CHAPTER I.

DISCOVERY OF PERUVIAN BARK. The Countess of Chinchon--Introduction of the use of bark into Europe--M. La Condamine's first description of a _Chinchona_-tree--J. de Jussieu--Description of the Chinchona region--The different valuable species--The discovery of quinine. THE whole world, and especially all tropical countries where intermittent fevers prevail, have long been indebted to the mountainous forests of the Andes for that inestimable febrifuge which has now become indispensable, and the demand for which is rapidly increasing, while the supply decreases, throughout all civilized countries. There is probably no drug which is more valuable to man than the febrifugal alkaloid which is extracted from the chinchona-trees of South America; and few greater blessings could be conferred on the human race than the naturalization of these trees in India, and other congenial regions, so as to render the supply more certain, cheaper, and more abundant. It will be the principal object of the following pages to relate the measures which have been adopted within the last two years to collect plants and seeds of these quinine-yielding chinchonæ, in the various regions of South America, where the most valuable species are found; and to give an account of their introduction into India, and of the hill districts in that country where it is considered most likely that they will thrive. But it is necessary that the reader should have a general knowledge of these precious trees, and of their history, before he accompanies the explorers who were sent in search of them over the cordilleras of the Andes, and into the vast untrodden forests. It would be strange indeed, if, as is generally supposed, the Indian aborigines of South America were ignorant of the virtues of Peruvian bark; yet the absence of this sovereign remedy in the wallets of itinerant native doctors who have plied their trade from father to son, since the time of the Incas, certainly gives some countenance to this idea. It seems probable, nevertheless, that the Indians were aware of the virtues of Peruvian bark in the neighbourhood of Loxa, 230 miles south of Quito, where its use was first made known to Europeans: and the Indian name for the tree _quina-quina_, "bark of bark," indicates that it was believed to possess some special medicinal properties.[3] The Indians looked upon their conquerors with dislike and suspicion; it is improbable that they would be quick to impart knowledge of this nature to them; and the interval which elapsed between the discovery and settlement of the country and the first use of Peruvian bark by Europeans may thus easily be explained.[4] The conquest and subsequent civil wars in Peru cannot be said to have been finally concluded until the time of the viceroy Marquis of Cañete, in 1560; and J. de Jussieu reports that a Jesuit, who had a fever at Malacotas,[5] was cured by Peruvian bark in 1600. M. La Condamine also found a manuscript in the library of a convent at Loxa, in which it was stated that the Europeans of the province used the bark at about the same time. Thus an interval of only forty years intervened between the pacification of Peru and the discovery of its most valuable product. It may be added, however, that though the Indians were aware of the febrifugal qualities of this bark, they attached little importance to them, and this may be another reason for the lapse of time which occurred before the knowledge was imparted to the Spaniards. Referring to this circumstance La Condamine says, "Nul n'est saint dans son pays." This indifference to, and in many cases even prejudice against the use of the Peruvian bark, amongst the Indians, is very remarkable. Poeppig, writing in 1830, says that in the Peruvian province of Huanuco the people, who are much subject to tertian agues, have a strong repugnance to its use. The Indian thinks that the cold north alone permits the use of fever-bark; he considers it as very heating, and therefore an unfit remedy in complaints which he believes to arise from inflammation of the blood.[6] Humboldt also notices this repugnance to using the bark amongst the natives; and Mr. Spruce makes the same observation with respect to the people of Ecuador and New Granada.[7] He says that they refer all diseases to the influence of either heat or cold; and, confounding cause and effect, they suppose all fevers to proceed from heat. They justly believe bark to be very heating, and hence their prejudice against its use in fevers, which they treat with _frescos_ or cooling drinks. Even in Guayaquil the prejudice against quinine is so strong that, when a physician administers it, he is obliged to call it by another name. In about 1630 Don Juan Lopez de Canizares, the Spanish Corregidor of Loxa, being ill with an intermittent fever, an Indian of Malacotas is said to have revealed to him the healing virtues of quinquina bark, and to have instructed him in the proper way to administer it, and thus his cure was effected. In 1638 the wife of Luis Geronimo Fernandez de Cabrera Bobadilla y Mendoza, fourth Count of Chinchon, lay sick of an intermittent fever in the palace at Lima. Her famous cure induced Linnæus, long afterwards, to name the whole genus of quinine-yielding trees in her honour _chinchona_. The godmother of these priceless treasures of the vegetable kingdom has, therefore, some claim upon our attention. This Countess of Chinchon was a daughter of the noble house of Osorio, whose founder was created Marquis of Astorga by Henry IV., King of Castille. The eighth marquis, who died at Astorga in 1613, had a daughter by his wife Dona Blanca Manrique y Aragon, named Ana,[8] born in 1576; and the ruins of the palace in the curious old town of Astorga, in which she passed her childhood, are still standing.[9] At the early age of sixteen she was married to Don Luis de Velasco, Marquis of Salinas, who was about to assume the important office of viceroy of Mexico. She probably accompanied her husband to Mexico, and afterwards to Lima, as he was viceroy of Peru from 1596 to 1604. In the latter year he resumed his former office in Mexico, and, on his return to Spain, he became President of the Council of the Indies from 1611 to 1617.[10] The lady Ana had thus been a great traveller, when, in the latter year, she found herself a widow. In 1621 she was married, in the city of Madrid, to her second husband the fourth Count of Chinchon, who was descended from a long line of proud and valiant Catalonian ancestors. One of his forefathers, Don Andres de Cabrera, who was created Marquis of Moya in 1480, married Beatriz de Bobadilla, so well known in history as the faithful attendant and confidential friend of Queen Isabella the Catholic. The Emperor Charles V., remembering the services and ancient dignity of the illustrious families of Cabrera and Bobadilla, created the second son of the Marquis of Moya, by Beatriz de Bobadilla, Count of his town of Chinchon, in the kingdom of Toledo, in 1517.[11] The third Count was one of the over-worked ministers of that most indefatigable of "red-tapists" Philip II.; and his son became the husband of the widow Ana, who accompanied him to Lima on his appointment as viceroy of Peru in 1629. Thus, for the second time, this lady entered the City of the Kings as Vice-Queen. While the Countess Ana was suffering from fever in 1638, in her sixty-third year, the Corregidor of Loxa, Don Juan Lopez de Canizares, sent a parcel of powdered quinquina bark to her physician, Juan de Vega, who was also captain of the armoury, assuring him that it was a sovereign and never-failing remedy for "tertiana." It was administered to the Countess and effected a complete cure; and Mr. Howard is of opinion that the particular plant which had this honour, and which, therefore, yields the true and original Peruvian bark, is the _Chahuarguera_ variety of the _C. Condaminea_.[12] This kind contains a large percentage of _chinchonidine_, an alkaloid, the great importance of which is only now just beginning to be recognised, so that it is to _chinchonidine_, and not to _quinine_, that the Countess's cure is due.[13] The Count of Chinchon returned to Spain in 1640, and his Countess, bringing with her a quantity of the healing bark, was thus the first person to introduce this invaluable medicine into Europe.[14] Hence it was sometimes called Countess's bark, and Countess's powder. Her physician, Juan de Vega, sold it at Seville for one hundred reals the pound. In memory of this great service Linnæus named the genus which yields it _Chinchona_, and afterwards the lady Ana's name was still further immortalized in the great family of _Chinchonaceæ_, which, together with _Chinchonæ_, includes ipecacuanhas and coffees. By modern writers the first _h_ has usually been dropped, and the word is now almost invariably, but most erroneously, spelt _Cinchona_. After the cure of the Countess of Chinchon, the Jesuits were the great promoters of the introduction of bark into Europe. In 1639, as the last act of his viceroyalty, her husband did good service to the cause of geographical discovery, by causing the expedition under the Portuguese Texeira to proceed from Quito to the mouth of the Amazons, accompanied by the Jesuit Acuña, who wrote a most valuable account of the voyage.[15] From that time the missionaries of Acuña's fraternity continued to penetrate into the forests bordering on the upper waters of the Amazons, and to form settlements; and Humboldt mentions a tradition that these Jesuits accidentally discovered the bitterness of the bark, and tried an infusion of it in tertian ague. In 1670 the Jesuit missionaries sent parcels of the powdered bark to Rome, whence it was distributed to members of the fraternity throughout Europe by the Cardinal de Lugo, and used for the cure of agues with great success. Hence the name of "Jesuits' bark," and "Cardinal's bark;" and it was a ludicrous result of its patronage by the Jesuits that its use should have been for a long time opposed by Protestants and favoured by Roman Catholics. In 1679 Louis XIV. bought the secret of preparing quinquina from Sir Robert Talbor, an English doctor, for two thousand louis-d'ors, a large pension, and a title. From that time Peruvian bark seems to have been recognised as the most efficacious remedy for intermittent fevers. The second Lord Shaftesbury, who died in 1699, mentions in one of his letters--"Dr. Locke's and all our ingenious and able doctors' method of treating fevers with the Peruvian bark:" he declares his belief that it is "the most innocent and effectual of all medicines;" but he also alludes to "the bugbear the world makes of it, especially the tribe of inferior physicians." There can be no doubt that a very strong prejudice was raised against it, which it took many years to conquer; and the controversies which arose on the subject between learned doctors were long and acrimonious. Dr. Colmenero, a professor of the University of Salamanca, wrote a work in which he declared that ninety sudden deaths had been caused by its use in Madrid alone.[16] Chiflet (Paris, 1653) and Plempius (Rome, 1656), two great enemies of novelty, prophesied the early death of quinquina, and its inevitable malediction by future ages; while the more enlightened Badius (Genoa, 1656) defended its use, and quoted more than twelve thousand cures by the aid of this remedy, performed by the best doctors of the hospitals in Italy. In 1692 Dr. Morton, one of the opponents of its use, was obliged to retract all he had said against quinquina; and it was then that it began to be generally admitted as a valuable medicine. It still, however, remained a subject of controversy, and as late as 1714 two Italian physicians, Ramazzini and Torti,[17] held opposite views on the subject. Ramazzini wrote against its use with much violence, while Torti maintained that, in proper doses, it would arrest remittent and intermittent fevers.[18] Whilst the inestimable value of Peruvian bark was gradually forcing conviction on the most bigoted medical conservatives of Europe, and whilst the number and efficacy of cures effected by its means were bringing it into general use, and consequently increasing the demand, it was long before any knowledge was obtained of the tree from which it was taken. In 1726 La Fontaine, at the solicitation of the Duchess of Bouillon, who had been cured of a dangerous fever by taking Peruvian bark, composed a poem in two cantos to celebrate its virtues; but the exquisite beauty of the leaves, and the delicious fragrance of the flowers of the quinquina-tree, with allusions to which he might have adorned his poem, were still unknown in Europe. The first description of the quinquina-tree is due to that memorable French expedition to South America, to which all branches of science owe so much. The members of this expedition, MM. De la Condamine, Godin, Bouguer, and the botanist Joseph de Jussieu, sailed from Rochelle on the 16th of May, 1735, to measure the arc of a degree near Quito, and thus determine the shape of the earth. After a residence at Quito, Jussieu set out for Loxa, to examine the quinquina-tree, in March, 1739, and in 1743 La Condamine visited Loxa, and stayed for some time at Malacotas, with a Spaniard whose chief source of income was the collection of bark. He obtained some young plants with the intention of taking them down the river Amazons to Cayenne, and thence transporting them to the Jardin des Plantes at Paris; but a wave washed over his little vessel near Para, at the mouth of the great river, and carried off the box in which he had preserved these plants for more than eight months. "Thus," he says, "I lost them after all the care I had taken during a voyage of more than twelve hundred leagues."[19] This was the first attempt to transport chinchona-plants from their native forests. Condamine described the quinquina-tree of Loxa in the 'Mémoires de l'Académie;'[20] he was the first man of science who examined and described this important plant; and in 1742 Linnæus established the genus CHINCHONA, in honour of the Countess Ana of Chinchon. He, however, only knew of two species, that of Loxa, which was named _C. officinalis_, and the _C. Caribæa_, since degraded to the medicinally worthless genus of _Exostemmas_. Joseph de Jussieu, whose name is associated with that of La Condamine in the first examination of the chinchona-trees of Loxa, continued his researches in South America after the departure of his associate. He penetrated on foot into the province of Canelos, the scene of Gonzalo Pizarro's wonderful achievements and terrible sufferings; he visited Lima with M. Godin; he travelled over Upper Peru as far as the forests of Santa Cruz de la Sierra; and he was the first botanist who examined and sent home specimens of the coca-plant, the beloved narcotic of the Peruvian Indian. After fifteen years of laborious work he was robbed of his large collection of plants by a servant at Buenos Ayres, who believed that the boxes contained money. This loss had a disastrous effect on poor Jussieu, who, in 1771, returned to France, deprived of reason, after an absence of thirty-four years. Dr. Weddell has named the shrubby variety of _C. Calisaya_ in honour of this unfortunate botanist _C. Josephiana_. For many years the quinquina-tree of Loxa, the _C. officinalis_ of Linnæus, was the only species with which botanists were acquainted; and from 1640 to 1776 no other bark was met with in commerce than that which was exported from the Peruvian port of Payta, brought down from the forests in the neighbourhood of Loxa. The constant practice of improvidently felling the trees over so small an area for more than a century, without any cessation, inevitably led to their becoming very scarce, and threatened their eventual extinction. As early as 1735 Ulloa reported to the Spanish Government, that the habit of cutting down the trees in the forests of Loxa, and afterwards barking them, without taking the precaution of planting others in their places, would undoubtedly cause their complete extirpation. "Though the trees are numerous," he added, "yet they have an end;" and he suggested that the Corregidor of Loxa should be directed to appoint an overseer, whose duty it should be to examine the forests, and satisfy himself that a tree was planted in place of every one that was felled, on pain of a fine.[21] This wise rule was never enforced, and sixty years afterwards Humboldt reported that 25,000 trees were destroyed in one year. The measures adopted by the Spanish Government towards the end of the last century, in sending botanical expeditions to explore the chinchona forests in other parts of their vast South American possessions, led to the discovery of additional valuable species, the introduction of their barks into commerce, and the reduction of the pressure on the Loxa forests, which were thus relieved from being the sole source whence Peruvian bark could be supplied to the world. The region of chinchona-trees extends from 19° S. latitude, where Weddell found the _C. Australis_, to 10° N., following the almost semicircular curve of the cordillera of the Andes over 1740 miles of latitude. They flourish in a cool and equable temperature, on the slopes and in the valleys and ravines of the mountains, surrounded by the most majestic scenery, never descending below an elevation of 2500, and ascending as high as 9000 feet above the sea. Within these limits their usual companions are tree ferns, melastomaceæ, arborescent passion-flowers, and allied genera of chinchonaceous plants. Below them are the forests abounding in palms and bamboos, above their highest limits are a few lowly Alpine shrubs. But within this wide zone grow many species of chinchonæ, each within its own narrower belt as regards elevation above the sea, some yielding the inestimable bark, and others commercially worthless. And the species of chinchonæ, in their native forests, are not only divided from each other by zones as regards height above the sea, but also by parallels of latitude. In Bolivia and Caravaya, for instance, the valuable _C. Calisaya_ abounds, but it is never found nearer the equator than 12° S. Between that parallel and 10° S. the forests are for the most part occupied by worthless species, while in Northern Peru the important grey barks of commerce are found. In each of these latitudinal regions the different species are again divided by belts of altitude. Yet this confinement within zones of latitude and altitude is not a constant rule; for several of the hardier and stronger species have a wider range; while the more sensitive, and these are usually the most precious kinds, are close prisoners within their allotted zones, and never pass more than a hundred yards beyond them. All the species are, of course, affected by local circumstances, which more or less modify the positions of their zones, as regards altitude. Thus, to give a geographical summary of the chinchona region, beginning from the south, it commences in the Bolivian province of Cochabamba in 19° S., passes through the yungus of La Paz, Larecaja, Caupolican, and Munecas, into the Peruvian province of Caravaya; thence through the Peruvian forests, on the eastern slopes of the Andes, of Marcapata, Paucartambo, Santa Anna, Guanta, and Uchubamba, to Huanuco and Huamalies, where the grey bark is found. It then continues through Jaen, to the forests near Loxa and Cuenca, and on the western slopes of Chimborazo. It begins again in latitude 1° 51´ N. at Almaguer, passes through the province of Popayan, and along the slopes of the Andes of Quindiu, until it reaches its extreme northern limit on the wooded heights of Merida and Santa Martha. Humboldt remarks that, beyond these limits, the Silla de Caraccas, and other mountains in the province of Cumana, possess a suitable altitude and climate for the growth of chinchona-trees, as well as some parts of Mexico, yet that they have never been found either in Cumana or Mexico; and he suggests that this may be accounted for by the breaks which take place in Venezuela on the one hand, and on the isthmus of Panama on the other, where tracts of country of low elevation intervene between the lofty mountains of Cumana and Mexico and the chinchona region of the main Andes. In these low districts the chinchona-trees may have encountered obstacles which prevented their propagation to the northward: otherwise we might expect to find them in the beautiful Mexican woods of Jalapa, whither the soil and climate, and their usual companions the tree ferns and melastomaceæ, would seem to invite them.[22] Be this how it may, the chinchona-plant has never been found in any part of the world beyond the limits already described. The chinchonas, when in good soil and under other favourable circumstances, become large forest trees; on higher elevations, and when crowded, and growing in rocky ground, they frequently run up to great heights without a branch; and at the upper limit of their zone they become mere shrubs. The leaves are of a great variety of shapes and sizes, but, in most of the finest species, they are lanceolate, with a shining surface of bright green, traversed by crimson veins, and petioles of the same colour. The flowers are very small, but hang in clustering panicles, like lilacs, generally of a deep roseate colour, paler near the stalk, dark crimson within the tube, with white curly hairs bordering the laciniæ of the corolla. The flowers of _C. micrantha_ are entirely white. They send forth a delicious fragrance which scents the air in their vicinity. The earliest botanists gave the name of Chinchona to a vast number of allied genera, which have since been separated, and grouped under other names.[23] There are three characteristics by which a true chinchona may invariably be known; the presence of curly hairs bordering the laciniæ of the corolla, the peculiar mode of dehiscence of the capsule from below upwards, and the little pits at the axils of the veins on the under sides of the leaves. These characters distinguish the chinchona from many trees which grow with it, and which might at first sight be taken for the same genus. The fact, established by the investigations of chemists, that none of these allied genera contain any of the medicinal alkaloids, has confirmed the propriety of their expulsion from the chinchona genus by botanists; and Dr. Weddell gives a list of seventy-three plants, once received as Chinchonæ, which are now more properly classed under allied genera, such as _Cosmibuena_, _Cascarilla_, _Exostemma_, _Remijia_, _Ladenbergia_, _Lasionema_, &c.[24] Thus thinned out and reduced in numbers, the list of species of Chinchonæ has been established by Dr. Weddell at nineteen, and two doubtful;[25] but even the classification of this eminent authority, published in 1849, already requires much alteration and revision. For instance: Dr. Weddell gives no place to the "red-bark" species, the richest in alkaloids, and one of the most important, which, through the recent investigations of Mr. Spruce, will now probably be admitted by botanists as a distinct species, the _C. succirubra_ (Pavon). A new grey bark now introduced into India as _C. Peruviana_ (Howard), and the _C. Pahudiana_ (Howard), a worthless kind, cultivated by the Dutch in Java, will also be received as additional species. It seems likely also that the _C. Condaminea_ requires to be divided into two or three distinct species; while the _C. Boliviana_ (Weddell) will sink into a mere variety of the _C. Calisaya_. The commercially valuable species, however, comprise but a small proportion of the whole; and, as all these have now been introduced into India, they alone deserve our attention. They are as follows:-- _C. succirubra_ (Pavon) yielding _Red bark._ {_C. Chahuarguera_ (Pavon) } _C. Condaminea._ {_C. crispa_ (Tafalla)} " _Crown bark._ {_C. Uritusinga_ (Pavon) } {_C. lancifolia_ (Mutis) " _Carthagena bark._ _C. nitida_ (Ruiz & Pavon)} _C. micrantha_ (Ruiz & Pavon)} " _Grey bark._ _C. Peruviana_ (Howard) } _C. Calisaya_ (Weddell) " _Yellow bark._ These species yield five different kinds of medicinal barks, which are collected from five different regions in South America; and in the following chapter I propose to give a brief account of each of these regions, of their chinchona-trees, and of the investigations of botanists down to the time when measures were taken to introduce these inestimable plants into Java and India. Such an account will naturally divide itself into five sections:-- I.--The Loxa region, and its _crown barks_. II.--The _red-bark_ region, on the western slopes of Chimborazo. III.--The New Granada region. IV.--The Huanuco region in Northern Peru, and its _grey barks_. V.--The _Calisaya_ region, in Bolivia and Southern Peru. Before entering on this subject, however, it will be well to cast a hasty glance at the progress of those investigations which ended in the discovery of the febrifugal principle in Peruvian bark. The roots, flowers, and capsules of the chinchona-trees have a bitter taste with tonic properties, but the upper bark is the only part which has any commercial value.[26] The bark of trees is composed of four layers--the epiderm, the periderm, the cellular layer, and the liber or fibrous layer, composed of hexagonal cells filled with resinous matter and woody tissue. In growing, the tree pushes out the bark, and, as the exterior part ceases to grow, it separates into layers, and forms the dead part or periderm; which in chinchonas is partially destroyed, and blended with the thallus of lichens. The bark is thus formed of the dead part, or periderm, and the living part, or derm. On young branches there is no dead part, the exterior layers remaining entire, while the inner layers have not had time to develop. In thick old branches, on the contrary, the periderm or dead part is considerable, while the fibrous layer of the derm is fully developed. In preparing the bark the periderm is removed by striking the trunk with a mallet, and the derm is then taken off by uniform incisions. The thin pieces from small branches are simply exposed to the sun's rays, and assume the form of hollow cylinders, or quills, called by the natives _canuto_ bark. The solid trunk bark is called _tabla_ or _plancha_, and is sewn up in coarse canvas and an outer envelope of fresh hide, forming the packages called _serons_. The character of the transverse fracture affords an important criterion of the quality of the bark. Cellular tissue breaks with a short and smooth fracture, woody tissue with a fibrous fracture, as is the case with the _calisaya_ bark. The best characteristics by which barks containing much quinine may be distinguished are the shortness of the fibres which cover the transverse fracture, and the facility with which they may be detached, instead of being flexible and adhering as in bad barks. Thus, when dry _calisaya_ bark is handled, a quantity of little prickles run into the skin, and this forms one of its distinguishing marks.[27] Until the present century Peruvian bark was used in its crude state, and numerous attempts were made at different times to discover the actual healing principle in the bark, before success was finally attained. The first trial which is worthy of attention was made in 1779 by the chemists Buguet and Cornette, who recognised the existence of an essential salt, a resinous and an earthy matter in quinquina bark. In 1790 Fourcroy discovered the existence of a colouring matter, afterwards called _chinchona red_, and a Swedish doctor named Westring, in 1800, believed that he had discovered the active principle in quinquina bark. In 1802 the French chemist Armand Seguin undertook the bark trade on a large scale, and found it necessary to study the means of discovering good barks, and distinguishing them from bad ones. He found that the best quinquina bark was precipitated by tannin, while the bad was not precipitated by that substance. In 1803 another chemist found a crystalline substance in the bark which he called "_sel essentiel fébrifuge_" but it was nothing more than the combination of lime with an acid which was named _quinic acid_. Reuss, a Russian chemist, in 1815, was the first to give a tolerable analysis of quinquina bark; and about the same time Dr. Duncan of Edinburgh suggested that a real substance existed as a febrifugal principle. Dr. Gomez, a surgeon in the Portuguese navy, in 1816, was the first to isolate this febrifugal principle hinted at by Dr. Duncan, and he called it _chinchonine_.[28] But the final discovery of quinine is due to the French chemists Pelletier and Caventou, in 1820. They considered that a vegetable alkaloid, analogous to morphine and strychnine, existed in quinquina bark; and they afterwards discovered that the febrifugal principle was seated in two alkaloids, separate or together, in the different kinds of bark, called _quinine_ and _chinchonine_, with the same virtues, which, however, were much more powerful in quinine. It was believed that in most barks chinchonine exists in the cellular layer, and quinine in the liber, or fibrous layer; but Mr. Howard has since shown that this view is quite incorrect.[29] In 1829 Pelletier discovered a third alkaloid, which he called _aricine_, of no use in medicine, and derived from a worthless species of chinchona, growing in most of the forests of Peru, called _C. pubescens_.[30] The organic constituents of chinchona barks are-- Quina. | Kinovic acid. Chinchonia. | Chinchona red. Aricina. | A yellow colouring matter. Quinidia. | A green fatty matter. Chinchonidia. | Starch. Quinic acid. | Gum. Tannic acid. | Lignin. These materials are in different proportions according to the barks. Grey bark chiefly contains chinchonine and tannin; Calisaya, or yellow bark, much quinine, and a little chinchonine; red bark holds quinine and chinchonine in nearly equal proportions; while the barks of New Granada chiefly contain chinchonidine and quinidine. The two latter alkaloids were definitively discovered in 1852 by M. Pasteur; although the Dutch chemist Heijningen had, in 1848, found what he called β quinine or quinidine. Chinchonidine is only second to quinine itself in importance as a febrifugal principle. _Quinine_ is a white substance, without smell, bitter, fusible, crystallized, with the property of left-handed rotatory polarization. The salts of quinine are soluble in water, alcohol, and ether. Of all the salts the bisulphate of quinine is preferred, because it constitutes a stable salt, easy to prepare, and containing a strong proportion of the alkaloid. It is very bitter and soluble, and crystallizes in long silky needles. It is prepared by adding sulphuric acid to the sulphate.[31] _Chinchonine_ differs from quinine in being less soluble in water, and being altogether insoluble in ether. It has the property of right-handed rotatory polarization. _Quinidine_ also has the property of right-handed rotatory polarization, and forms salts like those of quinine. It becomes green by successive additions of chlorine and ammonia. _Chinchonidine_ has not the property of turning green, and forms a sulphate almost exactly like sulphate of quinine.[32] The discovery of these alkaloids in the quinquina[33] bark, by enabling chemists to extract the healing principle, has greatly increased the usefulness of the drug. In small doses they promote the appetite and assist digestion; and chinchonine is equal to quinine in mild cases of intermittent fever; but in severe cases the use of quinine is absolutely necessary. Thus these alkaloids not only possess tonic properties to which recourse may be had under a multitude of circumstances, but also have a febrifugal virtue which is unequalled, and which has rendered them almost a necessary of life in tropical countries, and in low marshy situations where agues prevail. Many a poor fellow's life was saved in the Walcheren expedition by the timely arrival of a Yankee trader with some chests of bark, after the supply had entirely failed in the camp.[34] Dr. Baikie, in his voyage up the Niger, attributed the return of his men alive to the habitual use of quinine; and the number of men whose lives it has saved in our naval service and in India will give a notion of the vast importance of a sufficient and cheap supply of the precious bark which yields it. India and other countries have been vainly searched for a substitute for quinine, and we may say with as much truth now as Laubert did in 1820--"This medicine, the most precious of all those known in the art of healing, is one of the greatest conquests made by man over the vegetable kingdom. The treasures which Peru yields, and which the Spaniards sought and dug out of the bowels of the earth, are not to be compared for utility with the bark of the quinquina-tree, which they for a long time ignored.[35]