Editing Quinine (section)

==History==
{{see also|History of malaria}}
[[Image:Cinchona calisaya - Köhler–s Medizinal-Pflanzen-179.jpg|thumb|19th-century illustration of ''Cinchona calisaya'']]

Quinine was used as a muscle relaxant by the [[Quechuas|Quechua]] people, who are indigenous to [[Peru]], [[Bolivia]] and [[Ecuador]], to halt shivering.<ref>{{cite book| vauthors = Flückiger FA, Hanbury D |authorlink1=Friedrich August Flückiger |authorlink2=Daniel Hanbury|title=Pharmacographia: A History of the Principal Drugs of Vegetable Origin, Met with in Great Britain and British India|chapter-url=https://books.google.com/books?id=ATQbAAAAYAAJ&pg=PA302|year=1874|publisher=Macmillan and Co.|location=London|pages=302–331|chapter=Cortex Cinchonæ}}</ref> The Quechua would mix the ground bark of [[cinchona]] trees with sweetened water to offset the bark's bitter taste, thus producing something similar to [[tonic water]].<ref>{{cite book | vauthors = Hobbs K, West D |title=The Story of Trees : and how they changed the way we live |date=2020 |others=illustrated by Thibaud Hérem |publisher=Laurence King |location=London |isbn=978-1-7862-7522-6 |page=148}}</ref>

Spanish [[Society of Jesus|Jesuit]] missionaries were the first to bring cinchona to Europe.  The Spanish had observed the Quechua's use of cinchona and were aware of the medicinal properties of cinchona bark by the 1570s or earlier:  [[Nicolás Monardes]] (1571) and Juan Fragoso (1572) both described a tree, which was subsequently identified as the cinchona tree, whose bark was used to produce a drink to treat [[diarrhea]].<ref>See:
* {{cite journal | vauthors = Ortiz Crespo FI |title=Fragoso, Monardes and pre-Chinchonian knowledge of Cinchona |journal=Archives of Natural History |date=1995 |volume=22 |issue=2 |pages=169–181 |doi=10.3366/anh.1995.22.2.169 |issn=0260-9541 |url=https://www.reumatologiaclinica.org/en-pdf-S2173574307702460}}
*  {{cite book| vauthors = Stuart DC |title=Dangerous Garden: The Quest for Plants to Change Our Lives|url=https://books.google.com/books?id=Ze0n0yeqsXUC&pg=PA28 |year=2004 |publisher=Harvard University Press |location=Cambridge, MA |isbn=978-0-674-01104-5 |page=28}}
*  {{cite book| vauthors = Monardes N |authorlink=Nicolás Monardes |title=Primera y segunda y tercera partes de la Historia medicinal, de las cosas que se traen de nuestras Indias Occidentales, que sirven en Medicina |url=https://books.google.com/books?id=BMiaWiCqFCMC&pg=RA1-PA75-IA2 |year=1580 |publisher=Fernando Díaz |location=Seville, Spain |language=es |pages=74–75 |trans-title=First and second and third parts of medicinal History, of the things that are brought from our West Indies, which are used in Medicine |quote=Del nuevo Reyno, traen una corteza, que dizen ser de un arbol, que es de mucha grandeza: el qual dizen que lleva unas hojas en forma de coraçon, y que no lleva fruto. Este arbol tiene una corteza gruessa, muy solida y dura, que en esto y en el color parece mucho a la corteza del palo que llaman Guayacan: en la superficie tiene una pelicula delgada blanquisca, quebrada por toda ella: tiene la corteza mas de un dedo de gruesso, solida y pesada: la qual gustada tiene notable amargor, como el de la Genciana: tiene en el gusto notable astriction, con alguna aromaticidad, porque al fin de mascar la respica della buen olor. Tienen los Indios esta corteza en mucho, y usan della en todo genero de camaras, que sean con sangre, o sin ella. Los Españoles fatigados de aquesta enfermedad, por aviso de los Indios, han usado de aquesta corteza y han sanado muchos dellos con ella.<br />Toman della tanto como una haba pequeña hecha polvos, tomase en vino tinto, o en agua apropiada, como tienen la calentura, o mal: hase de tomar por la mañana en ayunas, tres o quatro vezes: usando en lo demas, la orden y regimiento que conviene a los que tienen camaras. |trans-quote=From the new kingdom, there is brought a bark, which is said to be from a tree, which is very large: it is said that it bears leaves in the form of a heart, and that it bears no fruit. This tree has a thick bark, very solid and hard, that in this and in its color looks much like the bark of the tree that is called ''[[lignum vitae|guayacán]]'': on the surface, it has a thin, discontinuous whitish film throughout it: it has bark more than one finger thick, solid and heavy: which, when tasted, has a considerable bitterness, like that of the gentian: it has in its taste a considerable astringency, with some aromaticity, because at the end of chewing it, one breathes with a sweet odor. The Indians hold this bark in high regard, and use it for all sorts of diarrhea, that are with blood [i.e., bloody] and without it.  The Spanish [who are] tired of this disease, on the advice of the Indians, have used this bark and have healed many of those with it. They take as much as a small bean, make [it into] powder, take it in red wine or in appropriate water, if they have fever or illness:  it must be taken in the morning on an empty stomach, three or four times: otherwise, using the order and regimen that suits those who have diarrhea.}}
* {{cite book| vauthors = Fragoso J |title=Discursos de las cosas aromaticas, arboles y frutales, y de otras muchas medicinas simples que se traen de la India Oriental y que sirven al uso de medicina |url=https://books.google.com/books?id=ZGpIEb3BRfAC |year=1572 |publisher=Francisco Sánchez |location=Madrid, Spain |language=es |page=35 |trans-title=Discourse on fragrant things, trees and fruits, as well as many other ordinary medicines that have been brought from India and the Orient and are of use to medicine |quote=En el nuevo mundo ay un grande arbol que lleva las hojas a forma de coraçon, y carece de fruto. Tiene dos cortezas, la una gruessa muy solida y dura, que assi en la sustancia como en el color es muy semejante al Guayacan: la otra es mas delgada y blanquezina, la qual es amarga con alguna estipticidad: y demas desto es aromatica. Tienenla en mucho nuestros Indios, porque la usan contra qualesquier camaras, tomando del polvo peso de una drama o poco mas, desatado en agua azerada, o vino tinto. |trans-quote=In the new world, there is a big tree that bears leaves in the form of a heart, and lacks fruit. It has two barks, one [is] thick, very solid, [and] hard, which in substance as well as in color is much like ''guayacan'' [i.e., ''lignum vitae'']: the other is thinner and whitish, which is bitter with some styptic [i.e., astringent] quality: and besides this, it is aromatic.  Our Indians regard it highly, because they use it against any diarrheas, taking a weight of a dram or a bit more of the powder, mixing it in mineral water, or red wine.}}</ref> Quinine has been used in unextracted form by Europeans since at least the early 17th century.<ref>{{cite journal | vauthors = Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, Rosenthal PJ, D'Alessandro U | title = Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria | journal = Malaria Journal | volume = 10 | pages = 144 | date = May 2011 | pmid = 21609473 | pmc = 3121651 | doi = 10.1186/1475-2875-10-144 | doi-access = free }}</ref>

A popular story of how it was brought to Europe by the [[Countess of Chinchon]] was debunked by medical historian [[Alec Haggis]] around 1941.<ref>{{cite journal | vauthors = Pain S |title=The Countess and the cure |journal=New Scientist |date=15 September 2001 |url=https://www.newscientist.com/article/mg17123085-200-the-countess-and-the-cure/}}</ref> During the 17th century, malaria was endemic to the [[swamp]]s and [[marsh]]es surrounding the city of [[Rome]]. It had caused the deaths of several [[pope]]s, many [[Cardinal (Catholicism)|cardinal]]s and countless common Roman citizens. Most of the Catholic [[priest]]s trained in Rome had seen malaria patients and were familiar with the [[shivering]] brought on by the [[wikt:febrile|febrile]] phase of the disease.

The [[Jesuit]] Agostino Salumbrino (1564–1642),<ref>{{cite book| vauthors = de Andrade A |authorlink=Alonso Andrada |others=Original series by [[Juan Eusebio Nieremberg]] |title=Varones ilustres en santidad, letras y zelo de las almas de la Compañía de Jesús |url=https://books.google.com/books?id=paaIyIGye1gC&pg=PA612 |series=Varones ilustres de la Compañía de Jesús |volume=5 |date=3 August 1642 |publication-date=1666 |publisher=José Fernandez de Buendía |location=Madrid, Spain |language=es |pages=612–628 |chapter=Vida del Devoto Hermano Agustin Salumbrino |trans-title=Illustrious men in holiness, letters, and zeal for souls of the [[Society of Jesus]] |trans-chapter=The life of the devout Brother Agustin Salumbrino |quote-page=612 |quote=Naciò el Hermano Agustin Salumbrino el año de mil y quinientos y sesenta y quatro en la Ciudad de Fḷọṛi en la Romania […] |trans-quote=Brother Agustino Salumbrino was born in the year 1564 in the city of [[Forlì]] in [[Romagna]]}}</ref> an [[apothecary]] by training who lived in [[Lima]] (now in present-day [[Peru]]), observed the Quechua using the bark of the cinchona tree to treat such shivering. While its effect in treating malaria (and malaria-induced shivering) was unrelated to its effect in controlling shivering from [[rigors]], it was a successful medicine against malaria. At the first opportunity, Salumbrino sent a small quantity to Rome for testing as a malaria treatment.<ref>See:
* {{cite journal | vauthors = Medina Rodríguez F, Aceves Ávila FJ, Moreno Rodríguez J |title=Precisions on the History of Quinine |journal=Reumatología Clínica |date=2007 |volume=3 |issue=4 |pages=194–196 |doi=10.1016/S2173-5743(07)70246-0 |series=Letters to the Editor |issn=2173-5743 |quote=In fact, though the last wordon this has not yet been spoken, there are Jesuit texts thatmention that quinine reached Rome in 1632, with theprovincial of the Jesuit missions in Peru, father AlonsoMessia Venegas, as its introducer, when he brought asample of the bark to present it as a primacy, and whohad left Lima 2 years earlier, because evidence of his stayin Seville 1632 has been registered, publishing one of hisbooks there and following his way to Rome as a procurator. |url=https://www.reumatologiaclinica.org/en-pdf-S2173574307702460}}
* {{cite book | vauthors = Torres Saldamando E |title=Los antiguos jesuitas del Perú |date=June 1882 |publisher=Imprenta Liberal |location=Lima, Peru |pages=180–181 |chapter-url=https://archive.org/details/losantiguosjesui00torr/page/180/mode/2up |language=es |chapter=El P. Diego de Torres Vazquez |quote=Al siguiente año se dirigieron á Europa los Procuradores P. Alonso Messía Venegas y P. Hernando de Leon Garavito, llevando gran cantidad de la corteza de la quina, cuyo conocimiento extendieron por el mundo los jesuitas. |quote-page=181 |trans-quote=In the following year [i.e., 1631] there went to Europe the procurators Father Alonso Messia Venegas and Father Hernando de Leon Garavito, taking a great quantity of cinchona bark, knowledge of which the Jesuits spread throughout the world.}}
* {{cite web | vauthors = Bailetti A |title=Capítulo 10: La Condesa de Chinchón |url=http://lamalariayelarboldequina.blogspot.com/2013/11/capitulo-9-proximamente.html |website=LA MISIÓN DEL JESUITA AGUSTÍN SALUMBRINO, la malaria y el árbol de quina |quote=A últimas horas de la tarde del treinta y uno de mayo de 1631 se hizo a la vela la Armada Real con dirección a Panamá llevando el precioso cargamento de oro y plata.<br />En una de las naves viajaban los procuradores jesuitas padres Alonso Messia y Hernando León Garavito custodiando los fardos con la corteza de quina en polvo preparados por Salumbrino. Después de casi veinte días de navegación el inapreciable medicamento llegó a la ciudad de Panamá, donde fue descargado para cruzar en mulas el agreste camino del itsmo palúdico hasta Portobelo para seguir a Cartagena y la Habana, cruzar el Atlántico y llegar a Sanlúcar de Barrameda en Sevilla. […]  Finalmente siguió su camino a Roma y a su destino final el Hospital del Espíritu Santo. |trans-quote=Late in the afternoon of 31 May 1631, the royal armada set sail in the direction of Panama, carrying its multimillion [dollar] cargo of gold and silver.<br />On one of the ships traveled the Jesuit procurators Fathers Alonso Messia and Hernando León Garavito, guarding the cases of powdered cinchona bark, prepared by Salumbrino.  After almost 20 days of sailing, medicine arrived in the city of Panama, where it was transloaded onto mules. It then traveled the malarial isthmus as far as Portobelo, thence to Cartagena [in Colombia] and Havana. It then traveled to Sanlúcar de Barrameda in Seville, [Spain]. […] Finally it followed the road to Rome and to its final destination, the Hospital of the Holy Spirit}}</ref> In the years that followed, cinchona bark, known as [[Jesuit's bark]] or Peruvian bark, became one of the most valuable commodities shipped from Peru to Europe. When [[Charles II of England|King Charles II]] was cured of malaria at the end of the 17th Century with quinine, it became popular in [[London]].<ref>{{cite book| vauthors = Rocco F |title=Quinine: malaria and the quest for a cure that changed the world |year=2004 |publisher=Perennial |location=New York, NY }}</ref> It remained the antimalarial drug of choice until the 1940s, when other drugs took over.<ref>{{cite book| vauthors = Humphrey L |title=Quinine and Quarantine|year=2000 | location = Columbia, Missouri | publisher = University of Missouri Press }}</ref>

The form of quinine most effective in treating malaria was found by [[Charles Marie de La Condamine]] in 1737.<ref>{{cite book | vauthors = Marie de la Condamine C |authorlink=Charles Marie de La Condamine |title=Histoire de l'Académie royale des sciences |chapter-url=https://books.google.com/books?id=yOAEAAAAQAAJ&pg=PA226 |date=29 May 1737 |publisher=Imprimerie Royale |pages=226–243 |chapter=Sur l'arbre du quinquina |publication-date=1740}}</ref><ref>De Jussieu accompanied de la Condamine on the latter's expedition to Peru: {{cite book | vauthors = de Jussieu J |author1-link=Joseph de Jussieu |title=Description de l'arbre à quinquina |date=1737 |publisher=Société du traitement des quinquinas |location=Paris |url=https://gallica.bnf.fr/view3if/ga/ark:/12148/bpt6k90339p |publication-date=1934}}</ref> In 1820, French researchers [[Pierre Joseph Pelletier]] and [[Joseph Bienaimé Caventou]] first isolated quinine from the bark of a tree in the genus ''[[Cinchona]]'' – probably ''[[Cinchona pubescens]]'' – and subsequently named the substance.<ref>{{cite journal | vauthors = Pelletier PJ, Caventou JB | title = Recherches Chimiques sur les Quinquinas | trans-title = Continuation: Chemical Research on Quinquinas | language = fr | publisher = Crochard | date = 1820 | journal = Annales de Chimie et de Physique | volume = 15 | pages =  337–365 | url = https://books.google.com/books?id=veE3AAAAMAAJ&pg=PA337 |quote=The authors name quinine on page 348: ''" …, nous avons cru devoir la nommer ''quinine'', pour la distinguer de la cinchonine par un nom qui indique également son origine."'' |trans-quote=…, we thought that we should name it "quinine" in order to distinguish it from cinchonine by means of a name that also indicates its origin.}}</ref> The name was derived from the original [[Quechua languages|Quechua]] (Inca) word for the cinchona tree bark, ''quina'' or ''quina-quina'', which means "bark of bark" or "holy bark". Prior to 1820, the bark was dried, ground to a fine powder, and mixed into a liquid (commonly wine) in order to be drunk. Large-scale use of quinine as a malaria [[prophylaxis]] started around 1850. In 1853 [[Paul Briquet]] published a brief history and discussion of the literature on "quinquina".<ref>{{cite book | vauthors = Briquet P |author1-link=Paul Briquet |title=Traité thérapeutique du quinone et de ses préparations |date=1853 |publisher= L. Martinet |location=Paris |url=https://archive.org/details/b23982135 |language=fr}}</ref>

Quinine played a significant role in the colonization of Africa by Europeans. The availability of quinine for treatment had been said to be the prime reason Africa ceased to be known as the "white man's grave". A historian said, "it was quinine's efficacy that gave colonists fresh opportunities to swarm into the [[Gold Coast (region)|Gold Coast]], [[Nigeria]] and other parts of west Africa".<ref name="clifford">{{cite book |title=A People's History of Science: Miners, Midwives, and 'Low Mechanicks' | vauthors = Conner CD |year=2005 |publisher=Nation Books |location=New York |isbn=978-1-56025-748-6 |pages=[https://archive.org/details/peopleshistoryof0000conn/page/95 95–96] |url=https://archive.org/details/peopleshistoryof0000conn|url-access=registration }} Also cites {{cite book |title=The Greatest Benefit to Mankind: A Medical History of Humanity | vauthors = Porter R |year=1998 |publisher=W. W. Norton |location=New York |isbn=978-0-393-04634-2 |pages=[https://archive.org/details/greatestbenefitt00port/page/465 465–466] |url=https://archive.org/details/greatestbenefitt00port/page/465 }}</ref>

To maintain their monopoly on cinchona bark, Peru and surrounding countries began outlawing the export of cinchona seeds and saplings in the early 19th century. In 1865, [[Manuel Incra Mamani]] collected seeds from a plant particularly high in quinine and provided them to [[Charles Ledger]]. Ledger sent them to his brother, who sold them to the Dutch government. Mamani was arrested on a seed collecting trip in 1871, and beaten so severely, likely because of providing the seeds to foreigners, that he died soon afterwards.<ref>{{Cite web | vauthors = Canales NA |date=7 April 2022 |title=Hunting lost plants in botanical collections |url=https://wellcomecollection.org/articles/YjyPpREAAB8AhS-R |access-date=2022-05-09 |website=Wellcome Collection |language=en}}</ref>

By the late 19th century the Dutch grew the plants in Indonesian plantations. Soon they became the main suppliers of the tree. In 1913 they set up the [[Kina Bureau]], a cartel of cinchona producers charged with controlling price and production.<ref name="Shah-2010">{{Cite book|title=The Fever: How Malaria Has Ruled Humankind for 500,000 Years| vauthors = Shah S |publisher=Farrar, Straus and Giroux|year=2010|pages=94}}</ref> By the 1930s Dutch plantations in [[Java]] were producing 22 million pounds of cinchona bark, or 97% of the world's quinine production.<ref name="clifford" /> U.S. attempts to prosecute the Kina Bureau proved unsuccessful.<ref name="Shah-2010" />

During [[World War II]], Allied powers were cut off from their supply of quinine when Germany conquered the Netherlands, and Japan controlled the [[Philippines]] and [[Indonesia]]. The US had obtained four million cinchona seeds from the Philippines and began operating cinchona plantations in [[Costa Rica]]. Additionally, they began harvesting wild cinchona bark during the [[Cinchona Missions]]. Such supplies came too late. Tens of thousands of US troops in Africa and the South Pacific died of malaria due to the lack of quinine.<ref name=clifford/> Despite controlling the supply, the Japanese did not make effective use of quinine, and thousands of Japanese troops in the southwest Pacific died as a result.<ref>{{cite book | vauthors = Morton L | title = The Fall of the Philippines | location = Washington, D.C. | publisher = United States Army | year = 1953 | chapter-url = http://www.history.army.mil/books/wwii/5-2/5-2_29.htm | chapter = 29 | page = 524 | url-status = live | archive-url = https://web.archive.org/web/20170525032120/http://www.history.army.mil/books/wwii/5-2/5-2_29.htm | archive-date = 25 May 2017}}</ref><ref>{{cite web | vauthors = Hawk A | url = http://ajrp.awm.gov.au/AJRP/remember.nsf/Web-Printer/1989A520D772FE7ECA256B5A0011AF2B?OpenDocument | title = Remembering the war in New Guinea: Japanese Medical Corps – malaria | url-status = live | archive-url = https://web.archive.org/web/20111122234912/http://ajrp.awm.gov.au/AJRP/remember.nsf/Web-Printer/1989A520D772FE7ECA256B5A0011AF2B?OpenDocument | archive-date = 22 November 2011}}</ref><ref>{{cite book | veditors = Heaton LD | title = Preventive Medicine in World War II: Volume VI, Communicable Diseases: Malaria | location = Washington, D.C. | publisher = Department of the Army | year = 1963 | chapter = 8 | chapter-url = http://history.amedd.army.mil/booksdocs/wwii/Malaria/chapterVIII.htm | pages = 401 and 434 | url-status = live | archive-url = https://web.archive.org/web/20120129130700/http://history.amedd.army.mil/booksdocs/wwii/Malaria/chapterVIII.htm | archive-date = 29 January 2012}}</ref><ref>{{cite journal | url = http://www.lonesentry.com/articles/ttt/japanese_medical_services.html | title = Notes on Japanese Medical Services | journal = Tactical and Technical Trends | issue = 36 | year = 1943 | url-status = live | archive-url = https://web.archive.org/web/20111014082451/http://lonesentry.com/articles/ttt/japanese_medical_services.html | archive-date = 14 October 2011}}</ref>

Quinine remained the antimalarial drug of choice until after World War II. Since then, other drugs that have fewer side effects, such as [[chloroquine]], have largely replaced it.<ref>{{Cite book|title=The Fever: How Malaria Has Ruled Humankind for 500,000 Years| vauthors = Shah S |publisher=Farrar, Straus and Giroux|year=2010|pages=102}}</ref>

''Bromo Quinine'' were [[brand name]] [[Cough medicine|cold tablets]] containing quinine, manufactured by Grove Laboratories. They were first marketed in 1889 and available until at least the 1960s.<ref>{{cite news |url=http://www.time.com/time/magazine/article/0,9171,939616,00.html |title=Medicine: What's Good for a Cold? |magazine=Time |access-date=27 April 2010 |date=22 February 1960 |url-status=dead |archive-url=https://web.archive.org/web/20100726032511/http://www.time.com/time/magazine/article/0,9171,939616,00.html |archive-date=26 July 2010}}</ref>

Conducting research in central Missouri, [[John Sappington|John S. Sappington]] independently developed an anti-malaria pill from quinine. Sappington began importing cinchona bark from Peru in 1820. In 1832, using quinine derived from the cinchona bark, Sappington developed a pill to treat a variety of fevers, such as scarlet fever, yellow fever, and influenza in addition to malaria. These illnesses were widespread in the Missouri and Mississippi valleys. He manufactured and sold "Dr. Sappington's Anti-Fever Pills" across Missouri. Demand became so great that within three years, Sappington founded a company known as Sappington and Sons to sell his pills nationwide.<ref>{{cite web|url=https://historicmissourians.shsmo.org/historicmissourians/name/s/sappington/ |title= John. S Sappington|work=Historic Missourians| publisher= State Historical Society of Missouri }}</ref>