A History of Quinine
A History of Quinine
Ara DerMarderosian, PhD
Professor of Pharmacognosy
Research Professor of Medicinal Chemistry
Roth Chair of Natural Products
Scientific Director USP/CAMI
The earliest recorded historical account of quinine comes from 1633 when an Augustinian monk in Lima, Peru wrote about a powder of cinchona “given as a beverage to cure the fevers.”1 According to legend, in 1638 the Jesuits used quina bark to cure the Countess of Cinchón, wife of the Viceroy of Peru, of her fevers. Both the Countess and the Jesuits then brought this Peruvian bark to Europe. It was called “Jesuit powder” or “Countess’s powder”.1
It was an English apothecary’s assistant named Robert Talbor who, in the mid-1600s, realized that the fevers responsive to cinchona bark were those specifically associated with malaria.5 Talbor pioneered the use of cinchona for this indication, although he kept secret his remedy (cinchona bark infusion in claret). He cured malaria in patients living in the fens and marshes of Southern England. He also treated the European royalty and administered his malaria cure to the English King Charles II in 1679, who awarded Talbor with a knighthood and an appointment as Royal Physician. After Talbor’s death in 1681, the King of France disclosed the secret ingredient.
In 1820, Pierre-Joseph Pelletier and Joseph Bienaimé Caventou isolated an alkaloid from cinchona (or quina) bark and named it quinine. The purified compound began to be used instead of powdered bark to treat malaria.4 Subsequent experiments established that this compound is the most active antimalarial constituent of cinchona bark, and Pelletier and Caventou set up a factory in Paris for quinine extraction.
It wasn’t until 1854 that the structure of quinine was elucidated.3,4 By the late 1800s, the malaria parasite had been identified and Ronald Ross had discovered the role of the mosquito vector.3,4,6 Ross launched “mosquito brigades” to eradicate the vector in England, while another public health advocate, S. P. James, advocated improving housing to separate humans from mosquitoes.3,4,6
The British and Dutch tried for years to smuggle cinchona seeds out of South America for cultivation in Java, India, and Ceylon. The Dutch finally succeeded in identifying a high-yield cultivar and establishing extensive and highly profitable plantations on Java. They soon dominated quinine production and, by 1918, controlled the global quinine supply.5 When the Japanese occupied Java in 1942, cutting off the Allies’ supply of quinine, the United States began smuggling seeds from the Philippines to keep World War II soldiers from dying from malaria.5 By 1998, Zaire became the top supplier of the world market for quinine along with Burundi, Cameroon, and Kenya.2 Indonesia and India still cultivate cinchona trees on plantations, while Colombia, Bolivia, and Ecuador still struggle to compete. It is Africa that is today’s leading supplier of cinchona bark from big plantations that were established there during World War II.3,4,6
Efforts to synthesize quinine in the laboratory had been underway since 1850, when the French Society of Pharmacy urged chemists to produce synthetic quinine. It took 50 years to progress from the identification of quinine’s empirical formula to an understanding of how the atoms are arranged in the molecule, and it took another 40 years before stereochemical problems could be worked out. Hoffmann-La Roche disclosed the first total synthesis of quinine in 1970, although stereocontrol was still incomplete.4 Gilbert Stork of Columbia University achieved fully stereochemically controlled total synthesis of quinine in 2001.4
Quinine has a long, rich history. The only FDA-approved indication for quinine sulfate is the treatment of uncomplicated P. falciparum malaria. AR Scientific, Inc.'s Qualaquin™ (quinine sulfate 324-mg capsules) is FDA-approved for treating uncomplicated P. falciparum malaria. Qualaquin oral capsules are not approved for patients with severe or complicated P. falciparum malaria. Qualaquin oral capsules are not approved for prevention of malaria. Qualaquin oral capsules are not approved for the treatment or prevention of nocturnal leg cramps.7
1 Brunton L, Lazo J, Parker K. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006.
2 Database file for quinine (cinchona officinalis). Available at: http://www.rain-tree.com/quinine.htm. Accessed June 2, 2006.
3 Bruce-Chwat LJ. Cinchona and its alkaloids: 350 years. N Y State J Med. 1988;88:318-322.
4 Dagani R. Quinine. The top pharmaceuticals that changed the world. Chem Eng News. 2005;83(25).
5 History: Malaria in England. Available at: http://www.wellcome.ac.uk/en/malaria/MalariaAndControl/chist1.html. Accessed June 2, 2006.
6 Kaufman TS, Rúveda EA. The quest for quinine: those who won the battles and those who won the war. Angew Chem Int Ed Engl. 2005;44:854-885.
7 Quinine sulfate [package insert]. Philadelphia, PA: Mutual Pharmaceutical Company; 2006. Available at: http://thomsonweb.esourcegroup.com/files/PI_0.pdf.