Clinical Infectious Diseases Advance Access published September 22, 2014
0 SEPTEMBER
Correspondence On Arsenic and Plague
arsenic in his treatise [11], and testifies of arsenic use in the early colonized United States. The Italian physician Bartolomeo Alizeri, in a publication of 1721 [12], warns against the use of arsenical compounds to cure human plague. An interesting observation of Alizeri underlines the efficacy of arsenic in temporarily attenuating some clinical manifestations of the disease, remarking on the subsequent insurgence of more severe symptoms in arsenic-exposed patients [12]. We are tempted to speculate that Alizeri anticipates the existence of Y. pestis strains resistant to arsenic in Europe in the 18th century. These early scientific writings testify to the use of arsenic in Western countries for centuries and in the United States for almost 150 years. Actually, arsenical and antimonial compounds, as part of the Pharmacopoeia and Materia Medica (Medical Materials), including plants, minerals, and animal derivatives, were in use in Europe upon the influence of the Middle Ages physicians Avicenna (Ibn Sina, 980–1037) and Averroes (Ibn Rushd, 1126–1198) and of Paracelsus (Theophrastus Phillipus Aureolus Bombastus von Hohenheim [1493–1541], German-Swiss physician and scholar) teachings in Renaissance medical schools. In the “Book of the Plague” ( published posthumously in 1576), Paracelsus suggested amulets containing arsenic or quicksilver (xenexicon), based on his experience to prevent and cure the plague that was raging in Switzerland in 1534. Paracelsus’s treatises on medicine were written in accessible vernacular German, in opposition to the official Latin Galenic texts. The medical approach of Paracelsus spread and persisted for centuries (the first edition of the Latin translation of Paracelsus’s
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CID
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Downloaded from http://cid.oxfordjournals.org/ at National Univ of Singapore on October 15, 2014
TO THE EDITOR—There is evidence that plague is not an ancient fear of the past centuries [1]. Different strains of Yersinia pestis actually give rise to sporadic outbreaks of zoonotic origin worldwide, with high incidence in African countries. Due to the attribution of reservoir to wild as well as domestic animals, including pigs and dogs [2], and the risk of person-to-person transmissibility [3], the acquisition of multidrug resistance in Y. pestis is a potentially serious threat to human health [4]. Several articles, and a more recent study [5], identified a selftransmissible genetic element conferring arsenic resistance in the Java 9 strain of Y. pestis mobilome, the transposon Tn2503. The acquisition of arsenic resistance in Yersinia enterocolitica through the homologous transposon Tn2502 was previously described in 1997 by Neyt and coworkers [6]. Of importance, arsenic resistance has been linked to multidrug-resistant phenotypes [7]. Eppinger et al [5] cite Neyt et al [6] as the only support to the hypothetical origin of arsenic resistance in Yersinia species, advancing that arsenic resistance might have been raised upon the traditional use of formulations containing arsenic derivatives to cure farm animals, in particular swine dysentery. However, Neyt et al were “unable to produce written documentation of this practice” [6]. Therefore, no reference relative to arsenic-based veterinary drugs was actually available in these publications. We wish to advise historical scientific literature documenting the use of arsenical compounds in veterinary (and human) medicine that adds to the suggestions on the origin of arsenic resistance previously proposed. In 1935,
E. Roberts and W. M. Dawson of the University of Illinois [8] tested experimentally the detrimental effects of arsenical Fowler solution. (The English physician Thomas Fowler invented the solution containing 1% potassium arsenite in 1786; it was prescribed to cure periodic fever and syphilis, and later as a tonic. Also called Kali arsenicosum, Kali arseniatum, Liquor potassii arseniti, or Liquor potassae arsenitis, it was in use until the late 1950s. Of note, considering the role of rodents as immune reservoirs of Y. pestis, the actual wide use of potassium arsenite as a pesticide and rodenticide raises concern.) The preparation reported in their article, containing 1% arsenic trioxide, was popular as a farm-animal feeding to accelerate fat accumulation and to obtain lucent hair [8]. From their critical point of view, Roberts and Dawson observed an increased susceptibility to infections in experimental rabbits fed Fowler solution, in line with the empirical experience of farmers. Thirty years earlier, in 1904, Quitman of the Veterinary College of the Chicago University [9] enumerated diverse arsenical preparations, including Fowler solution, to treat farm animals. Before him, in 1857, Redwood, in his pharmacopoeia [10] ( p. 804), reports 2 Fowler solution formulas (solution of arsenite of potash, Liquor arsenicalis): one from the 1851 London Pharmacopoeia and the 1841 Edinburgh Pharmacopoeia, and another from the 1841 Dublin Pharmacopoeia. The medical use for which they were usually prescribed to humans included intermittents, or ague, the archaic terms for periodic or malarial fever. Interestingly, several years before, in 1796, Potter of the first American medical school at the University of Pennsylvania envisaged the deleterious effects of
Note Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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CID
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CORRESPONDENCE
Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Francesca Tosetti Molecular Oncology and Angiogenesis Unit, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
References 1. Butler T. Plague into the 21st century. Clin Infect Dis 2009; 49:736–42. 2. Wang H, Cui Y, Wang Z, et al. A dogassociated primary pneumonic plague in Qinghai province, China. Clin Infect Dis 2011; 52:185–90. 3. Kool JL. Risk of person-to-person transmission of pneumonic plague. Clin Infect Dis 2005; 40:1166–72. 4. Welch TJ, Fricke WF, McDermott PF, et al. Multiple antimicrobial resistance in plague: an emerging public health risk. PLoS One 2007; 2:e309. 5. Eppinger M, Radnedge L, Andersen G, et al. Novel plasmids and resistance phenotypes in Yersinia pestis: unique plasmid inventory of strain Java 9 mediates high levels of arsenic resistance. PLoS One 2012; 7:e32911. 6. Neyt C, Iriarte M, Thi VH, Cornelis GR. Virulence and arsenic resistance in Yersiniae. J Bacteriol 1997; 179:612–9. 7. Mallik S, Virdi JS, Johri AK. Proteomic analysis of arsenite-mediated multiple antibiotic resistance in Yersinia enterocolitica biovar 1A. J Basic Microbiol 2012; 52:306–13.
8. Roberts E, Dawson WM. Effect of Fowler’s solution on animals. Agricultural Experiment Station, Bulletin 413. University of Illinois, 1935. 9. Quitman EL. Synopsis of veterinary materia medica, therapeutics and toxicology. 2nd ed. Revised and enlarged. Chicago: Alexander Eger Publisher, 1904. 10. Redwood T. A supplement to the pharmacopoeia: being a concise but comprehensive dispensatory and manual of facts and formulae. London: Longman and Co; Simpkin and Co; John Churchill; Henry Bohn and Henry Renshaw, 1857. 11. Potter N. An essay on the medicinal properties and deleterious qualities of arsenic. Philadelphia: William W. Woodward, 1796. 12. Alizeri B. Della peste cioè della sua natura e de’ rimedi per la preservazione, e per la cura della medesima. Genova, Italy: Stamperia del Franchelli, 1721.
Correspondence: Francesca Tosetti, PhD, IRCCS AOU S. Martino-IST, Largo Rosanna Benzi 10, 16132 Genova, Italy ([email protected]). Clinical Infectious Diseases © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/cid/ciu704
Downloaded from http://cid.oxfordjournals.org/ at National Univ of Singapore on October 15, 2014
collected writings appeared in 1658 in England, under the auspices of the newborn Royal Society), was diffused in the United States after colonization, and was still in use until the middle 19th century. In Eastern countries, traditional Chinese medicine prescribes ointments for topical use or beverages containing arsenic sulfide (realgar) to treat human and animal diseases, including swine hyperpyrexia syndrome. The discontinuous exposure to low, nontoxic doses of arsenical preparations present in almost all coded pharmacopoeias in Western and Eastern countries might have favored the development and exchange of plasmids carrying arsenic resistance in host microorganisms. It cannot be excluded that farm animals arriving from England and Germany during the colonization of America could have already been exposed to low-dose arsenic and become carriers of arsenicresistant bacteria in their gut.
0 SEPTEMBER
Correspondence On Arsenic and Plague
arsenic in his treatise [11], and testifies of arsenic use in the early colonized United States. The Italian physician Bartolomeo Alizeri, in a publication of 1721 [12], warns against the use of arsenical compounds to cure human plague. An interesting observation of Alizeri underlines the efficacy of arsenic in temporarily attenuating some clinical manifestations of the disease, remarking on the subsequent insurgence of more severe symptoms in arsenic-exposed patients [12]. We are tempted to speculate that Alizeri anticipates the existence of Y. pestis strains resistant to arsenic in Europe in the 18th century. These early scientific writings testify to the use of arsenic in Western countries for centuries and in the United States for almost 150 years. Actually, arsenical and antimonial compounds, as part of the Pharmacopoeia and Materia Medica (Medical Materials), including plants, minerals, and animal derivatives, were in use in Europe upon the influence of the Middle Ages physicians Avicenna (Ibn Sina, 980–1037) and Averroes (Ibn Rushd, 1126–1198) and of Paracelsus (Theophrastus Phillipus Aureolus Bombastus von Hohenheim [1493–1541], German-Swiss physician and scholar) teachings in Renaissance medical schools. In the “Book of the Plague” ( published posthumously in 1576), Paracelsus suggested amulets containing arsenic or quicksilver (xenexicon), based on his experience to prevent and cure the plague that was raging in Switzerland in 1534. Paracelsus’s treatises on medicine were written in accessible vernacular German, in opposition to the official Latin Galenic texts. The medical approach of Paracelsus spread and persisted for centuries (the first edition of the Latin translation of Paracelsus’s
CORRESPONDENCE
•
CID
•
1
Downloaded from http://cid.oxfordjournals.org/ at National Univ of Singapore on October 15, 2014
TO THE EDITOR—There is evidence that plague is not an ancient fear of the past centuries [1]. Different strains of Yersinia pestis actually give rise to sporadic outbreaks of zoonotic origin worldwide, with high incidence in African countries. Due to the attribution of reservoir to wild as well as domestic animals, including pigs and dogs [2], and the risk of person-to-person transmissibility [3], the acquisition of multidrug resistance in Y. pestis is a potentially serious threat to human health [4]. Several articles, and a more recent study [5], identified a selftransmissible genetic element conferring arsenic resistance in the Java 9 strain of Y. pestis mobilome, the transposon Tn2503. The acquisition of arsenic resistance in Yersinia enterocolitica through the homologous transposon Tn2502 was previously described in 1997 by Neyt and coworkers [6]. Of importance, arsenic resistance has been linked to multidrug-resistant phenotypes [7]. Eppinger et al [5] cite Neyt et al [6] as the only support to the hypothetical origin of arsenic resistance in Yersinia species, advancing that arsenic resistance might have been raised upon the traditional use of formulations containing arsenic derivatives to cure farm animals, in particular swine dysentery. However, Neyt et al were “unable to produce written documentation of this practice” [6]. Therefore, no reference relative to arsenic-based veterinary drugs was actually available in these publications. We wish to advise historical scientific literature documenting the use of arsenical compounds in veterinary (and human) medicine that adds to the suggestions on the origin of arsenic resistance previously proposed. In 1935,
E. Roberts and W. M. Dawson of the University of Illinois [8] tested experimentally the detrimental effects of arsenical Fowler solution. (The English physician Thomas Fowler invented the solution containing 1% potassium arsenite in 1786; it was prescribed to cure periodic fever and syphilis, and later as a tonic. Also called Kali arsenicosum, Kali arseniatum, Liquor potassii arseniti, or Liquor potassae arsenitis, it was in use until the late 1950s. Of note, considering the role of rodents as immune reservoirs of Y. pestis, the actual wide use of potassium arsenite as a pesticide and rodenticide raises concern.) The preparation reported in their article, containing 1% arsenic trioxide, was popular as a farm-animal feeding to accelerate fat accumulation and to obtain lucent hair [8]. From their critical point of view, Roberts and Dawson observed an increased susceptibility to infections in experimental rabbits fed Fowler solution, in line with the empirical experience of farmers. Thirty years earlier, in 1904, Quitman of the Veterinary College of the Chicago University [9] enumerated diverse arsenical preparations, including Fowler solution, to treat farm animals. Before him, in 1857, Redwood, in his pharmacopoeia [10] ( p. 804), reports 2 Fowler solution formulas (solution of arsenite of potash, Liquor arsenicalis): one from the 1851 London Pharmacopoeia and the 1841 Edinburgh Pharmacopoeia, and another from the 1841 Dublin Pharmacopoeia. The medical use for which they were usually prescribed to humans included intermittents, or ague, the archaic terms for periodic or malarial fever. Interestingly, several years before, in 1796, Potter of the first American medical school at the University of Pennsylvania envisaged the deleterious effects of
Note Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
2
•
CID
•
CORRESPONDENCE
Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Francesca Tosetti Molecular Oncology and Angiogenesis Unit, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
References 1. Butler T. Plague into the 21st century. Clin Infect Dis 2009; 49:736–42. 2. Wang H, Cui Y, Wang Z, et al. A dogassociated primary pneumonic plague in Qinghai province, China. Clin Infect Dis 2011; 52:185–90. 3. Kool JL. Risk of person-to-person transmission of pneumonic plague. Clin Infect Dis 2005; 40:1166–72. 4. Welch TJ, Fricke WF, McDermott PF, et al. Multiple antimicrobial resistance in plague: an emerging public health risk. PLoS One 2007; 2:e309. 5. Eppinger M, Radnedge L, Andersen G, et al. Novel plasmids and resistance phenotypes in Yersinia pestis: unique plasmid inventory of strain Java 9 mediates high levels of arsenic resistance. PLoS One 2012; 7:e32911. 6. Neyt C, Iriarte M, Thi VH, Cornelis GR. Virulence and arsenic resistance in Yersiniae. J Bacteriol 1997; 179:612–9. 7. Mallik S, Virdi JS, Johri AK. Proteomic analysis of arsenite-mediated multiple antibiotic resistance in Yersinia enterocolitica biovar 1A. J Basic Microbiol 2012; 52:306–13.
8. Roberts E, Dawson WM. Effect of Fowler’s solution on animals. Agricultural Experiment Station, Bulletin 413. University of Illinois, 1935. 9. Quitman EL. Synopsis of veterinary materia medica, therapeutics and toxicology. 2nd ed. Revised and enlarged. Chicago: Alexander Eger Publisher, 1904. 10. Redwood T. A supplement to the pharmacopoeia: being a concise but comprehensive dispensatory and manual of facts and formulae. London: Longman and Co; Simpkin and Co; John Churchill; Henry Bohn and Henry Renshaw, 1857. 11. Potter N. An essay on the medicinal properties and deleterious qualities of arsenic. Philadelphia: William W. Woodward, 1796. 12. Alizeri B. Della peste cioè della sua natura e de’ rimedi per la preservazione, e per la cura della medesima. Genova, Italy: Stamperia del Franchelli, 1721.
Correspondence: Francesca Tosetti, PhD, IRCCS AOU S. Martino-IST, Largo Rosanna Benzi 10, 16132 Genova, Italy ([email protected]). Clinical Infectious Diseases © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/cid/ciu704
Downloaded from http://cid.oxfordjournals.org/ at National Univ of Singapore on October 15, 2014
collected writings appeared in 1658 in England, under the auspices of the newborn Royal Society), was diffused in the United States after colonization, and was still in use until the middle 19th century. In Eastern countries, traditional Chinese medicine prescribes ointments for topical use or beverages containing arsenic sulfide (realgar) to treat human and animal diseases, including swine hyperpyrexia syndrome. The discontinuous exposure to low, nontoxic doses of arsenical preparations present in almost all coded pharmacopoeias in Western and Eastern countries might have favored the development and exchange of plasmids carrying arsenic resistance in host microorganisms. It cannot be excluded that farm animals arriving from England and Germany during the colonization of America could have already been exposed to low-dose arsenic and become carriers of arsenicresistant bacteria in their gut.
