Doctor's Review: Medicine on the Move

November 22, 2017
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The quest for quinine

How mosquitoes and malaria met their match

As Canadian physicians hunker down against frigid temperatures once again, we would perhaps do well to remember one benefit afforded by life in these harsh northern climes: the cold protects people here from a host of deadly infectious illnesses by controlling the insect population. The world of tropical medicine is a complicated one. Hundreds of millions each year are exposed to infection by beast, bug and bacteria — deadly diseases transmitted by bite, by water and by breath. From Dengue fever and simple diarrhea to typhoid and yellow fever, staying healthy is a veritable crapshoot in most places around the world. However, it is malaria which arguably remains the most storied of all tropical diseases, perhaps as much for its frequency as its ferocity.

Clooney killer?

Indeed, it seems that this grim disease has been romanticized at times, both at the hands of intrepid pith-helmeted colonialists and the silver-screen sirens swooning beneath swaths of mosquito netting. More recently, Hollywood heavyweight George Clooney glibly referred to his recent bout of malaria, contracted on a visit to Sudan, as “good fun.”

For most, it is anything but. According to the World Health Organization, there are some 250 million cases of malaria each year, responsible for nearly one million deaths, most in children living in sub-Saharan Africa. It’s hard for most of us to imagine a time when the great citizens of Rome were equally susceptible to this mosquito-borne killer; yet this surprising reality was actually the impetus behind the search for a cure and the eventual discovery of quinine.

During the 17th century, the city of Rome was pretty much a glorious jewel set in a festering swamp. The city was surrounded by a vast network of putrid and stagnant water — a fetid sewer above which swarmed an infected multitude of mosquitoes. These marshes were the prefect breeding ground for bugs, and yet medical minds at the time blamed the air itself. Mal’aria — Italian for “bad air” — was the bane of this city for centuries. By the 1600s, the body count was at an all-time high. Four popes for sure and likely even Dante himself were taken down by this disease believed to be caused by swamp fumes.

New World wonders

For the Jesuit missionaries commissioned to travel to the New World, the promise of fresh air in faraway lands and escaping the various plagues and poxes of 17th-century Europe likely beckoned as much as their devotion to “curing” Indian heathenism.

These itinerant priests and the Spanish conquerors they followed could not help but be impressed by some local customs, however, and found in Peru among the Quechua Indians an amazing remedy for fever: the bark of the quina quina, or “fever tree,” a relatively rare evergreen found on the slopes of the Andes.

The Quechua would mix the bark with sugared water to mask its bitterness. For as far back as they could remember, the Indians knew that quina quina bark could calm febrile shivering. And so the Jesuit missionaries spread the word of God, as well as word of this miraculous medicine. In 1630, a high-profile case of the benefits of the bark caused quite a stir. When the wife of the Spanish ambassador to Peru, Countess Anna del Chinchón, came down with a nasty case of malaria, her physician, Juan del Vega, was inspired by local custom and prepared a concoction made of quina quina. The countess was cured, the tree renamed in her honour, and a medicinal star was born.

Transplant attempts

A Jesuit living in Lima by the name of Agostino Salumbrino (1561-1642) sent a care package back home to Rome in 1632, prompting the first recorded case of using the so-called quina quina cure to treat malaria. It worked like a charm. Several ill-fated expeditions were sent back to Peru to fetch cinchona seeds and saplings to be transplanted back in Italy in the attempt to create a home-grown cure.

The Andes, however, proved a formidable obstacle; many men died trying to track down and transport specimens, and many of the fragile trees froze in the process. Those that did make it across the Atlantic rarely survived transplantation. (It would be several centuries before the cinchona found favourable ground and climate on plantations in India and throughout the Pacific Islands). The newly renamed treatment known as Jesuit’s Bark became all the rage and trade for this valuable South American commodity exploded. The Spanish moved into Peru and set up shop, slowly eradicating the natural cinchona forests in the process.

For the following few centuries, this basic recipe of powdered bark and water or wine was the primary treatment for malaria throughout Europe. In 1737, a curious Frenchman delved a little deeper into the mysterious concoction, trying to figure out exactly what it was about the cinchona tree that rendered it an effective remedy in treating fever.

Charles Marie de la Condamine (1701-1774) had no medical training — he was primarily a geographer and a mathematician — but his extended geographical survey in South America in 1735 was a fateful trip: He measured the equator, mapped the Amazon, “discovered” rubber, and developed an interest in the quina quina cure, publishing its correct usage in the treatment of malaria upon his return to France.

Tonic with a twist

Building on the old spoonful of sugar notion, German beverage company Schweppes would perfect the Jesuit bark recipe with a twist, offering up to the shivering masses its iconic tonic water — the first soft drink in the world — in 1771. It was the malaria-prone British colonialists living in India, who first decided to add the extra “medicinal” component of gin to carbonated tonic water, thus creating a partnership that is still going strong.

The actual medicine behind the magic, however, was more or less a mystery until 1820. It was in that year that two French chemists, Pierre-Joseph Pelletier (1788-1842) and Joseph-Bienaimé Caventou (1795-1877), isolated a compound they found in the bark of the cinchona tree. They christened it quinine, in deference to the native name for it, and from that point on it was refined and purified, increasing its effectiveness. The prescient pair of pharmacists didn’t patent their discovery, hoping it would be available for all who needed it, though they did perfect a technique for extracting the alkaloid, and their Paris purification plant was quite successful.

Demand increased as British, French and Dutch colonialists invaded the tropical and subtropical regions of the world. European agencies began calling for a more effective and inexpensive way to produce quinine, rather than importing the rare and expensive bark from South America. Wise to the value of their precious natural resource, the Peruvians banned the export of cinchona seeds and saplings in the 19th century. Nevertheless, the Dutch finally established successful cinchona plantations in Java and became the world suppliers of quinine. Demand only intensified when the drug began being used prophylactically around the middle of the 19th century for those travelling or living abroad.

Fake it till you make it

Success in synthesizing quinine was a long and difficult task that wasn’t accomplished until the 1940s. There was a great impetus to discover an alternative cure for malaria due to the fact that the Japanese presence in the South Pacific during these years meant a world-wide shortage of quinine — a war-time tactic that actually led to the deaths of thousands of Allied solders from malaria.

Two chemists at Harvard University, Robert B. Woodward and William von E. Doering, hit the jackpot in 1944 when they came up with chloroquine. It wasn’t exactly a total synthesis of quinine (that wouldn’t come until 1970), but it was extremely effective with fewer side effects. Eventually, however, the malaria parasite developed a resistance to this synthetic version of quinine. By the 1990s, it was obvious that nothing worked like good, old-fashioned quina quina.

Quinine extracted from cinchona bark remained the top treatment for malaria until 2006, when the WHO replaced it with artemisinin combination therapies (ACT) as the go-to drug of choice. Despite the debates over effectiveness, side effects and resistance swirling around malarial medicines, these cures, and so any others, largely remain out of reach for those who need it the most.

It’s certainly something to think about for anyone out there dreaming of enjoying a lazy day on a tropical beach, swatting away those pesky mosquitoes, gin n’ tonic in hand.

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Comments

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  1. On February 15, 2011, Emmanuel Maicas said:
    Thank you for this very nice article about a dreaded disease. But I would like to correct a common misconception: cold weather offers no protection from Malaria. Anopheles quadrimaculatus is the main mosquito vector of Plasmodium falciparum in North America; its range extends to most of the populated areas of Canada. There was a time when malaria was endemic in Canada; the contruction of the Rideau canal was slowed by the death of numerous workers to malaria. (1) There is currently no endemic malaria in chilly Canada. But the same is also true of balmy Florida. Malaria was eradicated not by climate but efficient separation of patients in acute phase from the mosquitoes. In other words, the main weapon against malaria is sealed hospital windows, standard in all modern hospitals (in older hospitals, windows must have a bug screen in good condition). This, combined with compulsory hospitalization of patients in acute crisis are the two tools responsible for eradication of Malaria. DDT did help a lot while it lasted but the climate has nothing to do with it. (1) G.H. Fisk, Malaria and the Anopheles mosquito in Canada. Can Med Assoc J 25:679-683 (1931).

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