EDGAR QUINET (1803-1875), French historian and man of letters, was born at Bourg-en-Bresse, in the department of the Ain, France, on the 17th of February 1803. His father, Jerome Quinet, had been a commissary in the army, but being a strong republican and disgusted with Napoleon's usurpation, he gave up his post and devoted himself to scientific and mathematical study. Edgar, who was an only child, was much alone, but his mother (Eugenie Rozat Lagis, who was a person of education and strong though somewhat unorthodox religious views) exercised great influence over him. He was sent to school first at Bourg and then at Lyons. His father wished him on leaving school to go into the army, and then suggested business. But Quinet was determined upon literature, and after a time got his way. His first publication, the Tablettes du juif errant, appeared in 1823. Being struck with Herder's Philosophic der Geschichte, he undertook to translate it, learnt German for the purpose, published his work in 1827, and obtained by it considerable credit. At this time he was introduced to Cousin, and made the acquaintance of Michelet. He had visited Germany and England before the appearance of his book. Cousin procured him a post on a government mission to the Morea in 1829, and on his return he published in 1830 a book on La Grece moderne. Some hopes of employment which he had after the revolution of February were frustrated by the reputation of speculative republicanism which he had acquired. But he joined the staff of the Revue des deux mondes, and for some years contributed to it numerous essays, the most remarkable of which was that on Les Epopees francaises du XIIeme siecle, an early, though not by any means the earliest, appreciation of the long-neglected chansons de geste. Ahasverus, his first original work of consequence, appeared in 1833. This is a singular prose poem, in language sometimes rather bombastic but often beautiful. Shortly afterwards he married Minna More, a German girl with whom he had fallen in love some years before. Then he visited Italy, and, besides writing many essays, produced two poems, Napoleon (1835) and Promethee (1838), which being written in verse (of which he was not a master) are inferior to Ahasverus. In 1838 he published a vigorous reply to Strauss's Leben Jesu, and in that year he received the Legion of Honour. In 1839 he was appointed professor of foreign literature at Lyons, where he began the brilliant course of lectures afterwards embodied in the Two years later he was transferred to the College de France, and the Genie des religions itself appeared (1842) .
Quinet's Parisian professorship was more notorious than fortunate, owing, it must be said, to his own fault. His chair was one of Southern Literature, but, neglecting his proper subject, he chose, in conjunction with Michelet, to engage in a violent polemic with the Jesuits and with Ultramontanism. Two books bearing exactly these titles appeared in 1843 and 1844, and contained, as was usual with Quinet, the substance of his lectures. These excited so much disturbance, and the author so obstinately refused to confine himself to literature proper, that in 1846 the government put an end to them - a course which was not disapproved by the majority of his colleagues. By this time Quinet was a pronounced republican, and something of a revolutionist. He appeared in arms during the disturbances which overthrew Louis Philippe, and was elected by the department of the Ain to the Constituent and then to the Legislative Assembly, where he figured among the extreme radical party. He had published in 1848 Les Revolutions d'Italie, one of his principal though not one of his best works. He wrote numerous pamphlets during the short-lived Second Republic, attacked the Roman expedition with all his strength, and was from the first an uncompromising opponent of Prince Louis Napoleon. He was banished from France after the coup d'etat, and established himself at Brussels. His wife had died some time previously, and he now married Mademoiselle Asaky, the daughter of a Roumanian poet. At Brussels he lived for some seven years, during which he published Les Esclaves (1853), a dramatic poem, Marnix de Sainte-Aldegonde (1854), a study of that Reformer in which he very greatly exaggerates. Sainte-Aldegonde's literary merit, and some other books. He then moved to Veytaux, on the shore of the Lake of Geneva, where he continued to reside till the fall of the empire. Here his pen was busier than ever. In 1860 appeared a singular book, somewhat after the fashion of Ahasverus, entitled Merlin l'enchanteur, in 1862 a Histoire de la campagne de 1815, in 1865 an elaborate book on the French Revolution, in which the author, republican as he was, blamed the acts of the revolutionists unsparingly, and by that means drew down on himself much wrath from more thoroughgoing partisans. Many pamphlets date from this period, as does La Creation (1870), a third book of the class of Ahasverus and Merlin, but even vaguer, dealing not with history, legend, or philosophy, but with physical science for the most part.
Quinet had refused to return to France to join the liberal opposition against Napoleon III., but immediately after Sedan he returned. He was then restored to his professorship, and during the siege wrote vehemently against the Germans. He was elected deputy by the department of the Seine in 1871, and was one of the most obstinate opponents of the terms of peace between France and Germany. He continued to write till his. death, which occurred at Versailles on the 2 7 th of March 1875. Le Siege de Paris et la defense nationale appeared in 1871, La Republique in 1872, Le Livre de l'exile in the year of its author's death and after it. This was followed by three volumes of letters and some other work. Quinet had already in 1858 published a semi-biographic book called Histoire de mes idees. Quinet's character was extremely amiable, and his letters to his mother, his accounts of his early life, and so forth, are likely always to make him interesting. He was also a man of great moral conscientiousness, and as far as intention went perfectly disinterested. As a writer, his chief fault is want of concentration;.
as a thinker and politician, vagueness and want of practical determination. His historical and philosophical works, though showing much reading, fertile thought, abundant facility of expression, and occasionally, where prejudice does not come in, acute judgment, are rather (as not a few of them were in fact) reported lectures than formal treatises. His rhetorical power was altogether superior to his logical power, and the natural consequence is that his work is full of contradictions. These contradictions were, moreover, due, not merely to an incapacity or an unwillingness to argue strictly, but also to the presence in his mind of a large number of inconsistent tastes and prejudices which he either could not or would not co-ordinate into an intelligible creed. Thus he has the strongest attraction for the picturesque side of medievalism and catholicity, the strongest repulsion for the restrictions which medieval and. Catholic institutions imposed on individual liberty. He refused to submit himself to any form of positive orthodoxy, yet when a man like Strauss pushed unorthodoxy to its extreme limits Quinet revolted. As a politician he acted with the extreme radicals, yet universal suffrage disgusted him as unreasonable in its principle and dangerous in its results. His pervading characteristic, therefore, is that of an eloquent vagueness, very stimulating and touching at times, but as deficient in coercive force of matter as it is in lasting precision and elegance of form. He is less inaccurate in fact than Michelet, but he is also much less absorbed by a single idea at a time, and the result is that he seldom attains to the vivid representation of which Michelet was a master.
Bibliography.-HiS numerous works appeared in a uniform edition of twenty-eight volumes (1877-79). His second wife, in 1870, published certain Memoires d'exil, and Lettres d'exil followed in 1885. In that year Prof. George Saintsbury published a selection of the Lettres a sa mere with an introduction. For many years Quinet received little attention in France, but it was revived, though not very strongly, by the publication in 1899 of Madame Quinet's Cinquante ans d'amitie (that between her husband and Michelet), and by the centenary of his birth. On this latter (1903) appeared A l'occasion du centenaire, by E. Ledrain; see also Libres Penseurs religieux, by E. Paris (1905). There is in English an elaborate Early Life and Writings of Edgar Quinet, by R. Heath (London, 1881). (G. SA.) Qtjinine, the most important alkaloid contained in cinchona bark (see Cinchona). In 1810 Gomez of Lisbon obtained a mixture of alkaloids which he named cinchonino, by treating an alcoholic extract of the bark with water and then adding a solution of caustic potash. In 1820 Pelletier and Caventou proved that the cinchonino of Gomez contained two alkaloids, which they named quinine and cinchonine. Later quinidine and cinchonidine were discovered, and subsequently several other alkaloids, but in smaller quantity.
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The alkaloids exist in the bark chiefly in combination with cinchotannic and quinic acids. The cinchotannic acid apparently becomes altered by atmospheric oxidation into a red-colouring matter, known as cinchono-fulvic or cinchona red, which is very abundant in some species, as in C. succirubra. For this reason those barks which, like C. Calisaya, C. officinalis, and C. Ledgeriana, contain but little colouring matter are preferred, the quinine being more easily extracted from them in a colourless form. The exact mode of extraction adopted by manufacturers is secret. That hitherto adopted by the Indian Government for the preparation of the cinchona febrifuge (see below) is simple, but the whole of the alkaloid present in the bark is not obtained by it. This method is to exhaust the powdered bark with water acidulated with hydrochloric acid and then to precipitate the alkaloids by caustic soda. Another method consists in mixing the powdered bark with milk of lime, drying the mass slowly with frequent stirring, exhausting the powder with boiling alcohol, removing the excess of alcohol by distillation, adding sufficient dilute sulphuric acid to dissolve the alkaloid and throw down colouring matter and traces of lime, &c., filtering, and allowing the neutralized liquid to deposit crystals. The sulphates of the alkaloids thus obtained are not equally soluble in water, and the quinine sulphate can be separated by fractional crystallization, being less soluble in water than the other sulphates.
Quinine of commerce is the neutral sulphate,C20H24N202 H2S04.8H20, which occurs in commerce in the form of very light slender white acicular crystals. It is soluble in about 780 parts of cold water, but in 30 of boiling water, 60 of rectified spirit (sp. gr. 0.83), and 40 of glycerin. Its solubility in water is lessened by sodium or magnesium sulphate, but is increased by potassium nitrate, ammonium chloride, and most acids. It is not soluble in fixed oils or in ether, although the pure alkaloid is soluble in both. It becomes phosphorescent on trituration. When prescribed it is generally rendered more soluble in water by the addition of dilute sulphuric acid or of citric acid, one drop of the former or 4ths of a grain of the latter being used for each grain of the quinine sulphate. Quinine is precipitated from its solution by alkalis and their carbonates. It is, however, very soluble in excess of ammonia.
The acid solution of sulphate of quinine is fluorescent, especially when dilute; and it is laevo-rotatory. When a solution of chlorine is first added and then ammonia an emerald green colour, due to the formation of thalleoquin, is developed. This test answers with a solution containing only 1 part of quinine in 5000, or in a solution containing not more than part if bromine be used instead of chlorine. The fluorescence is visible in an acid solution containing I part in 200,000 of water. By adding an alcoholic solution of iodine to a solution of the sulphate in acetic acid a compound known as herapathite, 4Qu3H 2 SO 4.2HIIe6H 2 O, is obtained, which possesses optical properties similar to those of tourmaline; it is soluble in Iwo parts of boiling water; and its sparing solubility in cold alcohol has been utilized for estimating quinine quantitatively. The other alkaloids are distinguished from quinine thus: quinidine resembles quinine, but is dextro-rotatory, and the iodide is very insoluble in water; the solution of cinchonidine, which is laevo-rotatory, does not give the thalleoquin test, nor fluorescence; cinchonine resembles cinchonidine in these respects, but is dextrorotatory.
Commercial sulphate of quinine frequently contains from I tc 10% of cinchonidine sulphate, owing to the use of barks containing it. The sulphate of cinchonidine is more soluble than that of quinine; and, when 1 part of quinine sulphate suspected to contain it is nearly dissolved in 24 parts of boiling water, the sulphate of quinine crystallizes out on' cooling, and the cinchonidine is found in the clear mother liquor, from which it can be precipitated by a solution of potassium and sodium tartrate. Samples of quinine in which cinchonidine is present usually contain a smaller percentage of water than the pure sulphate. Traces of quinidine are also sometimes, though rarely, found in commercial quinine, but its presence does not detract in a medicinal point of view from the value of the latter.
Owing to its voluminous character as much as 18% of water may remain present in apparently dry samples of sulphate of quinine. If it loses more than 14.6% of water when dried at loo 0 C. it contains an excessive amount of moisture. Owing to its variability in this respect, and to its insolubility, certain other salts have largely replaced the sulphate in modern medicine.
Sulphate of quinine manufactured from cuprea bark (Remijia pedunculata) may contain from -Do to. 90% of sulphate of homoquinine, which almost coincides in solubility with sulphate of quinine. Homoquinine is decomposed on treatment with caustic soda into quinine and a new alkaloid, cupreine, in the proportion of 2 to 3. Cupreine is soluble in a solution of caustic soda (differing in this respect from quinine), and therefore it is easy to prepare sulphate of quinine perfectly free from either homoquinine or cupreine. The medicinal properties of cupreine and homoquinine are of no practical importance.
In consequence of the high price of the alkaloid an attempt was made some years ago by the Government of India to manufacture from cinchona bark a cheap febrifuge which should represent the alkaloids contained in the bark and form a substitute for quinine. This mixture is known as cinchona febrifuge, and is prepared chiefly from C. succirubra, which succeeds better in India than the other species in cultivation, and grows at a lower elevation, being consequently procurable in large quantities at a comparatively low price. A mixture of the cinchona alkaloids, consisting principally of cinchonidine sulphate, with smaller quantities of the sulphates of quinine and cinchonine, is sold under the name of "quinetum" at a cheaper rate than quinine.
The chemical constitution of quinine and the allied alkaloids is not definitely settled, although certain relationships are well established. Thus quinine is methoxycinchonine or methylcupreine, cupreine being an oxycinchonine. These relations are shown by the formulae: - cinchonine = C19H21N2. OH; cupreine = C19H20N2(OH)21 quinine =C19H20N2(OH) (OCH 3). Cinchonine yields on oxidation cinchoninic acid (y - quinoline carboxylic acid). C9H6NC02H, whilst quinine gives quininic acid, C9H5(OCH3)(C02H). This permits the writing of cinchonine, for example, as C,H6NCioH15(OH)N, the hydroxy group being in the part CioH15(OH)N, about which the constitution is uncertain. The subject has been especially studied by Skraup, Konigs, and von Miller; Kiinigs and von Miller have proposed formulae consisting of a piperidine ring substituted with a vinyl group; in the former that is a bridge of CH 2 C(OH)from the nitrogen atom to the -y-carbon atom, connexion with the quinoline residue being made at the hydroxylic carbon atom through a CH2 group: whilst in the latter the piperidine ring is substituted by a methyl group in addition to the vinyl group and the bridge is simply C(OH), with which connexion is made as before.
The sulphate is still used in medicine, and the British Pharmacopeia has admitted two others, which are much more valuable - the hydrochloride and the acid hydrochloride - whilst the hydrobromide is also used. The hydrochloride - formerly known as the hydrochlorateC20H24N202HCl. 2H20, resembles the sulphate in appearance, the crystals being, however, somewhat larger. It is soluble in less than 40 parts of cold water, and in 3 parts of alcohol (go%). The doses are similar to those of the sulphate, but somewhat smaller, owing to its greater solubility. The acid hydrochloride is the most valuable of all salts of quinine. It is soluble in its own weight of water, and is the most rapidly and completely absorbed of all the salts of this alkaloid. It occurs in a colourless crystalline powder, having the formula C20H24N202.2HC1.3H20.
The sulphate of quinine used in medicine may contain up to 3% of cinchonidine, but should be free from cinchonine, quinidine and cupreine. There are four pharmacopeial preparations. The ferri et quininae citras, one of the "scale preparations" of iron, is given as a haematinic and tonic in doses of about to grains. It is very unpleasant to take. The pharmacopeial pilule quininae contains 5 parts of the sulphate in 6. The syrupus ferri phosphatis cum quinina et strychnina (Easton's Syrup) contains IIths of a grain of quinine in each drachm, that is, in each dose. Here the quinine acts as a bitter tonic. The tinctura quininae ammoniata or "ammoniated quinine" is made by mixing t 75 grains of quinine sulphate, 2 fluid oz. of liquor ammoniae (the pharmacopeial solution of ammonia), and 18 fluid oz. of a, 60% solution of alcohol. The dose of 2 to drachm contains little more than a grain of quinine, the antipyretic action of which is negligible. Its value in the early stages of a bronchitis or tracheitis is due to the ammonia. The small quantity of quinine it contains is conditioned by the solubility of the alkaloid, which is precipitated when this tincture is diluted with water. No particular value attaches to the pharmacopeial preparations of the hydrochloride.
Our knowledge of this subject is mainly due to Professor Binz of Bonn. Quinine has considerable powers as an .antiseptic, this term defined for some time as indicating the power to kill bacteria. Whilst quinine possesses this power, however, it is far more potently lethal to a particular form of animal organism known as the plasmodium malariae. Against the bacteria quinine is not at all an exceptionally powerful antiseptic, though more powerful than carbolic acid. Many bacteria are killed by a 2 solution of the alkaloid. Quinine does not affect the unbroken skin, and cannot be absorbed from it, but it is slightly irritant to the pain-conducting nerves of a raw surface.
The first feature of the internal action of quinine is its intensely bitter taste. This induces a reflex secretion from the salivary and gastric glands, which is followed or accompanied by increased vascularity of the gastric mucous membrane, and by some degree of activity on the part of the muscular wall of the stomach. This means that the appetite is strengthened, and digestion rendered more rapid and complete. In this sense alone quinine is a tonic. The hydrochloric acid of the gastric juice is stated to convert any salt of quinine into a chloride, and it seems probable that the absorption of quinine takes place mainly from the stomach, for when the drug reaches the alkaline secretions of the duodenum it is precipitated, and probably none of it is thereafter absorbed. The greater part of a dose of quinine sulphate administered by the mouth may be recovered, as a rule, from the faeces, this being much the most wasteful method of giving quinine. The absorption of the acid hydrochloride is much more complete. Quinine hydrochloride circulates in the alkaline blood without precipitation, probably owing to the presence of carbonic acid in the blood.
The action of quinine on the blood itself - quite apart from its action on malarial blood - is of great complexity and importance. Whilst it is not a haematinic, in that it does not increase the number of the red blood corpuscles, it very markedly influences the stability of the compounds of the haemoglobin with oxygen. Like alcohol and prussic acid, quinine interferes with oxidation, so that oxyhaemoglobin is relatively unable to give up its oxygen to the tissues, the metabolism of which is therefore greatly modified. This property is doubtless partly - though not wholly - explanatory of the antipyretic action of quinine. The leucocytes or white blood corpuscles are very markedly affected by quinine, the characteristic "amoeboid" movements of the cells being arrested. Hence quinine stops the process of diapedesis or emigration of the leucocytes from the blood-vessels into the tissues, and if applied to the, extravascular spaces it arrests the leucocytic movements there. The explanation that this influence on the leucocytes explained the favourable action of quinine on certain inflammatory processes no longer holds, since we know that the inflammatory conditions are of microbic origin, and that the movements of the leucocytes are not objectionable, but highly desirable as a means of defence against bacteria and their products. Quinine, therefore, is not beneficial in inflammatory conditions as far as this particular property is concerned.
The action of quinine on the circulatory apparatus is not marked. It is only in very large doses that it weakens the intracardiac nervous ganglia, slows and weakens the pulse, and dangerously lowers the blood pressure. Similarly the depressant action on the respiratory centre in the medulla oblongata occurs only after the administration of enormous doses.
The action of quinine on the temperature is important, for it is the safest of all known antipyretics. Its action on the normal temperature is nil. The drug is not an antithermal. But when the temperature is raised, quinine will frequently lower it. The action is not due to any influence on the thermic centres, nor to any production of diaphoresis, but to the influence of quinine upon the stability of oxyhaemoglobin. Quinine was the first antipyretic used, and after the introduction of such preparations as antipyrin and acetanilide it may still be said to be the safest, though it is much less powerful. The maximum dose of the sulphate is about 40 grains, and of the acid hydrochloride about 25 grains. The temperature usually begins to fall in about two hours. The influence of quinine upon a malarial temperature is due to an entirely different cause (see below).
In some of the lower vertebrates quinine reduces the activity of the spinal cord, but in the human species it appears to stimulate the nervous mechanism of the uterus under certain conditions, and it is therefore included under the class of oxytocic or ecbolic drugs.
Quinine is excreted in some degree by nearly all the glands of the body, but mainly by the kidneys. Traces of it may be detected in the urine within an hour of its administration, and most of it is eliminated within eight or ten hours. The study of the urine is highly interesting in correlation with that of the influence of quinine upon the oxidising power of the blood, and upon the movements of the leucocytes. The amount of urea, creatin, creatinin, sulphates and phosphates in the urine is diminished, clearly showing that quinine exerts an inhibitory influence over the metabolic processes of the body. This conclusion is further confirmed by the observation that the amount of carbonic acid excreted by the lungs is also diminished. The uric acid excreted in the urine (mostly in the form of urates) is markedly diminished. This product is largely derived from the nuclei of the leucocytes, which contain large quantities of the nucleo-proteids, of which uric acid is a decomposition product. It is therefore plain that the diminution of leucocytic movement is to be regarded as a sign of diminished metabolism within the cells.
The supreme value of quinine is as a specific antidote to malaria, against which it also possesses a powerful prophylactic action. Ten or fifteen grains of the sulphate are often given three times a day for this latter purpose, and smaller doses of the much more efficacious acid hydrochloride will be found to convey even more certain immunity. In treating malaria (including ague, remittent fever, intermittent fever, and all its other forms) with this drug certain important facts are to be observed. Quinine administered by the mouth or by any other means will soon enter the blood, and will then kill the haematozoon malariae, whether it be free in the blood-plasma, in the leucocytes or in the red blood corpuscles. There is one exception, however. Quinine is apparently powerless to kill the organism when it is in its reproductive phase. This phase corresponds to the pyretic attack. There is therefore no purpose to be served by administering quinine during a malarial paroxysm. Two successful methods may be adopted. The quinine may be given in a single large dose-30 grains of the sulphate. or 20 of the acid hydrochloride - an hour or two before the attack is due, i.e. just before the parent organism in the red blood corpuscles is about to discharge the new generation of young parasites into the blood-plasma. An equally effective method, which may be combined with the above, is to give the quinine in so-grain doses of the acid hydrochloride every four hours between the attacks. Whichever method be adopted, the paroxysm that was expected will probably not appear. After a single full dose of quinine no parasites can as a rule be observed in the blood for several days. In beginning treatment, it is well to clear the hepatic and alimentary passages by a preliminary dose of calomel combined with a secretory cholagogue, such as enonymin or iridin. The quinine treatment may be begun with success on the day following an attack. Quinine is much less efficacious in the treatment of post-malarial symptoms, such as neuralgia and haematuria, when no parasites can be detected in the blood. In such cases quinine is often inferior to arsenic.
Quinine is largely used as a bitter tonic in doses of about half a grain. The acid hydrochloride is the best salt to employ.
Quinine has some analgesic power, and is a safe and often efficient drug in the treatment of neuralgia, even when the patient has not had malaria. Somewhat smaller doses than those given in pyrexia should be employed.
Cinchonism is the name applied to the congeries of toxic symptoms which follow the prolonged administration of quinine, but may appear after one small dose in certain persons. The symptoms closely resemble those of salicylism, and also, though in less degree, those of carbolism. The patient is deaf, but complains of ringing in the ears, which may assume various forms, especially in musical people. There is headache, which, with the continuance of the drug, becomes exceedingly severe, the vision and equilibrium are affected, and there is often some gastro-intestinal irritation. In cases where the drug has been deliberately given for its poisonous action the results are still more severe. There may be bleeding from the nose, cutaneous congestion, deafness, blindness, coma or delirium, and even death from cardiac failure. After death there is found one noteworthy lesion, a commencing acute inflammation of the internal ear. In persons who have a marked idiosyncrasy towards cinchonism, the symptoms may often be successfully averted if small doses of hydrobromic acid - io minims of the dilute solution - are given with the quinine.
A non-official preparation of quinine - Warburg's Tincture - occasionally succeeds where the ordinary preparations fail. The dose is i to 4 drachms. It contains i part of quinine in 50. Of the thirteen or more other ingredients, there may specially be noticed the salicylic and benzoic acids.
The other alkaloids of cinchona bark - quinidine, cinchonidine, and cinchonine - also possess similar properties, but all are much less effective than quinine. This is also the case with the cinchona febrifuge prepared from C. succirubra. The great disadvantage of the official preparations is the bitter taste and insolubility. It is found, however, that all the soluble salts are bitter, whilst the tasteless ones are insoluble. Substitutes may therefore be divided into those administered orally and those administered hypodermically. Of the insoluble salts we may notice the tannate, the propionic acid ester (euquinine) and carbonic acid ester (aristoquin), the salicylic acid ester. (saloquinine); and of the soluble substitutes, quinopyrine (a compound of quinine hydrochloride and antipyrine) and quinine hydrochlorocarbamide (a compound of quinine, urea and hydrochloric acid).
Until 1867 English manufacturers of quinine were entirely dependent upon South America for their supplies of cinchona bark, which were obtained exclusively from uncultivated trees, growing chiefly in Bolivia, Peru, and Ecuador, the principal species which were used for the purpose being Cinchona Calisaya; C. officinalis; C. macrocalyx, var. Fallon; C. Pitayensis, C. micrantha and C. lancifolia. Since the cultivation of cinchona trees was commenced in Java, India, Ceylon and Jamaica, several other species, as well as varieties and hybrids cultivated in those countries, have been used.' Later, C. lancifolia, var. Calisaya, known as the calisaya of Santa Fe, was strongly recommended for cultivation, because the shoots of felled trees afford bark containing a considerable amount of quinine; C. Pitayensia has been introduced into the Indian plantations on account of yielding the valuable alkaloid quinidine, as well as quinine.
The first importation from India took place in 1867, since which time the cultivated bark has arrived in Europe in constantly increasing quantities, London being the chief market for the Indian barks and Amsterdam for those of Java. Cinchona Calisaya has also been cultivated extensively in Bolivia and in Tolima, United States of Columbia.
In order to obtain the cultivated bark as economically as possible, experiments were made which resulted in the discovery that, if the bark were removed from the trunks in alternate strips so as not to injure the cambium, or actively growing zone, a new layer of bark was formed in one year which was richer in quinine than the original bark and equal in thickness to that of two or three years' ordinary growth. This is known in commerce as "renewed bark." The process has been found to be most conveniently practised when the trees are eight years old, at which age the bark separates most easily. The yield of quinine has been ascertained to increase annually until the eleventh year, at which it seems to reach its ' In Java, C. Calisaya, vars. anglica, javanica, Hasskarliana and Ledgeriana; C. officinalis, var. angustifolia; C. lancifolia, C. caloptera C..micrantha and C. succirubra. In India, C. succirubra, C. officinalis, vars. angustifolia, crispa, Uritusinga and Bonplandiana, and to a lesser extent C. Calisaya, vars. Boliviana and microcar pa; C. micrantha, C. Peruviana and C. nitida form only a small proportion of the plantations. Since J. E. Howard pointed out that C. Pahudiana, and C. Calisaya, vars. javanica, Hasskarliana and anglica, were likely to lead to disappointment as quinineyielding species, these have been replaced in the plantations as rapidly as possible by the more valuable species, of which C. Ledgeriana, yielding from 5 to io% or even more of quinine, C. officinalis, and a hybrid between C. officinalis and C. succirubra, which has been named C. robusta, are the most important.
maximum. The portion of the trunk from which the bark has been, removed is sometimes protected by moss, and the new bark which forms is then distinguished by the name of "mossed bark." The species which yield the largest amount of quinine are by no means. the easiest to cultivate, and experiments have consequently been made in cross-fertilization and grafting with the view of giving vigour of growth to delicate trees yielding a large amount of alkaloid or of increasing the yield in strong-growing trees affording but little quinine. Grafting, however, has not been found to answer the purpose, since the stock and the graft have been found to retain their respective alkaloids in the natural proportion just as if growing separately. Hybridization also is very uncertain, and is very difficult to carry out effectually; hence the method of propagating the best varieties by cuttings has been adopted, except in the case of those which do not strike readily, as in C. Ledgeriana, in which the plants are grown from the shoots of felled trees.
Some years ago it was discovered that a bark imported from Colombia under the name of cuprea bark, or "hard" bark, and derived from Remijia pedunculata, Triana, and other species, contained quinine to the extent of 4 to 22%, and in 1881 this bark was exported in enormous quantities from Santander, exceeding in amount the united importations of all the other cinchona barks;: and by reason of its cheapness this has since that date been largely used for the manufacture of quinine.
Cinchona bark as imported is never uniform in quality. The South American kinds contain a variable admixture of inferior barks, and the cultivated Indian barks comprise, under the respective names of yellow, pale, and red barks, a number of varieties. of unequal value.
The alkaloids are contained, according to Howard, chiefly in the cellular tissue next to the liber. No definite knowledge has as yet been attained of the exact steps by which quinine is formed in nature in the tissues of the bark. From analyses of the leaves, bark and root, it appears that quinine is present only in small quantities in the leaves, in larger quantity in the stem bark, and increasing in proportion as it approaches the root, where quinine appears to decrease and cinchonine to increase in amount, although the root bark is generally richer in alkaloids than that of the stem. The altitude at which the trees are grown seems to affect the production of quinine, since it has been proved that the yield of quinine in C. officinalis is less when the trees are grown below 600o ft. than above that elevation, and that cinchonidine, quinidine, and resin are at the same time increased in amount. It has also been shown by Broughton that C. Peruviana, which yields cinchonine but no quinine at a height of 6000 ft., when grown at 7800 ft. gives nearly as much quinine, and almost as readily, as C. officinalis. Karsten also ascertained by experiments made at Bogota on C. lancifolia that the barks of one district were sometimes devoid of quinine, while those of the same species from a neighbouring locality yielded 32 to 42% of the sulphate; moreover, Dr De Vrij found that the bark of C. officinalis cultivated at Utakamand varied in the yield of quinine from I to 9%. In these cases the variation may have been due to altitude. Free access of air to the tissues also seems to increase the yield of quinine, for the renewed bark is found tocontain more quinine than the original bark
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