A short history of Cinchona

The discovery of cinchona 1630-1650

Cinchonais a genus of 23 species, all trees, growing on the eastern slopes of the Andes, mainly in Bolivia, Ecuador and Peru. The cinchona tree is first mentioned in a religious chronicle published in Lima in 1633. It is not known how its effectiveness against malarial fever was discovered. Malaria was absent from the Americas prior to European contact, and cinchona is not mentioned in the lists of remedies compiled by early chroniclers. The widely told story that the Condesa de Chinchón was cured by cinchona bark is now known to be untrue, but led Linnaeus to name the genus after her.

It is, however, certain that by 1650 regular shipments of cinchona bark were reaching Spain. By the 1670s the bark was a well-established remedy in Britain.

Exports from the Spanish Empire 1650-1850

Cinchona bark was a lucrative but problematic export from Spain’s Latin American colonies. The bark was often adulterated with useless bark from other trees. In 1751 the Spanish Crown declared a monopoly on imports. As well as trading in bark, the King gave away large quantities to hospitals throughout Spain. Spanish botanists were commissioned to investigate the cinchona plant, leading to important studies by Ruiz and Pavón, José Celestino Mutis, and Francisco José de Caldas.

A further problem was that harvesting the bark of cinchona trees often led to their death. As the trees grew wild, regeneration was not sufficient to maintain supplies. By the beginning of the 19th century, as Spain’s American colonies gained independence, there was serious concern in Europe over the quality, quantity and price of exports of bark. Cinchona was taking on an increasingly important role in the occupation and safe administration of tropical colonies in Asia (India, Indonesia) and Africa.

Cracking the cinchona code: botany and pharmacy 1850-1930

Up until the 1820s pharmacists had to judge the quality of cinchona bark, as it arrived at London Docks, by colour and taste. The relationship between commercial barks and botanical species was unclear, and there was no assay to measure the active components.

In 1820 the first quinine alkaloids were extracted and described by Pierre Pelletier and Joseph Caventou.

Within five years, the extracted alkaloids had become standard treatment for malaria. The following three decades were critical for the history of cinchona as a standardised and cheap modern medicine, and it is this phase of its history that is best represented in Kew’s collections. It became possible to correlate alkaloid content with botanical species and commercial name. This both enhanced quality control in pharmaceutical manufacturers, such as Howards and Sons, and allowed botanists to search for species ofCinchonalikely to be rich in quinine alkaloids. A new type of scientist appeared, equally able to handle botanical and chemical data: the quinologist. Perhaps the most distinguished of these was John Eliot Howard F.R.S., of Howards and Sons, whose collections account for over half of the Kew specimens.

Transplantation 1860-1880

Concern over the quality and cost of cinchona bark, and the desire to find new plantation crops, led to several unsuccessful attempts to cultivateCinchonain Europe’s Asian colonies. In 1859 Kew and the India Office set in motion a series of plant-collecting trips that were to lead to the widespread planting of cinchona in British India, the Dutch colony of Java, and in British colonies such as Sri Lanka, Jamica and east Africa.

In 1860 Richard Spruce, an intrepid botanical explorer of the Amazon, collected seeds and plants ofCinchona succirubraat Limon, in Ecuador. Arriving in India in 1861, via Kew, these plants became the most widely planted species in India. Clements Markham collectedC. calisayaplants in Peru; by the time the plants arrived at government plantations in India, all were dead. In 1865 Charles Ledger, a trader, bought cinchona seeds from Mamami, a Bolivian native. Charles sent the seeds to his brother George in London, who (after finding no takers in Britain) sold some of the seed to the Dutch. These seeds proved to be from a form ofC. ledgerianathat was exceptionally rich in quinine, and well adapted to Java’s climate. Botanical exploration continued until the 1870s, with introductions of further species into India by Robert Cross.

The transplantation of cinchona is controversial. It formed part of a wider pattern of plant exchange in the 18th and 19th centuries, with extensive flow of plant germplasm out of - and into- the Americas. Although cinchona plantation lead to a massive drop in quinine prices, from 1890 onwards, it is disputed whether or not cheaper quinine really reached the poor in the colonies. this was certainly the intention in India, where large amounts of quinine were distributed free.

The decline of quinine

In the early 20th century quinine was proving ineffective in some patients: the malarial parasite was evolving resistance to the drug. Quinine also has a number of unpleasant side-effects, if consumed in quantity, including nausea and tinnitus. However, the most important factor in the replacement of quinine was the Second World War. The Japanese occupation of Java cut off exports of quinine to Europe and North America, stimulating research into synthetic antimalarials such as Atrabine and Chloroquinine. These largely replaced quinine (although in turn being affected by resistance), but quinine still remains useful for the treatment of some serious forms of malaria, and has potential as a cheap and at least partly effective treatment in areas where no other treatment is available.

Selected reading

  1. Bynum, W. F., and B. Fantini. Editors. 1994.Malaria and ecosystems: historical aspects. Proceedings of a Rockefeller Foundation conference, Bellagio, 18-22 October 1993.Rome: Lombardo Editore Parassitologia 36 (1-2).
  2. Crawford, M. J. 2007. “Para desterrar las dudas y adulteraciones”: scientific expertise and the attempts to make a better bark for the royal monopoly of quina (1751-1790). Journal of Spanish Cultural Studies 8:193-212.
  3. Honigsbaum, M. 2001.The fever trail: in search of the cure for malaria. London: MacMillan.
  4. Honigsbaum, M., and M. Willcox. 2004. “Cinchona,” inTraditional medicinal plants and malaria, Edited by M. Willcox, G. Bodeker, and P. Rasoanaivo, pp. 21-41. Boca Raton, FL: CRC Press.
  5. Jaramillo-Arango, J. 1949. A critical review of the basic facts in the history of cinchona.Journal of the Linnean Society (Botany)53:272-311.
  6. Developing treatments: Malariaexcellent online leaflet from the Royal Pharmaceutical Society of Great Britain.