Pelletier and Caventou: Quinine from Cinchona Bark

Table of Contents

1. Deep-Dive Articles
2. 1. Who Pelletier and Caventou Were
3. 2. The Discovery on One Page
4. 3. The Natural Source: Cinchona Bark
5. 4. The Other Plant Alkaloids
6. 5. Timeline at a Glance
7. 6. Later Significance: Quinine Since 1820
8. Key Research Papers
9. Connections
10. Featured Videos

Deep-Dive Articles

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1. Who Pelletier and Caventou Were

Pierre-Joseph Pelletier was born in Paris in 1788 into a family of pharmacists. His father, Bertrand Pelletier (1761–1797), was a pharmacist-chemist and a follower of Lavoisier’s new chemistry, and his grandfather had been a master apothecary in Bayonne. Pelletier took his pharmacy degree at the École de pharmacie in Paris in 1810 and a doctorate in sciences in 1812, with a thesis on gum-resins. He taught natural history at the school from 1815, became a full professor in 1827 and its assistant director in 1832, and was elected to the Académie des sciences in 1840. He died in July 1842.

Joseph Bienaimé Caventou was born on 30 June 1795 in Saint-Omer, in the Pas-de-Calais. He studied at the École de pharmacie and the Faculté des sciences in Paris and in 1816 became pharmacist at the Hôpital Saint-Antoine, where he had a laboratory to work in. From 1817 the two men worked together, the older teacher and the younger hospital pharmacist forming one of the best-known partnerships in the history of chemistry. Caventou was elected to the Académie de médecine in 1821 and taught toxicology at the École de pharmacie from 1835 until he retired in 1859. He died in Paris on 5 May 1877. Short biographical tributes by Haas and by the chemist Marcel Delépine are listed below; the full story is in Pelletier and Caventou: Life and Times.

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2. The Discovery on One Page

Chemists had tried for decades to find what made cinchona bark work. The Lisbon physician Bernardino Antonio Gomes had obtained a crystallisable substance from grey cinchona bark that he called cinchonin, and Pelletier and Caventou credited him in their memoir with the discovery of a particular principle in the bark — one that they recognised to be an organic base able to form salts, like the morphine that Friedrich Sertürner had drawn from opium. They kept Gomes’s name at first and, at the request of the Académie’s commissioners Vauquelin, Thénard and Deyeux, changed it to cinchonine to fit the naming of the vegetable alkalis.

Working through three kinds of bark, they found cinchonine in grey bark, a different alkali in yellow bark and both in red bark. The new alkali, very bitter and in their hands never crystallising as the free base, they named quinine, to distinguish it from cinchonine “by a name that also indicates its origin” (their French: par un nom qui indique également son origine). They argued by analogy that the alkali was the bark’s active principle — morphine carried the calming action of opium, strychnine the convulsive action of nux vomica — but they did not claim that whole bark should be abandoned, and they ended by hoping that some skilful and prudent physician would test the cinchona alkalis in patients. The Paris physician François-Joseph Double ran early trials in fever patients, and Magendie’s Formulaire, which Ségal and Trépardoux describe as built around the new pure alkaloids, carried quinine to prescribers.

The partners published their method in full and did not patent it, according to later accounts, including the 1911 Catholic Encyclopedia; they also went on to manufacture quinine sulphate themselves. In 1827 the Académie des sciences awarded them a shared Montyon prize of 10,000 francs. Military physicians confirmed quinine’s effect in Spain in 1823 and in the Morea in 1828, and François Clément Maillot reported his large-scale use of it in Algeria to the Académie de médecine in 1835. The whole account is in The Discovery of Quinine (1820).

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3. The Natural Source: Cinchona Bark

Cinchona bark comes from trees of the genus Cinchona, which grow on the eastern slopes of the Andes and belong to the Rubiaceae, the coffee family. Miller and colleagues write that the origin of the remedy in Peru remains a mystery because the primary Jesuit records are lacking: Jesuits learned from the Quechua-speaking people that the bark eased chills, but whether Andeans themselves used it for malarial fever is unknown. Permin and co-authors date the first European use against malaria to the 1630s, and Klein and Pieters show that although the bark reached the European market around 1640, it took decades to become accepted, with Paris a central place in that story. The English physician Thomas Sydenham was among those who established its value. The popular story that the bark was named after a cured Countess of Chinchón is a legend.

The barks sold in Pelletier and Caventou’s day differed in colour and in strength. Their memoir explains why: grey bark yielded mainly cinchonine, yellow bark mainly quinine, and red bark both. For the first time a physician could, in principle, know how much of the active substance a dose contained instead of relying on a bark of unknown quality. The plant side of the story is in Cinchona and the Plant Alkaloids of Pelletier and Caventou.

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4. The Other Plant Alkaloids

Quinine was the climax of five busy years. In 1817 Pelletier, working with the physiologist François Magendie rather than with Caventou, isolated emetine from ipecacuanha root, the old emetic; a century later, in 1912, Leonard Rogers reported curing amoebic dysentery with injections of emetine salts. The same year the two partners studied the green pigment of leaves and gave it the name chlorophyll, as Govindjee and colleagues document in their 2024 translation of the 1817 and 1818 papers. In 1818 they found strychnine in the Saint-Ignatius bean and in nux vomica, and in 1819 brucine, in the “false angostura” bark that turned out to come from the same nux vomica tree. They also obtained veratrine from white hellebore and sabadilla, and around 1819–1820 a particular substance from the roots of autumn crocus, Colchicum autumnale, which the German pharmacist Geiger studied further and named colchicine in 1833, according to Karamanou and colleagues.

In 1821, looking for quinine in coffee — coffee was considered a fever remedy and belongs to the same plant family as cinchona — they obtained caffeine. The German chemist Runge had isolated it first in 1819, and Robiquet obtained it independently in 1821, so the pair are counted among its early discoverers rather than as its discoverers. The French historian Fournier places Pelletier and Caventou at the close of the first great era of alkaloid chemistry, which began with Derosne and Sertürner’s work on opium.

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5. Timeline at a Glance

• 1788 — Pierre-Joseph Pelletier is born in Paris.
• 1795 — Joseph Bienaimé Caventou is born in Saint-Omer on 30 June.
• 1810–1812 — Pelletier takes his pharmacy degree and his doctorate in sciences.
• 1816 — Caventou becomes pharmacist at the Hôpital Saint-Antoine.
• 1817 — Pelletier and Magendie report emetine from ipecacuanha; Pelletier and Caventou name chlorophyll.
• 1818 — Strychnine is found in the Saint-Ignatius bean and nux vomica.
• 1819 — Brucine from false angostura bark; veratrine; the colchicum substance around 1819–1820.
• 1820 — The memoir on cinchona barks, naming quinine, is read to the Académie des sciences on 11 September.
• 1821 — Caffeine obtained from coffee; Caventou elected to the Académie de médecine.
• 1823 and 1828 — French military physicians confirm quinine’s effect in Spain and in the Morea.
• 1827 — Shared Montyon prize of 10,000 francs from the Académie des sciences.
• 1835 — Maillot reports on quinine in Algeria; Caventou becomes professor of toxicology.
• 1840 — Pelletier is elected to the Académie des sciences.
• 1842 — Pelletier dies in July.
• 1877 — Caventou dies in Paris on 5 May.
• 1900 — A monument to both men, paid for by international subscription, is raised in Paris.
• 1941 — The monument is destroyed by the German occupiers; a replacement follows in 1951.
• 1942 — The Japanese occupation of Indonesia cuts off the Java cinchona supply.
• 2005 and 2010 — The SEAQUAMAT and AQUAMAT trials compare artesunate with quinine in severe malaria.

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6. Later Significance: Quinine Since 1820

Pure quinine sulphate became a standard medicine, and cinchona became a strategic plant. Lee describes how the bark made it possible for Europeans to explore and settle malarial regions, and how nineteenth-century powers competed for it. Gramiccia tells how the trader Charles Ledger and his Bolivian servant Manuel collected seeds of an exceptionally quinine-rich cinchona; the British government passed them by, the Dutch planted them in Java, and Java came to dominate the world’s supply. When Japan occupied Indonesia in 1942 that supply was cut, which Permin and co-authors link to the push for synthetic antimalarials such as chloroquine. Chemists, meanwhile, spent more than a century trying to make quinine in the laboratory; Kaufman and Rúveda review that quest, from the 1918 Rabe–Kindler work and the 1944 Woodward–Doering claim to the first stereoselective total synthesis in 2001.

In modern medicine quinine has been overtaken but not abandoned. Achan and colleagues describe it in 2011 as still important almost 400 years after its effect was first documented, though limited by poor tolerability and complex dosing regimens. In the AQUAMAT trial of 5,425 African children with severe malaria, deaths were 8.5% with intravenous artesunate and 10.9% with quinine, and the authors concluded that artesunate should replace quinine for severe malaria in children; an earlier Asian trial, SEAQUAMAT, had found a similar advantage in adults and children in Asia. Findings on quinine’s adverse effects, including its use for leg cramps, are set out in Quinine After 1820: Legacy and Later Research. The artemisinin story that followed is told on the Tu Youyou wing.

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Key Research Papers

1. Haas LF. Pierre Joseph Pelletier (1788-1842) and Jean Bienaime Caventou (1795-1887). J Neurol Neurosurg Psychiatry. 1994;57(11):1333. PubMed PMID: 7964807
2. Delepine M. Joseph Pelletier and Joseph Caventou. J Chem Educ. 1951;28(9):454. DOI: 10.1021/ed028p454
3. Pai-Dhungat JV. Caventou, Pelletier &--History Of Quinine. J Assoc Physicians India. 2015;63(3):58. PubMed PMID: 26540843
4. Fournier J. [Alcaloids discovery, markers for the history of organic chemistry]. Rev Hist Pharm (Paris). 2001;49(331):315-32. PubMed PMID: 11776272
5. Ségal A, Trépardoux F. [The Formulaires of Magendie (1821-1840) of the chemical pharmacy to pharmacology]. Hist Sci Med. 2015;49(2):141-56. PubMed PMID: 26492670
6. Govindjee G, Stirbet A, Lindsey JS, Scheer H. On the Pelletier and Caventou (1817, 1818) papers on chlorophyll and beyond. Photosynth Res. 2024;160(1):55-60. PubMed PMID: 38488941
7. Karamanou M, Tsoucalas G, Pantos K, Androutsos G. Isolating Colchicine in 19th Century: An Old Drug Revisited. Curr Pharm Des. 2018;24(6):654-658. PubMed PMID: 29336251
8. Rogers L. THE RAPID CURE OF AMOEBIC DYSENTERY AND HEPATITIS BY HYPODERMIC INJECTIONS OF SOLUBLE SALTS OF EMETINE. Br Med J. 1912;1(2686):1424-5. PubMed PMID: 20766221
9. Miller LH, Rojas-Jaimes J, Low LM, Corbellini G. What Historical Records Teach Us about the Discovery of Quinine. Am J Trop Med Hyg. 2023;108(1):7-11. PubMed PMID: 36410328
10. Klein W, Pieters T. The Hidden History of a Famous Drug: Tracing the Medical and Public Acculturation of Peruvian Bark in Early Modern Western Europe (c. 1650-1720). J Hist Med Allied Sci. 2016;71(4):400-421. PubMed PMID: 26895817
11. Permin H, Norn S, Kruse E, Kruse PR. On the history of Cinchona bark in the treatment of Malaria. Dan Medicinhist Arbog. 2016;44:9-30. PubMed PMID: 29737660
12. Lee MR. Plants against malaria. Part 1: Cinchona or the Peruvian bark. J R Coll Physicians Edinb. 2002;32(3):189-96. PubMed PMID: 12434796
13. Gramiccia G. Ledger's cinchona seeds: a composite of field experience, chance, and intuition. Parassitologia. 1987;29(2-3):207-20. PubMed PMID: 3334083
14. 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(6):854-85. PubMed PMID: 15669029
15. Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, Rosenthal PJ, D’Alessandro U. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144. PubMed PMID: 21609473
16. Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, et al.; AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647-57. PubMed PMID: 21062666
17. Urdang G. The Pelletier and Caventou Monument in Paris. Science. 1946;103(2662):25. PubMed PMID: 17742674

PubMed Topic Searches

1. PubMed: Pelletier Caventou
2. PubMed: quinine history
3. PubMed: cinchona bark history
4. PubMed: alkaloids history discovery

Further Reading

• Pelletier PJ, Caventou JB. “Recherches chimiques sur les quinquinas.” Annales de chimie et de physique 15 (1820). Internet Archive (Wellcome Library copy)
• Magendie F, Pelletier PJ. Recherches chimiques et physiologiques sur l’ipécacuanha. Paris, 1817. Wellcome Collection

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Connections

• Pharmacology
• Pelletier and Caventou: Life and Times
• The Discovery of Quinine (1820)
• Cinchona and the Plant Alkaloids of Pelletier and Caventou
• Quinine After 1820: Legacy and Later Research
• Friedrich Sertürner — Morphine, the Opium Poppy and the First Alkaloid
• Thomas Sydenham: The English Hippocrates, Laudanum and the Jesuits’ Bark
• Tu Youyou: Artemisinin, Sweet Wormwood, and a Nobel Prize
• Ronald Ross: The Mosquito and the Malaria Parasite
• Malaria — The Plasmodium Parasite
• Malaria: History and Discovery
• Antimalarial Drugs and Artemisinin Combination Therapy
• Coffee
• Chlorophyll and Chlorophyllin

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