Chapter XXII: Part 22

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Talbor’s reputation increasing, he was appointed in 1678 physician in ordinary to Charles II., and in 1679, the king being ill of tertian fever at Windsor, Talbor cured him by his secret remedy.[1310] He acquired similar favour in France, and upon Talbor’s death (1681), Louis XIV. ordered the publication of his method of cure, which accordingly appeared by Nicolas de Blegny, surgeon to the king.[1311] This was immediately translated into English, under the title of _The English Remedy: or, Talbor’s Wonderful Secret for Cureing of Agues and Feavers.—Sold by the Author Sir Robert Talbor to the most Christian King and since his Death, ordered by his Majesty to be published in French, for the benefit of his subjects, and now translated into English for Publick Good_ (Lond. 1682).

Cinchona bark was now accepted into the domain of regular medicine, though its efficacy was by no means universally acknowledged. It first appeared in the London Pharmacopœia in 1677, under the name of _Cortex Peruanus_.

[1307] 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.

[1308] 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.

[1309] Ph. Journ. vi. (1876) 1022.

[1310] In the _Recueil_ for 1680, p. 275 (see appendix, Talbor) the king is said to have had another attack of fever at Windsor, for which he took “_du Quinquina préparé_,” which again cured him.

[1311] _Le Remède anglais pour la guérison des fièvres, publié par ordre du Roy, avec les observations de Monsieur le premier Médecin de sa Majesté, sur la composition, les vertus, et l’usage de ce remède_, par Nicolas de Blegny, Chirurgien ordinaire du corps de Monsieur, et Directeur de l’Académie des nouvelles découvertes de Médecine, Paris, 1682. 12°.

For the first accurate information on the botany of Cinchona, science is indebted to the French.[1312]

Charles-Marie de la Condamine, while occupied in common with Bouguer and Godin, as an astronomer from 1736 to 1743, in measuring the arc of a degree near Quito, availed himself of the opportunity to investigate the origin of the famous Peruvian Bark. On the 3rd and 4th of February, 1737, he visited the Sierra de Cajanuma, 2½ leagues from Loxa, and there collected specimens of the tree now known as _Cinchona officinalis_ var. _a. Condaminea_. At that period the very large trees had already become rare, but there were still specimens having trunks thicker than a man’s body. Cajanuma was the home of the first cinchona bark brought to Europe; and in early times it enjoyed such a reputation, that certificates drawn up before a notary were provided as proof that parcels of bark were the produce of that favoured locality.

Joseph de Jussieu, botanist to the French expedition with which La Condamine was connected, gathered, near Loxa in 1739, a second _Cinchona_ subsequently named by Vahl _C. pubescens_, a species of no medicinal value.

In 1742 Linnæus established the genus _Cinchona_,[1313] and in 1753 first described the species _C. officinalis_, recently restored and exactly characterized by Hooker, aided by specimens supplied to him by Mr. Howard.

The cinchona trees were believed to be confined to the region around Loxa, until 1752 when Miguel de Santisteban, superintendent of the mint at Santa Fé, discovered some species in the neighbourhood of Popayan and Pasto.

In 1761 José Celestino Mutis, physician to the Marquis de la Vega, viceroy of New Granada, arrived at Carthagena from Cadiz, and immediately set about collecting materials for writing a _Flora_ of the country. This undertaking he carried on with untiring energy, especially from the year 1782 until the end of his life in 1808,—first for seven years at Real del Sapo and Mariquita at the foot of the Cordillera de Quindiu, and subsequently at Santa Fé de Bogotá. Mutis gave up his medical appointment in 1772, for the purpose of entering a religious order, and ten years later was entrusted by the Government with the establishment and direction of a large museum of natural history, first at Mariquita, afterwards at Santa Fé.

A position similar to that of Mutis in New Granada had also been conferred in 1777 on the botanists Hipolito Ruiz and José Pavon with regard to southern Peru, whence originated the well-known _Flora Peruviana et Chilensis_,[1314] as well as most important direct contributions to our knowledge on the subject of Cinchona.

About the same time (1776), Renquizo (Renquifo or Renjifo) found cinchona trees in the neighbourhood of Huanuco, in the central tract of Peru, whereby the monopoly of the district of Loxa was soon broken up.

[1312] _Sur l’arbre de Quinquina_ par M. de la Condamine—_Mém. de l’Académie royale des Sciences pour l’année 1738_. pp. 226-243, with two plates.

[1313] Markham has vigorously contended that the name _Cinchona_ should be altered to _Chinchona_ as better commemorating the countess of Chinchon. But the inconvenience of changing so well-established a name and its many derivatives, has out-weighed these considerations.—See list of works relating to Cinchona at the end of the present article.

[1314] Published at Madrid, 1798-1802, in 4 volumes folio, with 425 plates.

Numerous and important quinological discoveries were subsequently made by Mutis, or rather by his pupils Caldas, Zea, and Restrepo,[1315] as well as on the other hand by Ruiz and Pavon, and their successors Tafalla and Manzanilla. Mutis did not bring his labours to any definite conclusion, and his extensive botanical collections and 5,000 coloured drawings, were sent to Madrid only in 1817, and there remained in a lamentable state of neglect.

Some of his observations first appeared in print in 1793-94, under the title of _El Arcano de la Quina_ in the _Diario_, a local paper of Santa Fé, and were reprinted at Madrid in 1828 by Don Manuel Hernandez de Gregorio. The botanical descriptions of the cinchonas of New Granada, forming the fourth part of the _Arcano_, remained forgotten and lost to science until rescued by Markham and published in 1867.[1316] The drawings belonging to the descriptions were photographed and engraved a little later, and form part of Triana’s _Nouvelles Etudes sur les Quinquinas_, which appeared in 1870.

The two Peruvian botanists succeeded somewhat better in securing their results. Ruiz in 1792, in his _Quinologia_,[1317] and in 1801 conjointly with Pavon in a supplement thereto, brought together a portion of their important labours relating to cinchona. But an essential part called _Nueva Quinologia_,[1318] written between 1821 and 1826, remained unpublished; and after an oblivion of over thirty years, it came by purchase into the hands of Mr. John Eliot Howard, who published it, and with rare liberality enriched it with 27 magnificent coloured plates, mostly taken from the very specimens of Pavon lying in the herbarium of Madrid.

Between the pupils of Mutis on the one hand, and those of Ruiz and Pavon on the other, there arose an acrimonious controversy regarding their respective discoveries, which has been equitably summarized by Triana in the work just mentioned.

=Production=—The hardships of bark-collecting in the primeval forests of South America are of the severest kind, and undergone only by the half-civilized Indians and people of mixed race, in the pay of speculators or companies located in the towns. Those who are engaged in the business, especially the collectors themselves, are called _Cascarilleros_ or _Cascadores_, from the Spanish word _Cascara_, bark. A major-domo at the head of the collectors directs the proceedings of the several bands in the forest itself, where provisions and afterwards the produce are stowed away in huts of slight construction.

Arrot in 1736, and Weddell and Karsten in our own day, have given from personal observation a striking picture of these operations.

[1315] “ ... Mutis n’avait qu’une notion inexacte et confuse du genre _Cinchona_ et de ses véritables caractères; c’est en définitive qu’aucune de ses espèces, dans le sens strict du mot, n’a été reconnue ni découverte par lui.”—Triana, _Nouv. Etudes_, p. 8.

[1316] Markham, _Chinchona Species of New Granada_, Lond. 1867.

[1317] _Quinologia, ó tratado de árbol de la Quina, ó Cascarilla_, Madrid, 1792. 4°. pp. 103.

[1318] _Supplemento á la Quinologia_, Madrid, 1801. 4°. pp. 154.

The cascarillero having found his tree, has usually to free its stem from the luxuriant climbing and parasitic plants with which it is encircled. This done, he begins in most cases at once to remove, after a previous beating, the sapless layer of outer bark. In order to detach the valuable inner bark, longitudinal and transverse incisions are made as high as can be reached on the stem. The tree is then felled, and the peeling completed. In most cases, but especially if previously beaten, the bark separates easily from the wood. In many localities it has to be dried by a fire made on the floor of a hut, the bark being placed on hurdles above,—a most imperfect arrangement. In Southern Peru and Bolivia however, according to Weddell, even the thickest Calisaya bark is dried in the sun without requiring the aid of the fire.

The thinner bark as it dries rolls up into tubes or quills called _canutos_ or _canutillos_, while the pieces stripped from the trunks are made to dry flat by being placed one upon another and loaded with weights, and are then known as _plancha_ or _tabla_. The bark of the root was formerly neglected, but is now in several instances brought into the market.

After drying, the barks are either assorted, chiefly according to size, or all are packed without distinction in sacks or bales. In some places, as at Popayan, the bark is even _stamped_, in order to reduce its bulk as much as possible. The dealers in the export towns enclose the bark in _serons_[1319] of raw bullock-hide, which, contracting as it dries, tightly compresses the contents (100 lb. or more) of the package. In many places however wooden chests are used for the packing of bark.

=Conveyance to the Coast and Commercial Statistics=—The ports to which bark is conveyed for shipment to Europe are not very numerous.

Guayaquil on the Pacific coast is the most important for produce of Ecuador. The quantity shipped thence in 1871 was 7,859 quintals.[1320] Pitayo bark is largely exported from Buenaventura in the Bay of Choco further north.

Payta, the most northerly port of Peru, and Callao, the port of Lima, likewise export bark, the latter being the natural outlet for the barks of Central Peru from Huanuco to Cusco.

Islay, and more particularly Arica, receive the valuable barks of Carabaya and of the high valleys of Bolivia. In 1877 the export of Arica was equal to 5100 cwt.

The barks of Peru and Bolivia find an exceptional outlet also by the Amazon and its tributaries, and are shipped to Europe from port of Brazil. Howard[1321] has given an interesting account of one of the first attempts to utilize this eastern route, made by Senr. Pedro Rada in 1868.

There is a large export of the barks of New Granada, principally from Santa Marta, whence the shipments[1322] in 1871 were 3,415,149 lb.; and in 1872, 2,758,991 lb. From the neighbouring port of Savanilla, which represents the city of Barranquilla, the sea-terminus of the navigation of the Magdalena, the export of bark in 1871 was 1,043,835 lb., value £38,715;[1323] it amounted to 2 millions of kilogrammes in 1877. All Columbia is stated, in 1877, to have shipped 3½ millions of kilogrammes of bark; yet a good deal of the excellent barks of the Columbian State of Santander, especially those of the neighbourhood of Bucaramanga, find their way to Maracaibo, taking the name of that place.

[1319] From _zurrón_, the Spanish name for a pouch or game-bag.

[1320] _Consular Reports_, presented to Parliament, July 1872.

[1321] Seemann’s _Journ. of Bot._ vi. (1868) 323.

[1322] _Consular Reports_, August 1873. 743.

[1323] _Ibid._ August 1872.

Some Cinchona bark is also shipped from Venezuela by way of Puerto Cabello.

The quantity of bark appearing in the _Annual Statement of Trade_ as “Peruvian Bark” imported into the United Kingdom in 1872, was 28,451 cwt., valued £285,620; of which 11,843 cwt. was shipped from New Granada, 4,668 cwt. from Ecuador, and 5,829 cwt. from Peru, the remainder being entered as from the ports of Chili, Brazil, Central America and other countries. The imports into the United Kingdom in 1876 were 26,021 cwt., valued at £272,154.

=Cultivation=—The reckless system of bark-cutting in the forests of South America, which has resulted in the utter extermination of the tree from many localities, has aroused the attention of the Old World, and has at length prompted serious efforts to cultivate the tree on a large scale in other countries.

The idea of cultivating Cinchonas out of their native regions was advanced by Ruiz in 1792, and by Fée of Strassburg in 1824.[1324] Royle[1325] pointed out in 1839 that suitable localities for the purpose might be found in the Neilgherry Hills and probably in many other parts of India, and argued indefatigably in favour of the introduction of the tree.

The subject was also urged in reference to Java in 1837 by Fritze, director of medical affairs in that island; in 1846 by Miquel, and subsequently by other Dutch botanists and chemists.[1326]

Living Cinchonas had been taken to Algeria as early as 1849, by the intervention of the Jesuits of Cusco, but their cultivation met with no success.

Weddell in 1848 brought cinchona seeds from South America to France, and strenuously insisted on the importance of cultivating the plant. His seeds, especially those of _C. Calisaya_, germinated at the Jardin des Plantes in Paris, and in June 1850, living seedlings were sent to Algeria; and in April 1852, through the Dutch Government, to Java.

The first important attempts at cinchona cultivation were made by the Dutch. Under the auspices of the Colonial Minister Pahud, afterwards Governor-General of the Dutch East Indies, the botanist Hasskarl was despatched to Peru for the purpose of obtaining seeds and plants. His mission was so far successful, that a collection of plants contained in 21 Wardian cases, was shipped in August 1854 from Callao, in a frigate sent expressly to receive them. Notwithstanding every care, the plants did not reach Java in good condition; and when Hasskarl resigned his appointment in 1856, he bequeathed to his successor Junghuhn only 167 young cinchonas, though 400 specimens had been shipped from South America.

[1324] _Cours d’Hist. nat. pharmaceutique_, ii. (1828) 252.

[1325] _Illustrations of the Bot. of the Himalayan Mountains_, i. (1839) 240.

[1326] According to K. W. van Gorkom, suggestions to the same end were made to the Dutch Government as early as 1829 by Reinwardt.

An impulse to the project of cinchona-planting was given in 1852 by Royle, in a report addressed to the East India Company, in which he pointed out that the Government of India were then spending more than £7,000 a year for Cinchona bark, in addition to about £25,000 for quinine.[1327]

After some unsatisfactory endeavours on the part of the British Government to obtain plants and seeds through the intervention of H. M. Consuls in South America, Mr. Markham offered his services, which were accepted. Markham, though not a professed botanist, was well qualified for the task by a previous acquaintance with the country and people of Peru and Bolivia, and by a knowledge of the Spanish and Quichua languages,—and even more so by a rare amount of zeal, intelligence, and forethought. Being fully aware of the difficulties of the undertaking, he earnestly insisted that nothing should be neglected which could ensure success; and in particular made repeated demands for a steam-vessel to convey the young plants across the Pacific to India, which unfortunately were not complied with. He further urged the desirableness of not confining operations to a single district, but of endeavouring to procure by different collectors all the more valuable species.

The prudence of this latter suggestion was evident, and Markham was enabled to engage the services of Richard Spruce, the distinguished botanist, then resident in Ecuador, who expressed his readiness to undertake a search for the Red Bark trees (_C. succirubra_) in the forests of Chimborazo. He also secured the co-operation of G. J. Pritchett for the neighbourhood of Huanuco, and of two skilful gardeners, John Weir and Robert Cross. The last named was employed in 1861 to procure seeds of _C. officinalis_ from the Sierra de Cajanuma near Loxa, and in 1868-64 those of _C. pitayensis_ from the province of Pitayo in Ecuador.[1328]

Markham reserved for himself the border-lands of Peru and Bolivia, in order to obtain _C. Calisaya_; and for this purpose started from Islay in March 1860. Arriving in the middle of April by way of Arequipa and Puno, at Curcero, the capital of the province of Carabaya, he made his way to the village of Sandia, near which he met with the first specimens of _Cinchona_ in the form of the shrubby variety of _C. Calisaya_, termed _Josephiana_. He afterwards found the better variety _a. vera_, and also _C. ovata_ R. et P., _C. micrantha_ R. et P., and _C. pubescens_ Vahl. Of these sorts, but chiefly of the first three, 456 plants were shipped at Islay in June 1860.

In consequence of the hostile attitude of the people, and the jealousy of the Bolivian Government, lest an important monopoly should be broken up, added to the difficulties arising from insalubrious climate and the want of roads, the obstacles encountered by Markham were very great, and no attempt could be made to wait for the ripening of the seeds of the Calisaya, which takes place in the month of August.[1329]

[1327] In 1870, the Indian Government purchased no less than 81,600 ounces of sulphate of quinine, besides 8,832 ounces of the sulphates of cinchonine, cinchonidine and quinidine. The quantities bought in subsequent years have been much smaller until the present year (1874).

[1328] _Report on the Expedition to procure seeds of C. Condaminea_ (1862); also _Report to the Under Secretary of State for India on the Pitayo Chinchona_, by Robt. Cross, 1865.

[1329] Great difficulty was at first experienced in successfully conveying living Cinchona plants to India, even in Wardian cases; and the collections formed by Hasskarl, Markham, and Pritchett almost all perished after reaching their destination (Markham’s letter, 26 Feb. 1861). But the propagation by seed has proved very rapid.

The expedition of Spruce was successful, but was also attended with much difficulty and danger, of which there are vivid pictures in the interesting narratives by himself and by Cross, published in the Parliamentary Returns of 1863 and 1866.[1330]

The service entrusted, to Pritchett was also efficiently performed; and he succeeded in bringing to Southampton six cases containing plants of _C. micrantha_ and _C. nitida_, besides a large supply of seeds.

Some important supplies of plants and seed for British India have likewise been obtained from the Dutch plantations in Java. Seeds of _C. lancifolia_, the tree affording the valuable bark of New Granada, were procured through Dr. Karsten.

Previously to the arrival in India of the first consignment of plants, careful inquiries were instituted from a meteorological and geological point of view, as to the localities most adapted for the cultivation. This resulted in the selection for the first trial of certain spots among the Neilgherry (or Nilgiri) Hills on the south-west coast of India and in the Madras Presidency. Of this district, the chief town is Ootocamund (or Utakamand), situated about 60 miles south of Mysore and the same distance from the Indian Ocean. Here the first plantation was established in a woody ravine, 7,000 feet above the sea-level, a spot pronounced by Mr. Markham to be exceedingly analogous, as respects vegetation and climate, to the Cinchona valleys of Carabaya. Other plantations were formed in the same neighbourhood, and so rapid was the propagation, that in September 1866, there were more than 1½ millions of Cinchona plants on the Neilgherry Hills alone.[1331] The species that grows best there is _C. officinalis_.

The number was stated to be in 1872, 2,639,285, not counting the trees of private planters. The largest are about 30 feet high, with trunks over 3 feet in girth. The area of the Government plantations on the Neilgherry Hills is 950 acres.[1332]

Plantations have also been made in the coffee-producing districts of Wynaad, and in Coorg, Travancore and Tinnevelly, in all instances, we believe, as private speculations.

Cinchona plantations have been established by the Government of India in the valleys of the Himalaya in British Sikkim,[1333] and some have been started in the same region by private enterprise. In the former there were on the 31st March 1870, more than 1½ millions of plants permanently placed, the species growing best being _C. succirubra_ and _C. Calisaya_. The Cinchona plantation of Rungbi near Darjiling (British Sikkim) covered in 1872 2,000 acres. In the Kangra valley of the Western Himalaya, plantations have been commenced, as well as in the Bombay Presidency, and in British Burma.

[1330] _Correspondence relating to the introduction of the Chinchona Plant into India_, ordered by the House of Commons to be printed 20 March 1863 and 18 June 1866.

[1331] Blue Book (Chinchona Cultivation, 1870. p. 30).—A name that must always be remembered in connection with the Neilgherry plantations, is that of William Graham McIvor, who by his rare practical skill and sagacity in the cultivation and management of the tree, has rendered most signal services in its propagation in India.

[1332] _Moral and material progress and condition of India during 1871-72_, presented to Parliament 1873. p. 33.

[1333] The first annual Report dates from 1862 to 1863; I am indebted to Dr. King for that of 1876-1877.—F. A. F.

Ceylon offers favourable spots for the cultivation of Cinchona, in the mountain region which occupies the centre of the island, as at Hakgalle, near Neuera-Ellia, 5,000 feet above the sea, where a plantation was formed by Government in 1861. The production of bark has been taken up with spirit by the coffee-planters of Ceylon.

The Government of India has acted with the greatest liberality in distributing plants and seeds of Cinchona, and in promoting the cultivation of the tree among the people of India; and it has freely granted supplies of seed to other countries.

The plantations of Java commenced by Hasskarl, increased under Junghuhn’s management to such an extent, that in December 1862 there were 1,360,000 seedlings and young trees, among which however the more valuable species, as _C. Calisaya_, _C. lancifolia_, _C. micrantha_ and _C. succirubra_, were by far the least numerous, whereas _C. Pahudiana_, of which the utility was by no means well established, amounted to over a million. The disproportionate multiplication of this last was chiefly due to its quickly yielding an abundance of seeds, and to its rapid and vigorous growth. Another defect in the early Dutch System of cultivation arose from the notion that the Cinchona requires to be grown in the shade of other trees, and to a less successful plan of multiplying by cuttings and layers.

These and other matters were the source of animated and often bitter discussions, which terminated on the one hand by the death of Junghuhn in 1864, and on the other by the skilful investigations of De Vry. This eminent chemist was despatched by the Government of Holland in 1857 to Java, that he might devote his chemical knowledge to the investigation of the natural productions of the island, including the then newly introduced Cinchona. It was March 16th, 1859, when Dr. de Vry laid before the governor-general, Mr. Pahud, the first crystals of sulphate of quinine he had prepared from bark grown in that island.

Under K. W. van Gorkom, who was appointed superintendent in 1864, the Dutch plantations have assumed a very prosperous state. J. C. Bernelot Moens,[1334] the present director, stated that at the end of 1878 the leading species was Calisaya in its various forms, including more than 400,000 plants of Ledger’s Calisaya. Numerous analyses of Bernelot Moens show a percentage of from 4½ to 10·6 of quinine in the latter variety. Some of them, however, in December 1878, afforded not more than 0·64 per cent. of quinine and 1·26 of cinchonidine.

The regular shipments of the barks from Java to the Amsterdam market are going on, and the barks are sold there with regard to the results of the government chemist’s analyses.

Cinchona Bark from the Indian plantations began to be brought into the London market in 1867,[1335] and now arrives in constantly increasing quantities.

The history of the transplantation of the Cinchona down to the year 1867 has been made the subject of the report of Soubeiran and Delondre mentioned at the end of the present article.

[1334] I am indebted to the Dutch administration for their interesting statistical documents relating to Cinchona.—F. A. F.

[1335] When I was in London, in August 1867, I went to Finsbury Place, to meet Mr. Spruce, and was happy enough to find there also Mr. Howard, who presented Mr. S. and myself with market samples of the _first_ importation of _C. succirubra_, from Denison plantation, Ootacamund.—F. A. F.

=Description=—(=A.=) _Of Cinchona Barks generally_—In the development of their bark, the various species of Cinchona exhibit considerable diversity. Many are distinguished from an early stage by an abundant exfoliation of the outer surface, while in others this takes place to a smaller degree, or only as the bark becomes old. The external appearance of the bark varies therefore very much, by reason of the greater or less development of the suberous coat. The barks of young stems and branches have a greyish tint more or less intense, while the outer bark of old wood displays the more characteristic shades of brown or red, especially after removal of the corky layers.

In the living bark, these colours are very pale, and only acquire their final hue by exposure to the air, and drying. Some of them however are characteristic of individual species, or at least of certain groups, so that the distinctions originated by the bark-collectors of _pale_, _yellow_, _red_, etc.[1336] and adopted by druggists, are not without reason.

In texture, the barks vary in an important manner by reason of diversity in anatomical structure. Their fracture especially depends upon the number, size, and arrangement of the liber-fibres, as will be shown in our description of their microscopic characters.

The taste in all species is bitter and disagreeable, and in some there is in addition a decided astringency. Most species have no marked odour, at least in the dried state. But this is not the case in that of _C. officinalis_, the smell of which is characteristic.

(=B.=) _Of the Barks used in pharmacy_—For pharmaceutical preparations as distinguished from the pure alkaloids and their salts, the Cinchona barks employed are chiefly of three kinds.

1. _Pale Cinchona Bark_, _Loxa Bark_, _Crown Bark_[1337]—This bark, which previous to the use of Quinine and for long afterwards, was the ordinary _Peruvian Bark_ of English medicine, is only found in the form of quills, which are occasionally as much as a foot in length, but are more often only a few inches or are reduced to still smaller fragments. The quills are from ¾ down to an ⅛ of an inch in diameter, often double, and variously twisted and shrunken. The thinnest bark is scarcely stouter than writing paper; the thickest may be ⅒ of an inch or more.[1338] The pieces have a blackish brown or dark greyish external surface, variously blotched with silver-grey, and often beset with large and beautiful lichens. The surface of some of the quills is longitudinally wrinkled and moderately smooth; but in the majority it is distinctly marked by transverse cracks, and is rough and harsh to the touch. The inner side is closely striated and of a bright yellowish-brown.

The bark breaks easily with a fracture which exhibits very short fibres on the inner side. It has a well-marked odour _sui generis_, and an astringent bitter taste. Though chiefly afforded by _C. officinalis_, some other species occasionally contribute to furnish the Loxa Bark of commerce as shown in the conspectus at p. 355.

[1336] The following are common terms in reference to the barks of Peru:—_Amarilla_ (yellow), _blanca_ (white), _colorado_ or _roja_ (red), _naranjada_ (orange), _negrilla_ (brown).

[1337] _Cortex Cinchonæ pallidæ_; F. _Quinquina Loxa_; G. _Loxachina_. The term _Crown Bark_ was originally restricted to a superior sort of Loxa Bark, shipped for the use of the royal family of Spain.

[1338] In the old collections of the Royal College of Physicians, there are specimens of very thick Loxa Bark, of a quality quite unknown there at the present day. They are doubtless the produce of ancient trees, such as were noticed by La Condamine.

2. _Calisaya Bark_, _Yellow Cinchona Bark_.[1339]—This bark, which is the most important of those commonly used in medicine, is found in flat pieces (α.), and in quills (β.), both afforded by _C. Calisaya_ Wedd., though usually imported separated.

α. _Flat Calisaya_—is in irregular flat pieces, a foot or more in length by 3 to 4 inches wide, but usually smaller, and ²/₁₀ to ⁴/₁₀ of an inch in thickness; devoid of suberous layers and consisting almost solely of liber, of uniform texture, compact and ponderous. Its colour is a rusty orange-brown, with darker stains on the outer surface. The latter is roughened with shallow longitudinal depressions, sometimes called _digital furrows_.[1340] The inner side has a wavy, close, fibrous texture. The bark breaks transversely with a fibrous fracture; the fibres of the broken ends are very short, easily detached, and with a lens are seen to be many of them faintly yellowish and translucent.

A well-marked variety, known as _Bolivian Calisaya_, is distinguished for its greater thinness, closer texture, and for containing numerous laticiferous ducts which are wanting in common flat Calisaya bark.

β. _Quill Calisaya_—is found in tubes ¾ to 1½ inch thick, often rolled up at both edges, thus forming double quills. They are always coated with a thick, rugged, corky layer, marked with deep longitudinal and transverse cracks, the edges of which are somewhat elevated. This suberous coat, which is silvery white or greyish, is easily detached, leaving its impression on the cinnamon-brown middle layer. The inner side is dark brown and finely fibrous. The transverse fracture is fibrous but very short. The same bark also occurs in quills of very small size, and is then not distinguishable with certainty from Loxa bark.

3. _Red Cinchona Bark._—Though still retaining a place in the British Pharmacopœia, this is by far the least important of the Cinchona barks employed in pharmacy. But as the tree yielding it (_C. succirubra_) is now being cultivated on a large scale in India, the bark may probably come more freely into use.

Red Bark of large stems, which is the most esteemed kind, occurs in the form of flat or channelled pieces, sometimes as much as ½ an inch in thickness, coated with their suberous envelope which is rugged and warty. Its outermost layer in the young bark has a silvery appearance. The inner surface is close and fibrous and of a brick-red hue. The bark breaks with a short fibrous fracture.[1341]

(=C.=) _Of the Barks not used in pharmacy_—Among the non-officinal barks, the most important are afforded by _Cinchona lancifolia_ Mutis and _C. pitayensis_ Wedd., natives of the Cordilleras of Columbia.

These barks are largely imported and used for making quinine, the former under the name of _Columbian_, _Carthagena_, or _Caqueta bark_. It varies much in appearance, but is generally of an orange-brown; the corky coat, which scales off easily, is shining and whitish. The barks of _C. lancifolia_ often occur in fine large quills or thick flattish pieces. Their anatomical structure agrees in all varieties which we have examined, in the remarkable number of thick-walled and tangentially-extended cells of the middle cortical layer and the medullary rays. In percentage of alkaloids, Carthagena barks are liable to great variation.

[1339] _Cortex Cinchonæ flavæ_, _Cortex Chinæ regius_; F. _Quinquina Calisaya_; G. _Königschina_.

[1340] From the notion that they resemble the marks left by drawing the fingers over wet clay.

[1341] Thick Red Bark that happens to have a very deep and brilliant tint is eagerly bought at a high price for the Paris market.

The _Pitayo Barks_ are restricted to the south-western districts of Columbia,[1342] and are usually imported in short flattish fragments, or broken quills, of brownish rather than orange colour, mostly covered with a dull greyish or internally reddish cork. The middle cortical layer exhibits but few thick-walled cells; the liber is traversed by very wide medullary rays, and is provided with but a small number of widely scattered liber-fibres, which are rather thinner than in most other Cinchona barks. The Pitayo barks are usually rich in alkaloids, quinine prevailing. _Cinchona pitayensis_ is one of the hardiest species of the valuable Cinchonas, and is therefore particularly suitable for cultivation, which however has not yet been carried out as largely as that of either _C. officinalis_ or _C. succirubra_.

In the Conspectus on the next page, we have arranged the principal species of _Cinchona_, with short indications of the barks which some of them afford.[1343]

=Microscopic Structure=—The first examination of the minute structure of Cinchona barks is due to Weddell, whose observations have been recorded in one of his beautiful plates published in 1849.[1344] Since that time numerous other observers have laboured in the same field of research.

_General Characters._—These barks, as contrasted with those of other trees, do not exhibit any great peculiarities of structure; and their features may be comprehended in the following statements. The _epidermis_, in the anatomical sense, occurs only in the youngest barks, which are not found in commerce. The _corky layer_, which replaces the epidermis, is constructed of the usual tabular cells. In some species as _C. Calisaya_, it separates easily, at least in the older bark, whereas in others as _C. succirubra_, the bark even of trunks is always coated with it. In several species the corky tissue is not only found on the surface, but strips of it occur also in the inner substance of the bark. In this case the portions of tissue external to the inner corky layers or bands are thrown off as _bork-scales_ (_periderm_ of Weddell). This peculiar form of suberous tissue[1345] was first examined (not in cinchona) in 1845 by H. von Mohl, who called it _rhytidoma_ (_Borke_ of the Germans). In _C. Calisaya_ it is of constant occurrence, but not so usually in _C. succirubra_ and some others; the rhytidoma therefore affords a good means of distinguishing several barks.

The inner portion of the bark exhibits a _middle_ or _primary layer_ (_mesophlœum_),[1346] made up of parenchyme; and a second inner layer or _liber_ (_endophlœum_)[1347] displaying a much more complicated structure. The primary layer disappears if rhytidoma is formed: barks in which this is the case are therefore at last exclusively composed of liber, of which Flat Calisaya Bark is a good example.

[1342] Pitayo is an Indian village eastward of Popayan; see map of the country between Pasto and Bogotá in Blue Book (East India Chinchona Plant) 1866. 257.

[1343] Two species included by Weddell in his _Notes sur les Quinquinas_, namely _C. Chomeliana_ Wedd. and _C. barbacoensis_ Karst., have been omitted, as not in our opinion belonging to the genus.

[1344] _Hist. nat. des Quinquinas_, tab. ii.

[1345] Flückiger, _Grundlagen_, Berlin, 1872. 61. fig. 48.

[1346] _Enveloppe ou tunique cellulaire_ of Weddell; _Mittelrinde_ of the Germans.

[1347] In German _Bast_, or _Phloëm_ of modern German botany.

CONSPECTUS OF THE PRINCIPAL SPECIES OF CINCHONA.

The liber is traversed by _medullary rays_, which in cinchona are mostly very obvious, and project more or less distinctly into the middle cortical tissue. The liber is separated by the medullary rays into wedges,[1348] which are constituted of a parenchymatous part and of yellow or orange fibres. The number, colour, shape, and size, but chiefly the arrangement of these fibres, confer a certain character common to all the barks of the group under consideration.

The liber-fibres[1349] are elongated and bluntly pointed at their ends, but never branched, mostly spindle-shaped, straight or slightly curved, and not exceeding in length 3 millimetres. They are consequently of a simpler structure than the analogous cells of most other officinal barks. They are about ¼ to ⅓ mm. thick, their transverse section exhibiting a quadrangular rather than a circular outline. Their walls are strongly thickened by numerous secondary deposits, the cavity being reduced to a narrow cleft, a structure which explains the brittleness of the fibres. The liber-fibres are either irregularly scattered in the liber-rays, or they form radial lines transversely intersected by narrow strips of parenchyme, or they are densely packed in short bundles. It is a peculiarity of cinchona barks that these bundles consist always of a few fibres (3 to 5 or 7), whereas in many other barks (as cinnamon) analogous bundles are made up of a large number of fibres. Barks provided with long bundles of the latter kind acquire therefrom a very fibrous fracture, whilst cinchona barks from their short and simple fibres exhibit a short fracture. It is rather granular in Calisaya bark, in which the fibres are almost isolated by parenchymatous tissue. In the bark of _C. scrobiculata_, a somewhat short fibrous fracture[1350] is due to the arrangement of the fibres in radial rows. In _C. pubescens_, the fibres are in short bundles and produce a rather woody fracture.

Besides the liber-fibres, there are some other cells contributing to the peculiarity of individual cinchona barks. This applies chiefly to the _laticiferous ducts_ or _vessels_[1351] which are found in many sorts; they are scattered through the tissue intervening between the middle cortical layer and the liber, and consist of soft, elongated, unbranched cells, mostly exceeding in diameter the neighbouring parenchymatous cells.

As to the _contents of the tissue_ of cinchona barks, crystallized alkaloids are not visible. Howard has published figures representing minute rounded aggregations of crystalline matter in the cells, which he supposes to be kinovates of the alkaloids; and also distinct acicular crystals which he holds to be of the same nature. These remarkable appearances are easily observable, yet only after sections of the bark have been boiled for a minute in weak caustic alkali and then washed with water; it may well be doubted whether they are strictly natural. The liquids which are capable of dissolving the alkaloids in the free state do not afford any if they are applied to the barks. The alkaloids being contained in the bark in the form of salts, the latter are decomposed by caustic lye, and the alkaloids set at liberty assume the crystallized state. This is in our opinion the origin of the crystals under notice.

[1348] _Baststrahlen_ or _Phloëmstrahlen_ of the Germans.

[1349] _Fibres corticales_ of Weddell; _Baströhren_ or _Bastzellen_ in German.

[1350] _Fracture filandreuse_, Weddel; _fädiger Bruch_ of the Germans.

[1351] _Vaisseaux laticifères_ of Weddell; _Milchsaftschläuche_ in German.

The greater number of the parenchymatous cells are loaded with small starch granules, or in young and fresh barks with chlorophyll. In several barks, as in that of _C. lancifolia_ Mutis, numerous cells of the middle cortical layer and even of the medullary rays, are provided with somewhat thick walls, and contain either a soft brown mass or crystalline oxalate of calcium. These cells have therefore been called _resin-cells_ and _crystal-cells_; they are mostly isolated, not forming extensive groups or zones, and their walls are not strongly thickened as in true sclerenchymatous tissue. If thin sections of the barks are moistened with dilute alcoholic perchloride of iron, the walls of the cells, except the fibres and the cork, assume a blackish-green due to cincho-tannic acid; this applies even to the starch granules.

_Characters of particular sorts._—The modifications of general structure just described, are sufficient to impart a special character to the bark of many species of Cinchona, provided the bark is examined at its full development, the structural peculiarities being far from well-marked in young barks.

Thus it is not possible to point out any distinctive features for the _Loxa Bark_ of commerce, because it is mostly taken from young wood. We may say of it, that neither resin-cells nor crystal-cells occur in its middle layer, that its laticiferous vessels become soon obliterated, and have indeed disappeared in the older quills; and that the liber-fibres form interrupted, not very regular, radial rows.

The quills of _C. Calisaya_ display large laticiferous ducts, which are wanting in the flat bark. There is a peculiar sort of the latter called _Bolivian Calisaya_ (already mentioned at p. 353), the flat pieces of which still possess very obvious laticiferous vessels. As to the liber-fibres of Calisaya bark, they are, as before stated (p. 356), scattered throughout the parenchymatous tissue or endophlœum. In the bark of _C. scrobiculata_, which might at first sight be confounded with Calisaya bark, the liber-fibres form radial, less interrupted rows. The microscope affords therefore the means of distinguishing these two barks.

The barks of _C. succirubra_ are particularly rich in laticiferous ducts, mostly of considerable diameter, in which the formation of new parenchyme may not unfrequently be observed. The orange liber-fibres occurring in this bark are less numerous, more scattered, and of smaller size than in Calisaya. The fracture of Red Bark, especially the flat sort, is therefore more finely granular and not so coarse as that of Calisaya.

The structural characters of Cinchona barks may lastly be fully appreciated by examining barks of the allied genera _Buena_, _Cascarilla_ and _Ladenbergia_, which were formerly known under the name of _False Cinchona Barks_. The microscope shows that the liber-fibres of the latter are soft, branched and long, densely packed into large bundles, imparting therefore a well-marked fibrous structure. The external appearance of these barks is widely different from that of true cinchona barks; none of them it would appear is now collected for the purpose of adulteration.

=Chemical Composition=—The most important and at the same time peculiar principles of Cinchona bark are the _Alkaloids_,—enumerated in the following table:—[1352]

Cinchonine C₂₀H₂₄N₂O.
or, as proposed by Skraup (1878) C₁₉H₂₂N₂O.
Cinchonidine (_Quinidine_ of many writers) same formula.
Quinine C₂₀H₂₄N₂O₂.
Quinidine (_Conquinine_ of Hesse) same formula.
Quinamine C₁₉H₂₄N₂O₂.
Conquinamine (_Conchinamine_) same formula.

B. A. Gomes[1353] of Lisbon (1810) first succeeded in obtaining active principles of cinchona, by treating an alcoholic extract of the bark with water, adding to the solution caustic potash, and crystallizing the precipitate from alcohol. The basic properties of the substance thus obtained, which Gomes called _Cinchonino_, were observed in the laboratory of Thénard by Houtou-Labillardière, and communicated to Pelletier and Caventou.[1354] Shortly before that time, Sertürner had asserted the existence of organic alkalis: and the French chemists, guided by that brilliant discovery, were enabled to show that the _Cinchonino_ of Gomes belonged to the same class of substances. Pelletier and Caventou, however, speedily pointed out that it consisted of two distinct alkaloids, one of which they named _Quinine_, the other _Cinchonine_. In 1827 the Institut de France awarded to the two chemists for their discovery the Montyon prize of 10,000 francs (see page 57, note 4).

[1352] Hesse, in 1877, pointed out the existence of a series of new alkaloids existing in Cinchona. We refrain from repeating his statements, which will be found abstracted in the _Yearbook of Pharm._ 1878. 63.

[1353] Ensaio sobre o Cinchonino, e sobre sua influencia na virtude da quina e d’outras cascas.—_Mem. da Acad. R. das Sciencias de Lisboa_, iii. (1812) 202-217.

[1354] _Ann. de Chim. et de Phys._ xv. (1820) 292.

_Cinchonidine_ (thus called by Pasteur in 1853) was first obtained and characterized under the name of _Quinidine_ in 1847, by F. L. Winckler of Darmstadt, from Maracaibo Bark (_C. tucujensis_ Karst.); and in 1852 it was more closely studied by Leers, still under the name of _quinidine_.

_Cinchovatine_, formerly stated to be a peculiar alkaloid, has been shown by Hesse in 1876 to agree with cinchonidine.

_Quinidine_ is the name applied by Henry and Delondre to an alkaloid they obtained in 1833; its peculiar nature was not clearly proved until 1853, when Pasteur examined it, and 1857 when De Vry showed its identity with the _Beta-quinine_ extracted in 1849 by Van Heijningnen from commercial quinoidin. The name _quinidine_ having been since applied to different basic substances more or less pure, Hesse (1865) has proposed to replace it by that of _Conquinine_ (Conchinin in German). The alkaloid is especially characteristic of the Pitayo barks, and also occurs in the Calisaya barks from Java.

_Quinamine_ was discovered in 1872 by Hesse, in bark of _C. succirubra_ cultivated at Darjiling in British Sikkim; it is also of common occurrence in the barks collected in Java. _Conquinamine_ was extracted in 1873 by Hesse from old barks from British India.

_Paricine_ is another basic substance discovered in 1845 by Winckler, in the bark of _Buena hexandra_ Pohl. Hesse detected it along with quinamine in the bark of _C. succirubra_; its composition is not yet known.

_Aricine_, C₂₃H₂₆N₂O₄, and _Cusconine_, C₂₃H₂₆N₂O₄ + 2 OH₂, occur in the so-called false Cinchona barks of not ascertained botanic origin. These alkaloids differ in many respects from those of true Cinchona barks.[1355]

_Pitoyine_ was pointed out by Peretti (1837), but Hesse has shown (1873) that the bark called _China bicolorata Tecamez_[1356] or _Pitoya Bark_ from which it was obtained, is altogether destitute of alkaloid.

Lastly may be mentioned _Paytine_, C₂₁H₂₄N₂O + OH₂, a crystallizable alkaloid discovered in 1870 by Hesse in a white bark of uncertain origin.[1357] It is allied to quinamine and quinidine, but has not been met with in any known cinchona bark.

By heating for a length of time solutions of the cinchona alkaloids with an excess of some mineral acid, Pasteur (1753) obtained amorphous modifications of the natural bases. Quinine thus afforded _Quinicine_, having the same composition; cinchonine and cinchonidine furnished _Cinchonicine_, likewise agreeing in composition with the alkaloids from which it originates. These amorphous products may also be obtained by heating the natural bases in glycerin at 200° C., when a red substance is also formed. In quinine manufactories, amorphous alkaloids are constantly met with, being partly produced in the course of the manipulations to which the materials are subjected. Yet cinchona barks also afford _amorphous alkaloids_ at the very outset of analysis, whence we must infer their existence in the living plant.

The name _Quinoidine_ (or rather “_Chinioïdin_”) was applied by Sertürner (1829) to an uncrystallizable basic substance, which he prepared from cinchona barks, and found to be a peculiar alkaloid. The term has subsequently been bestowed upon a preparation which has found its way into commerce and medical practice, in the form of a dark brown brittle extractiform mass, softening below 100° C., and having usually a slight alkaline reaction. It is obtained in quinine factories by precipitating the brown mother-liquors with ammonia, and contains the amorphous alkaloids naturally occurring in the barks. Quinoidin should not be used unless, when previously dried at 100°, it proves to afford at least 70 per cent. of alkaloids soluble in ether.

Quinine and the allied alkaloids have not been met with in any appreciable amount in other parts of the cinchonas than the bark, nor has their presence been ascertained in other plants than those of the tribe _Cinchoneæ_.

[1355] _Yearbook of Pharm._ 1878. 59.

[1356] So called from Tecamez or Tacames, a small port of Ecuador in about lat. 1° N. The bark which was first noticed in Lambert’s _Description of the Genus Cinchona_, 1797. 30. tab. ii., is of unknown botanical origin. In its external appearance, as well as in its structure, this bark is widely different from any Cinchona bark.—See also Vogl, in the second pamphlet quoted at page 391. 10; Oberlin and Schlagdenhauffen, _Journ. de Pharm._ 28. (1878) 252.

[1357] Flückiger in Wiggers and Husemann, _Jahresbericht_ for 1872. 132.

Characters of the Cinchona Alkaloids.

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PharmacographiaChapter XXII: Part 22

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