Cinchona comes to rescue the world

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Man has known malaria for centuries. It is a fever, that comes with shaking chills, a lot of pain, and turns white of the eyes yellow. Sometimes this fever also affects the brain, intestines, and kidneys. While, its cause was known only in 1880s, ancient physicians knew this fever well. It would strike, go-away for a while, and again return back. This return could be every third (tertian fever) or fourth (quartan fever) day. Rarely, it may come back on a second day or quotidian fever. Till 1500s, this fever was all over the “old-world” Asia, Europe, and Africa.

European travellers, and slave trade carried malaria to the “new-world” of South, Central and North Americas. Modern genotype studies have confirmed this fact. Strangely however, first “cure” of this disease of the “old-world”, was to come from the “new-world.”

Stories around chance discovery

There are many stories about how first cure for malaria was discovered. Maybe it was a local Peruvian inhabitant, who had fever. He was passing by a lake, drank its bitter water, and was cured. Story goes that lake-water was made bitter as a tree (called qui-qui by the locals) had fallen in that lake. Some accounts identify this person as a local Peruvian Pedro Leiva . Probably, this knowledge reached Juan Lopez, a Jesuit missionary in Peru who around 1630s, sampled bark of this tree and found it to cure “fevers”. His colleague, Cardinal Lugo, another Jesuit missionary probably brought bark of this tree to Europe around 1640s, as a secret recipe for malarial fever.

There is another disputed story. In 1631 a Spaniard countess of Cinchona, married to a Peruvian nobleman developed fever. Her fever was cured by a concoction, that contained bark of a native tree. Maybe she ordered bark of the tree to be brought to Spain. Regardless, this tree got its name from her as Cinchona or Chinchona.

Bark of the Cinchona tree, was regularly transported from Peru to Europe. Priests brought it as a powder, and over next few years, this was an important and even a secret remedy. It cured many fevers, but not all. Overdose, as well as counterfeits were common. Robert Talbor, an english medical apprentice, managed to get this secret remedy. He sold it to King Louis of France for a large sum, and made huge profits. This secret remedy, turned out to be Cinchona powder. However, dosage was not yet known, while some were cured, others died of an overdose.

Cinchona and Hahnemann

Hahnemann was a German medical doctor, and in 1779 he had completed his studies. As a young doctor, he started consuming cinchona bark. He made a discovery, that this bark, when consumed in large amounts, itself causes fever. We know this phenomenon as cinchonism. Based on this finding, Hahnemann gave his philosophy – “Like cures like”. This philosophy was basis of a new science, we all know as Homeopathy. “Same substance that causes an illness in a large dose, is its cure when given in small dosages”.

No other plant can ever take a credit, as an idea behind an entire system of healing. None-the-less cinchona was famous, it was over-harvested and was a major export from Peru and Bolivia to Europe. Meanwhile, in 1825 Peru declared cinchona as its national tree.

Quinine – another chance discovery

By 1820 counterfeits of cinchona were common, and some of such powders led to deaths. Pelletier and Caventou were French chemists. They could isolate strychnine from one sample of the “fever-powder”, and proved that nux-vomica, was the culprit. In the same process, they isolated another compound. They could isolate the same compound from cinchona tree (also called qui-qui by the locals). They called this isolated compound “quinine”, that proved better than cinchona bark.

This discovery led to cinchona-quinine industry. While Peru, Bolivia, Ecuador and Columbia – countries that were growing these trees for profit at that time, did not want profits going out of their hands. However, around 1843 a Bolivian seed hunter Manuel Incra Mamani managed to smuggle seeds of a high-yield cinchona tree. These seeds eventually reached Dutch, who successfully planted these in Java. Meanwhile, Mamani was caught, and beaten to death in 1871. By 1930s, Dutch were providing most raw materials for quinine. Today only a few endangered Cinchona trees survive in Peru and Ecuador.

Wars, malaria and quinine derivatives

Quinine was not only used as a medicine for malaria, but also in tonics, and drinks. During the first world war, more British soldiers died of malaria, rather than injuries. As a result quinine also became a drug to prevent malaria. During the second world war, Japanese invaded Dutch East-Indies (or Indonesia). Global supply of quinine dwindled. Allied armies were at risk. In 1944, US scientists William Doering and Robert Woodward could chemically synthesise quinine. However, this process was of little commercial use.

Two years later, in 1946 we could synthesise a quinine derivative – Chloroquine. This instantly was a commercial as well as a public health success. In 1955, WHO adopted policy of treating every fever with Chloroquine. For many parts of the world, malaria had become resistant to chloroquine. By 1970s, chloroquine was of little use to the American Army, who was then engaged in Vietnam war.

Two new drugs as an outcome of Vietnam war

As Vietnam war progressed, warring armies on both sides badly needed a new drug. US synthesised Mefloquine. Around the the same time, China discovered Artemesinin – another plant product in our struggle against malaria. Artemisinins are derived from extracts of sweet wormwood (Artemisia annua). Today this is a front-line drug for the treatment of malaria, especially highly drug-resistant strains.

Giving credit to malaria elimination

Today, Malaria is on decline. There are many who deserve credit for this feat. Maybe Ronald Ross, who discovered that mosquito is a culprit, or National health programs that continue to run malaria-elimination programs. However, Cinchona tree and Quinine remain unsung heros in this saga. Probably, some credit also goes to an unknown indigenous Peruvian, who first drank water from a lake, that was made bitter by the cinchona tree. Rest all is just history.