Monmouth's Ask the Doctor January-February 2020

The History of Quinine By Pam Teel

D O C T O R A D V I C E

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 malar- ia-ridden areas of the world. 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. It was used as a treatment to treat malaria infections. The disease seems to have been introduced into America by seafaring Europeans. By the time Europeans reached and colonized the Andes the indigenous population already used the bark of the Cinchona tree to treat malar- ia and other types of fever. Malaria 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. 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. 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 into malaria-ridden parts of the world. They 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. It was Charles Ledger, who with the help of a local, 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 cultivat- ed and improved the species in their colony of Java (now Indonesia). This species was called Cinchona ledgeriana in honor of Charles Ledger, and formed the subsequent basis of much of the world’s supply of quinine. Sadly the local who helped Ledger steal the seeds was imprisoned, beaten, and later died from his wounds. In America, during the Civil War quinine was the closest thing to a miracle drug known to Civil War physicians. Malaria, yellow fever, and other tropical diseases had several symptoms in common, including fevers, chills, and nausea. In the early stages of these diseases, Southern Civil War physicians gauged the illness by the frequency of recurring fever, hence “intermit- tent,” “remittent,” “tertiary,” or “quotidian” fevers. Physicians of the time did not connect mosquitoes to malaria, but they did know quinine was a sure way to ease its symptoms. The problem was getting and administering the drug, especially getting it in quantity. Sadly, the South struggled through the war years with what quinine it could smuggle or capture. It was a different story for the North, which had excess quinine. Philadelphia-based Zeitler and Rosengarten had the foresight to hire French chemist, John Michael Maisch, who first isolated the alkaloid from cinchona bark and within three years of the discovery was selling quinine. They obtained cinchona in bulk at low cost and processed it to obtain the quinine, which was then extracted into sulfate. Maisch, working for the Union army, ensured the purity of the drug, developed standard doses, and oversaw the packaging and labeling of the drugs for distribution to the army medical depots. Today, quinine is rarely used for medicinal purposes. It's not used to prevent malaria, but rather to kill the organism respon- sible for the disease. When used to treat malaria, quinine is given in a pill form. It is still sold in the form of quinine water or tonic water, which is consumed around the world as a popular mixer with spirits such as gin and vodka. The FDA recently banned its use as a cure for leg cramps due to the negative side effects that can result from ingesting large amounts, such as headaches and fever. Some bad reactions to quinine have even been fatal, but don't let that stop you from or- dering a gin and tonic next time you're at the bar, because tonic water contains very low levels of quinine. A glass of tonic water holds roughly 20 mg of quinine, whereas a dose for the treatment of leg cramps would be in the 200 to 300 mg range.

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