Thread by @Paracelsus1092

Why did a type of Peruvian bark become the most important military drug for centuries, enable Europeans to colonise Africa and found the anti-malaria drug industry?

Let's take a look at quinine.

Sometime between 1620 and 1630, Jesuit missionaries were introduced to the bark of the cinchona tree. Many legends surround this moment, but Peruvian Quechuan natives seem to have helped cure malarial and other fevers using this extremely bitter extract.

Jesuit's Bark, as it became known, was exported to Europe in the 1640's. Pharmacies in Rome and Lima, overseen by Cardinal Juan de Lugo, began experimenting with and documenting the effects of the bark on different fevers.

Cinchona bark began to move through Europe, with books written by Roland Sturm and Sebastiano Bado. Charles II was secretly cured of fever by Robert Talbor in 1679, who then cured the French Dauphin. Louis XIV's physicians were shocked by the efficacy of the 'remède anglois'

Even at this point observers were describing cinchona as one of the greatest discoveries of the age. Bado wrote that it was worth more than all the gold and silver of Potosi.

But let's take a step back, what is cinchona bark and why does it cure fever?

Since 1820 we have known that cinchona bark contains some powerful alkaloids, most prominently quinine. Although we don't know how, quinine appears to interfere with Plasmodium falciparum - the malarial parasite - thus reducing fever and helping prevent further attacks.

This was a game-changer, and soon the bark found military application. When Prince Eugene of Savoy reclaimed Belgrade from the Ottomans in 1717, his troops were issued with the medicine. Likewise the British navy in West Africa was well supplied with powdered cinchona bark.

Trouble was, noone knew how much bark to take, quinine content varied widely. Moreover, excessive quinine leads to 'cinchonism' - a horrible syndrome of tinnitus, vertigo, headache, dysphoria, nausea, and vomiting. If soldiers didn't take it frequently then malaria returned.

More dangerously, quinine can interact with the malarial parasite and cause a fatal dump of hemoglobin into the body, known as 'blackwater fever'. Strangely, when modern medicines were used instead, African soldiers began to die from it, potentially due to G6PD deficiency.

Despite these adverse effects, quinine was the most effective way to combat malaria for centuries. Acquiring the cinchona plant became big business - seed smuggling, private plantations and the science of quininology began to take off.

Dutch, Spanish and French expeditions and scientists scrambled to understand and start cultivating cinchona varieties. Peru outlawed exports, but the Dutch created state backed plantations in Indonesia, forming a monopoly on quinine production by the 1880s.

The British explorer Sir Clements Markham smuggled seeds from the Amazon in 1860. These were destined for British India and Sri Lanka, exports peaked at 15 million pounds in 1886 from these plantations. Quinologists were appointed to oversee the extraction process.

Dutch market strength and the German quinine medical industry clashed, resulting in the 1913 Cinchona Agreement, which stabilised prices for quinine production.

Quinine was an imperfect drug, but without it there was no way to move large numbers of soldiers and administrators into West and Central Africa, India and other regions of the world. Prior to the drug, fatality from disease was the largest impediment to colonial expeditions.

During WW2, the Japanese invaded Java, cutting off crucial quinine exports to American and allied forces. 95% of global supplies came from Java, and the US launched the Cinchona Expeditions in 1942 to find new sources in South America.

Today malarial medicines number in the dozens, but many are derived from quinine. Quinine therapy is considered unsafe and unreliable, but still useful where other drugs are unavailable.

Culturally the legacy of military quinine remains with us through gin and tonic. Quinine is so unpleasantly bitter that soldiers would mix it with anything to mask the taste, or find ways to avoid taking it altogether.

So there we have it, the story of a Peruvian wonder drug. Without the efforts of generations of physicians, botanists, chemists and entrepreneurs the world would look very different, and our ability to treat malaria likely still in its infancy.