55 - The Fever Tree

Where did cinchona, the first medication to cure malaria, come from? This episode explores the murky history of the bark of the fever tree and its derivative chloroquine with mysterious pre-Columbian Pacific crossings of the plasmodium parasite, Jesuit priests and Inca healers, a Chinese Emperor performing a clinical trial to treat his fever, chemistry leading to the first modern pharmaceuticals, and imperialism on a global scale. This episode is the first of a multi-part series exploring how hydroxychloroquine became the great hope for treating COVID-19.

Sources:

1. Jaramillo‐Arango, J. A Critical Review of the Basic Facts in the History of Cinchona. J Linn Soc Lond Botany 53, 272–311 (1949).
2. Smith, N. K. A Cure for Ague. J Roy Soc Med 90, 589–590 (1997).
3. Potter, C. W. A history of influenza. J Appl Microbiol 91, 572–579 (2001).
4. Cunha, C. B. & Cunha, B. A. Brief history of the clinical diagnosis of malaria: from Hippocrates to Osler. J Vector Dis 45, 194–9 (2008).
5. Goss, A. Building the world’s supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry. Endeavour 38, 8–18 (2014).
6. Al-Bari, Md. A. A. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemoth 70, 1608–1621 (2015).
7. Guastalegname, M. & Vallone, A. Could chloroquine /hydroxychloroquine be harmful in Coronavirus Disease 2019 (COVID-19) treatment? Clin Infect Dis (2020) doi:10.1093/cid/ciaa321.
8. Alia, E. & Grant-Kels, J. M. Does Hydroxychloroquine Combat COVID-19? A Timeline of Evidence. J Am Acad Dermatol (2020) doi:10.1016/j.jaad.2020.04.031.
9. Seeler, A. O., Graessle, O. & Ott, W. H. Effect of Quinine on Influenza Virus Infections in Mice. J Infect Dis 79, 156–158 (1946).
10. Savarino, A., Boelaert, J. R., Cassone, A., Majori, G. & Cauda, R. Effects of chloroquine on viral infections: an old drug against today’s diseases. Lancet Infect Dis 3, 722–727 (2003).
11. Chakrabarti, P. Empire and Alternatives: Swietenia febrifuga and the Cinchona Substitutes. Med Hist 54, 75–94 (2010).
12. Lonie, I. M. Fever pathology in the sixteenth century: tradition and innovation. Med Hist 25, 19–44 (1981).
13. Luke, T. C. et al. Hark back: Passive immunotherapy for influenza and other serious infections. Crit Care Med 38, e66–e73 (2010).
14. Shanks, G. D. Historical Review: Problematic Malaria Prophylaxis with Quinine. Am J Tropical Medicine Hyg 95, 269–272 (2016).
15. Harrison, N. In celebration of the Jesuit’s powder: a history of malaria treatment. Lancet Infect Dis 15, 1143 (2015).
16. Gerszten, E., Allison, M. J. & Maguire, B. Paleopathology in South American Mummies: A Review and New Findings. Pathobiology 79, 247–256 (2012).
17. Haas, L. F. Pierre Joseph Pelletier (1788-1842) and Jean Bienaime Caventou (1795-1887). J Neurology Neurosurg Psychiatry 57, 1333 (1994).
18. PROPHYLACTIC QUININE IN INFLUENZA. Lancet 204, 1152 (1924).
19. Gensini, G. F. & Conti, A. A. The evolution of the concept of ‘fever’ in the history of medicine: from pathological picture per se to clinical epiphenomenon (and vice versa). J Infection 49, 85–87 (2004).
20. Bergman, G. J. The history and importance of cinchona bark as an anti‐malarial febrifuge. Sci Educ 32, 93–103 (1948).
21. Thompson, C. & MBE. The History and Lore of Cinchona. (n.d.).
22. THE HUXLEY MEMORIAL. Lancet 146, 1381 (1895).
23. Urdang, G. The Legend on Cinchona. (n.d.).
24. Castro, M. C. de & Singer, B. H. Was malaria present in the Amazon before the European conquest? Available evidence and future research agenda. J Archaeol Sci 32, 337–340 (2005).
25. Kummu M et al, How Close Do We Live to Water? A Global Analysis of Population Distance to Freshwater Bodies. PLoS One. 2011; 6(6): e20578.
26. Dawson WT et al, IDIOSYNCRASY TO QUININE, CINCHONIDINE AND ETHYLHYDROCUPREINEv AND OTHER LEVOROTATORY ALKALOIDS OF THE CINCHONA SERIES: PRELIMINARY REPORT. JAMA 8 Mar 1930.
27. Bynum WF, Cullen and the study of fevers in Bitain, 1760-1820. Medical History, supplement no 1, 1981.  
28. Rodrigues PT et al, Human migration and the spread of malaria parasites to the New World. Nature, 31 January 2018. 
29. Achan J et al, Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011; 10: 144.
30. Norn PH, On the history of Cinchona bark in the treatment of Malaria.Dansk Medicinhistorisk Arbog, 31 Dec 2015, 44:9-30.
31. Cook H (2010). Testing the effects of Jesuit’s bark in the Chinese Emperor’s court. JLL Bulletin: Commentaries on the history of treatment evaluation (https://www.jameslindlibrary.org/articles/testing-the-effects-of-jesuits-bark-in-the-chinese-emperors-court/)