead of blood [5]. Eventhough two major pathogens, i.e. Treponema pallidum and Mycobacterium leprae, remain to be cultured in axenic medium as they have been propagated only in animals. Nowadays, the discovery of microbes has moved towards organisms in complex microbiota, including by-passing organisms, resident organisms and opportunistic pathogens. Bacterial culturomics, using diversification of culture media and culture conditions (atmosphere, temperature of incubation), now yields hundreds of colonies per culture plate, to be identified [10]. This rebirth of culture is then made possible by a new technology for rapid identification of such huge amount of colonies, by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry [11]. Therefore, more and more organisms do share their discovery in common, being cultured in the same laboratory from the very same specimen, instead of the singular history of their predecessors.
Also, the four histories reported in this thematic issue, teach us not to fall into some pitfalls of scientific communication in microbiology, the last and not least step of microbe discovery. The dispute over who was the very first inventor of Y. pestis, after the controversial 1894's paper by Shibasaburo Kitasato in the Lancet, is well known [5,12]. Rush in publication before getting pure culture of the new microbe, mixing his own data with those of another doctor led S. Kitasato to publish inaccurate data, and finally ternished the glory of the discover of Clostridium tetani. Influence of Kitasato's reputation over neutral review of the data by the Lancet, also had a negative role in this history [13]. Ignoring and underreporting previously published data is another pitfall when dealing with microbe discovery. Even Nobel-prized R. Koch failed to mention contributive previous works by Jean Antoine Villemin [14], who in 1865 established the transmissibility of tuberculosis, in his very first paper on M. tuberculosis [15]; R. Koch finally acknowledged this contribution in his second paper, published two years later in 1884 [16]. Likewise, R. Koch clearly missed previous work by F. Paccini, regarding the discovery of V. cholerae [4].
This article is protected by copyright. All rights reserved.
Accepted Article
In conclusion, the four microbe discovery stories here reported, are a source of lessons for microbiologists fishing for new microbes. Using new laboratory tools, not mentioning new conceptual ones, is a source of discovery. Fair report of unique discovery, using modern standards of species definition and modern tools to communicate, is a source of perenity.
References
1. Lagier JC, Armougom F, Million M, Hugon P, Pagnier I, Robert C, Bittar F, Fournous G, Gimenez G, Maraninchi M, Trape JF, Koonin EV, La Scola B, Raoult D.Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect. 2012;18:1185-93. 2. Thèves C, Biagini P, Crubézy E. The re-discovery of smallpox. Clin Microbiol Infect 2014 (in press). 3. Cambau E, Drancourt M. Steps towards the discovery of m. tuberculosis by R. Koch, 1882. Clin Microbiol Infect 2014 (in press). 4. Lippi D. The greatest steps towards the discovery of Vibrio cholerae. Clin Microbiol Infect 2014 (in press). 5. Butler T. Plague history: discoveries of the causative bacterium, transmission by rodent flea bites, effective antimicrobial therapies, fluctuations in incidence, diagnostic tests, vaccines, virulence plasmids, and cause of ancient epidemics. Clin Microbiol Infect 2014 (in-press). 6. Drancourt M, Raoult D. Palaeomicrobiology: current issues and perspectives. Nat Rev Microbiol. 2005;3:23-35. 7. Biagini P, Thèves C, Balaresque P, Géraut A, Cannet C, Keyser C, Nikolaeva D, Gérard P, Duchesne S, Orlando L, Willerslev E, Alekseev AN, de Micco P, Ludes B, Crubézy E. Variola virus in a 300-year-old Siberian mummy. N Engl J Med. This article is protected by copyright. All rights reserved.
Accepted Article
2012;367:2057-9. 8. Donoghue HD. Insights into ancient leprosy and tuberculosis using metagenomics. Trends Microbiol. 2013; 21:448-50. 9. Raoult D, Mouffok N, Bitam I, Piarroux R, Drancourt M. Plague: history and contemporary analysis. J Infect. 2013;66:18-26. 10. Lagier JC, Million M, Hugon P, Armougom F, Raoult D. Human gut microbiota: repertoire and variations. Front Cell Infect Microbiol. 2012;2:136. 11. Seng P, Rolain JM, Fournier PE, La Scola B, Drancourt M, Raoult D. MALDI-TOFmass spectrometry applications in clinical microbiology. Future Microbiol. 2010;5:1733-54. 12. Solomon T. Hong Kong, 1894: the role of James A Lowson in the controversial discovery of the plague bacillus. Lancet. 1997;350:59-62. 13. Kitasato S. The bacillus of bubonic plague. Lancet 1894; ii: 428–30. 14. Villemin, JA. Études sur la tuberculose : preuves rationnelles et expérimentales de sa spécificité et de son inoculabilité. Paris : J.-B. Baillière, 1868. 15. Koch R. Die Äetiologie der Tuberkulose. Berliner klinische Wochenschrift 1882; 15: 221-30. 16. Koch R. Die aetiologie der tuberculose. Mittheilungen aus dem Kaiserlichen Gesundheitsamt 1884; 2; 1-88.
This article is protected by copyright. All rights reserved.
