The History of Quinine Should Make Us Wary of Leaders Who Claim Hydroxychloroquine Can Cure COVID-19

by Aditya Iyer

by Gabriela Sibilska

Is hydroxychloroquine the miracle drug that will save us from COVID-19? Unlikely, endorsements by a certain short-fingered vulgarian in The White House notwithstanding. Trials of the drug, which President Trump claims to have dosed himself with, have recently ground to a halt after the WHO intervened based on the advice of the global medical community. This isn’t the first time an antimalarial has been touted as a potential cure for a global virus; indeed, the story of the quinine alkaloid that hydroxychloroquine was synthesised from highlights how scientific advice often takes a backseat to political imperatives.


The history of antimalarials begins with the Spanish colonisation of the Andes, when Christian missionaries and conquistadors observed Incan healers using the quinine-containing bark of the cinchona tree to treat high fevers. As the legend goes, during the early 17th century, the wife of the Viceroy of Peru, the Countess of Chinchon, fell ill with malaria and became the first European to be cured with the powdered bark. As a sign of gratitude, she gave the Andean tree the dubious honour of being named after her.


It’s a nice story, with only one minor wrinkle; according to the Franciscan Lima Archives, the countess died of malaria on 14th January 1641, making it highly unlikely she ever received the treatment.


The timeline, though, is accurate. Jesuit priests did hoard the miraculous bark, whose powdered form they used to heal the faithful during this period, and the Spanish soon began exporting it across the Atlantic.


The Andean bark’s first appearance in a European text was in the Belgian Herman van der Heyden’s 1643 book Discours et avis sur les flux de ventre douloureux. In 1660, the British medical practitioner Robert Tabor (also known as Brady) prescribed a Peruvian bark concoction to an ailing King Charles II for his fever. Its success, although temporary, prompted the monarch to appoint Tabor as a royal physician in 1672, and five years later it was added to the third edition of the medical encyclopaedia London Pharmacopoeia under the entry “Cortex peruanas.”


Its widespread and successful application inspired the Swedish botanist Carl Linnaeus in 1742 to give the plant its modern name, “cinchona,” after the legend of the countess. Its misspelling aside (clearly Linnaeus was not that fond of the legend), the Swede also referred to it as “quinquina.”


Cinchona proved to be a catalyst for European colonial expansion across the globe because of its effectiveness in treating cases of malaria. By the 18th century, as venal mercantile corporations began undertaking putative imperial conquests across Africa, South America, and the Indian subcontinent, malaria and yellow fever seemed to be insurmountable obstacles. Expeditions to the tropics were often referred to as “the white man’s grave.” In 1764, for example, the French sent an expeditionary force of 12,000 people to forcibly settle Kourou in French Guiana; after 10 months, malaria had killed all but 900 of them.


A French colonial postcard exhorting soldiers to take quinine regularly and the consequences for those that did not. Wellcome Collection

The death toll caused by malaria would continue to plague French colonial efforts for more than a century because of their refusal to adopt a comprehensive antimalarial program. In 1890, during the Dahomey (modern Benin) conquest, the head of the colonial medical service in French Sudan (the republic of Mali since 1960), Dr. Gustave Reynard, noted that military campaigns were “…but a diversion from the constant struggle against that most redoubtable of diseases.” The importance of mandatory quinine prophylactics as the bedrock of colonial expansion during the late 19th century’s “Scramble for Africa” is revealed by a 1903 article in the Journal of the Royal African Society, which proclaimed that the “…arch enemy of the white man in the colonies,” malaria, was finally bested.


Troops employed by the English East India Company to aggressively increase their holdings on the Indian subcontinent were given regular cinchona bark infusions in the form of tonic water. To mask the bitter taste, they were ordered to dilute the medicinal tonic with gin—a spirit considered to be fit (at least by the English at the time) for the dregs of society.


The bark’s usage also served to validate the ethos of the Enlightenment period, when European intellectuals sought to morally justify violent colonial expansion with claims of mastering the new environments they encountered through science and rationality.


This dependence on cinchona bark, however, soon faced a major obstacle. Between 1808 and 1826, successive independence movements in South America had transformed the main exporters of the medicinal plants—Peru, Ecuador and Bolivia—from Spanish colonies to proud republics aware of the potential political advantage their newfound monopoly granted them.


Europeans embarked on two parallel courses of action. The first was to create a synthetic version of quinine—a process that became more critical in 1820 after the French chemists Pelletier and Caventou succeeded in isolating quinine from the cinchona bark and producing a more reliable sulphate form. This was a long-term goal, destined to fail until World War II. The second is perhaps more familiar to anyone with a basic understanding of colonial history—theft.


An illustration commemorating the planting of cinchona trees in the Nilgiri hills plantation in the former Madras Presidency. British colonial attempts to cultivate enough quinine to not depend on Dutch products failed miserably throughout their occupation of the Indian subcontinent. Wellcome Collection

A raft of men, remembered by history as adventurers because their illegal activities were conducted on behalf of European nations, were chartered to steal seeds and plants from the new republics. Men like Clement Markham, Richard Spruce, and Robert Cross engaged in an arms race of smuggling various cinchona plants and seeds to their employers in Great Britain, France, and the Netherlands. Botanical gardens, like those in Kew, were used to try and successfully grow the plant and thus break the South American monopoly.


Out of all these men, one—Charles Ledger—would prove to be instrumental in shaping the history of the drug. An alpaca farmer, Ledger smuggled 14 pounds of cinchona seeds taken from the headwaters of the Mormore River in Bolivia back to his brother in London. Those seeds contained a marginally higher percentage of quinine than those of his rivals. The British government chose to ignore the Ledgers, who sold most of their seeds to the Dutch for the price of £24 (approximately £1,500 today). The remainder were sold to the East Indian Company, which unsuccessfully tried to germinate them in their South Indian plantations.


The Dutch, however, had enormous success in cultivating the seeds in their colony of Java (present-day Indonesia). By the turn of the 20th century, the vast majority of the world’s antimalarials were produced by just 100 Dutch Indonesian plantations. The trade was so profitable that the Dutch formed the world’s first drug cartel to ensure that cinchona bark prices would not fluctuate. The cartel also established the Quinine Institute in 1912, which sponsored research that claimed quinine could be used to treat any malady—propaganda that led to its widespread and largely ineffective use during the 1918 Spanish Flu outbreak. The use of the antimalarial to try and counter influenza was a prime example of how social practices and public perceptions of medicine drowned out medical expertise. Since quinine was one of the few products that was a reliable treatment for a serious ailment, was widely available in a variety of forms, and relatively affordable, people used it almost out of reflex in the face of a deadly and new disease.


The Dutch monopoly vexed their European colonial rivals to no end (British India repeatedly called for a cheaper source of antimalarials) and continued until 1942 with the Japanese invasion of Java.


Experiments in creating effective synthetic counterparts to quinine failed until the interwar period, but they did have odd side-effects. William Henry Perkin’s 1856 attempt, for example, led to the creation of the world’s first synthetic purple dye “Mauveine” which revolutionised the mass-production of clothes. In 1935, the first synthetic antimalarial—chloroquine—was developed, though soon abandoned for being too toxic. Hydroxychloroquine was synthesised 10 years later by modifying the 1935 compound via hydroxylation. The result was an antimalarial fit for regular human consumption, which is still in use to this day.


The story of quinine, in many ways, is about science triumphing over disease. For most of its lifetime in the globalised colonial world, it was a real wonder drug that worked, despite there being no accurate understanding at the time of how it worked.


But its history is also tied to power, racism, and greed. Its use went hand in hand with colonial theories of sanitisation—which in turn led to racist depictions of “clean” and “unclean” races not dissimilar to the hateful rhetoric surrounding the East Asian diaspora in the wake of the pandemic. In colonial India, for example, nascent epidemiological programs to combat cholera and malaria blamed the “apathy, fatalism, and resentment of interference” of the “uneducated masses” for their proliferation rather than the real causes: a paucity of resources and lack of medical understanding on the part of the coloniser.


A British advertisement for "Orange Quinine Wine" circa 1900. A wide variety of quinine products were sold across the colonial world as, it was common knowledge that the antimalarial was one of the few products that actually worked. Wellcome Collection

The story of its production and popularisation is also a stark reminder that, though scientists have always experimented with alternative applications of quinine, businessmen and politicians who overstate its efficiency were more concerned with political and economic profits than actual public good. The success of the US government’s threats towards India to provide it with hydroxychloroquine tablets last month, for example, have seemingly set the contours for a new type of pandemic-related diplomacy: one where political pressure, rather than scientific advice, dictates medical exports. Brazil’s rightwing president Jair Bolsonaro’s advocacy of a 19th-century treatment for a 21st-century problem has resulted in the country becoming the ground zero for the coronavirus in Latin America.


As we continue to try and make sense of COVID-19, perhaps this is the greatest lesson we can learn from the medicinal wonder from the Andes. Our current situation, with its medical marvels, greater understanding of infection rates, supply of antibiotics and antivirals, and global communication networks is a vastly different one to that of 1918, save for one respect: people are terribly afraid.


And when leaders put politics above medical advice in that context, there are severe consequences.

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INTERZINE | 2020