part 7

(1876).

[1276] _Dictionary of the Indian Islands_, 1865. 142.

[1277] Beautifully figured in Berg und Schmidt, _Offizinelle Gewächse_, xxx. c. 1863.

[1278] _Herb. Amb._ v. 63. tab. 34.

Thus, if we may credit Rumphius, it would seem that the important manufacture of gambier had no existence at the commencement of the last century. As to “_Gatta Gambir_,” his statements are scarcely in accord with those of more recent writers. We may however remark that that name is very like the Tamil _Katta Kāmbu_, signifying _Catechu_, which drug is sometimes made into little round cakes, and was certainly a large export from India to Malacca and China as early as the 16th century (p. 241).

That gambier was unknown to Europeans long after the time of Rumphius, is evident from other facts. Stevens, a merchant of Bombay, in his _Compleat Guide to the East India Trade_, published in 1766, quotes the prices of goods at Malacca, but makes no allusion to gambier. Nor is there any reference to it in Savary’s _Dictionnaire de Commerce_ (ed. of 1750), in which Malacca is mentioned as the great entrepôt of the trade of India with that of China and Japan.

The first account of gambier known to us, was communicated to the Batavian Society of Arts and Sciences in 1780, by a Dutch trader named Couperus. This person narrates[1279] how the plant was introduced into Malacca from Pontjan in 1758, and how gambier is made from its leaves; and names several sorts of the drug and their prices.

In 1807, a description of “the drug called _Gutta Gambeer_,” and of the tree from which it is made, was presented to the Linnean Society of London.[1280] The writer, William Hunter, well known for scientific observations in connection with India, states that the substance is made chiefly at Malacca, Siak and Rhio, that it is in the form of small squares, or little round cakes almost perfectly white, and that the finer sorts are used for chewing with betel leaf in the same manner as catechu, while the coarser are shipped to Batavia and China for use in tanning and dyeing.

=Manufacture=—The gambier plant is cultivated in plantations. These were commenced in 1819 in Singapore, where there were at one time 800 plantations; but owing to scarcity of fuel, without an abundant supply of which the manufacture is impossible, and dearness of labour, gambier-planting was in 1866 fast disappearing from the island.[1281] The official Blue Book, printed at Singapore in 1872, reports it as “_much increased_.” It is largely pursued on the mainland (Johore), and in the islands of the Rhio-Lingga Archipelago, lying south-east of Singapore. On the island of Bintang, the most northerly of the group, there were about 1,250 gambier-plantations in 1854.

The plantations are often formed in clearings of the jungle, where they last for a few years and are then abandoned,[1282] owing to the impoverishment of the soil and the irrepressible growth of the _lalang_ grass (_Imperata Königii_ P. de B.), which is more difficult to eradicate than even primæval jungle. It has been found profitable to combine with the cultivation of gambier that of pepper, for which the boiled leaves of the gambier form an excellent manure.

[1279] _Verhandelingen van het Bataviaasch Genootschap_, ii. (derde druk) 217-234.

[1280] _Linn. Trans._ ix. (1808) 218-224.

[1281] Collingwood, _Journ. of Linn. Soc._, Bot., x. (1869) 52.

[1282] This abuse of land has been repressed in Singapore.

The gambier plants are allowed to grow 8 to 10 feet high, and as their foliage is always in season, each plant is stripped 3 or 4 times in the year. The apparatus and all that belongs to the manufacture of the extract are of the most primitive description.[1283] A shallow cast-iron pan about 3 feet across is built into an earthen fireplace. Water is poured into the pan, a fire is kindled, and the leaves and young shoots, freshly plucked, are scattered in, and boiled for about an hour. At the end of this time they are thrown on to a capacious sloping trough, the lower end of which projects into the pan, and squeezed with the hand so that the absorbed liquor may run back into the boiler. The decoction is then evaporated to the consistence of a thin syrup, and baled out into buckets. When sufficiently cool it is subjected to a curious treatment:—instead of simply stirring it round, the workman pushes a stick of soft wood in a sloping direction into each bucket; and placing two such buckets before him, he works a stick up and down in each. The liquid thickens round the stick, and the thickened portion being constantly rubbed off, while at the same the whole is in motion, it gradually sets into a mass, a result which the workman affirms would never be produced by simple stirring round. Though we are not prepared to concur in the workman’s opinion, it is reasonable to suppose that his manner of treating the liquor favours the crystallization of the catechin in a more concrete form than it might otherwise assume. The thickened mass, which is said by another writer to resemble soft yellowish clay, is now placed in shallow square boxes, and when somewhat hardened is cut into cubes and dried in the shade. The leaves are boiled a second time, and finally washed in water, which water is saved for another operation.

From informations obtained in 1878 it would appear that now the prevailing part of gambier is made by means of pressure into blocks.

A plantation with five labourers contains on an average 70,000 to 80,000 shrubs, and yields 40 to 50 catties (1 catty = 1⅓ lb. = 604·8 grammes) of gambier daily.

=Description=—Gambier is an earthy-looking substance of light brown hue, consisting of cubes about an inch each side, more or less agglutinated, or it is in the form of entirely compact masses. The cubes are externally of a reddish-brown and compact, internally of a pale cinnamon hue, dry, porous, friable, devoid of odour, but with a bitterish astringent taste, becoming subsequently sweetish. Under the microscope, the cubes of gambier are seen to consist of very small acicular crystals.

=Chemical Composition=—In a chemical point of view, gambier agrees with cutch, especially with the pale variety made in Northern India (p. 242). Both substances consist mainly of _Catechin_,[1284] which may be obtained in the hydrated state as slender colourless needles, by exhausting gambier with cold water, and crystallizing the residue from 3 or 4 parts of hot water, which on cooling deposits nearly all the catechin. Ferric chloride strikes with the solution of catechin, even when much diluted, a green tint. If it is shaken with ferrous sulphate and an extremely small quantity of bicarbonate of sodium, a violet colour makes its appearance. The same reactions are produced by various substances of the tannic class.

[1283] We borrow the following account, which is the best we have met with, from Jagor’s _Singapore, Malacca, und Java_, Berlin, 1866. 64.

[1284] Gautier (1877) suggests that it is not identical with catechin from Acacia Catechin (p. 244).

The yellowish colouring matter of gambier was determined by Hlasiwetz (1867) and Löwe (1873) to be _Quercetin_, which is also a constituent of cutch. Quercetin is but very sparingly soluble in water, yet it is nevertheless found, in small quantity, in the aqueous extract of cutch, from which it may be removed by means of ether. As many species of _Nauclea_ contain, according to De Vry,[1285] _Quinovic Acid_, it is probable that that substance may be detected in gambier.

Some fine gambier in regular cubes which we incinerated left 2·6 per cent. of ash, consisting mainly of carbonates of calcium and magnesium.

=Commerce=—Singapore, which is the great emporium for gambier, exported in 1871 no less than 34,248 tons, of which quantity 19,550 tons had been imported into the colony chiefly from Rhio and the Malayan Peninsula.[1286] In 1876 the export had increased to more than 50,000 tons of pressed block gambier and 2,700 tons of cubes. In 1877 it diminished to 39,117 tons, owing to difficulties which had arisen between the Chinese dealers, who supplied the drug in a rather wet state, and the European exporters. Of the above quantity 21,607 tons were shipped for London, 7,572 for Liverpool, 2,345 for Marseilles. Gambier usually fetches a lower price[1287] in the London market than cutch.

The quantity imported into the United Kingdom in 1872 was 21,155 tons, value £451,737, almost the whole being from the Straits Settlements.

=Uses=—Gambier, under the name of _Catechu_, is used medicinally as an astringent, but the quantity thus consumed is as nothing in comparison with that employed for tanning and dyeing.

[1285] _Pharm. Journ._ vi. (1865) 18.

[1286] _Blue Book of the Colony of the Straits Settlements for 1871._

[1287] 17_s._ per cwt., March 1879; see Catechu, page 242, note 3.

CORTEX CINCHONÆ.

_Cortex Peruvianus_, _Cortex Chinæ_; _Cinchona Bark_, _Peruvian Bark_; F. _Ecorce de Quinquina_; G. _Chinarinde_.

=Botanical Origin=—The genus _Cinchona_ constitutes together with _Cascarilla_ (including _Buena_ and _Cosmibuena_), _Remijia_, _Ladenbergia_, _Macrocnemum_, and about 30 other nearly allied genera, the well-characterized tribe _Cinchoneæ_ of the order _Rubiaceæ_. 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 weak 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 fruit-stalk 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 well-marked 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, in 1873, estimated the species as about 36.

Kuntze, in the book quoted at the end of the present article, proposed to reduce all the species to the four following:

1. _Cinchona Weddelliana_ O. Kuntze, nearly answering to _C. Calisaya_ Weddell.

2. _C. Pavoniana_ O. Kuntze, including _C. micrantha_ Ruiz and _Pavon_ and several allied plants.

3. _C. Howardiana_ O. Kuntze, constituted of _C. succirubra_ Pavon and a few other species of former authors.

4. _C. Pahudiana_ Howard.

Kuntze, who has examined the living Cinchonæ as cultivated in India, is of the opinion that all the numerous forms hitherto observed, both in the wild plants and in cultivation, are merely either belonging to the above four species or deriving from them chiefly by hybridation. Though much in favour of a reduction of the species, we are not yet prepared to accept Kuntze’s arrangement.

(=B.=) _Area, Climate and Soil._—The Cinchonas are natives of South America, where they occur exclusively on the western side of the continent 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.[1288] 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.[1289]

(=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_ Hooker[1290]—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, ½ an inch or more in length.

2. _C. Calisaya_ Weddell—Discovered by Weddell in 1847,[1291] although its bark had been an object of commerce since the latter half of the previous century.

[1288] That is to say the _eastern_ Cordillera, the western and lower range being called the _Cordillera of the Coast_; no Cinchonas grow on the latter.

[1289] Broughton, in _Pharm. Journ._ Jan. 4, 1873. 521.

[1290] Figured in _Bot. Magazine_, vol. 89 (1863) tab. 5364, including _C. Condaminea_ Humb. et Bonpl. and _C. Uritusinga_ Pavon.

[1291] _Ann. des Sciences nat._, Bot. x. (1848) 6, and _Hist. nat. des Quinquinas_, 1849, tab. 3, figured in _Botanical Magazine_, 1873. 6052, and 1879. 6434.

The tree inhabits the warmest woods of the declivities which border the valleys of Bolivia and South-eastern Peru, at an altitude of 5000 to 6000 feet above the sea-level. More precisely, the chief localities for 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 (½ 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, β. _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_.

Towards the middle of the year 1865, _Charles Ledger_, an English traveller, obtained seeds of a superior Cinchona, which had been collected near Pelechuco, eastwards of the lake Titicaca, about 68° W. long. and 15° S. lat., in the Bolivian province of Caupolican. In the same year the seeds arrived in England, but were subsequently sold to the Dutch government, and raised with admirable success in Java, and a little later also in private plantations in British India. The bark of “_Cinchona Ledgeriana_” has since proved by far the most productive in quinine of all Cinchona Barks. The tree is a mere form of C. Calisaya.[1292]

3. _C. succirubra_ Pavon,[1293]—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.[1294] 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 1¼ 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 355.

=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.

[1292] Ledger’s Calisaya is beautifully figured and exactly described in Howard’s _Quinology of the East Indian Plantations_, parts ii. and iii.

[1293] Figured in Howard’s _Nueva Quinologia_, art. _Chinchona succirubra_.

[1294] Howard, _l.c._ p. 9.

William Arrot,[1295] 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.

Humboldt[1296] declares that at Loxa the natives would rather die than have recourse to what they consider so dangerous a remedy. Pöppig[1297] (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[1298] 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[1299] 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 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,[1300] 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 Canizares, 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.[1301] 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_, i.e. _The Countess’ Powder_. It was certainly known in Spain the following year (1639), when it was first tried at Alcala de Henares near Madrid.[1302]

[1295] _Phil Trans._ xl. for 1737-38. 81.

[1296] _Der Gesellsch. naturf. Freunde zu Berlin Magaz._ i. (1807) 60.

[1297] _Reise in Chile, Peru_, etc. ii. (1836) 222.

[1298] Blue Book—_East India Chinchona Plant_, 1863. 74. 75.

[1299] _Travels in Peru and India_, 1862. 2.

[1300] 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.

[1301] 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 Peruviæ, seu Chinæ Chinæ 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.

[1302] Villerobel, quoted by Bado, _op. cit._ 202.

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 (or 1651?). He says that among the wonders of the day, many reckon the tree growing in the kingdom of Peru, which the Spaniards call _Polo 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, and thence sent to the Jesuit Cardinal Joannes de Lugo at Rome.[1303] 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 Bado[1304] 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,[1305] 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 _Peruvianam Febrifugum_. At Rome it bore the name of _Pulvis eminentissimi Cardinalis de Lugo_, or _Pulvis patrum_; the Jesuits at Rome received it from the establishments of their order in Peru, and used to give it away to the poor in Cardinal de Lugo’s palace. In 1658 Sturm saw 20 doses sent to Paris which cost 60 florins. He gives a copy of the handbill[1306] of 1651 which the apothecaries of Rome used to distribute with the costly powder.

[1303] The cardinal belonged to a family of Seville, which town had the monopoly of the trade with America.

[1304] Bado in his _Anastasis_, lib. 3, quotes the opinion of many persons as coinciding with his own.

[1305] _Febrifugi Peruviani Vindiciarum pars prior—Pulveris Historiam complectens ejusque vires et proprietates ...exhibens_, Delphis, 1669. 12°.

[1306] 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 la febre quartans, e terzana, che venga con freddo: s’adropra 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 commincia 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.

The drug began to be known in England about 1655.[1307] The _Mercurius Politicus_ one of the earliest English newspapers, contains in several of its numbers for 1658,[1308] 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 Jesuit’s Powder_”—brought over by James Thomson, merchant of Antwerp.

Brady, professor of physic at Cambridge, prescribed bark about this time; and in 1660, Willis, a physician of great eminence, reported it as coming into daily use. This is also evidenced, with regard to the continent, by the pharmaceutical tariffs of the cities of Leipzig and Frankfurt of the year 1669, where “_China Chinæ_” has a place. ⅛ of an ounce (a “quint”) is quoted in the latter at 50 kreuzers (about 1s. 6d.), whereas the same quantity of opium is valued at 4 kreuzers,[1309] camphor 2 kreuzers, balsam of Peru 8 kreuzers.

Among those who contributed powerfully to the diffusion of the new medicine, was Robert Talbor _alias_ Tabor. In his “Pyretologia” (see Appendix, T.) he by no means intimates that his method of cure depends on the use of bark. On the contrary, he cautions his readers against the dangerous effects of Jesuit’s Powder when administered by unskilful persons, yet admits that, properly given, it is a “noble and safe medicine.”

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.

---------------------------------+----------------+-------------+------ SPECIES (EXCLUDING SUB-SPECIES | | | WHERE AND VARIETIES) | WHERE FIGURED. | NATIVE | CULTI- ACCORDING TO WEDDELL. | | COUNTRY. | VATED. ---------------------------------+----------------+-------------+------- I. Stirps Cinchonæ officinalis | | | 1. Cinchona officinalis Hook |Bot. Mag. 5804 |Ecuador |India, | | (Loxa) |Ceylon, | | |Java. 2. ” macrocalyx Pav. |Howard N. Q. |Peru | | | | 3. ” lucumæfolia Pav. | Do. |Ecuador, | | |Peru. | 4. ” lanceolata R. et P.(?)| Do. |Peru | 5. ” lancifolia Mutis |Karsten tab. 11.|New Granada |India | 12.| | 6. ” amygdalifolia Wedd. |Wedd. tab. 6. |Peru, Bolivia| | | | II. Stirps Cinchonæ rugosæ | | | 7. Cinchona pitayensis Wedd. |Karst. tab. 22. |New Granada |India |(C. Trianæ). |(Popayan) | 8. ” rugosa Pav. |Howard N. Q. |Peru | 9. ” Mutisii Lamb. | Do. |Ecuador | 10. ” hirsuta R. et P. |Wedd. tab. 21. |Peru | 11. ” carabayensis Wedd. |Wedd. tab. 19. |Peru, Bolivia| 12. ” Pahudiana How. |Howard N. Q. |Peru |India, | | |Java 13. ” asperifolia Wedd. |Wedd. tab. 20. |Bolivia | 14. ” umbellulifera Pav. |Howard N. Q. |Peru | 15. ” glandulifera R. et P. | Do. |Peru | 16. ” Humboldtiana Lamb. | Do. |Peru | | | | III. Stirps Cinchonæ micranthæ | | | 17. Cinchona australis Wedd. |Wedd. tab. 8. |South Bolivia| 18. ” scrobiculata H. et B. | Do. |Peru | 19. ” peruviana How. |Howard N. Q. |Peru |India 20. ” nitida R. et P. | Do. |Peru |India 21. ” micrantha R. et P. | Do. |Peru |India | | | IV. Stirps Cinchonæ Calisayæ | | | 22. Cinchona Calisaya Wedd. |Wedd. tab. 9. |Peru, Bolivia|India, | | |Ceylon, | | |Java, | | |Jamaica, | | |Mexico. 23. ” elliptica Wedd. | |Peru | | | (Carabaya) | | | | V. Stirps Cinchonæ ovatæ | | | 24. Cinchona purpurea R. et P. |Howard N. Q. |Peru | | | (Huamalica) | 25. ” rufinervis Wedd. | Do. |Peru, | | |Bolivia | 26. ” succirubra Pav. | Do. |Ecuador |India, | | |Ceylon, | | |Java, | | |Jamaica. 27. ” ovata R. et P. | Do. |Peru, |India(?), | |Bolivia |Java(?) 28. ” cordifolia Mutis |Karsten tab. 8. |New Granada, | | |Peru | | | | 29. ” tucujensis Karst. |Karsten tab. 9. |Venezuela | 30. ” pubescens Vahl |Wedd. tab. 16. |Ecuador, | | | Peru, | | |Bolivia | | | | 31. ” purpurascens Wedd. |Wedd. tab. 18 |Bolivia | ---------------------------------+----------------+-------------+

---------------------------------+------------------------------------ SPECIES (EXCLUDING SUB-SPECIES | AND VARIETIES) | PRODUCT ACCORDING TO WEDDELL. | ---------------------------------+------------------------------------ I. Stirps Cinchonæ officinalis | 1. Cinchona officinalis Hook | Loxa or Crown Bark, Pale Bark. | 2. ” macrocalyx Pav. | Ashy Crown Bark. The sub-species | _C. Palton_ affords an important | sort called _Palton Bark_ much | used in the manufacture of quinine. 3. ” lucumæfolia Pav. | | 4. ” lanceolata R. et P.(?)| Carthagena Bark, confounded with | Palton Bark, but is not so good. 5. ” lancifolia Mutis | Columbian Bark. Imported in large | quantities for manufacture of | quinine.The soft Columbian Bark is | produced by Howard’s var. | _oblonga_. | 6. ” amygdalifolia Wedd. | A poor bark, but not now imported. | II. Stirps Cinchonæ rugosæ | 7. Cinchona pitayensis Wedd. | Pitayo Bark. Very valuable; used by | makers of quinine; it is the chief | source of quinidine. | 8. ” rugosa Pav. | Bark unknown, probably valueless. 9. ” Mutisii Lamb. | Bark not in commerce, contains only | aricine. 10. ” hirsuta R. et P. | 11. ” carabayensis Wedd. | Bark not collected. 12. ” Pahudiana How. | A poor bark, yet of handsome | appearance; propagation of tree | discontinued. | 13. ” asperifolia Wedd. | Bark not collected. 14. ” umbellulifera Pav. | Bark not known as a distinct sort. 15. ” glandulifera R. et P. | Do. 16. ” Humboldtiana Lamb. | False Loxa Bark, Jaen Bark. A very | bad bark. | III. Stirps Cinchonæ micranthæ | 17. Cinchona australis Wedd. | An inferior bark, mixed with | Calisaya. 18. ” scrobiculata H. et B. | Bark formerly known as _Red | Cusco Bark_ or _Santa Ana Bark_. 19. ” peruviana How. | 20. ” nitida R. et P. | Grey Bark, Huanuco or Lima Bark. | Chiefly consumed on the Continent. 21. ” micrantha R. et P. | | IV. Stirps Cinchonæ Calisayæ | 22. Cinchona Calisaya Wedd. | Calisaya Bark, Bolivian Bark, | Yellow Bark. The tree exists under | many varieties, bark also very | variable. | 23. ” elliptica Wedd. | Carabaya Bark. Bark scarcely now | imported. _C. sunsura_ Miq. | (flower and fruit unknown) | may perhaps be this species. | V. Stirps Cinchonæ ovatæ | 24. Cinchona purpurea R. et P. | Huamalies Bark. Not now Imported. | 25. ” rufinervis Wedd. | Bark, a kind of light Calisaya. | 26. ” succirubra Pav. | Red Bark. Largely cultivated in | British India. | 27. ” ovata R. et P. | Inferior Brown and Grey Barks. | 28. ” cordifolia Mutis | Columbian Bark (in part). Tree | exists under many varieties; bark | of some used in manufacture of | quinine. | 29. ” tucujensis Karst. | Maracaibo Bark. | 30. ” pubescens Vahl | Arica Bark (Cusco Bark from var. | _Pelletieriana_). Some of the | varieties contain aricine. | _C. caloptera_ Miq. is probably | a var. of this species. | 31. ” purpurascens Wedd. | Bark unknown in commerce. ---------------------------------+-----------------------------------------

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.

1. _Quinine._—It is obtained from alcoholic solutions, in prisms of the composition C₂₀H₂₄N₂O₂ + 3 OH₂, fusing at 57° C. The crystals may be deprived of water by warming or exposure over oil of vitriol, and they fuse at 177° C. The anhydrous alkaloid is likewise crystallizable; it requires about 21 parts of ether for solution, but dissolves more readily in chloroform or absolute alcohol. These solutions deviate the ray of polarized light to the left, and so do likewise solutions of the salts of quinine. Yet one and the same quantity of alkaloid exhibits a very different rotatory power according to the solvent used, though the volume of the solution remain the same. Even the common sulphate differs in this respect from the two other sulphates of quinine. The same remark applies to the optical power of the other alkaloids.

If ten volumes of a solution of quinine, or of one of its salts, are mixed in a test tube with one volume of chlorine water, and a drop of ammonia is added, a brilliant green colour makes its appearance. In solutions rich in quinine, a green precipitate, _Thalleioquin_ or _Dalleiochine_ is produced; in solutions containing less than ¹/₁₀₀₀ of quinine, no precipitate is formed, but the fluid assumes a green even more beautiful than in a stronger solution. The test succeeds with a solution containing only one part of quinine in 5,000, and in a solution containing not more than ¹/₂₀₀₀ of quinine, if bromine is used instead of chlorine.[1358]

The bitter taste of quinine is not appreciable in solutions containing less than one part in 100,000. The blue fluorescence displayed by a solution of quinine in dilute sulphuric acid is observable in solutions containing much less than one part in 200,000 of water; yet it is not apparent in very strong solutions.

Besides the _common medicinal_ sulphate, 2 C₂₀H₂₄N₂O₂ + SO₄H₂ + 8 OH₂, quinine forms two other crystallizable sulphates, namely the sulphate, C₂₀H₂₄N₂O₂ + SO₄H₂ + 7 OH₂, and a third having the composition C₂₀H₂₄N₂O₂ + 2 SO₄H₂ + 7 OH₂.

Herapath, at Bristol, showed in 1852 that quinine forms with sulphuric acid and iodine a peculiar compound, _Iodo-sulphate of Quinine_, having the composition (C₂₀H₂₄N₂O₂)₄ + 3 (SO₄H₂) + 2 HI + 4 I + 3 OH₂. As this substance possesses optical properties analogous to those of tourmaline, it was called by Haidinger, _Herapathite_. It may be easily obtained by dissolving sulphate of quinine in 10 parts of weak spirit of wine containing 5 per cent. of sulphuric acid, and adding an alcoholic solution of iodine until a black precipitate is no longer formed. This precipitate is collected on a filter and washed with alcohol; then dissolved in boiling spirit of wine and allowed to crystallize. The tabular crystals thus obtained are extremely remarkable on account of their dichroism and polarizing power, as well as for the sparing solubility, since they require 1000 parts of boiling water for solution; their sparing solubility in cold alcohol may be utilized for separating quinine from the other cinchona alkaloids and estimating its quantity.

2. _Quinidine_ or _Conquinine_—forms crystals having the composition, C₂₀H₂₄N₂O₂ + 2 OH₂; the anhydrous alkaloid melts at 168° C., and requires about 30 parts of ether for solution. Its solutions are strongly dextrogyre; it agrees with quinine as regards bitterness, fluorescence and the thalleioquin test, and forms a neutral and an acid sulphate. The most striking character of quinidine is afforded by its hydriodate, the crystals of which require for solution at 15° C., 1250 parts of water or 110 parts of alcohol sp. gr. ·834. Quinidine may therefore be separated from the other alkaloids of bark by a solution of iodide of potassium which will precipitate the hydriodate. According to Hesse (1873), quinidine is further characterized by the fact that its sulphate is soluble in 20 parts of chloroform at 15° C., the sulphates of the other cinchona alkaloids being far less soluble in that liquid. The common medicinal sulphate of quinine, _e.g._, requires for solution 1000 parts of chloroform.

[1358] _Pharm. Journ._, May 11, 1872. 901.

3. _Cinchonine._—This alkaloid forms crystals which are always anhydrous; they fuse at 257° C., and require about 400 parts of ether and 120 of spirit of wine for solution. Cinchonine further differs from quinine by its dextrogyre power, its want of fluorescence, and its non-susceptibility to the thalleioquin test. Its hydriodate is readily soluble in water, and still more so in alcohol whether dilute or strong.

4. _Cinchonidine._—forms anhydrous crystals melting at 206° C., soluble in 76 parts of ether, or 20 of spirit of wine, then affording levogyre liquids, devoid of fluorescence, and not acquiring a green colour (thalleioquin) by means of chlorine water and ammonia. Hydrochlorate of cinchonidine forms pyramidal crystals of the monoclinic system, very different from the hydrochlorates of the allied alkaloids.

5. _Quinamine._—The crystals are anhydrous, fuse at 172° C., and form at a temp. of 20°, with 32 parts of ether or 100 parts of spirit of wine, a dextrogyre solution. Quinamine is even to some extent soluble in boiling water, and abundantly in boiling ether, benzol, or petroleum ether. The solutions of quinamine do not stand the thalleioquin test, nor do they display fluorescence; in acid solution, the alkaloid is liable to be transformed into an amorphous state. Quinamine moistened with concentrated nitric acid, assumes like paytine a yellow coloration. Its hydriodate is readily soluble in boiling water, but very sparingly in cold water, especially in presence of iodide of potassium, in which respect it is allied to quinidine as well as to paytine.

The more important properties of the Cinchona alkaloids may be summarized as follows:—

a. _Hydrated_ crystals are formed by Quinine, Quinidine, (or Conquinine). _No hydrated_ crystals by Cinchonine, Cinchonidine, Quinamine.

b. _Abundantly_ soluble in ether Quinine, Quinidine, Quinamine, and the amorphous alkaloids. _Sparingly_ soluble in ether Cinchonidine. _Almost insoluble_ in ether Cinchonine.

c. _Levogyre_ solutions afforded by Quinine, Cinchonidine. _Dextrogyre_ solutions by Cinchonine, Quinidine, Quinamine, Conquinamine, and the amorphous alkaloids.

d. Thalleioquin is formed by Quinine, Quinidine, and also by Quinicine. Thalleioquin cannot be obtained from Cinchonine, Cinchonidine, Quinamine, nor from Cinchonicine.

e. Fluorescence is displayed by solutions of Quinine, Quinidine. No fluorescence in solutions of pure Cinchonine, Cinchonidine, Quinamine.

=Proportion of Alkaloids in Cinchona Barks=—This is liable to very great variation. We know from the experiments of Hesse (1871), that the bark of _C. pubescens_ Vahl is sometimes devoid of alkaloid.[1359] Similar observations made near Bogota upon _C. pitayensis_ Wedd., _C. corymbosa_ Karst., and _C. lancifolia_ Mutis, are due to Karsten. He ascertained[1360] that barks of one district were sometimes devoid of quinine, while those of the same species from a neighbouring locality yielded 3½ to 4½ per cent. of sulphate of quinine.

[1359] _Berichte der Deutschen Chem. Gesellschaft zu Berlin_, 1871. 818.

[1360] _Die medicinischen Chinarinden Neu-Granada’s_, 17. 20. 39.

Another striking example is furnished by De Vry[1361] in his examination of quills of _C. officinalis_ grown at Ootacamund, which he found to vary in percentage of alkaloids, from 11·96 (of which 9·1 per cent. was quinine) down to less than 1 per cent. An extremely remarkable variation has also been displayed, as already alluded to at p. 351, by Ledger’s Calisaya.

Among the innumerable published analyses of cinchona bark, there are a great number showing but a very small percentage of the useful principles, of which quinine, the most valuable of all, is not seldom altogether wanting. The highest yield on the other hand hitherto observed, was obtained by Broughton[1362] from a bark grown at Ootacamund. This bark afforded not less than 13½ per cent. of alkaloids, among which quinine was predominant. In Java too, Cinchona Ledgeriana (see pp. 341, 351) has proved since to afford much more alkaloid than any American barks; as much as 13·25 per cent. of quinine have been observed in its bark.

The few facts just mentioned show that it is impossible to state even approximately any constant percentage of alkaloids in any given bark. We may however say that good _Flat Calisaya Bark_, as offered in the drug trade for pharmaceutical preparations, contains at least 5 to 6 per cent. of quinine.

As to _Crown_ or _Loxa Bark_, the _Cortex Cinchonæ pallidæ_ of pharmacy, its merits are, to say the least, very uncertain. On its first introduction in the 17th century, when it was taken from the trunks and large branches of full-grown trees, it was doubtless an excellent medicinal bark; but the same cannot be said of much of that now found in commerce, which is to a large extent collected from very young wood.[1363] Some of the Crown Bark produced in India is however of extraordinary excellence, as shown by the recent experiments of De Vry.[1364]

As to _Red Bark_, the thick flat sort contains only 3 to 4 per cent. of alkaloids, but a large amount of coloring matter. The quill Red Bark of the Indian plantations is a much better drug, some of it yielding 5 to 10 per cent. of alkaloids, less than a third of which is quinine and a fourth cinchonidine, the remainder being cinchonine and sometimes also traces of quinidine (conquinine).

The variations in the amount of alkaloids relates not merely to their total percentage, but also to the proportion which one bears to another. Quinine and cinchonine are of the most frequent occurrence; cinchonidine is less usual, while quinidine is still less frequently met with and never in large amount. The experiments performed in India[1365] have already shown that external influences contribute in an important manner to the formation of this or that alkaloid; and it may even be hoped that the cultivators of cinchona will discover methods of promoting the formation of quinine and of reducing, if not of excluding, that of the less valuable alkaloids.

[1361] _Pharm. Journ._ Sept. 6, 1873. 181.

[1362] Blue Book—“_East India Chinchona Plant_,” 1870. 282; _Yearbook of Pharmacy_, 1871. 85.

[1363] See Howard’s analyses and observations, _Pharm. Journ._ xiv. (1855) 61-63.

[1364] _Pharm. Journ._ Sept. 6, 1873. 184.

[1365] Blue Book, 1870. 116. 188. 205.

Most salts of the alkaloids of cinchona afford a beautiful purple tar when they are heated in a test tube, and the same is also produced with the powdered bark, provided alkaloids be present. No other bark, as far as we know, yields a similar product of the dry distillation. It is not observed even in using true Cinchona barks, which are devoid of alkaloids. This method for ascertaining the presence of alkaloids in Cinchona barks has been proposed in 1858 by Grahe of Kasan. Hesse has improved Grahe’s test in the following way: he extracts the powdered bark with slightly acidulated water and dries up the liquid with a little of the powder. _Grahe’s test_ at once shows whether a given bark contains Cinchona alkaloids or not.

=Acid principles of Cinchona Barks=—Count Claude de la Garaye[1366] observed (1746) a crystalline salt deposited in extract of cinchona bark, which salt was known for some time in France as _Sel essential de la Garaye_. Hermbstädt at Berlin (1785) showed it to be a salt of calcium, the peculiarity of whose acid was pointed out in 1790 by C. A. Hoffmann,[1367] an apothecary of Leer in Hanover, who termed it _Chinasäure_. The composition of this substance, which is the _Kinic Acid_ of English chemists, was ascertained by Liebig in 1830 to be C₇H₁₂O₆, or now C₆H₇(OH)₄COOH. The acid forms large monoclinic prisms, fusible at 162° C., of a strong and pure acid taste, soluble in two parts of water, also in spirit of wine, but hardly in ether. The solutions are levogyre. Kinic acid appears to be present in every species, and also to occur in barks of allied genera; and in fact to be of somewhat wide distribution in the vegetable kingdom. By heating it or a kinate, interesting derivatives are obtained; thus, by means of peroxide of manganese and sulphuric acid, we get yellow crystals of _Kinone_ or _Quinone_, C₆H₄O₂,—a reaction which may be used for ascertaining the presence of kinic acid. Kinic acid is devoid of any noteworthy physiological action.

_Cincho-tannic Acid_—is precipitated from a decoction of bark by acetate of lead, after the decoction has been freed from cinchona-red by means of magnesia. Dr. de Vry informed us that the Indian barks are usually richer in cincho-tannic acid; their cold infusion becomes turbid on addition of hydrochloric acid, which forms an insoluble compound with the former.

The cincho-tannate of lead decomposed by sulphuretted hydrogen, and the solution cautiously evaporated _in vacuo_, yields the acid as an amorphous, hygroscopic substance, readily soluble in water, alcohol, or ether. The solutions, especially in presence of an alkali, are quickly decomposed, a red flocculent matter, _Cinchona-red_, being produced. Solutions of cincho-tannic acid assume a greenish colour on addition of a ferric salt. By destructive distillation, cincho-tannic acid affords pyrocatechin.

_Quinovic_ (or _Chinovic_) _Acid_, C₂₄H₃₈O₄, crystallizes in hexagonal scales which are sparingly soluble in cold alcohol, more readily in boiling alcohol, but not dissolved by water, ether, or chloroform. It occurs in cinchona barks, and has been met with by Rembold (1868) in the rhizome of _Potentilla Tormentilla_ Sibth.

[1366] _Chimie hydraulique_, Paris, 1746. 114.

[1367] Crell’s _Chem. Annalen_, 1790, ii. 314-317.

=Other Constituents of Cinchona Barks=—Quinovic acid is accompanied by _Quinovin_ (or _Chinovin_), C₃₀H₄₈O₈, an amorphous bitter substance, first obtained (1821) by Pelletier and Caventou under the name of _Kinovic Acid_, from _China nova_,[1368] in which it occurs combined with lime. Quinovin in alcoholic solution was shown in 1859 by Hlasiwetz to be resolved by means of hydrochloric gas into quinovic acid, C₂₄H₃₈O₄, and an uncrystallizable sugar, _Mannitan_, C₆H₁₂O₅, with subtraction of H₂O. The formation of quinovic acid takes place more easily, if quinovin is placed in contact with sodium amalgam and spirit of wine, when, after 12 hours, mannitan and quinovate of sodium are formed (Rochleder, 1867).

Quinovin, although an indifferent substance, may be removed from cinchona barks by weak caustic soda, from which it is precipitable by hydrochloric acid, together with quinovic acid and cinchona-red. Milk of lime then dissolves quinovin and quinovic acid, but not the red substance. Quinovic acid and quinovin again precipitated by an acid, may be separated by chloroform in which the latter only is soluble, or also by cold dilute alcohol sp. gr. about 0·926, quinovin being readily removed by this liquid.

Quinovin dissolves in boiling water; its solutions, as well as those of quinovic acid, are dextrogyre. Quinovin seems to be a constituent of almost every part of the cinchonas and the allied _Cinchoneæ_, although the amount of it in barks does not apparently exceed 2 per cent. It is accompanied by quinovic acid: both substances are stated to have tonic properties.

_Cinchona-red_, an amorphous substance to which the red hue of cinchona barks is due, is produced as shown by Rembold (1867), when cincho-tannic acid is boiled with dilute sulphuric acid, sugar being formed at the same time. By fusing cinchona-red with potash, protocatechuic acid, C₇H₆O₄, is produced. Cinchona-red is sparingly soluble in alcohol, abundantly in alkaline solutions, but neither in water nor in ether. Thick Red Bark in which it is abundant, affords it to the extent of over 10 per cent.

The Cinchona barks yield but a scanty percentage of ash, not exceeding 3 per cent., a fact well according with the small amount they contain of oxalate and kinate of calcium.

=Estimation of the Alkaloids in Cinchona Bark=—The microscope will enable us, as already shown, to ascertain whether a given bark is derived from _Cinchona_, but it can furnish no exact information as to the actual value of such bark as a drug.

Yet there is a very simple test by which the presence of a cinchona-alkaloid may be demonstrated. These alkaloids heated in a glass tube in the presence of a volatile acid or of substances capable of producing a volatile acid, evolve heavy vapours of a beautiful crimson colour, as mentioned p. 363.

[1368] The bark of _Buena magnifolia_ Wedd., a tree with fragrant flowers and magnificent foliage, figured in Howard’s “_Nueva Quinologia of Pavon_” as Cinchona magnifolia. Its bark is destitute of alkaloids; it also used to appear occasionally in the London market since about the year 1820.—See also our article on _Cortex Cascarillæ_.

But to ascertain the real value of a cinchona bark, a quantitative estimation of the alkaloids is necessary. A good process for this operation has been given by De Vry.[1369] It is as follows:—Mix 20 grammes of powdered bark, dried at 100° C., with milk of lime (5 grm. slaked lime to 50 grm. water), dry the mixture slowly; by stirring it frequently, the cincho-tannic acid loses its solubility, being gradually transformed into cinchona-red. Then boil the dry powder with 200 cubic centimetres of alcohol 0·830 sp. gr. Pour the liquid on to a small filter, and afterwards the residual bark and lime mixed with 100 cub. cent. more alcohol. Wash the powder on the filter with 100 cub. cent. of spirit From the mixed liquids, about 370 cub. cent., separate the calcium by a few drops of weak sulphuric acid. Filter, distill off the spirit and pour into a capsule the residual liquid,—to which add a small quantity of spirit and water with which the distilling apparatus has been rinsed out. Let the capsule be now heated on a water-bath until all the spirit shall have been expelled; and let the remaining liquor which contains all the alkaloids in the form of acid sulphates be filtered. There will remain on the filter quinovic acid and fatty substances, which must be washed with slightly acidulated water. The filtrate and washings reduced to about 50 cub. cent., should be treated while still warm with caustic soda in excess. After cooling, this is decanted off from the precipitate, and then water added to it before throwing it on to a filter. It is then to be washed with the smallest quantity of water pressed between folds of blotting paper, removed therefrom and dried. The weight multiplied by 5 will indicate the percentage of _mixed_ alkaloids in the bark.

[1369] _Pharm. Journ._ iv. (1873) 241, and Dr. de Vry’s papers mentioned at the end of the present article, p. 369; also private communications.

To separate the alkaloids from each other, treat the powdered mass with ten times its weight of ether. This will resolve it into two portions—(a) _insoluble in ether_, (b) _soluble in ether_.

(a.) This should be converted into neutral acetates, and to the solution there should be added iodide of potassium, which will possibly separate a little _quinidine_. After removal of the latter (if present), add solution of tartrate of potassium and sodium, which will throw down in a crystalline form tartrate of _cinchonidine_; from the mother-liquor, _cinchonine_ may be precipitated by caustic soda.

(b.) The ether having been evaporated, the residue is to be dried at 100° C. and weighed. It may in many cases practically be considered as consisting of quinine only. If however the estimation of quinidine (conquinine) and quinamine is required, the residue, or a determined portion of it, should be dissolved in acetic acid just as much as will be necessary for affording a neutral solution. From this the hydroiodate of quinidine is precipitated by means of an alcoholic solution of iodide of potassium. In the filtrate quinine may be precipitated by adding a few drops of dilute sulphuric acid and an alcoholic tincture of iodine. The herapathite thus formed (see p. 360) is collected after a day, dried at 100° and weighed; it then contains 55 per cent. of quinine.

After adding a few drops of sulphurous acid, the alcohol should now be evaporated from the fluid from which the crystals of herapathite have been removed, and caustic lye added, by which the amorphous alkaloids will be precipitated, including _quinamine_ if present.

=Uses=—Cinchona bark enjoys the reputation of being a most valuable remedy in fevers. But the uncertainty of its composition and its inconvenient bulk render it a far less eligible form of medicine than the alkaloids themselves. It is nevertheless much used as a general tonic in various pharmaceutical preparations.

As to the alkaloids, the only one which is in general use is _quinine_. The neglect of the others is a regrettable waste, which the result of recent investigations ought to obviate. In the year 1866 the Madras Government appointed a Medical Commission to test the respective efficacy in the treatment of fever, of Quinine, Quinidine, Cinchonine and Cinchonidine. Of the sulphates of these alkaloids, a due supply, specially prepared under Mr. Howard’s superintendence, was placed at the disposal of the Commission. From the report[1370] it appears that the number of cases of paroxysmal malarious fevers treated was 2472,—namely 846 with Quinine, 664 with Quinidine, 569 with Cinchonine, and 403 with Cinchonidine. Of these 2472 cases, 2445 were cured, and 27 failed. The difference in remedial value of the four alkaloids, as deduced from these experiments, may be thus stated:—

Quinidine—ratio of failure per 1000 cases treated 6 Quinine ” ” 7 Cinchonidine ” ” 10 Cinchonine ” ” 23

The Indian Government, acting on the recommendation of Mr. Howard, has officially advised (Dec. 16, 1873) the more free use India of cinchona alkaloids other than quinine, and especially of _sulphate of cinchonidine_, which is procurable in abundance from Red Bark.[1371] Quinidine on the other hand, which has proved the most valuable of all, is only obtainable from a few barks and in very limited amount.

Dr. de Vry since 1876 advocates the use of what he calls _Quinetum_. This preparation is obtained by exhausting the barks with slightly acidulated water, and precipitating the whole amount of alkaloids by caustic soda. In India the remedy is known as “the Febrifuge.”[1372]

=Adulteration=—There is not now any frequent importation of _spurious_ cinchona barks, but the substitution of bad varieties for good is sufficiently common. To discriminate these in a positive manner by ascertaining the percentage of quinine, which is the chief criterion of value, recourse must be had to chemical analysis, a method of performing which has been described. Entirely worthless barks may be easily recognized by means of Grahe’s test (p. 363).

[1370] Blue Book—_East India Cinchona Cultivation_, 1870. pp. 156-172.—The report contains very interesting and important medical details. See also Dougal in _Edin. Med. Journ._ Sept. 1873.

[1371] We heard that the Government has purchased (April 1874) by tender between 300 and 400 lb. of cinchonidine.

[1372] _Pharm. Journ._ viii. (1878) 1060.

Modern Works relating to Cinchona.

The following enumeration has been drawn up for the sake of those desiring more ample information than is contained in the foregoing pages, but it has no pretension to be a complete list of all publications that have lately appeared on the subject.

Berg (Otto), _Chinarinden der pharmakognostischen Sammlung zu Berlin_. Berlin, 1865, 4°. 48 pages and 10 plates showing the microscopic structure of barks.

Bergen (Heinrich von), _Monographie der China_. Hamburg, 1826, 4°. 348 pages and 7 coloured plates representing the following barks:—China rubra, Huanuco, Calisaya, flava, Huamalies, Loxa, Jaen. An exhaustive work for its period in every direction.

Blue books—_East India_ (_Chinchona Plant_). Folio.

=a.= _Copy of Correspondence relating to the introduction of the Chinchona Plant into India, and to proceedings connected with its cultivation from March 1852 to March 1863._ Ordered by the House of Commons to be printed, 20 March 1863. 272 pages.

Contains Correspondence of Royle, Markham, Spruce, Pritchett, Cross, McIvor, Andersen and others, illustrated by 5 maps.

=b.= _Copy of further Correspondence relating to the introduction of the Chinchona Plant into India, and to proceedings connected with its cultivation, from April 1863 to April 1866._ Ordered by the House of Commons to be printed, 18 June 1866. 379 pages.

Contains Monthly Reports of the plantations on the Neilgherry Hills; Annual Reports for 1863-64, 1864-65, with details of method of propagation and cultivation, barking, mossing, attacks of insects, illustrated by woodcuts and 4 plates; report of Cross’s journey to Pitayo, with map; Cinchona cultivation in Wynaad, Coorg, the Pulney Hills and Travancore, with map; in British Sikkim, the Kangra, Valley (Punjab), the Bombay Presidency, and Ceylon.

=c.= _Copy of all Correspondence between the Secretary of State for India and the Governor-General, and the Governors of Madras and Bombay, relating to the cultivation of Chinchona Plants, from April 1866 to April 1870._ Ordered by the House of Commons to be printed, 9 August 1870. 285 pages.

Contains reports on the Neilgherry and other plantations, with map; appointment of Mr. Broughton as analytical chemist, his reports and analyses; reports on the relative efficacy of the several cinchona alkaloids, on cinchona cultivation at Darjiling and in British Burma.

=d.= _Copies of the Chinchona Correspondence (in continuation of return of 1870), from August 1870 to July 1875._ Ordered by the House of Commons to be printed, 21 June 1877. 190 pages.

Contain also reports on the alkaloid manufactory in India, collection and shipment of barks, and analyses of barks.

Delondre (Augustin Pierre) et Bouchardat (Apollinaire), _Quinologie_, Paris, 1854, 4°. 48 pages, and 23 good coloured plates exhibiting all the barks then met with in commerce.

Delondre (Augustin), see Soubeiran.

Gorkom (K. W. van), _Die Chinacultur auf Java_, Leipzig, 1869, 61 pages. An account of the management of the Dutch plantation.

Hesse (Oswald). This chemist has summarized his elaborate researches on Cinchona in the German Dictionary of Chemistry, articles Chinin, Cinchonin, etc. 1876-1877.

Howard (John Eliot), _Illustrations of the Nueva Quinologia of Pavon_. London, 1862, folio, 163 pages and 30 beautiful coloured plates.—Figures of Cinchona mostly taken from Pavon’s specimens in the herbarium of Madrid, and three plates representing the structure of several barks.

Howard (J. E.), _Quinology of the East India Plantations_. London, 1869, folio x. and 43 pages, with 3 coloured plates exhibiting structural peculiarities of the barks of cultivated _Cinchonæ_.

Howard (J. E.) The same, parts ii. and iii., Lond. 1876, folio xiv. and 74 p., with 2 views, 2 black plates and 13 coloured figures of _Cinchona Calisaya_ (_Ledgeriana_), _C. officinalis_, _C. pitayensis_, and others.

Karsten (Hermann), _Die medicinischen Chinarinden Neu-Granada’s_. Berlin, 1858, 8°. 71 pages, and 2 plates showing microscopic structure of a few barks. An English translation prepared under the supervision of Mr. Markham, has been printed by the India Office under the title of _Notes on the Medicinal Cinchona Barks of New Granada by H. Karsten_, 1861. The plates have not been reproduced.

Karsten (Hermann), _Floræ Columbiæ terrarumque adjacentium specimina selecta_. Berolini, 1858, folio. Beautiful coloured figures of various plants including Cinchona, under which name are several species usually referred to other genera. Only three parts have been published.

King (George), _A Manual of Cinchona cultivation in India_. Calcutta, 1876, 80 pages, small folio.

Kuntze (Otto), _Cinchona. Arten, Hybriden and Cultur der Chininbäume._ Leipzig, 1878. 124 pages and 3 plates. A review of this book will be found in the _Archiv der Pharmacie, 213_, (1878) 473-480.

McIvor (W. G.) _Notes on the propagation and cultivation of the medicinal Cinchonas or Peruvian bark trees._ Madras, 1867, 33 pages, 9 plates. The author explains the “motsing system” alluded to p. 362.

McIvor (William Graham), _A letter on the cultivation of Chinchona on the Nilgiris_. Ootacamund, 1876, 27 pages.

Markham (Clements Robert), _The Chinchona Species of New Granada, containing the botanical descriptions of the species examined by Drs. Mutis and Karsten; with some account of those botanists, and of the results of their labours_. London, 1867, 8°. 139 pages and 5 plates. The plates are not coloured, yet are good reduced copies of those contained in Karsten’s _Floræ Columbiæ_; they represent the following:—_Cinchona corymbosa_, _C. Trianæ_, _C. lancifolia_, _C. cordifolia_, _C. tucujensis_.

Markham. _A Memoir of the Lady Ana de Osorio, Countess of Chinchon, vice-queen of Peru_ (A.D. 1629-1639), _with a plea for the correct spelling of the Chinchona genus_. London, 1874, 4°. 99 pages, with a map, heraldic figures and views.

See also Hanbury, _Science Papers_, 1876, p. 475.

Miquel (Friedrich Anton Wilhelm), _De Cinchonæ speciebus quibusdam, adjectis iis quæ in Java coluntur. Commentatio ex Annalibus Musei Botanici Lugduno-Batavi exscripta._ Amstelodami, 1869,4°. 20 pages.

Oudemans (Anthony Cornelis), _Sur le pouvoir rotatoire spécifique des principaux alcaloïdes du quinquina_. _Archives néerlandaises_, x. (1875), 193-268, and xii. (1877).

Phoebus (Philipp), _Die Delondre-Bouchardat’schen China-Rinden_. Giessien, 1864, 8°. 75 pages and a table. The author gives a description without figures, of the microscopic structure of the type-specimens figured in Delondre and Bouchardat’s _Quinologie_.

Planchon (Gustave), _Des Quinquinas_. Paris et Montpellier, 1864, 8°. 150 pages. A description of the cinchonas and their barks. An English translation has been issued under the superintendence of Mr. Markham by the India Office, under the title of _Peruvian Barks by Gustave Planchon_. London, printed by Eyre and Spottiswoode, 1866.

Soubeiran (J. Léon) et Delondre (Augustin), _De l’introduction et de l’acclimation des Cinchonas dans les Indes néerlandaises et dans les Indes britanniques_. Paris, 1868, 8°. 165 pages.

Triana (Josè), _Nouvelles études sur les Quinquinas_. Paris, 1870, folio, 80 pages, and 33 plates. An interesting account of the labours of Mutis, illustrated by uncoloured copies of some of the drawings prepared by him in illustration of his unpublished _Quinologia de Bogotá_, especially of the several varieties of _Cinchona lancifolia_; also an enumeration and short descriptions of all the species of _Cinchona_, and of New Granadian plants (chiefly _Cascarilla_) formerly placed in that genus.

An abstract of the book will be found in Just’s _Botanischer Jahresbericht_ für 1873, 484-494.

Vogl (August), _Chinarinden des Wiener Grosshandels und der Wiener Sammlungen_. Wien, 1867, 8°. 134 pages, no figures. A very exhaustive description of the microscopic structure of the barks occurring in the Vienna market, or preserved in the museums of that city.

Vogl (A.), _Beiträge zur Kenntniss der sogenannten falschen Chinarinden_. Wien, 1876, 4°. 26 pages, 7 microscopic sections.

Vrij (John Eliza de), _Kinologische studiën_. More than 30 papers published since 1868 in the _Nieuw Tijdschrift voor de Pharmacie in Nederland_. They are chiefly devoted to the chemistry of the barks from Java and British India.

Weddell (Hugh Algernon), _Histoire naturelle des Quinquinas, ou monographie du genre Cinchona, suivie d’une description du genre Cascarilla et de quelques autres plantes de la même tribu_. Paris, 1849, folio, 108 pages, 33 plates, and map. Excellent uncoloured figures of Cinchona and some allied genera, and beautiful coloured drawings of the officinal barks. Plate I. exhibits the anatomical structure of the plant; Plate II. that of the bark.

Weddell (H. A.), _Notes sur les Quinquinas, Extrait des Annales des Sciences naturelles_, 5ᵉ série, tomes xi. et xii. Paris, 1870, 8°. 75 pages. A systematic arrangement of the genus _Cinchona_, and description of its (33) species, accompanied by useful remarks on their barks. An English translation has been printed by the India Office with the title—_Notes on the Quinquinas by H. A. Weddell_, London, 1871, 8°. 64 pages. A German edition by Dr. F. A Flückiger has also appeared under the title _Uebersicht der Cinchonen von H. A. Weddell_. Schaffhausen and Berlin, 1871, 8°. 43 pages, with additions and indexes.

RADIX IPECACUANHÆ.

_Ipecacuanha Root_, _Ipecacuan_; F. _Racine d’Ipécacuanha annelee_; G. _Brechwurzel_.

=Botanical Origin=—_Cephaëlis[1373] Ipecacuanha_ A. Richard—This is a small shrub, 8 to 16 inches high, with an ascending, afterwards erect, simple stem, and somewhat creeping root, growing socially in moist and shady forests of South America, lying between 8° and 22° S. lat., especially in the Brazilian provinces of Pará, Maranhão, Pernambuco, Bahia, Espiritu Santo, Minas, Rio de Janeiro, and São Paulo. Within the last half century, it has been discovered in the vast interior province of Matto Grosso, chiefly in that part of it which forms the valley of the Rio Paraguay. From information given to Weddell,[1374] it would seem probable that the plant extends beyond the frontiers of Brazil to the Bolivian province of Chiquitos.

The root which is brought into commerce is furnished chiefly by the region lying between the towns of Cuyabá, Villa Bella, Villa Maria, and Diamantina in the province of Matto Grosso; but to some extent also by the woods in the neighbourhood of the German colony of Philadelphia on the Rio Todos os Santos, a tributary of the Mucury, north of Rio de Janeiro.

Prof. Balfour of Edinburgh, who has paid much attention to the propagation of ipecacuanha, finds that the plant exists under two varieties, of which he has published figures;[1375] they may be thus distinguished:

_a._ Stem woody, leaves of firm texture, elliptic or oval, wavy at the edges, with but few hairs on surface and margin. Long in cultivation: origin unknown.

_b._ Stem herbaceous, leaves less firm in texture, more hairy on margin, not wavy. Grows in the neighbourhood of Rio de Janeiro.

The plant cultivated in India seems disposed to run into several varieties, but according to the experience gained in Edinburgh, the diversity of form apparent in young plants tends to disappear with age.

=History=—In an account of Brazil, written by a Portuguese friar, who, it would seem, had resided in that country from about 1570 to 1600, and published by Purchas,[1376] mention is made of three remedies for the bloody flux, one of which is called _Igpecaya_ or _Pigaya_; the drug here spoken of is probably that under notice.

[1373] I am informed by my friend Professor Müller of Geneva that in describing the Rubiaceæ for the _Flora Brasiliensis_ he will include Cephaëlis Ipecacuanha in the genus _Mapouria_.—F. A. F.. March 1879.

[1374] _Ann. des Sciences nat._ Bot. xi. (1849) 193-202.

[1375] _Trans. of Roy. Soc. of Edinb._ xxvi. (1872) 781. plates 31-32.—Fig. in Bentley and Trimen, _Med. Plants._