The global history of quinine, the world’s first anti-malaria drug
Disclaimer: I wrote this blog five years ago because I noticed the anti-malaria drug quinine had a fascinating history. Since the outbreak of COVID-19, however, quinine has in some quarters been signalled as a potential treatment or preventive measure for the disease. Which has led to a growing interest in this blog. I just want to note that nothing here says that quinine is a potential treatment for COVID-19, and additionally that quinine can have serious side-effects (one of the reasons it was replaced by synthetic anti-malaria drugs). This blog is about history, consult your doctor for health advice.
Up until the 1940s quinine was the go-to way to treat malaria infections. Its history is one tightly entangled with the history of European empires, and their quests for domination in the malaria-ridden areas of the world. Just like the empires quinine supported the history of this drug, and the plant it derives from, stretches the globe: from the Andean jungles of South-America to the global network of British botanical gardens, from the colonial plantations of Southern-India to the Indonesian island of Java.
Quinine is extracted from the Cinchona tree that is native to the Andean regions of South America. While there is some doubt about whether malaria was already present in the Americas before European colonization, academic consensus suggests that it was not. The disease seems to have been introduced by seafaring Europeans, after the so-called Columbian Exchange.
By the time Europeans reached and colonized the Andes the indigenous population already used the bark of the Cinchona tree to treat malaria and other types of fever. The disease had spread faster than the European colonizers could. Note that at this stage the bark itself was used as a medicine, the chemical processes to extract the quinine from the bark were only invented later.
The European colonizers first sent the bark to Europe around the 17th century, probably by way of Jesuit missionaries. Thereby cementing it as a “popish” medicine in the minds of many protestants. Nevertheless it provided a superior cure to a variety of fevers prevalent in Europe, particularly in its swampish regions. The bark was ground down into a powder and then mixed with wine to counter its bitter taste. Problems with dosage and classifying exactly which tree yielded the correct bark hampered its use as a medicine.
Quinine and empire
In 1820 French scientists Pierre Pelletier and Joseph Caventou discovered the process to extract quinine from the Cinchona bark, which improved the potency of the medicine markedly. The discovery came just in time for European empires, as they were expanding at dizzling paces into malaria-ridden parts of the world. Now they just needed enough bark to supply their armed forces with quinine. Thus began an arms-race for the precious bark among European powers.
Several newly independent South-American republics, however, controlled supply of Cinchona. After their independence from Spain in the early 19th century they inherited the monopoly on the exploitation of the Cinchona tree.
The republics of Peru, Ecuador, Colombia, and Bolivia jealously guarded their monopoly of the crucial Cinchona trees. They imposed strict export restrictions on seeds and plants, while gaining significant profits from exporting the bark. European powers, particularly France, Great-Britain and the Netherlands, needed the bark and wanted to break the South-American monopoly. So they sent out several expeditions to procure seeds and plants, often by smuggling them out illegally so they could be replanted in colonial plantations.
Expeditions by explorers such as Clements Markham, Richard Spruce, and Robert Cross all managed to procure seeds and trees of varying quality. It was Charles Ledger, however, who, thanks to a local named Manuel Incra Mamani, managed to procure seeds from the Peruvian/Bolivian border for a species of Cinchona whose bark contained up to 10% quinine (a significant improvement over other species). In 1865 these were sent to London, where the British government showed little interest in them. They were eventually sold to the Dutch who cultivated and improved the species in their colony of Java (now Indonesia). This species was called Cinchona ledgeriana in honour of Charles Ledger, and formed the subsequent basis of much of the world’s supply of quinine.
The story of Manuel Incra Mamani ends on a more depressing note: he did not get a plant named after him and during a seed-collecting trip in 1871 was arrested, imprisoned, and savagely beaten by the police. A beating from which he died some time after his release.
Once seeds and plants had been gathered, botanical gardens fulfilled a key role for colonial powers. They provided key nodes for the transfer of plants throughout empires. Potentially useful plants and seeds were shipped to these botanical gardens where they were analysed, and their cultivation experimented with. Afterwards they were moved to colonial plantations for actual exploitation.
Kew gardens, or as it is officially called: Royal Botanic Gardens, Kew, formed the centerpiece of the expansive British network of botanical gardens. 1841 marked the year when the botanist William Hooker was appointed as director of the gardens. This started the so-called “Hooker dynasty” at Kews, as he was succeeded by his son Joseph Dalton Hooker, who in turn was succeeded by his son-in-law William Turner Thiselton-Dyer. Under the leadership of these men Kew gardens was put firmly into the service of the British empire, and stood at the head of a network of more than a hundred botanical gardens stretching out across the empire.
Kew gardens received part of the Cinchona seeds procured by the Andean expeditions, other specimens were directly shipped to colonial areas, mainly India. At Kews a special greenhouse was even erected specifically for the Cinchona trees. In India the botanical gardens of Ootacamund and Calcutta were crucial for species selection and developing planting and harvesting methods. This prepared the South-American tree for cultivation in the Indian subcontinent.
Cultivating the Cinchona tree proved to be quite difficult when the plant actually arrived in India. They required quite peculiar conditions to thrive, for example a cool climate with little temperature variation, besides not being able to be grown on flatlands. Their medicinal purpose also required them to have high enough yields of quinine, yet few species of Cinchona possess this quality. Particularly because the British did not have in their possession the Cinchona ledgeriana species sold to the Dutch by Charles Ledger.
British Cinchona cultivation was largely concentrated in the Nilgiri hills of South India, close to the Ootacamund botanical garden. Ootacamund received the specimens and experimented with keeping and growing them. The new plants were then cultivated by local gardeners, and, more importantly, plantations. During the 1880s the plantations up in the hills of Nilgiri provided much of the British supply of Cinchona bark and thus quinine. They were located at high altitudes to accommodate the needs of the Cinchona trees. Scores of local labourers died clearing up the thick highland forests as the hills were filled with dangerous wildlife and possessed rather harsh climates.
Cinchona cultivation eventually proved to be a commercial failure in India. After a peak in production at the end of the 1880s it was largely replaced with tea by planters. This left the world market for quinine largely to the Dutch. Yet the limited Indian production was crucial in maintaining British colonial domination in malaria infested areas, Indian Cinchona was at least a political success in the absence of an economic counterpart.
The Dutch were the first to make growing Cinchona commercially successful. They created plantations in their colony of Java that eventually dominated world production of quinine. The tree was successfully introduced on the island in the 1850s and 1860s through the cooperation of private planters, the Dutch government, and scientists. Java further solidified its grasp of world production by introducing the quinine-laden Cinchona ledgeriana species. Javan market dominance was eventually established at the end of the 1880s when overproduction of Cinchona and falling prices forced British planters in India to switch over to other crops. Dutch planters coped with this overproduction by further increasing harvests and relying upon the high quinine content of the Cinchona ledgeriana.
Until 1913 Cinchona production was characterized by perpetual low prices. Partly because of overproduction of the crop, partly because of market manipulation by associations of European quinine producers. These associations, who controlled the industrial process of deriving quinine from the Cinchona tree, coordinated their efforts to keep the price of Cinchona bark low, while artificially keeping prices of their manufactured product, quinine, high. Eventually these practices prompted the Dutch government and Javanese planters to act. In 1913 the so-called quinine agreement was put into force and established set prices for Cinchona bark, creating the world’s first pharmaceutical cartel.
This cartel existed until 1942 when Japanese troops invaded Java and took over Cinchona production. Because the allies needed the medicine for their troops in tropical areas, this caused a sudden, desperate search for other Cinchona sources. The Americans even sent expeditions to the Andes in search of Cinchona.
This sudden shortage of quinine forced world science to speed up its research into synthetic medicines. This eventually produced drugs that would replace quinine as the main anti-malaria medicine in use in the world. Yet quinine is still valued today as a secondary medicine, and in Java there are even some Cinchona plantations still in existence. Plantations that remind the island of its one-time domination of world production of this life-saving drug.
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Castro, Marcia Caldas De, and Burton H. Singer. “Was Malaria Present in the Amazon before the European Conquest? Available Evidence and Future Research Agenda.” Journal of Archaeological Science 32.3 (2005): 337–40
Goss, Andrew, ”Building the world’s supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry“, Endeavour, Volume 38, Issue 1, March 2014, Pages 8–18
Lee, M.R. , ‘Plants against Malaria: Part 1: Cinchona or the Peruvian Bark’, Journal of the Royal college of Physicians of Edinbrugh, 2002;32(3):189–96
Veale, Lucy (2010) An historical geography of the Nilgiri Cinchona plantations, 1860–1900. PhD thesis, University of Nottingham.