The Jesuits' Bark: Sydenham, Cinchona and the Intermittent Fevers

Table of Contents

1. Agues: The Disgrace of Physicians
2. The Cinchona Tree and Its Bark
3. From Peru to Rome to London
4. Sydenham’s Cautious Beginning (1666)
5. Sudden Deaths and Relapses
6. Robert Talbor and the Essex Marshes
7. The Sheet-Anchor Letter (1680)
8. Quinine Isolated (1820)
9. Cinchonism and the Narrow Path of Quinine
10. From Bark to Artemisinin
11. Key Research Papers
12. Connections
13. Featured Videos

1. Agues: The Disgrace of Physicians

An ague announced itself in stages that every seventeenth-century household recognised: a shaking chill, then a burning fever, then a drenching sweat, after which the patient might feel almost well — until the next fit arrived. Physicians sorted these fevers by their rhythm. A tertian fever returned every other day (on the “third” day, counting the first fit as day one); a quartan returned every third day. Modern medicine matches these rhythms to the life cycles of different species of the malaria parasite, Plasmodium, which bursts out of red blood cells in synchronised waves; each wave brings a fit. The disease itself, and its long history, are described on the site’s Malaria and History of Malaria pages.

Agues were common in the low, marshy country of eastern and south-eastern England, and in the London of Sydenham’s day they were part of ordinary practice. They were also humiliating for physicians, because the standard treatments of the time — bleeding, purging and vomiting to rebalance the humours — did little to stop the fits, and a quartan could drag on for months. Sydenham himself, looking back in 1680, wrote that intermittent fevers “were justly called the opprobria medicorum” — the reproach, or disgrace, of physicians.

It was against this background of repeated failure that a bark which could stop the fits within days caused such excitement, and such suspicion. A remedy that worked when learned theory predicted failure was, for many physicians, as troubling as one that did not work at all.

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2. The Cinchona Tree and Its Bark

The bark came from trees of the genus Cinchona, which grow wild on the forested eastern slopes of the Andes, in the lands that are now Peru, Ecuador and Bolivia. The medicine was the dried bark of the trunk and branches, stripped from the tree and ground to a reddish-brown, intensely bitter powder. For Europeans of the seventeenth century it was simply “the bark” — the most valuable bark in the world.

The genus name itself carries a legend. In 1742 the Swedish botanist Carl Linnaeus named the tree after the Countess of Chinchón, wife of a Spanish viceroy of Peru, who according to a story told by later writers was cured of a fever by the bark in the 1630s and carried it back to Spain. Historians have long treated this tale as a legend rather than a record; it is repeated here only because it explains the name.

What made the bark work was unknown for nearly two centuries after Sydenham. It is now known to contain a family of alkaloids — nitrogen-containing plant compounds — of which quinine is the best known, alongside quinidine, cinchonine and cinchonidine. Their amounts differ greatly between species of Cinchona, between individual trees, and between batches of bark, which is one reason the bark of Sydenham’s day was so unpredictable: one parcel might be strong, another nearly worthless, and adulterated powders were sold as well. One of the bark’s alkaloids, quinidine, later became the first standard drug for irregular heart rhythm, a story told on the History of Arrhythmia page.

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3. From Peru to Rome to London

R. G. Latham, in the Life of Sydenham that opens the Sydenham Society edition, set out a chronology drawn from the eighteenth-century physician Sir George Baker. In that account the bark was first introduced into Spain in 1632. In 1643 Juan de Lugo, a Spanish Jesuit, was made a cardinal and promoted the remedy in Italy. In 1649 a large supply was brought to Rome and distributed through the Jesuits — the source of the name “Jesuits’ bark”. A modern review of the bark’s history by Permin and colleagues agrees on the broad outline: the bark was first given to a European in the 1630s, was recommended by Juan de Lugo, and was known in England by the 1660s.

According to Latham’s chronology the bark “appears to have been first introduced into England” in about 1655. By December 1658 a London newspaper was carrying an advertisement for “Jesuites powder”, and the physician Richard Morton later fixed 1663 as the year it came into general use in Britain. Latham also quotes Robert Boyle’s account of a friend whose winter quartan fever was cured by two doses of the bark — the kind of story that circulated among the learned men of Restoration London.

The Roman and Jesuit connection mattered in Protestant England. The bark arrived bearing the name of a religious order that many English people of the time regarded with deep hostility, and it was promoted by men whose medicine was not that of the English College of Physicians. Prejudice against “Jesuites powder” was therefore partly religious and partly professional, and it shaped how cautiously English physicians, Sydenham among them, first wrote about it.

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4. Sydenham’s Cautious Beginning (1666)

Sydenham’s first book, the Methodus curandi febres of 1666 (dedicated to Robert Boyle), was a book about fevers, and so it had to deal with the bark. His verdict was guarded. In the Sydenham Society translation he writes: “Sometimes, indeed, when given just before the fit, it has killed the patient. Nevertheless, I will not deny that, in the decline of these fevers, Peruvian bark, cautiously given, has sometimes done good, and removed the fits altogether.”

That sentence holds both halves of his early view. On one side was a real fear: patients had died when the bark was given just before an expected fit. On the other was an admission drawn from experience: given later in the illness, and with care, the bark had sometimes stopped the fever outright. He did not yet treat it as a specific remedy — a medicine aimed at one disease — but as one tool among many, to be handled warily.

Latham traces how that caution eased over the following decade. By the Observationes medicae of 1676 his confidence had grown, although Latham still describes his use of the bark in 1666, 1668 and 1676 as partial and hesitant. For quartan fevers, Latham writes, by 1676 “he trusts to bark more than to anything else”, and in the preface to that work he “makes Peruvian bark the type of specific remedies” — the model example of a medicine that cures a particular disease by some power of its own, rather than by purging or bleeding the body. Historians of medicine, including Lester King in his study of empiricism and rationalism in Sydenham’s works, have pointed to this as an example of Sydenham letting experience at the bedside outweigh the theories of his training.

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5. Sudden Deaths and Relapses

In his 1680 letter (described in section 7), Sydenham named the two objections that had held back the bark in London. The first was that when it was given a few hours before the fit it “would sometimes kill the patient at once”. He mentioned specific cases remembered in London: an alderman named Underwood and a Captain Potter. The second objection was relapse: the fits stopped, but often came back after about a fortnight.

Why some patients died suddenly after the bark is not known with certainty. The patients were already gravely ill with fever; the bark of the period was of wildly varying strength; and any death that followed a new and suspect remedy was likely to be blamed on it. In 1985 a short letter in the Lancet by Ouzts, Magill and Miller, titled “Thomas Sydenham and quinine syncope?”, raised the question of whether a fainting reaction to the bark’s alkaloids might explain some of these deaths. The question mark in its title is part of the record: it was a suggestion, not a finding.

The relapses have a clearer modern explanation, although Sydenham could not have known it. Some malaria parasites, notably Plasmodium vivax and P. ovale, can lie dormant in the liver and re-emerge weeks or months later, while bark alkaloids act mainly on the parasites in the blood. A fever could therefore be stopped and yet return. Sydenham’s own words in 1680 show that relapse remained his chief doubt: “If I were only as sure of the permanence of the effect as I am of the harmless character of Peruvian bark, I should look upon it as the prince of medicines.”

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6. Robert Talbor and the Essex Marshes

While Sydenham was writing cautiously about the bark, a young man with no medical degree was building a career on it. Robert Talbor (1642–1681) practised among the ague-ridden marshes of Essex from about 1666, using a remedy whose composition he kept secret. His success brought him to London and then to the courts of England and France: he was knighted, and Louis XIV paid him for the secret of his remedy, which was revealed after Talbor’s death to be based on the bark. T. W. Keeble’s 1997 paper in the Journal of the Royal Society of Medicine examines Talbor’s contribution to the cure of the ague.

The relationship between Talbor’s practice and Sydenham’s growing confidence is a question discussed by historians rather than a settled fact. Sir George Baker raised it in the eighteenth century, and Latham weighed it in 1848. Latham’s conclusion was careful: “That Talbor used bark with success and confidence, when Sydenham used it partially and with hesitation (i.e. in the years 1666, 1668, and 1676) is certain.” Whether Talbor’s example actually changed Sydenham’s practice is not something the surviving records settle. Latham was also sceptical of Talbor’s reputation; that judgement is Latham’s own, and is reported here only as part of the historiography.

Talbor’s story shows how the bark crossed the line between learned medicine and popular practice. A secret preparation sold by an unlicensed practitioner achieved results that the College’s physicians struggled to match, and royal patronage followed the results. Permin and colleagues list Sydenham, Talbor and the Italian physician Francesco Torti together as the figures historians credit with establishing successful treatment of intermittent fever with the bark.

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7. The Sheet-Anchor Letter (1680)

In 1680 Sydenham published his Epistolae responsoriae, two letters in reply to colleagues. The first, addressed to Robert Brady, Regius Professor of Physic at Cambridge, dealt with the epidemics of the preceding years — and in it Sydenham set out his mature view of the bark. A sheet-anchor was a ship’s largest anchor, kept for emergencies; to call something your sheet-anchor was to call it the thing you relied on when all else failed. In the Sydenham Society translation he writes that “the Peruvian bark became my sheet-anchor; concerning which, in spite of the prejudices of many learned men, as well as those of almost all the vulgar, I may safely affirm that I have neither seen nor suspected any evil effects” — with one exception he did note, a rare “scorbutic rheumatism” after long courses.

The same letter records how long the bark had been in use. It had, he wrote, “if I rightly remember, been famous in London for the cure of intermittent fevers for upwards of five and twenty years”. That places its London reputation back to about the mid-1650s, consistent with Latham’s chronology.

Sydenham also addressed a theory of the time: that the bark worked because it was astringent — that it tightened or bound the tissues, as many bitter barks do. He rejected it in two sentences: “Let those who think this, try other astringents. I know none that take effect.” The reasoning is a small example of his method. Rather than accept an explanation because it fitted the theory, he proposed a test: if astringency were the cause, other astringents would cure agues too, and in his experience they did not. Later chemistry bore out his suspicion that the bark held something particular, not merely astringent. Elsewhere in his writings he described the physician’s task as the “industrious investigation of the history of diseases and of the effect of remedies, as shown by the only true teacher — experience”. His bedside method is explored further on the Bedside Observation page.

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8. Quinine Isolated (1820)

For more than a century and a half after Sydenham, physicians went on giving the bark itself, with all its variation in strength. The change came from chemistry. In 1820 the French pharmacists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou isolated the main active alkaloid from cinchona bark and named it quinine. It was one of a run of discoveries in the early nineteenth century in which chemists extracted pure active substances from medicinal plants — following the isolation of morphine from opium, told on the Sydenham’s Laudanum page.

A pure substance could be weighed, so a dose could at last be made consistent, and quinine could be manufactured and traded as a chemical rather than as an uncertain bark. Sydenham himself never used quinine: he gave the powdered bark, which contained quinine among other alkaloids. Writing of “Sydenham’s quinine” is an anachronism.

Demand for quinine soon outstripped the wild trees of the Andes. Permin and colleagues describe how cinchona was taken into plantation cultivation, with Dutch plantations on Java coming to dominate world supply. Quinine remained the principal treatment for malaria into the twentieth century, through the years in which the cause of the disease was finally found: the parasite was identified by Alphonse Laveran in 1880 and its mosquito transmission shown by Ronald Ross and Giovanni Battista Grassi at the end of the century.

How quinine acts on the parasite

Quinine acts mainly on the malaria parasite during its stage inside red blood cells. There the parasite digests the cell’s haemoglobin and must dispose of the toxic haem left over, which it normally locks away in an inert crystal pigment. The leading explanation is that quinine, like the later drug chloroquine, accumulates in the parasite’s digestive compartment and interferes with this disposal, so that haem builds up and poisons the parasite. Because the drug acts on blood-stage parasites, it ends the fits but does not clear the dormant liver forms of some species — consistent with the relapses Sydenham described.

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9. Cinchonism and the Narrow Path of Quinine

The bark and its alkaloids are not harmless, whatever Sydenham’s confidence in 1680. Doses of quinine large enough to treat malaria are not far from doses that cause toxic effects, so the drug has what pharmacologists call a narrow therapeutic range. The characteristic toxic syndrome is called cinchonism, after the tree. A 1989 historical note by A. J. Balfour, “The bite of Jesuits’ bark”, describes how quinine overdose disturbs vision, hearing and balance. In the medical literature the picture typically includes ringing in the ears (tinnitus), muffled hearing, headache, nausea, dizziness and blurred vision; severe poisoning can affect heart rhythm and sight more seriously.

Quinine’s relative, quinidine, acts powerfully on the electrical behaviour of heart muscle — the property that made it a heart-rhythm drug — and quinine shares some of that action. This is one reason the 1985 Lancet letter asked whether a cardiovascular or fainting reaction might lie behind some of the sudden deaths reported in Sydenham’s London, though the letter offered a question rather than proof.

Despite its hazards, quinine has kept a place in malaria treatment. Achan and colleagues, reviewing the drug in 2011 — “almost 400 years after its effectiveness was first documented” — report that artesunate is the first-line treatment for severe malaria, with quinine as an alternative, and that quinine remains important for treating malaria in the first trimester of pregnancy. For uncomplicated malaria, the same review reports that artemisinin-based combination therapies performed better. These are statements about treatment guidelines and trial results as the review describes them. The site’s Antimalarial Drugs and ACT page covers the modern drugs.

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10. From Bark to Artemisinin

The bark’s descendants shaped the twentieth century. Chemists built synthetic antimalarials modelled in part on quinine’s structure, and chloroquine, developed in the 1930s and used on a vast scale after the Second World War, became the mainstay of malaria treatment and control. Permin and colleagues trace this line from the bark through quinine to chloroquine, and then to the problem that followed it: the parasite developed resistance. Chloroquine-resistant Plasmodium falciparum, the species behind the most dangerous form of malaria, spread across much of the malarial world in the second half of the century, and resistance to quinine and other drugs also appeared.

The answer came, once again, from a plant. In China in the late 1960s and 1970s, a research group led by Tu Youyou turned to traditional Chinese medical texts and to sweet wormwood, Artemisia annua (qinghao). Tu’s own account, published in Nature Medicine in 2011 under the title “The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine”, describes how the active compound, artemisinin, was obtained from the herb. Artemisinin and its derivatives, such as artesunate, act quickly on blood-stage parasites and are the basis of today’s artemisinin-based combination therapies. The herb and its compound are described on the site’s Artemisinin and Malaria page. Tu Youyou shared the Nobel Prize in Physiology or Medicine in 2015 for this work.

The line from Sydenham to Tu Youyou is a line of observation applied to natural sources. A bitter Andean bark, used first by people who did not know why it worked, was accepted in England partly because physicians like Sydenham trusted what they saw at the bedside over what theory predicted; two centuries later chemistry found quinine inside it; and another three-quarters of a century after that, an ancient Chinese herbal remedy gave the world its next great antimalarial. Sydenham’s wider life and reputation are covered on the Life and Times page and the Thomas Sydenham hub.

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Key Research Papers

1. 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
2. Keeble TW. A cure for the ague: the contribution of Robert Talbor (1642-81). J R Soc Med. 1997;90(5):285-90. PubMed PMID: 9204030
3. Ouzts HG, Magill DH, Miller JS. Thomas Sydenham and quinine syncope? Lancet. 1985;1(8437):1112. PubMed PMID: 2860330
4. Balfour AJ. The bite of Jesuits' bark. Aviat Space Environ Med. 1989;60(7 Pt 2):A4-5. PubMed PMID: 2775119
5. 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
6. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17(10):1217-20. PubMed PMID: 21989013
7. King LS. Empiricism and rationalism in the works of Thomas Sydenham. Bull Hist Med. 1970;44(1):1-11. PubMed PMID: 4909172
8. Dewhurst K. Thomas Sydenham (1624-1689) reformer of clinical medicine. Med Hist. 1962;6(2):101-18. PubMed PMID: 16562238
9. Pearce JM. Thomas Sydenham "The British Hippocrates". J Neurol Neurosurg Psychiatry. 1995;58(3):292. PubMed PMID: 7897408

PubMed Topic Searches

1. Cinchona bark, history and malaria
2. History of quinine
3. Cinchonism (quinine toxicity)
4. Thomas Sydenham, history

Further Reading

• The Works of Thomas Sydenham, M.D., translated from the Latin edition of Dr Greenhill, with a Life of the Author by R. G. Latham. Sydenham Society, London; vol. 1, 1848 — Internet Archive, volume 1 (Latham’s Life; the 1666 and 1676 passages on the bark).
• The same, vol. 2, 1850 — Internet Archive, volume 2 (the 1680 letter to Robert Brady).

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Connections

• Thomas Sydenham: The English Hippocrates, Laudanum and the Jesuits’ Bark
• Thomas Sydenham: Life and Times
• Sydenham’s Laudanum: Opium as a Seventeenth-Century Remedy
• Bedside Observation: Sydenham’s Method, His Diseases and His Legacy
• Pharmacology
• Tu Youyou
• Ronald Ross
• Malaria
• History of Malaria
• Antimalarial Drugs and ACT
• Artemisinin and Malaria
• History of Arrhythmia (Quinidine)

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