Where Andes hides his cloud-wreathed crest in snow,
And roots his base on burning sands below;
Cinchona, fairest of Peruvian maids,
To Health’s bright goddess, in the breezy glades
Of Quito’s temperate plains, an alter reared,
Trilled the loud hymn, the solemn prayer preferred
Inaugural Dissertation upon the Cinchonas, their History, Uses and Effects, Hooker (1839)
The story of the cinchona tree is mysterious and remarkable. The bark of the tree eventually managed to influence the geopolitical machinations of colonial powers, accelerate the transition away from the embedded Galenic system of medicine and revolutionise the treatment of malaria. However, as this post will explore, the path was controversial and convoluted.
Learning objectives
1. Explore the confusion around the history of cinchona
2. Consider the societal factors that influence the perception of a medication
3. Reflect on how we can try to avoid the mistakes of the past
The amount of contradictory and uncertain information about cinchona can feel a bit meandering and sometimes frustrating. Therefore, I have attempted to compartmentalise the story into smaller chunks by dividing the blog post into different sections/time periods. The years may overlap in some sections but I hope this minor thematic simplification will help readability.
Some sources report that Jesuit missionaries noticed that the indigenous Quechua population made tea from the bark of certain trees to manage individuals who were shivering. The bark was considered febrifugal, a term that appears to have gone out of fashion as it is sometimes considered synonymous with antipyretic.
However, the legendary but disputed event that really brought the cinchona to European attention supposedly happened as follows…
Around the year 1630, Don Juan López de Cañizares (Corregidor of Loja) became ill with an intermittent fever in what is now modern day Ecuador. A Jesuit missionary named Juan López recommended a remedy that had helped him 30 years earlier in a village called Malacatos, south of Loja. He learned of the bark from Pedro Leiva, cacique of the Malacatos tribe. Levia had told the Corregidor that the tribe had used it for many centuries to treat fever. López tried the bark and quickly recovered.
Some time later, perhaps between 1631-1638, Doña Francisca Henríquez de Ribera, the Countess of Chinchón (the wife of the Spanish viceroy in Lima) became ill with a similar fever. The Corregidor sent some of the bark to the Count (Viceroy Don Luis Gerónimo Fernádez de Cabrera Bobadilla y Mendoza, Fourth Countif Chinchón) explaining its curative properties. The Countess agreed to try the remedy and was miraculously cured.
The supposed details of the story are elaborated further…
“When this [the happy cure] was learned in the City of Lima, the people approached the Vivereine by intermediaries, not so much joyfully and congratucalanlatory, but supplicatingly, begging her to deign to help them, and say, if they would, by what remedy she had at last so marvellously, so quickly, recovered, so that they, who often suffered from precisely this fever could also provide for themselves… The Countess at once agreed. She not only told them what the remedy was, but ordered a large quantity of it to be sent to her, to relieve the suffering of the citizens, who often suffered from the fever. Nor did she only order this great remedy the Bark to be brought, but she wished to dispense it to the many sick with her own hands. And the thing turned out so well that just as she herself had experienced the generous hands of God in that miraculous remedy, so all the needy who took it marvellously recovered their health. And this bark was afterwards called Countess’s Powder…”
The story of the Countess has become even more embellished with time which is perhaps unsurprising as the importance of the bark became more apparent. Bado reportedly said that the bark “proved more precious to mankind than all the gold and silver that the Spaniards had obtained from South America”.
However, there was actually no mention of any serious illness regarding the Countess nor remedy in the official and meticulous diary of the Count of Chinchon. Rather, the Count himself is reported to have had intermittent fevers and was ‘bled’ by his physicians. Returning to the Countess, she never returned to Spain to personally disseminate her miraculous powdered bark but is instead reported to have died in Columbia in the year 1641. It has been suggested that the Countess may have had the fever prior to the diary starting 1631, although most authors seem to agree that the Countess legend (or at least some of it) is a fabrication.
Questions
What really happened?
The eventual importance of cinchona has led many authors to retrospectively ponder the origins of the tree. Over time, fact and fiction have been blurred. Even the term cinchona itself is a generic one and it is unclear exactly what species many of the historical texts refer to. This ambiguity has added to the mystery around the tree and its history.
The stories may have been false, yet the tree was real. The bark and its derivatives eventually came to be known by various names, perhaps both because of uncertainty regarding the precise origin and the differing preparations created to appeal to diverse markets.
A tree grows which they call “the fever tree” in the country of Loxa, whos bark, of the colour of cinnamon, made into powder amounting to the weight of two small silver coins and given as a beverage, cures the fevers and tertians; it has produced miraculous results in Lima.
We do know that the cinchona tree was also called the ‘fever-tree’ but it was also known as the quina-quina. Readers with an interest in etymology may have already made the association with quinine. Indeed, quinine was the active component of the bark and physicians today know it is still indicated for the treatment of malaria. Remaining with etymology for a moment, the word ‘quinine’ comes from the Spanish quina ‘cinchona bark’ and from Quechua kina ‘bark’.
However, quinine was not isolated until much later in the story. Instead, it was the cinchona bark and its crudely refined derivatives that were used for many years. The reputed properties made cinchona highly valuable, not only to treat individuals with fever but also to realise the ambitions of European colonialism at the time. It acquired many names including (but not limited to): Countess’s powder, Jesuits’ bark/powder, Jesuitarum, Pulvis Jesuiticus, Cardinal’s bark/powder, Pulvis cardinalis, Popish powder, quina bark, sacred bark, kina-kina, China-China, China bark, Peruvian bark (Cortex peruanus or peruvianus), Cincona red and even the ‘bark of barks’ (Cortex cortocorum). These various names themselves shine a light and help explain the story. For the purposes of this post and to highlight the ambiguity surrounding the cinchona bark in the past, I will generally refer to it as the bark.
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1640s: Movement to Europe
I would like to say it gets less confusing but the tale of cinchona making the journey from South America to Europe is no less mysterious than those regarding its supposed origin.
“There are probably few events of history about which so many legends and false statements have grown as about the history of cinchona. Many writers have tried to discover its origin, and how first it came to our hemisphere, and for lack of precise information have endeavoured to supplement their scanty resources by calculations or guesses of their own. Those calculations, once set in type, have been willingly accepted by succeeding authors.”
The activity of the Jesuits has no rest, the Jesuit Father Alfonso Mesias Venegas introduced quina into Italy in 1642, Cardinal de Lugo became interested in the new drug and at the Congress of the Order in 1649, the powder of the quina bark is distributed through the good offices of the Brothers who returned to their Provinces, and thenceforward people began to talk of the ‘Powders of the Cardinal’, this being the name by which the powder of the quina bark was designated. Appointed Pope, with the name of Innocent X, Cardinal de Lugo ordered Gabriel Fonseca, in 1668, to examine the curative effects of quina and after the issue of his report, it was provided in the Pharmacy of the Medical College.
Two ‘dragmae’ of finely ground and sieved Bark to be mixed in a glass of strong white wine three hours before the fever is due; and as soon as the shivers begin, or the first symptoms are noted, the patient is made to drink the whole infusion thus prepared, and put to bed. It is to be noted, that in the event of tertian fever this bark can be administered, as stated above, when the fever has persisted for many days. The constant use of this remedy has cured practically all the patients who have taken it, having at first well cleared the bowels. For four days after no other medicine whatsoever must be taken. It must be used only on the advice of the Physicians, who may consider whether it is timely and appropriate to administer it.
By 1647, the bark was arriving regularly from Peru to Italy. However, the associations with the Jesuits created religious and political intrigue, if not outright hostility from some. High profile treatment failures, especially Archduke Leopold of Austria (who was upset that a single dose only resolved his fever for a month) led to physicians being commissioned to denounce the remedy. The negative publicity was compounded by the failure of the miraculous bark to (unsurprisingly) curtail a bubonic plague epidemic in Rome in 1655. Such events caused a serious credibility problem for the bark.
…are to give notice, that the excellent Powder known by the name of the Jesuits Powder, which cureth all manner of Agues, Quotidians, Tertian or Quartan, brought over by James Tompson Merchant of Antwerp, is to be had at Mr. Wilfords in Angel Court, just over against Sepulchre’s Church in the Old Baily or at the shop of Mr. John Crook, at the sign of the ship in St. Pauls Churchyard, a bookseller, with directions for using of the same.
Are there any parallels with the historic credibility of cinchona with contemporary drugs or vaccines?
However, the reputational damage to Jesuits’ power had become too much for it to gain significant traction as a remedy at this point. Even Thomas Sydenham, known for a number of superlatives and sometimes considered the ‘father of English medicine’ or even ‘The English Hippcrates’ was initially unfavourable about the bark. Nevertheless, his friend, Cambridge Professor of medicine, Robert Brady is credited to have made the first prescription for Jesuits’ bark in England dated 1660. By 1666, Sydenham had begun to slowly change his mind and published his renowned book Methodus curandi febres describing the bark, eventually advocating the use of bark for the treatment of ague in future works. However, the bark challenged the traditional Galenic system of medicine. This added another layer of hesitancy and suspicion about the Jesuit’s bark beyond that of pure religious prejudice.
1660 – 1680: The secret of the “debauched apprentice”
Enter Robert Talbor (sometimes also known as Tabor or Talbot). Born about 1642 in Ely, he apprenticed to a Cambridge apothecary named Peter Dent but left in 1668 without a degree. He began practising in marshy malaria ridden Essex where he reported developing a cure for the agues or “marsh fever” through observation and experiment. In 1672 he published his ‘Pyretologia’ which ambiguously describes his secret remedy while simultaneously warning against the use of Jesuits’ powder, particularly in non-expert hands:
And let me advise the world to beware of all palliative Cures and especially that known by the name of Jesuits’ Powder, as it is given by unskillful hands for I have seen most dangerous effects follow the taking of the medicine incorrected and unprepared… Yet this Powder not altogether to be condemned; for it is a noble and safe medicine, if rightly prepared and corrected, and administered by a skilful hand; otherwise as pernicious a medicine as can be taken.
As Keeble suggests, Talbor’s last caveat raises the suspicion that he is protecting his position. Indeed, Talbor goes on to say of his secret method that he will only reveal it once he has “made some little advantage to myself” for his troubles. And he certainly was going to take advantage… Talbor ended up making a fortune. The Royal College of Physicians tried to prosecute him for practising without a licence, but the King intervened.
Question
How did a University drop-out trump the established medical hierarchy and orthodoxy?
What was Talbor’s secret? In a fortuitous turn, the subsequent sequence of events were seemingly revealed when a copy of Le Clerc’s 1702 book, Histoire de la Médecine was purchased by medical historian Rudolph E. Siegel in the early 1960s. The copy he brought probably once belonged to Joseph Constantine Carpue (1746-1846). Of interest, on the fly-leaves there was a note written in French by an even earlier owner, perhaps in response to an allusion to cinchona in Le Clerc’s book. The note gives an extraordinary and seemingly relatively contemporary insight into Talbor and cinchona fits into his story:
I feel obliged to report how Quinquina became finally established all over Europe after it had been (it must be admitted) practically concealed for 30 years by the efforts and the greed of certain people unworthy of such an honourable profession. Being very ill with an intermittent fever which I contracted in Flanders and which afflicted almost our entire army during that year, the woman attending our quarters brought to me a very poor man who had cured several of my servants. He appeared to me so assured of this fact that, seeing that there was nothing of the charlatan about him, I had no hesitation whatever in taking his remedy, although both it and he were quite unknown to me at that time. It was a powder steeped in a large glass of white wine, the whole of which he ordered me to drink three times in 24 hours. But the mixture was so thick that my stomach could not tolerate the weight more than two repeated doses.This however was sufficient to protect me from the fit in such a manner that I was able to embark on my week’s service at the Court of King Charles II, who however had to go by water to Sheerness, the most fever-ridden place in the whole of England. I told this to my little doctor, who gave me permission not only to go there, but also to amuse myself swimming, and even in debauchery if I felt inclined. Thus, when I went on board ship I could not avoid telling the whole story to the most inquisitive King in the whole world, who is also the greatest patron of empirics. At length he ordered me to bring the man to him and he made many experiments with the powder. Since the physicians could not guess what it was, the King gave him a pension of 300 pieces and a Knighthood and made him one of his personal physicians,solely in order to find out and eventually to publish a secret of such importance for the health of mankind.
My little fellow called himself Taber [Talbor]. He was quite ignorant, but so devoted to his project that he stayed especially in an unhealthy district in order to try out and improve his remedy. Having been hard pressed by the physicians of France (where the King had sent him in order to cure his niece) so that he might expose his ignorance in explaining the origin of fevers, he made this celebrated reply: ‘Gentlemen, I do not pretend to know anything about fever except that it is a disease which all you others do not know how to cure, but which I cure without fail.’
Tabor became very rich in Europe, a notable highlight being his remedy (known as ‘le reméde anglais’) being used to treat the Dauphin in 1680. Louis XIV paid him 2000 Louis d’or (a handsome amount at the time), gave him a lucrative pension of 2000 livres plus a title to buy ‘Chevalier’ Talbor’s secret. Talbot agreed on the condition it only be disclosed after he [Talbor] had died. Talbor returned to England becoming a Fellow at St John’s College in 1681 and died later that year (aged about 40) hailed as the ‘Febrium Malleus’ (fever smasher).
The secret remedy was published in Paris in 1686 entitled ‘La connaissance certaine et la prompte et facile guerison des fieveres’ [Certain knowledge and the prompt and easy cure of fevers] and in England in the volume ‘The English Remedy or Talbor’s Wonderful Secret for Curing of Agues and Feavers etc’. Lee reports that the publication of the books increased the price of the bark considerably across Europe.
The French note elaborates on the feelings at the time:
It was very surprising to find that it [Talbor’s remedy] was nothing but Quinquina well disguised. It was only given, in contrast to the method of the physicians, immediately after the fit. One cannot imagine the confusion of the King’s physicians, whom he made great fun of, as was his way, because they had expressly forbidden me Quinquina as a useless and dangerous drug. But the joke was that, some years afterwards [1679], the King himself being dangerously ill at Windsor with an intermittent fever, the Council of State forced a dozen physicians to declare if Quinquina, which they were about to give the King, was not sometimes harmful or, at least, useless. To this they were obliged to answer promptly, and without an opportunity consulting amongst themselves beforehand, and each one frankly assured them that he had often tried it, even on small children, and always with success. After which, the King, already half cured, pressed Dr. [Richard] Lower maliciously, asking him how the very thing which was so bad for me had become so wonderfully good for him. The embarrassed doctor could only reply in a similar tone of railery, that this was a remedy from which only kings were worthy of profiting.
Elsewhere, physician Thomas Short is said to intervened and permitted Talbor to treat Charles II. The author of the note continues:
He [Talbor] became very rich in Paris as well as in Madrid. Having returned from there to Windsor where the Queen presented him her hand for the kiss according to the custom of our country, instead of kneeling down he stretched out his own hand which was completely covered with valuable rings given to him in those countries, from which one can judge both his arrogance and his stupidity. There,it seems to me, was a great victory for the empirics that they should be obliged at the same time to defend me against disease, and, what is still more dangerous, against the doctors too!
The writer of the note is unknown but Siegel reports he must have been a nobleman to introduce Talbor to the King. Talbor’s reputation today is controversial. It has even been alleged that Talbor “stole the knowledge of the bark from Robert Brady, Professor of Physic at Cambridge. Regardless, we can probably assume that Talbor’s secret, success and wealth made him an easy target for jealous medical colleagues keen to tarnish his reputation. He was sometimes called the ‘charlatan of Essex’.
Question
What do you think of Talbor? Could he be described as duplicitous, a charlatan or a pragmatist?
Talbor’s secret had upset and exposed the established medical orthodoxy of the time. Indeed, the reasons behind Sydenham’s change of stance toward the bark has sparked some debate. Latham speculates whether Sydenham was told the secret of the bark by Talbor or perhaps he came to the knowledge by other means or even independently. Either way he goes on to say “what Sydenham gave away, Talbor sold.” Consider how the following passage by Sydenham highlights the conflicting medical ideologies facing physicians at the time:
As I was thinking over the inefficacy of such measures and purging, measures which by weakening the blood protract the disease, the Peruvian bark became my sheet-anchor; concerning which, in spite of the prejudices of many learned men, as well as those almost all the vulgar, I may safely affirm that I have neither seen nor suspected any evil effects, except only such as I noted in my chapter on Rheumatism, wherein I remark, that those who have undergone long courses of it, are liable to a certain sort of scorbutic rheumatism. This, however, is rare, and when it happens is easily cured… If I were only 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; since it not only shows eminent efficiency in agues, but is also useful in affections of the stomach and womb.
Carlos: Oh, Madam, Marriage!
Theodosia: Is to love as the Jesuit’s powder is to an Aguem it stops the fit and in a little time wears it quite off.
Shadwell’s A True Widow in 1679.
How do we reduce the environmental impact of health care?
The race was on to develop successful cinchona plantations elsewhere and outside of South America and break the monopoly and facilitate imperial ambitions. In the meantime, with cinchona prices rising considerably, it is perhaps unsurprising that other barks and bitter substances started to appear on markets.
The increasing European acceptance of cinchona showcases the harsh economics of supply and demand. While attempts continued to get cinchona out of South America, finding various alternatives and imitations had the potential to be a highly profitable venture. Indeed, the market became flooded with supposed cinchona, its various preparations, imitations and fakes, efficacious or not. This was facilitated by the fact that transportation of cinchona was so poor being hampered by delay and packaging, that by the time it reached Europe it could more easily be mixed in with other barks without being detected by buyers.
Indeed, another tree already being exported to Europe was called the Peruvian Balsam Tree (Myroxylon peruiferum). (Un)helpfully, it was also known as Quinaquina or the Quina-Quina tree and was similar to the cinchona and also reputed to have febrifugal properties. It was often difficult to distinguish between the various different barks and bark that had already been used (thereby losing most of its therapeutic activity) was also resold.This was all probably too tempting for unscrupulous merchants with large stocks of out-of-favour or recycled barks and an eye for profit.
As demand grew, however, lack of experience of the bark, uneven consignments, incorrect identification, and the frequent and deliberate pollution of the product by adding the bark of other trees, all ensured the argument over its value was kept alive well into the 19th century.
There is a considerable variety in the external appearance of the Angostura bark, owing however, probably, to its having been taken from trees of different sizes and ages, or from various parts of the same tree, as the states and other properties perfectly agree… Of the natural history of the Angustora bark, we are hitherto completely ignorant: and I have in vain turned over and carefully examined many hundred weight, hoping to find the fruit, or some part of the tree which produces it. I found, indeed, one imperfect leaf, resembling the Bruceal but from this nothing can be inferred. It has, by some German botanists, been considered as the bark of a species of Magnolia – probably the Glauca. But the bark, both of that and the Grandiflora, differ completely from the Angostura… I have, I confess, formed a very favourable opinion of its virtues, and consider it as a generally safe and powerful tonic and antiseptic medicine; as an excellent febrifuge…
Every endeavour has been used to obtain an account of the place of its growth… but hitherto in vain: their supposition is that it grows near the river Oronoko. I find Angostura to be merely the Spanish term for a narrow pass between mountains…
Brande goes on to mention that some, including botanist Joseph Banks had noted Angustora’s resemblance to Brucea antidysenterica, synonymous with Brucea ferruginea. More confusion arises as the specimens of bark being tested although nominally the same appear to be very different. It seems that although various bark products were being sold in Europe, it seemed that the true identity of exactly what was being sold and purchased was a bit of a lottery and was so for some time. I suspect this was permissible since few people knew the nature of the original tree(s) since they were usually from far away exotic places. Perhaps this added to the myth and the appeal. What could possibly go wrong?
Question
What systems are in place to verify the authenticity of medicines?
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1800 – 1820: Barking up the wrong tree
In an excellent account by John Buckingham in his book Bitter Nemesis, he notes that in 1803, Dr Rambach, the state physician of Hamburg was tasked to investigate a child death following the use of Angostura. Rambach noted that the bark being sold in Hamburg was a mixture of two different barks, one true Angostura and the other a potentially poisonous imitation or false Angostura. In 1804, Hamburg apothecaries were threatened with fines if they sold Angostura without official inspection and approval and in 1808 Rambah suggested that the false Angostura was either from Strychnos nux-vomica or similar. Further fatalities occurred around Europe and contamination of the Angostura noted in almost every sample taken from apothecary warehouses in different central European countries. Finally in 1815, the governments of Bavaria, Austria, Baden, and Wueremburg ordered all the Angostura bark in the possession of chemists to be seized and physicians asked not to prescribe it.
It was still not clear where the false Angostura originated and how it managed to contaminate European markets. Husemann gives one version:
One can imagine that zealous efforts were made to track down the source of the false Angostura. It was initially possible to trace this to Holland and it turned out that the Dutch were the actual forgers. Pursued by Holland one goes on to England and thence to the native land of the bark, the East Indies; From there a quantity of the false Angostura had been sent to England, and as John Bull did not know what to do with them, he sent them to the far more shrewd and unscrupulous Mynher, who immediately placed them under a quantity of Bonplandia trifoliata [synonymous with Angostura trifoliata] bark, without caring whether human lives would be endangered by this act. It must be admitted, however, that the druggists had absolutely no scruples in professing that there were two varieties of Angostura, of which they sold one, the fake, at first half cheaper than the genuine one, later the price of the latter rose fivefold, while the wrong one fell below the old price. The druggists also did not conceal the origin and the fatherland, but described them in their price courants as “East Indian” Angostura. This circumstance could easily have led the investigators to the tree to which the poisonous bark belonged. But that by no means happened…
Intoxications caused by the bark of Strychnos nux vomica, Husemann: Strychnine poisoning (1857). Translated via Google Translate. Husemann attacking both the Dutch and English (conjuring up the stereotypical English John Bull) as well as highlighting the financial benefits of introducing fake products into a marketplace at the expense of safety.
Cases such as this along with a desire to get an authentic medicine (or at least one that wasn’t toxic) added pressure to increase genuine supply. The late 1700s and early 1800s were also a time where there was increased interest in isolating the active principles of the barks. There were multiple failed attempts to get seeds and decent specimens out of South America. However, they were plagued with practical issues, not only with the true identities of the specimens involved but also the degradation that would occur in transit between the natural source and the chemist’s laboratory or prospective plantation. Kaufman and Ruveda provide an excellent summary:
In 1746 the Count Claude Toussaint Marot de la Garaye obtained a crystalline substance in France from the [cinchona] bark which he termed “sel essentiel de quinquina”. A few years later, the two French chemists Buquet and Cornette intro- duced a new “sel essentiel de quinquina”; however, both proved to be the inactive calcium salt of quininic acid. In another failure, the Swedish physician Westerling announced in 1782 the discovery of the active principle, which he called “vis coriaria” and later shown to be “cinchotannic acid.”
Antoine François Fourcroy systematically analyzed the bark by extracting it with water, alcohol, acids, and alkaline solutions. In 1790 he was finally able to obtain a dark red, resinous, odorless, and tasteless mass, which he called “chinchona red”. Fourcroy claimed this to be the essential pharmacologic constituent of the bark; however, in contra- diction to his affirmations, it was demonstrated that “chinchona red” was unable to cure malaria. Fourcroy also observed that the water placed in contact with the bark gave litmus a blue color—then a known property of alkalis— and that a green precipitate was produced when the infusion of the bark was treated with lime water. This French scientist was very close to entering the history books as the first to isolate quinine, but, surprisingly, he decided to abandon his research on the bark. Perhaps as a premonition, he com- mented that “doubtlessly, this research work will lead some day to the discovery of a febrifuge for the periodic fever that, once identified, will be extracted from different plants”.
In 1811 the Portuguese navy surgeon Bernardo Antonio Gomes extracted the bark of the gray variety with alcohol, added water and a small amount of potassium hydroxide, and observed the separation of a few crystals. Gomes called this substance cinchonine, which had been previously isolated by Duncan in Edinburgh from certain varieties of quina trees. Interestingly, it seems that the botanist Aylmer B. Lambert was also able to prepare the same compound; however, neither of them suspected the alkaline (alkaloidal) nature of the substance. In 1817 the German Chemist Friedrich Wilhelm Sertürner reported that morphine forms salts in the presence of acids, an observation that led him to the isolation of this important alkaloid. Driven by Sertürner’s findings, Jose- ph Louis Gay-Lussac commissioned his colleague Pierre Jean Robiquet of the Ecole de Pharmacie of Paris with the task of searching for useful applications of the reported strategy. Robiquet’s co-worker Pierre Joseph Pelletier was selected to conduct this study in collaboration with Joseph Bienaime Caventou…
Let us consider Pelletier and Caventou further. Bukingham suggests that after isolating strychnine from nux-vomica, the chemists also expected to also isolate it from false Angostura in 1819. However, they found a much more soluble substance. Initially thinking of the name Angosturine for this new alkaloid, thank goodness they changed their minds to avoid perpetuating the confusion with the unrelated true Angostura. Having said this, the name that stuck, brucine, was itself based on error. Indeed, at this point Pelletier and Caventou actually thought that the false Angostura bark was from African Brucea. One story is that nux vomica was reputedly placed on the drug market under the name Brucea antidysenterica. Buckingham explains:
Pelletier and Caventou had therefore isolated strychnine and brucine from different parts of the same plant. Both occur together in all parts of the tree, and the isolation of the substance they called strychnine on the first occasion, and of brucine on the latter, was partly due to higher concentrations of brucine in the bark and of strychnine in the seeds.
Buckingham goes on to say that “the bark of the nux vomica tree as well as the seeds had been used in Indian medicine, and it had reached the European market for many years past under the name of Lignum colubrinum” although there is again uncertainty about the authenticity of what was actually being sold in European markets. Indeed, Lignum colubrinum was itself sold as an imitation for yet another bark… For a more detailed look into the confusion about Lignum colubrinum which is also unhelpfully known as Strychnos colubrina, have a look at the article Identification and Clarification of Strychnos colubrina L. (Loganiaceae) which is beyond the scope of this blog but more specifically my comprehension.
In 1820, Pelletier and Caventou actually worked with cinchona which was more effective in treating malaria than the grey bark passed to them from Gomes:
The alcoholic extract did not produce a precipitate when diluted with water and basified with potassium hydroxide; instead, a pale yellow gummy mass formed. The compound, which was extraordinarily bitter in taste, was soluble in water, alcohol, and diethyl ether. The latter feature was a key difference between its behavior and that of Gomes’ material. Pelletier and Caventou cleverly demonstrated that the cinchonine isolated by Gomes was a mixture of two alkaloids which they named as quinine and cinchonine, thus successfully crowning a 70 year search.
‘Sappington’s Anti-Fever Pills’ marketed in 1832. John Sappington (1776-1858) imported cinchona from Peru, developed a quinine containing pill at a time when physicians in the US were weary and suspicious of it, perhaps a final hangover from the Galenic system. Source: https://mohistory.org/collections/item/A0181-25248
Question
How do you feel about modern medical patents and drug exclusivity?
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1830 – 1870: Empire and export
The isolation of quinine understandably created even more pressure on supply and the identification of alternatives. In a rare case of a loose end actually being tied up in this story, in 1837, someone called Mr Piddington, perhaps the coroner of Calcutta, made what he thought was a new alkaloid. However…
In vol. iv. Trans. Med Phys. Society of Calcutta there is a paper by Mr. Piddington on the rohuna bark, and the sulphate of its bitter principle. Mr Piddington stated that he had applied the bark to the process described by Paris for preparing sulphate of quinine, and with perfect cuccess. He presented to the society a small specimen of the alleged sulphate of rohuna, and described in full detail the process of its preparation. In 1836, however, it was ascertained by the editor of this work that the salt prepared by Mr Piddington was sulphate of Brucine, and that the bark he operated on was that of the nux-vomica tree. On inquiry in the bazars it was found that in several shops the nux-vomica was sold for the rohun.
Indeed, another doctor (professor at the Calcutta Medical College), Dr William Brooke O’Shauhnessey discovered the true nature of the quinine substitute which was actually from nux-vomica and therefore prevented a large quantity of the material being delivered to Indian hospitals. Rambach’s early supposition was proved right that the false Angostura he encountered in Hamberg many years previously was indeed nux-vomica, or at least what he thought nux-vomica was at the time. Little consolation for those who died at the time.
Back in South America, cinchona was being over harvested but was highly profitable. Colombia, Ecuador and Peru banned the export of seeds which predictably encouraged smuggling efforts.
Samples and seeds of cinchona often perished from on long sea journeys. The invention of the Wardian case (a sealed protective container for plants) by doctor Nathaniel Bagshaw Ward facilitated further attempts to smuggle cinchona out of South America. Source: https://en.wikipedia.org/wiki/Wardian_case
It was only a matter of time. Some seeds were eventually smuggled out and the Dutch began trying to cultivating cinchona in Indonesia while the British attempted the same in India through an expedition led by Sir Clements Markham in 1860. However, cinchona was a challenge to grow in different climates and these early attempts did not yield a worthwhile (i.e profitable) amount of quinine.
Cinchonas exposed not only some of the commercial temptations of British Empire, but also featured as amongst Empire’s many ideological justifications. Particularly, in the immediate aftermath of the Sepoy mutiny of 1857, cinchonas were upheld as emblematic of benevolent Victorian governance. The arrival of cinchonas in British India was presented as ushering in ‘the pleasantest episode of British rule’ which would be characterised by the charitable dispensation of medical relief to the colonial poor.
Today, quinine is perhaps best known by many physicians as a medication used for night cramps and by consumers as a tonic mixed with gin. Tonic water now has limits on how much quinine can be added and the increasing amount of sweetness used make it much less bitter than those used in the 1800s.
Pictures from my local supermarket. The recipe for the modern day Angostura bitters remains a secret. Does it contain Angostura? Apparently it doesn’t. It was originally used as a medicinal product created by revolutionary army surgeon Dr Johann Siegert in 1824 while stationed in the town of Angostura (in Venezuela). It is now more commonly used by bartenders rather than being dispensed by health professionals. On a similar note, the more modern Fever-Tree aromatic tonic water is reported as containing Angostura bark from somewhere in South America. I guess some things never change.
Does history repeat itself or can we learn from the mistakes of our past? Are medicines, money and monopoly inexorably linked? Please consider sharing your thoughts in the comments section.
Summary
Political and religious intrigue, economic factors, ideologies of empire, and personal ambition all contributed to the story of cinchona. The manufactured mystery around its discovery and properties shines a light on the behaviour of patients, doctors and those involved in the markets of health care. Despite the noted benefits of cinchona, it took considerable time for societies and the medical orthodoxy to adapt to the challenge it posed. In the interim, charlatanism and exploitation were given an opportunity to flourish with all the usual consequences. The physicians of today still work with the legacy of colonialism and scarcity of resources in medicine but through understanding the lessons of the past, they can influence and improve the global health care systems of today.
UNEXAMINED MEDICINE 
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