INTRODUCTION

The year 1492 stands out as a landmark in the history of the world. In that year, and thanks to the intrepidity of the greatest of navigators, Christopher Columbus, a vast new continent was discovered. This continent was not only destined to become the cradle. of twenty-two new nations which in peace as well as in war, as was proved during the last World conflict, have played a vital role in the destiny of the World Community of Nations; but also to bring to humanity the benefit of half a dozen or more new products, without which it is doubtful whether the progress achieved during the last five centuries could have been realized.

All of these products have played a definite part in the progress and well-being of mankind, and some have become essential to large groups of the world's population. Without mani, the subsistence of the African races would be poor indeed. Without the potato, which is second in importance only to wheat as a staple diet throughout the world, the dietetic needs of Europe could scarcely be met. Not without sentiment and symbolism was a monument erected to that tuber in Braunlage (Germany), with the inscription 'The greatest antidote against starvation'. Without rubber, we cannot imagine how the development achieved in electricity, transport and communications during the last century could have been accomplished.

These three outstanding contributions, not to mention maize, an extended and nourishing food, both for human and animal consump­tion; the turkey, which yearly graces our Christmas dinner; the cup of cocoa, which some people enjoy as much as the Anglo-Saxons do their cup of tea, and the smoke of the cigarette, cigar or pipe, which we inhale for stimulus or relaxation.

But there is another product which mankind owes to the New World, and the benefits it has derived from this are no less valuable than those which it has derived from the others. This product is Cinchona. We will more readily acknowledge its importance when we realize that malaria is, and has always been one of the most widespread scourges of‍ humanity—800 million people are attacked by malaria every year-and that Cinchona, with the crystalline products extracted from it, was until recent years the only effective remedy against the disease.

The different aspects of the history of Cinchona have for a long time been the subject of innumerable essays. Interest was once again especially focused on them during the second quarter of the present century, when the Tercentenary Celebrations of the first use of Cinchona by the Europeans were held in various countries, particularly in Great Britain and the United States.

[…]

Nevertheless, that history is still in many a particular rather obscure. What is more, on points which are more or less established facts, or which should have been established facts, one often reads statements which not op.ly contradict each other but are themselves contradicted by the actual, unassailable facts, so that one wonders how these could have passed unchallenged for generations.

[…]

The first of the above questions, whether the aboriginal Indians knew the virtues of Cinchona or not, is a point that has been the subject of contrary and still unreconciled divergencies of opinion. The answer to it, naturally, depends upon the answer which we give to a closely related question: Was or was not malaria known in America before the discovery of Christopher Columbus?

According to responsible and documented writers, malaria was completely unknown in America before the arrival of the Spaniards, and it was carried to the New World either by the Europeans or by the African Negro slaves. Dr Gualberto Arcos, the famous Ecuadorean historian, on the contrary, asserts that malaria has existed in America from pre-Columbian times, that the disease was rampant in the armies of Pachacutec in the year A.D. 1378, and that later it [the bark] was successfully used to treat the intermittent fevers by the tribes of the Paltas and Zaraguros, who administered the bark macerated in Chicha (a kind of fermented maize wine).¹

Without becoming too deeply involved in this argument, we believe that malaria was a known disease among the American Indians from the earliest times, and that Cinchona was familiar to them.

[…]

Without arguing about hieroglyphic documents and writings in unknown languages, whose interpretation is so fortuitous, and observing that, in the same way, those early chroniclers, conquistadores and missionaries do not say anything to the contrary, that the disease was unknown—as neither do they, in general, refer to diseases which certainly must have existed there at the time of the discovery, in the second of the points alluded to, the above-mentioned affirmation is not so absolute: even more, it is rather dogmatic. Moreover, we have it on the authority of Oviedo's Historia General de las Indias that the first two settlements that the Spaniards founded on the Mainland, San Sebastián de Urabá and Santa María de la Antigua del Darién, on the Gulfs of the same name, had both to be abandoned one after the other, the first a short time after its establishment, «under the onslaught of hunger, fever and the Indians»; the second, a few years later, because «on account of its low and marshy site, it was found to be unsanitary»: «Fever became epidemic and about seven hundred soldiers died within two months». In other chroniclers' narrations we find that Don Diego de Ordáz, during his exploration of the Orinoco River in 1534, lost more than 300 men «enfeebled by fever and other diseases induced by the hot, damp atmosphere of the lower stretches of the river». Similarly, when Jiménez de Quesada sailed up the Magdalena River in his endeavour to explore the centre of New Granada (Colombia), «one hundred of them [his men], [a fifth of his force] died during the first weeks», affected also by fevers.³ As a last instance, we have the first-hand evidence of Don Pedro de Alvarado, Governor of Guatemala, who refers to the fact that, when pursuing his design of conquering the northern capital of the Incas, he disembarked in Caraques and marched upon Quito, «the dense forests and swamps of the Ecuadorean lowlands, the declivities of the Andes, the fevers of the tropical coast... presented conditions under which a quarter of the soldiers, a large number of the horses and the greater part of the Indian carriers succumbed and perished».² Malaria «attacked the troops of Alvarado in the pernicious form termed by Krafft-Ebing, malarial delirium, which consists in marked psychic symptoms and terrible excitement».³

As for the original question whether the aborigines knew and used Cinchona, Humboldt, Mutis, Poppig, Spruce, Markham, etc., and other modern explorers and naturalists who, in the last century, visited the "Quina Empire", held the view—a remark which was first made by Ulloa⁵—that, because they had found that among the peoples of these regions there not only prevailed a strong prejudice against Cinchona as a cure for fevers, but that many natives would die rather than have recourse to a remedy which they considered so dangerous, the latter were ignorant of the virtues of Cinchona, and that these were discovered by the Europeans. These commentators, nevertheless, seem to have forgotten two important facts. First, that naturalists like William Arrot, the Scottish surgeon,⁶ Jussieu and La Condamine, who visited Ecuador a century earlier, all explicitly state that the current opinion in Loxa was that the qualities and use of the Quina Bark were known to the Indians long before the arrival of any Spaniard. Secondly, that one of the tragic features of the "Conquest of the New World" was the almost complete extermina­tion in many parts of the native population, so that it cannot be wondered at if, already by the beginning of the nineteenth century, and still more so to-day, the actual country folk nearly everywhere had lost their traditions. Furthermore, it must not be forgotten that Bollus, to whom more extensive reference will be made further on, who lived for many years in Perú, and who wrote the first detailed account of the use of Cinchona in America, definitely affirms that «the bark was known to the Indians and that they used it upon themselves in disease; but that they always tried with all means in their power to prevent the remedy becoming known to the Spaniards, who of all Europeans particularly aroused their ire».⁷ Bollus goes even further: he states that among the Indians «the bark was commonly used for every fever and that the manner in which the Indians employed the bark was in no way different from ours».⁸ Finally, it is well to remember also that owing to its bitterness, Cinchona was always one of the most disagreeable of medicines to take, a fact which has created a marked prejudice against it everywhere. Indeed, the former con­siderations do not mean that the use of the bark was known to all native communities: most probably it was circumscribed to certain tribes, especially in the neighbourhood of Loxa.

As for the highly imaginative stories that the Indians learned of the curative properties of the bark of the Fever Tree by observing that «fever-ailing mountain lions would chew the bark of a particular tree, which turned out to be the Fever Tree», or that the Europeans learned of it because «a Spanish soldier who, seized with a fit of malaria in a deserted spot, drank from a lake surrounded by trees bearing the Peruvian Bark, into which some of them had fallen and impregnated the water, thus making a natural infusion, then fell asleep and when he awoke the fever was gone», just because they are so fanciful such colourful legends deserve to survive. It is an established fact, supported by the accounts of the early missionaries and chroniclers, that the Indians were both natural observers and talented botanists, with a wide knowledge of medicinal plants.

With the discovery of the New World, Cinchona, then, came into the Materia Medica. And for the first time a given remedy, a specific, in the pharmaco-therapeutical sense was introduced into medicine. Strictly speaking, a great and dreaded plague could be combated by individual medicine. The foundation stone of chemotherapy was thus laid. But, what is still more striking, the formula of quinine was due to become later the proto­type formula on the study of the synthetic chemo-therapeutic drugs that were to come.

The legendary story—with rare exceptions, commonly held in the past as authentic⁹— today, thanks in particular to the interesting and documented works of J. Rompel,¹⁰ C. E. Paz-Soldán,¹¹ and A. W. Haggis,¹² almost proved to be a fiction – as to how the virtues of Cinchona were first known by the Europeans and when it was first introduced to Europe is well worth recording here. Its account not only enfolds a tale of great romantic character but, whatsoever the historical veracity, this version impressed a seal upon a scientific fact, which, in any circumstance, would ensure its transmission to posterity. This fact consists in that—impressed and convinced by the account—Linnaeus wished to immortalize the heroine by giving her name to the genus of the quina tree. With the result that, misinformed as to the correct spelling of the name, he wrote "Cinchona" instead of "Chinchona", beginning the word with C instead of Ch, as it should have been, an omission to which Don Hipólito Ruiz, in his Quinología, o tratado del Arbol de la Quina, o Cascarilla (Madrid, 1792), as well as in the earlier manuscript¹³ on which this printed work was based, was the first to call attention, and of which correction Linnaeus himself could never have been aware, for he died the very year (1778) in which Ruiz and Pavón landed in Peru at the head of their celebrated expedition.

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Le Poeme du Quinquina,¹⁴ an ode to the drug in two cantos of 28 pages each, written by La Fontaine at the request of Uranie,¹⁵ name meant to identify the Duchess of Bouillon, and dedicated to her, is a composition which, if in more than one respect is worthy of admiration, in truth adds but little to the reputation of the famed fabulist, neither does it shed any new light upon the history of the medicament. One amongst all of La Fontaine's remarks in this poem is of interest to mention: it is that the discovery of quina was far more valuable than the treasures that the Spaniards were so anxiously searching for in the New World, treasures upon which, we could add, by one of fate's ironies, the conquistadores were never able to lay their hands.¹⁶

Rendons grace au hazard; cent machines sur l'onde
Promenoient l’avarice en tous les coins du monde:
L'or entouré d'ecueils avoit des poursuivans:
Nos mains l'alloient chercher au sein de sa patrie,
Le Quina vint s'offrire a nous en même tems,
Plus digne mille fois de nôtre idolâtrie.Cependant,
près d'un siècle on la vû sans honneurs.
—
Let's give thanks to hazard;
a hundred machines on the waves
Promote avarice in every corner of the world:
Gold surrounded by reefs had pursuers:
Our hands went to seek it in the bosom of its homeland,
The Quina came to offer itself to us at the same time,
More worthy a thousand times of our idolatry.
However, for nearly a century it was seen without honors.

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Early controversy about the medicinal value of Cinchona

If, without any reserve, the discovery of Cinchona was an incalculable benefit for humanity, it does not follow that its merits were immediately and universally recognized. On the contrary. Although it may appear strange today, from the dawn of its introduction into Europe, after the publication of the Schedula Romana, a bitter controversy regarding its virtues raged between the various schools and practitioners for half a century or more. Yet, only when the historical conditions predominant in that epoch are studied, can that singular fact be explained. One of the chief factors in this dispute was religious intolerance, for many Protestants carried their hatred of the Roman Church, and particularly of the Jesuits, to such a point as to condemn a priori a remedy which the efforts of the Jesuits had made available to sick humanity in Europe.

The leading figures in this controversy were Ioannes lacobus Chiffletus (Chifflet), physician to the Archduke Leopold of Austria, Regent of Belgium and Burgundy,¹⁷ who wrote against the bark; the Jesuit Father Honoratus Faber (Fabri), who, under the pseudonym of Antimus Conygius, championed the bark against the attacks .of Chifflet and Renatus Moraeus (Moreau), Professor of Medicine in the Sorbonne and physician to the King of France; Vopiscus Fortunatus Plempius (Plemp), "Rector Magnificus" of the University of Louvain, and Professor of Medicine in it, writing against Fabri under the name of Melippus Protimus; Badus, Sturm and Brunacius who entered the lists against Chiffiet and Plemp; while in England, Gideon Harvey poured scorn on Sir Robert Talbor, his claims as "pyretiatro" and his "method" of treating them: the "Jesuits' Bark".

Ignorance of and inexperience in the use of the bark, the unequal quality of the various consignments of bark which arrived in Europe at that time, the confusion which reigned concerning its correct identification, all these factors contributed powerfully to keeping alight the controversy referred to. The effect of this state of affairs on the reputation of Cinchona was, as much later it was put by a famous Colombian, Don Francisco Antonio Zea,¹⁸ the first Colombian Minister to Great Britain, «its alternating epochs of depression and glory». Relevant to this is that, if in 1655, Moreau wrote from Paris to a friend in Brussels (Plemp), «the reputation of the Peruvian powder is so dead in this city that it is no longer mentioned and we no longer prescribe it»,¹⁹ in 1702, the celebrated Italian clinician Bernardino Ramazzini in a university lecture declared that «surely after the use of this remedy has become known, it must be avowed that, concerning the doctrine of fevers and the method of curing them, a change (revolution) has been made comparable to that which all know followed, in military affairs, the invention of gunpowder».²⁰

The extraordinary career of Sir Robert Talbor²¹ the "charlatan of Essex" (1639-81), still the subject of opposing views, and which had such an adverse effect on the prestige of the physicians of his day, unquestionably must be recognized as one of the most influential factors in the introduction of Cinchona into the pharmacopoeia. As will be remembered, by means of his "marvellous secret", the arcanum, known to the French as le remede de l'Anglais, from his position as simple "Apothecary's man", as Sydenham referred to him, Talbor attained the highest social and professional distinction to which a physician could aspire. Appointed personal physician to Charles II of England, Louis XIV of France and Marie-Louise of Orleans, wife of Charles II of Spain, he was knighted by the kings of France and England and made a Fellow-commoner of St John's College, Cambridge. In order that his subjects might benefit from his "secret", Louis XIV also paid him 2000 louis d'or and an annual pension of £2000 for his prescription. Talbor's "marvellous secret", revealed at his death, did not turn out to be anything else than the discredited Cinchona.

From the point of view of medical ethics, Talbor's general behaviour cannot be excused. At the same time we must acknowledge that he must have been a man of great natural gifts, brilliant intelligence and singular personal charm.

Some antecedents on the botanical classification of Cinchona

It was Linnaeus who, then as now regarded as one of the greatest naturalists of all time., in 1742, established the classification of the "Quina" tree, giving to the genus the name Cinchona. He based his classification upon the drawing of the leaves, flowers and fruit of the tree (Plate 18) made by La Condamine in Cajanuma, two and a half leagues south of Loja (Plate 19), in February 1737, and upon his accompanying description.

On the occasion of the "Cinchona Tercentenary," celebrated in London and the United States in 1930, to commemorate the first recognized use of Cinchona by the Europeans (case of the Corregidor of Loxa), statements were made²² in the sense that the first person to suggest the name Cinchona appears to have been Sebastiano Bado, and that this had been accepted and confirmed by the Communal Council of Ghent. This body was responsible for the regulations governing medical and pharmaceutical practice in Flanders and supervised the admission of new candidates into these professions, receiving their "oaths", in accordance with the resolutions of the Collegium Medicum. Nowhere in Bado's work have we found any support for this statement. Moreover, in response to our inquiries, Prof. Ruyssens, the Rector, and Prof. Apers, the Librarian of the University of Ghent, have made in that respect a careful search in the Antidotarivm Gandavense: the name Cinchona does not appear in it.

This was the official pharmacopoeia used in Ghent and it was completed in 1690. In the earlier edition of 1663, however, an entry appears which may have given rise to some confusion. In the section devoted to powders²³ there is a reference to Pulvis indicus, sive Catholicus, Autrore Marco Cornacchino. Nevertheless, the formula of this powder is given in detail²⁴ in the Antidotarivm and it does not include Cinchona. In these circumstances, and as far as our investigations have revealed, the first official Pharmacopoeia to include Cinchona among the official remedies was the Pharmacopoeia Londinensis of 1677, referred to on p.,297, where it appeared with the name Cortex Peruanus. This first classification of Linnaeus, made just in time to be included as the last of the 'Addenda' which follow the 'Appendix' in his Genera Plantarum of 1742, was by no means definitive. Indeed, it could not be so, for the learned Swede had never seen the plant for himself and La Condamine's Memoir and drawings lacked certain data which were essential for the establishment of all the characters of the genus. In his subsequent works, Linnaeus continued to develop his description. In his Materia Medica (1749) he added some pharmaceutical particulars, and in the Species Plantarum (1753) he first gave to the "Quinquina Condamin" the specific epithet "officinalis".

The Spanish Government, meanwhile, had sent to Loxa Don Miguel de Santisteban, Director of the Upper Mint of Santa Fe (New Granada, Colombia), with instructions to organize locally the trade in the bark (Cabildo de la Quina).²⁵ Back in Bogotá, Santisteban presented samples and a beautiful coloured drawing of the tree to the learned philosopher, mathematician and naturalist Don Jose Celestino Mutis, who, in turn, sent them to Linnaeus, in 1764 (Plate 20). Upon these, Linnaeus supplemented his classification. The consequence was that, as they represented the variety Palo de Requesón, Yellow Bark or Cinchona cordifolia, whereas the drawing and description of La Condamine depicted the Cascarilla fina, Cascarilla de Uritusinga or Cinchona lancifolia, in the far more detailed description included in the twelfth edition of his Systema Naturae of 1767, Cinchona officinalis no longer represents the variety drawn by La Condamine (C. lancifolia) but that of Santisteban and Mutis (C. cordifolia). In his Supplementum Plantarum the younger Linnaeus perfected the description of the genus Cinchona with new information and samples provided also by Mutis.

Two extracts from the Latin correspondence which passed between Mutis and Linnaeus, which resulted in the latter's definitive classification of the genus Cinchona, are worth recording here. We quote Mutis's letter from the English translation published by Sjr James Edward Smith, first President of the Linnaean Society, in the volume devoted to the correspondence of Linnaeus,²⁶ and Linnaeus's letter from Dr Blanco-Juste.²⁷

In his letter to Linnaeus, dated in Santa Fe de Bogota 24 September 1764, Mutis writes:

«…But that my present letter may not seem entirely unprofitable, I send you a drawing, with some of the flowers, of the Peruvian Bark. I am not certain whether the celebrated Monsieur de la Condamine has given any drawing along with his description, nor whether you had an opportunity of examining a dried specimen, as I find no mark indicative of this, in the generic description of Cinchona, in your Stockholm edition of 1754».²⁸

In his reply to Mutis, Linnaeus says:

«...I received in due time, eight days ago, your letter dated the 24th day of September of 1764, and was greatly moved and overjoyed by it, as it contained a beautiful drawing of the quina bark, together with the leaves and flowers, which flowers, never seen by me until now, really have given me an idea of a very rare genus, and very different from that which I acquired through the figure of Monsieur Conda.mine. I am very grateful for everything».²⁹

Final words

The varieties of Cinchona known at present exceed 150, and since the plant is hetero­-stylous, a natural characteristic which prevents auto-pollination and conduces to hybridism, their number tends to increase indefinitely. It was this fact, not then clearly established, which was mainly responsible for the long, acrimonious and generally futile controversies in which some eminent naturalists engaged for many years, regarding the botanical characteristics of this or that species or variety of Cinchona. Arguing from the inspection of different samples, they were attempting to define characteristics which were changing, even within their lifetime.

Foremost among the botanists and naturalists who contributed to the study of the Ecuadorean, Peruvian and Bolivian quinologies were Hipólito Ruiz, Jose Antonio Pavón, Juan Tafalla and Juan Manzanilla; of that of New Granada (Colombia), Jose Celestino Mutis (Plate 21), Francisco Jose de Caldas, Fray Diego Garcia, Francisco Antonio Zea, Jose Joaquin Triana and Nicolas Osorio. Thanks to the discoveries of Cinchona to the north of the equator by Santisteban, Sebastián José López Ruiz, Mutis and García, the bark which until then had to make the long circuitous journey around Cape Horn to reach Europe, to the great disadvantage of its condition, was now sent directly across the Atlantic, from the port of Cartagena, a circumstance which greatly reflected at the time not only upon the commercial aspects of the bark, but consequently upon its medical implications. Great and learned contributions to our present knowledge of the plant were made by various distinguished European naturalists and botanists: among them the most outstanding were Joseph de Jussieu, Jacquin, Humboldt, Bonpland, Kunth, Karsten, Laubert, Weddell, Delondre, Poppig, Swartz, Wahl, Spruce, Lambert, Markham, etc.

The beautiful Cinchona plantations of Java, which, before the war, supplied the bark from which 85 to 90% of the world consumption of quinine was extracted, a yearly average of 750 tons, were developed from the seeds of Cinchona calisaya collected for Charles Ledger in the year 1864 in the Yungas of the Department of La Paz, in the region of Chulumani, near the River Beni (tributary of the Upper Amazon), by the Indian Manuel Icamanahi (Norman Taylor, wrongly, refers to him as Manuel Incra Mamani).

This action of Manuel Icamanahi cost him his life. Humanity, it may be added, owes him the belated honour of a memorial, for his seeds were the source of the quinine which has been used ahnost everywhere for nearly a century, not only against malaria, but in the treatment of influenza!, cardiac and other affections. As it should also acknowledge its immense debt to Charles Ledger, who wandered for years looking for those seeds, and to the distinguished agronomist and arboriculturist L. C. Bernelot Moenz, Director of the Government Cinchona Plantations of the Netherlands East Indies. With great skill, perseverance and insight, the latter carried out an exhaustive series of experiments, particularly by means of grafts, in order to select, cultivate and improve a plant with a high alkaloid yield: the result, as we all know, is the Cinchona ledgeriana, which is now grown throughout the plantations of that island.

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Excerpt from “A Critical Review of the Basic Facts in the History of Cinchona”, published in 1949 by Jaime Jaramillo-Arango.
Complete article available here.

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REFERENCES

1. Arcos, Gualberto, Evolución de la Medicina en el Ecuador. (In Anales de la Universidad Central de Quito), 1938. (p. 1024).
2. Moses, Bernard, The Spanish Dependencies in South America (London, 1914), pp. 8, 19, 40, 106, 126.
3. ibid.
4. Arcos, Gualberto. Op. cit. (p. 1052).
5. Ullóa, Don Jorge Juan y Don Antonio de: Relación Histórica del Viaje hecho de Orden de S. Mag. a la América Meridional etc.— Madrid. 1748.
6. Philosophical Transactions. 1 737-38. (pág. 81).
7. Bado, Sebastiano, Anástasis Corticis Pérvviae, Sev China Chinae Defensio.— Genvae.— 1663. (Cap. 2, ipp. 21-22). Text in latin: Appendix 1.
8. Bado, Sebastiano, Op. cit. Cap. l, pg. 19. Text in latin: Appendix 2.
9. Perhaps only Humboldt, based on the fact that when he visited Loja he found no oral or written reminiscence of it, questioned its veracity.
10. Rompel, Josef, Kristiches Studien zur altesten Geschichte der Chinarinde.— Feldkirch.— 1905.
11. Paz-Soldán, Carlos Enrique, Las Tercianas del Conde de Chinchón (According to Diario de Lima de Juan Antonio Suarda).— Lima.— 1938.
12. Haggis, A. W., Fundamental Errors in the Early History of Cinchona, Reimpreso del Bulletin of the History of Medicine,— Vol. X, 3 y 4. October, November, 1941.
13. Commercial Historical and Medical Compendium of Cinchona - Botanical Department (Natural History) of the British Museum.— Londres.
14. Poeme / du /'Q uinquina, / et autres Oüvrages / en Vers / de M. de la Fontaine,— A París, Chez Denis Thierry, 1682.
15. One of the nine Muses, daughters of Jupiter, who presided over the Arts: Clio over History; Euterpe over Music; Talia over Comedy; Melpomene over Tragedy; Terpsichore over Dance; Erato over Elegy; Polymnia over Lyric Poetry; Urania over Astrology; Calliope over Eloquence and Heroic Poetry.
16. The three great treasures of America, which the Spaniards most feverishly coveted, that of Cuzco, that of El Dorado and that of Montezuma, it is known, escaped their unveiled hunt: the secret of the site where that of “Cuzco” was hidden was lost when, upon the death of Huascar and Atahualpa, sons of the last Imperial Inca Huayna Capac, the former murdered by order of his brother, the latter by order of Pizarro, Carlos Inca, his descendant, left Peru in exile; that of “El Dorado” was never found; and that of Montezuma fell into the hands of the pirate Giovanni da Verazzano, alias Juan Florentin.
17. Archduke Leopold was himself attacked by malarial fevers. Chifflet administered to the august patient the “Peruvian Powders (Peruviani Pulverses”), but, at the request of the Archduke, who detested their bitter taste, he discontinued their use. Soon after, the Prince suffered a relapse. For this unfortunate accident the bark was made responsible.
18. Zea, Francisco Antonio. Memoria sobre la quina según los principios del Sr. Mutis.— Anal. Hist. Nat.— Madrid.— 1800. (II. pp.—196-235).
19. Conygio, Antimo, Pervviani Pvíveris Febrifugi Defensor Repvlsvsa Melippo Protimo Belga. pág. 4.— Texto francés; Apéndice II.
20. Ramazzini, Bernardino, Orationes Jatrici Argumentó etc. Patavii. M . DCC. V III.: Oratio Tertia: Veram Febrium Theoriam & Praxim inter ea, quae al huc desiderantur esse recensendam.— Habita die 6. Novembris M. DCC. II. (pág. 102). Text in latin: Appendix 12.
21. His name is often given as Tabor and is so spelled in Linnaeus' Plate II (q.v.). There are now many Tabors in Essex and their genealogy is traced back 2 or 3 centuries. When in France, Talbor changed its name to Talbot.
22. Dock, George, The Medicinal Use of Cinchona. En, "Proceedings of the Celebration of the Three Hundredth Anniversary of the First recognised Use of Cinchona.— St. Louis, Mo.— 1931", (pág. 157)
23. Tractatus XI, de pulvis simplieibus, & solutivis. _(pág. 134)'.
24. R/ .Scammoneae per sulphur praeparatae § j / Antimonii praepárati ut dicetur § vj / Crystalli tartarí § iiij / Misce fiat pulvis.
25. Relación informativa práctica de la quina de la ciudad de Loxa y demás territorios donde se creía según demostración que hizo el año de 1753 Dn. Miguel de Santisteban, para que se plantificase, conduciéndola por los parages y puertos que cita, a España, con igual cuenta del costo hasta almacenarla. Santa Fe, 4 de junio de 1753. Biblioteca de Palacio.— Madrid. Miscelánea de Ayala. MS. N° 2823. Tomo V III, pp. 82-88.
26. Smith, Sir James Edward, Selection of the Correspondence of Linnaeus.— London— 1 821.— Vol. II.
27. Blanco-Juste, doctor Francisco J., Historia del Descubrimiento de la Quina.— Madrid— 1934.
28. Smith, Sir James Edward, Op. cit. Appendix 13.