CORTEX CINCHONE.

Cortex Peruvianus, Cortex China; Cinchona Bark, Peruvian Bark; F. Ecorce de Quinquina; G. Chinarinde.

Botanical Origin―The genus Cinchona from which the drug under notice is derived, constitutes together with several nearly allied genera, the well-characterised tribe Cinchonea of the order Rubiacea. This tribe consists of shrubs or trees with opposite leaves, 2-celled ovary, capsular fruit, and numerous minute, vertical or ascending, peltate, winged, albuminous seeds.

(A). Remarks on the genus.-The genus Cinchona is distinguished by deciduous stipules, flowers in terminal panicles, 5-toothed superior calyx, tubular corolla expanding into 5 lobes fringed at the margin. The corolla is of an agreeable odour, and of a rosy or purplish hue or white.

The fruit is a capsule of ovoid or subcylindrical form, dehiscing from the base (the fruitstalk also splitting) into two valves, which are held. together at the apex by the thick permanent calyx. The seeds, 30 to 40 in number, are imbricated vertically; they are flat, winged all round by a broad membrane, which is very irregularly toothed or lacerated at the edge.

The Cinchonas are evergreen, with finely-veined leaves, traversed by a strong midrib. The thick leafstalk often of a fine red, is sometimes a sixth the length of the whole leaf, but usually shorter. The leaves are ovate, obovate, or nearly circular; in some species lanceolate, rarely cordate, always entire, glabrous or more rarely hirsute, often variable as to size and form in the same species.

Among the valuable species, several are distinguished by small pits called scrobiculi, situated on the under side of the leaf, in the axils of the veins which proceed from the midrib. These pits sometimes exude an astringent juice. In some species they are replaced by tufts of hair. The young leaves are sometimes purplish on the under side; in several species the full-grown foliage assumes before falling, rich tints of crimson or orange.

The species of Cinchona are so much alike that their definition is a matter of the utmost difficulty, and only to be accomplished by resorting to a number of characters which taken singly are of no great importance. Individual species are moreover frequently connected together by wellmarked and permanent intermediate forms, so that according to the expression of Howard, the whole form a continuous series, the terminal members of which are scarcely more sharply separated from the allied genera, than from plants of their own series.

As to the number and value of the species known, there is some diversity of view. Weddell, in 1870, enumerated 33 species and 18 sub-species, besides numerous varieties and sub-varieties. Bentham and Hooker,1 in 1873, estimated the species as about 36.

(B). Area, Climate and Soil.-The Cinchonas are all natives of South America, where they occur exclusively on the western side of the conti

1 Genera Plantarum, ii. 32.

nent between 10° N. lat. and 22°S. lat., an area which includes portions of Venezuela, New Granada, Ecuador, Peru, and Bolivia.

The plants are found in the mountain regions, no species whatever being known to inhabit the low alluvial plains. In Peru and Bolivia, the region of the Cinchona forms a belt, 1300 miles in length, occupying the eastern slope of the Cordillera of the Andes. In Ecuador and New Granada, the tree is not strictly limited to the eastern slopes, but occurs on other of the Andine ranges.

The average altitude of the cinchoniferous region, is given by Weddell as 5,000 to 8,000 feet above the sea-level. The highest limit, as noted by Karsten, is 11,000 feet. One valuable species, C. succirubra, occurs exceptionally as low as 2,600 feet. Generally, it may be said that the altitude of the Cinchona zone decreases in proportion as it recedes from the equator, and that the most valuable sorts are not found lower than 5,000 feet.

The climate of the tropical mountain regions in which the Cinchonas flourish, is extremely variable,-sunshine, showers, storms, and thick mist, alternating in rapid succession, yet with no very great range of temperature. A transient depression of the thermometer even to the freezing point, and not unfrequent hail-showers, may be borne without detriment by the more hardy species. Yet the mean temperature most favourable for the generality of species, appears to be 12 to 20° C. (54 to 68° F.)

Climatic agencies appear to influence the growth of Cinchona far more than the composition of the soil. Though the tree occurs in a great variety of geological formations, there is no distinct evidence that these conditions control in any marked manner, either the development of the tree or the chemical constitution of its bark. Manure on the other hand, though not increasing perceptibly luxuriance of growth, has a decided effect in augmenting the richness of the bark in alkaloids.2

(C). Species yielding officinal barks.-The Cinchona Barks of commerce are produced by about a dozen species; of these barks the greater number are consumed solely in the manufacture of quinine. Those admitted for pharmaceutical use, are afforded by the following species :

1. Cinchona officinalis Hooker3-A native of Ecuador and Peru, existing under several varieties. It forms a large tree, having lanceolate or ovate leaves, usually pointed, glabrous and shining on the upper surface, and scrobiculate on the under. The flowers are small, pubescent and in short lax panicles, and are succeeded by oblong or lanceolate capsules, an inch or more in length.

2. C. Calisaya Weddell-Discovered by Weddell in 1847, although its bark had been an object of commerce since the latter half of the previous century.

The tree inhabits the warmest woods of the declivities which border the valleys of Bolivia and South-eastern Peru, at an altitude of 5,000 to 6,000 feet above the sea-level. More precisely, the chief localities for

1 That is to say the castern Cordillera, the western and lower range being called the Cordillera of the Coast; no Cinchonas grow on the latter.

2

Broughton, in Pharm. Journ. Jan 4, 1873. 521.

3 Figured in Bot. Magazine, vol. 89 (1863) tab. 5364, including C. Condaminea Humb. et Bonpl. and C. Uritusinga Pavon.

4 Ann. des Sciences nat., Bot. x. (1848) 6, and Hist. nat. des Quinquinas, 1849, tab. 3, figured in Botanical Magazine 1873. 6052.

6

the tree are the Bolivian provinces of Enquisivi, Yungas de la Paz, Larecaja or Sorata, Caupolican or Apolobamba, and Muñecas: thence it passes northward into the Peruvian province of Carabaya, suddenly ceasing on the confines of the valley of Sandia, although as Weddell observed, the adjacent valleys are to all appearance precisely similar.

When well grown, C. Calisaya has a trunk often twice as thick as a man's body, and a magnificent crown of foliage overtopping all other trees of the forest. It has ovate capsules of about the same length (an inch) as the elegant pinkish flowers, which are in large pyramidal panicles. The leaves are 3 to 6 inches long, of very variable form, but usually oblong and obtuse, rarely acute.

A variety named after Joseph de Jussieu who first noticed it, B. Josephiana, but known in the country as Ichu-Cascarilla or Cascarilla del Pajonal, differs from the preceding in that it is a shrub, 6 to 10 feet high, growing on the borders of mountain meadows and of thickets in the same regions as the larger form.

Other forms known in Bolivia as Calisaya zamba, morada, verde or alta, and blanca, have been distinguished by Weddell as varieties of C. Calisaya.

3. C. succirubra Pavon,1-a magnificent tree, 50 to 80 feet high, formerly growing in all the valleys of the Andes which debouch in the plain of Guayaquil. The tree is now almost entirely confined to the forests of Guaranda on the western declivities of Chimborazo, at 2,000 to 5,000 feet above the level of the sea.

The bark appears to have been appreciated in its native country at an early period, if we may conclude that the Red Bark mentioned by La Condamine in 1737, was that under notice. It would seem, however, to have scarcely reached Europe earlier than the second half of the last century. The tree has broadly oval leaves, attaining about a foot in length, nearly glabrous above, pubescent beneath, large terminal panicles of rosy flowers, succeeded by oblong capsules, 1 to 1 inches long.

The other species of Cinchona, the bark of which is principally consumed by the manufacturers of quinine, will be found briefly noticed together with the foregoing, in the conspectus at page 318.

History-The early native history of Cinchona is lost in obscurity. No undoubted proofs have been handed down, to show that the aborigines of South America had any acquaintance with the medicinal properties of the bark. But traditions are not wanting.

William Arrot,3 a Scotch surgeon who visited Peru in the early part of the last century, states that the opinion then current at Loxa, was that the qualities and use of the barks of Cinchona were known to the Indians before any Spaniard came among them. Condamine, as well as Jussieu, heard the same statements, which appear to have been generally prevalent at the close of the 17th century.

It is noteworthy on the other hand, that though the Peruvians tenaciously adhere to their traditional customs, they make no use at the present day of Cinchona bark, but actually regard its employment with repugnance.

1 Figured in Howard's Nueva Quinologia, art. Chinchona succirubra.

2 Howard, 1.c. p. 9.

3 Phil. Trans. xl. for 1737-38. 81.

Humboldt declares that at Loxa, the natives would rather die than have recourse to what they consider so dangerous a remedy. Pöppig 2 (1830) found a strong prejudice to prevail among the people of Huanuco against Cinchona as a remedy for fevers, and the same fact was observed farther north by Spruce in 1861. The latter traveller narrates, that it was impossible to convince the cascarilleros of Ecuador that their Red Bark could be wanted for any other purpose than dyeing cloth; and that even at Guayaquil there was a general dislike to the use of quinine.

Markham notices the curious fact that the wallets of the native itinerant doctors, who from father to son have plied their art since the days of the Incas, never contain cinchona bark.

Although Peru was discovered in 1513, and had submitted to the Spanish yoke by the middle of the century, no mention has been found of the febrifuge bark with which the name of the country is connected, earlier than the commencement of the 17th century.

Joseph de Jussieu,5 who visited Loxa in 1739, relates that the use of the remedy was first made known to a Jesuit missionary, who being attacked by intermittent fever, was cured by the bark administered to him by an Indian cacique at Malacotas, a village near Loxa. The date of this event is not given. The same story is related of the Spanish corregidor of Loxa, Don Juan Lopez de Čanizares, who is said to have been cured of fever in 1630.

Eight years later, the wife of the viceroy of Peru, Luis Geronimo Fernandez de Cabrera y Bobadilla, fourth count of Chinchon, having been attacked with fever, the same corregidor of Loxa sent a packet of powdered bark to her physician Juan de Vega, assuring him of its efficacy in the treatment of “tertiana." The drug fully bore out its reputation, and the countess Ana was cured. Upon her recovery, she caused to be collected large quantities of the bark, which she used to give away to those sick of fever, so that the medicine came to be called Polvo de la Condesa, ie. The Countess' Powder. It was certainly known in Spain the following year (1639), when it was first tried at Alcala de Henares near Madrid.

The introduction of Peruvian Bark into Europe is described by Chifflet, physician to the archduke Leopold of Austria, viceroy of the Netherlands and Burgundy, in his Pulvis Febrifugus Orbis Americani ventilatus, published at Brussels in 1653. He says that among the wonders of the day, many reckon the tree growing in the kingdom of Peru, which the Spaniards call Palo de Calenturas, i.e. Lignum febrium. Its virtues reside chiefly in the bark, which is known as China febris, and which taken in powder drives off the febrile paroxysms. He further states, that during the last few years the bark has been imported into Spain,

1 Der Gesellsch. naturf. Freunde zu Berlin Magaz. i. (1807) 60.

2 Reise in Chile, Peru, etc. ii. (1836). 222. 3 Blue Book East India Chinchona Plant, 1863. 74. 75.

4 Travels in Peru and India, 1862. 2. 5 Quoted by Weddell in his Hist. des Quinquinas, p. 15, from De Jussieu's unpublished MS. The town of Loxa or Loja was founded by the Spaniards in 1546.

The circumstances are fully narrated by

La Condamine (Mém. de l'Acad. royale des Sciences, année 1738). But the cure of the countess was known in Europe much before this, for it is mentioned by Sebastiano Bado in his Anastasis, Corticis Peruvia, seu China China defensio, published at Genoa in 1663. When Bado wrote, it was a debated question whether the bark was introduced to Europe by the count of Chinchon or by the Jesuit Fathers.

7 Villerobel, quoted by Bado, op. cit. 202.

and thence sent to Cardinal Joannes de Lugo1 at Rome.

Chifflet adds, that it has been carried from Italy to Belgium by the Jesuit Fathers going to the election of a general, but that it was also brought thither direct from Peru by Michael Belga, who had resided some years at Lima.

Chifflet, though candidly admitting the efficacy of the new drug when properly used, was not a strong advocate for it; and his publication started an acrimonious controversy, in which Honoratius Faber, a Jesuit (1655), Fonseca physician to Pope Innocent X., Sebastiano Bado2 of Genoa (1656 and 1663), and Sturm (1659) appeared in defence of the febrifuge; while Plempius (1655), Glantz an imperial physician of Ratisbon (1653), Godoy physician to the king of Spain (1653), René Moreau (1655), Arbinet and others contended in an opposite sense.

From one of these disputants, Roland Sturm, a doctor of Louvain, who wrote in 1659,3 we learn that four years previously, some of the new febrifuge had been sent by the archduke Leopold to the Spanish ambassador at the Hague, and that he (Sturm) had been required to report upon it. He further states, that the medicine was known in Brussels and Antwerp, as Pulvis Jesuiticus, because the Jesuit Fathers were in the habit of administering it gratis to indigent persons suffering from quartan fever; but that it was more commonly called Pulvis Peruanus or Peruvianum Febrifugum, while at Rome it bore the name of Pulvis eminentissimi Cardinalis de Lugo, because Cardinal de Lugo used to give it away to the poor:-that it was very scarce :-that in 1658, he saw 20 doses sent to Paris which cost 60 florins. He gives a copy of the handbill which the apothecaries of Rome used to distribute with the powder.

The drug began to be known in England about 1655.5 The Mercurius Politicus, one of the earliest English newspapers, contains in several of its numbers for 1658,6 a year remarkable for the prevalence in England of an epidemic remittent fever, advertisements offering for sale-" the excellent powder known by the name of the Jesuits' Powder"-brought over by James Thompson, merchant of Antwerp.

Brady, professor of physic at Cambridge, prescribed bark about this

1 The cardinal belonged to a family of Seville, which town had the monopoly of the trade with America.

2 Bado in his Anastasis, lib. 3, quotes the opinion of many persons as coinciding with his own.

Febrifugi Peruviani Vindiciarum pars prior-Pulveris Historiam complectens ejusque vires et proprietates. . . exhibens, Delphis, 1659. 12°.

It is in these words :-Modo di adoprare la Corteccia chiamata della Febre. -Questa Corteccia si porta dal Regno di Peru, e si chiama China, o vero China della febre, laquale si adopra per le febre quartana, e terzana, che venga con freddo: s'adopra in questo modo, cioè:

Se ne piglia dramme due, e si pista fina, con passarla per setaccio; e tre hore prima incirca, che debba venir la febre si mette in infusione in un bicchiero di vino bianco gagliardissimo, e quando il freddo com

mincia à venire, ò si sente qualche minimo principio, si prende tutta la presa preparata, e si mette il patiente in letto.

Avertasi, si potrà dare detta Corteccia nel modo sudetto nella febre terzana, quando quella sia fermata in stato di molti giorni.

L'esperienza continua, hà liberata quasi tutti quelli, che l'hanno presa, purgato prima bene il corpo, e per quattro giorni doppo non pigliar' niuna sorte di medicamento, ma auvertasi di non darla se non con licenza delli Sig. Medici, acciò giudicano se sia in tempo à proposito di pigliarla.

5 So says Sir G. Baker, who has traced the introduction of Cinchona in a very able paper published in the Medical Transactions of the College of Physicians of London, iii. (1785)

141-216.

6 Namely No. 422. June 24-July 1; No. 426. July 22-29; No. 439. Oct. 21-28; No. 545. Dec. 9-16.- We have examined the copy at the British Museum.