Chapter from My PhD Thesis
Notes from the Eclectic Physicians

Chapter from my PhD Thesis

Part used: Bark

Chemical Constituents: Significant phytochemicals include alkaloids, cinchonain, cinchonidine, cinchonine, quinicine, quinine, and quininidine. (13)

History
The native people of South America knew the medicinal applications of Cinchona before the colonials arrived. Upon arrival, the colonials were taught that fever could be allayed with the use of its bark. In 1638, the wife of the Viceroy of Peru, the fourth Count of Chinchon, was afflicted with Malaria and was cured by cinchona. After that high profile cure, the bark became known as “The Countess Powder” or Cinchona. It was introduced into Spain as Cinchona, but in time became known as Jesuit bark. This was probably due to the fact the Jesuit Fathers distributed it around Europe . The drug was introduced into medical circles in London in 1656. From there it made its way back to the New World where it was favoured in North and South American for the treatment of malaria and other infectious diseases.

Eclectic uses (1–14)
Actions
Tonic, alterative, antiperiodic, corroborant, slightly astringent, topically antiseptic, improves appetite, promotes digestive functions, increases strength of the pulse, increases muscular power, increases capacity to exert the body and mind, firms tissues and reduces flabbiness, improves quality of the blood, stimulates digestive organs locally, uterine stimulant, stimulates uterine contractions, arrests or prevents fermentation, destroys living germs, antiseptic in septic diseases, prophylactic against malarial disease, vulnerary, antagonises the erysipelatous poison, invigorates the nervous and muscular systems in all diseases with general debility, convalescent in exhausting diseases, supports the powers of the constitution, removes abnormal physiological functions associated with chronic disease.

Indications
“Periodicity and, like quinine, effective when the pulse is soft and open, the tongue moist and cleaning, the skin soft and most, and the nervous system free from irritation. If opposite conditions prevail, cinchona will be likely to aggravate. Empyema; gastric debility; anaemia and debility from chronic suppuration; afternoon febrile conditions; weakness, with pale surface, loss of appetite, feeble digestion, and deficient recuperative powers.” (9)

General
Chronic affections attended with periodicity, great feebleness, and nocturnal perspiration, malarial fevers and allied conditions, debility, diseases of an intermittent character, diseases assuming a periodic nature, debility unattended by local inflammation, profuse and debilitating night sweats and other profuse discharges associated with debility, convalescent stages of fever, advanced stages of fevers with great debility with no symptoms of cerebral, digestive or vital organ inflammation, intermittent fevers, during intermission, during period of apyrexia, diseases which manifest with periodicity(ague, bilious fever, intermittent neuralgia), fevers of children, typhoid fever, putrid fevers, chronic periodic disease, chronic ague, congestive chill, remittent fevers with well marked remissions, diphtheria, erysipelas with great debility, debility following severe haemorrhage, febrile, eruptive, and inflammatory diseases with periodicity(administered during remission), low and typhoid conditions, excessive and continued secretion of pus resulting in enfeeblement and prostration, diseases accompanied with symptoms marked with periodicity(neuralgia, hemicrania, dyspepsia, diarrhoea, or dysentery).

Cardiovascular
Splenic abnormalities, splenic swelling, ague cake.

Digestive
Diarrhoea, dysentery, functional derangement’s of the stomach, dyspepsia, poor digestion, poor appetite, and inadequate secretion of digestive fluids.

Musculoskeletal
Rheumatism

Nervous
Intermittent neuralgia with intense pain, neuralgic affections following other diseases such as small pox.

Respiratory
Hay fever, lung diseases attended with colliquative sweating.

Skin
Ulcers, felons, fetid and gangrenous ulcers.

The drug from Selye’s perspective

State of Resistance
The drug was used to raise resistance to typhoid fever, low and typhoid conditions, putrid fever, septicaemia, diphtheria, malaria, erysipelas, debility attending local inflammation, convalescent stage of fever, intermittent fever during apyrexic phase, chronic diseases assuming a periodic nature, debility following severe haemorrhage, febrile, inflammatory, eruptive disease displaying periodicity (during remission).

State of Exhaustion
The drug was used when resistance to disease could no longer be maintained and State of Exhaustion set in. Examples include viral disease followed by neuralgic complaints, end phase malaria(collapse, ague, digestive ulceration, skin ulceration, erratic temperature, sweating, etc.), erysipelas with great debility, and end phase tuberculosis. Symptoms of State of Exhaustion treated with the drug included neuralgia, hemicrania, dyspepsia, diarrhoea, dysentery, ulcers, fetid and gangrenous ulcers, felons, joint abnormalities, mucous membrane abnormalities, temperature abnormalities, secretion abnormalities (night sweats, excessive/inadequate mucous, digestive, etc.), and wasting.

Adaptation Energy
From Selye’s perspective, the drug augmented the GAS, which suggests it increases adaptation energy. Evidence to this effect includes the following. The Eclectics used this drug to increase resistance to acute and chronic microbial infection. It was used when State of Exhaustion commenced and the usual physiological abnormalities were present. It was applied to non-healing wounds to stimulate the healing process. The drug, when taken internally, or applied externally, was said to stimulate the recuperative powers in a powerful manner. In fact, so powerful, it was contraindicated when the body was mounting sufficient resistance. The drug was used when chronic disease was in remission to perpetuate the remission. Lastly, the drug was used to stimulate body systems to heightened action. When the vital forces were depressed, and body functions were thereby diminished, the drug was administered.

Brekhman’s Adaptogen Criterion
An adaptogen should be innocuous and cause minimal disorders in the physiological functions of an organism.

Eclectic and contemporary literature indicates the drug is safe when administered in reasonable doses and in appropriate cases. (1–15) The Eclectics specified that it was contraindicated in inflammatory states, active haemorrhages, and all nervous and vascular irritations. (1–14)

The action of an adaptogen should be non-specific i.e. it should increase resistance to adverse influences of a wide range of factors of physical, chemical, and biological nature.

Clinically, the drug was used to raise resistance to a wide range of acute and chronic microbial infections (viral, bacterial, and protozoan). (1–14)

Experimentally, the drug contains compounds which increase resistance to bacterial, viral (adenovirus, influenza, herpes, HIV), protozoan (malaria, amoebas), and fungal infection (Candida). The drug acts directly through antibiotic activity and indirectly via immune stimulation. In addition, compounds have been shown to increases resistance to protista, tryptosoma, tumours, cancer, mutation, liver damage, and free radical damage. (15)

An adaptogen may possess normalising action irrespective of the direction of the foregoing pathological changes.

Clinically, the drug was used to normalise the physiological abnormalities associated with State of Exhaustion (abnormal sweating, abnormal mucous secretion, perverted glandular secretion, temperature abnormalities, ulceration, wasting, and neurological deficits). (1–14)

Experimentally, the drugs constituents have been shown to correct a host of physiological abnormalities including platelet stickiness, abnormal inflammation (antihistaminic, antiprostaglandin, antileukotriene), ulceration, temperature irregularities, hypertension, pain, inadequate liver filtration, inadequate digestive enzyme production, poor appetite, abnormal membrane permeability (oedema), inadequate immune function, and inadequate bile production. (15).

Discussion
The drug exhibits properties consistent with Brekhman’s definition of an adaptogen. It is innocuous; it raises resistance to a wide variety of biological challenges, and normalises function.

In the last century, Cinchona rubra was used to raise resistance to virtually every known infection. We think of it as a malaria remedy but that was not the case in days gone by. The Eclectics were emphatic the drug was indispensable when it came to treating infectious disease and research bears this out.

Cinchona was not used when an infection was in the acute phase but rather after this phase had passed. In acute infection, it was used when all active inflammation subsided to prevent a second infection from taking hold. In the case of chronic infection (malaria), it was used when the fever ended as a means of keeping the disease in remission. Though we are not in the habit of drugging people while in recovery, this was precisely when the Eclectics used this remedy.

Potential Clinical Applications
Historically, this drug was used to treat any infection assuming a chronic nature. Therefore, it may have a role in sinusitis, tonsillitis, urethritis, herpes, hepatitis, and HIV infection. It should be remembered that the drug was administered in the intermission following an acute attack and not while the infection was active.

In addition, the drug may have a role in preventing post-viral syndrome. The drug was used to treat the neuralgic sequelae to viral infection. At the moment, clinicians see patients complaining of vague neuralgic deficits following acute viral infections. The condition is referred to as post-viral syndrome. Complaints include depression, mental fatigue, debility, and listlessness. The prior use of this drug to treat similar symptoms suggests it may have a role to play in raising resistance to post-viral syndrome.

Future research
• Cinchona rubra and its effect on the GAS. The drug should be tested out in the animal model. Particular attention should be paid to its effect on stamina and endurance. As the Eclectics found it increased capacity to do mental and physical work in stressed individuals.
• Cinchona rubra and State of Exhaustion . Clinically the drug was used to remedy State of Exhaustion in many chronic diseases (malaria, rheumatoid arthritis, and tuberculosis). Its role in raising resistance to State of Exhaustion in chronic disease should be examined.
• Cinchona rubra and infectious disease. Though largely known as a malaria drug, it was used to increase resistance to many different infectious diseases. Some chronic, some acute. Research has demonstrated the drug acts both as an antibiotic and an immune stimulant. Its ability to increase resistance to infectious disease needs to be examined.
• Cinchona rubra and slow healing wounds. The drug was used to inspire healing in slow healing wounds and pressure sores. Its role in raising resistance to these sores in diabetics and other stressed individuals should be examined.
• Cinchona rubra and post-viral syndrome. Clinically, the drug was used to treat neuralgic deficits following viral disease. Its role in raising resistance to virus related neural deficits should be examined.

Eco-availability
The drug is readily available.

References
• Dyer, D. The Eclectic Family Physician A scientific System of Medicine on Vegetable Principles Designed for Families. 1855.
• Scudder, J. M. Specific Medication and Specific Medicines. Revised. Fifth Edition. Wilstach, Baldwin and Company. Cincinnati . 1874. P. 217.
• Scudder, J. M. the American Eclectic Materia Medica and Therapeutics. Published by the Author. Cincinnati . 1883. P. 433.
• Watkins, Lyman. An Eclectic Compendium of the Practice of Medicine. John M.Scudder’s Sons. Cincinnati . 1895. P. 430.
• Felter, Harvey Wickes and Lloyd, John Uri. Kings’ American Dispensatory. Volume one and Volume two. Ohio Valley Company. Cincinnati . 1898. P. 1620.
• Felter, Harvey. Syllabus of Eclectic Materia Medica and Therapeutics. Compiled from notes taken from the lectures of F.J.Locke. Edited with pharmacological additions by H.W.Felter. Second edition, with appendix. Scudder Brothers Company. Cincinnati.1901. P. 144.
• Peterson, F.J. Materia Medica and Clinical Therapeutics. Published by the Author. Los Olivos , California . 1905. P. 132.
• Lloyd, JU. History of the Vegetable Drugs of the Pharmacopoeia of the United States . Bulletin number 18: pharmacy number 4. 1911. P. 17.
• Fyfe, John William. Pocket Essentials of Modern Materia Medica and Therapeutics. The Scudder Brothers Company. 1911. P. 91.
• Ellingwood, Finley. American Materia Medica, Therapeutics, and Pharmacognosy. Ellingwood’s Therapeutist. Chicago . 1919. P. 171.
• Lloyd, John Uri. Origin and History of all the Pharmacopeial Vegetable Drugs, Chemicals and Preparations. Volume 1: Vegetable Drugs. The Caxton Press. Cincinnati . 1921. P. 62.
• Lloyd Brothers. Dose book of Specific Medicines. Lloyd Brothers, Cincinnati . 1930.
• Dr. Dukes Phytochemical and Ethnobotanical Databases. Agriculture Research Service. USDA.

Notes from Eclectic Physicians

1855; Dyer (Vegetable Principles) – CINCHONA RUBRA – PERUVIAN BARK
Some are in the habit of using this bark for a tonic, but as it is adulterated it is not best to use it, so long as we have so many others quite as good.

1874: Scudder
There is no occasion to give a lengthy description of the specific action of Quinine, as every one of my readers is thoroughly conversant with it. But it may be of use to some, to state the conditions neccessary to its kindly and medicinal action.

Probably there is no remedy in the materia medica that gives so many failures as this, and I think we may be safe in assuming that it is given ten times where its specifc action is btained once. Everyone will recollect the cases in which it did not breaik up periodic diseases, many more cases in which its influence was but temproary, a large number in which it produced unplesant cergral symptoms, and some in which a quiniea disease was deeloped which was much worse than the original malady.

Why is this? Is it the fault of the remedy, the fulut of the patient, or the fault of the practitioner? O,the doctor answers, it is form idiosyncrasy. So we believe, but we locate the idiosyncrasy in the doctors head, and not in the patient.

I have taught for years, that if we are to expect the kindly and curative action of quiia, the somtach must be in condition to recieve and absorb it, and the system in condition for its action. If we have a proper condition in these respects, we will hear nothing of roaring in the ears, vertigo, etc., nut its action will be most kindly. The rule is very simple, given a soft and open pulse, a moist skin, moist and cleaning tongue, and quinia will act kindly, antidote the malarial poison, or in small doses improve innervation. Always get this condition before prescribing the remedy, and you will never be disappointed in its action.

As an antiperiodic I believe in prescribing single doses. Put the stomach in proper condition, regulate the circulation, establish secretion, and then give one full dose of the remedy, 10-15 grs. The best form of the remdy is in solution with one or two ounces of water, using a suficient quantity of sulphuric acid.

This is not only the most certain method of administration, but I think it will be found the most pleasant.

It is hardly neccessary to impress upon the reader the neccessity of determining the periodic element in disease. Whilst we may not know what it is, or how quinine antidotes it, we know that its removal cures, ar atleast paves the way to a cure.

But quinine is not specific in all agues. We see it given day after day, week after week, in many cases, without any advantage. But on the contrary, it excites the nervous and vascular system, and at last products a chronic erythism of them, that is coreectly named the quinine disease. From this, recovery is far more difficult than than the malarial affection.

Is it possible then, to determie the cases in which quinine will prove specific, and the cases in which it will fail? I think it is. It antidotes the malarial poison only when kindly received and absorbed, and when the system in in such condition that it can be readily excreted. Given, the condition of pulse, skin and tongue, that we have already named, and its action is as certain as could be desired.

In some cases, the general treatment directed to obtaining normal activity of the various functions, is the most successful. In some cases nux vomica or strychnia is preferable. In others minute doses of arsenic antagonizes the malarial poison. Whilst in some rare cases, I have treated the disease successfully with aconite and belladona.

As a stimulant to the cerebrospinal centres, its use is very important. In many forms of disease, especially in the advanced stages, we find an impaired inervation, preventing functional activity, or its restoration and continuance by the use of remedies. It is essential to success that innervatin be incrased, not temproarily by the use of stimulant, but somewhat permantyly. This we accomplish by the adminsraito of small doses of quinine, gres..5to gre.ij. Even here, we find it neccessary to obsere the rules for its administrtion already noticed, the patient must be prepared for its use.

It favorably influences the nutrition of the nerve centres, and hence is employed in the treatment of chronic disease with efebbeld innervation, with marked advantage. There are two sclasses of chronic disease in which it is useful, the one in which there is a malraial influence, wit hobscure periodicity, and the other the enfeebled innervation, as namely above.

Its general tonic and stomachic influence, when obtained, is most certainly form this action upon the nervous system, the influence extending to the sympathetic ganglia, as well as to the cerebrospinal centers. In some cases this action is very important, improving digestion and blood making, and nutrition, as well as waste and excretion, aiding the “renewal of life”.

1883: Scudder(tonic)
(The Bark of C. Flava, C. Rubra, C. Pallida. – South America )

Therapeutic Action – Cinchona is tonic, antiperiodic, corroborant, stimulant, astringent and antiseptic. It is justly placed at the head of the tonics. The profession generally regard it as one of the most important remedies in the materia medica. Since its first introduction into the list of therapeutic agents, it has lost none of the high reputation which it at first enjoyed. On the contrary, the same popularity and the high confidence then resposed in it as a permanent tonic and antiperiodic are now freely awarded to it. The peruvian bark – its alkaloid principles – the cinchonia or qunia, or their salts – is more frequently resorted to as corroborants in cases of debility, and more especially in diseases of an intermittent character as antiperiodics, than any one or all others belonging to this class of remedial agents. The reason is obvious: no other article has so uniformly proved successful. It is the article upon which reliance has to a great extent been placed for two hundred years, during which time it has gained the confidence of physicians and secured a reputation in the treatment of diseases assuming periodicity which no other article now enjoys.

As a therapeutic agents, the cinchona is mostly employed in cases of debility, unattended with local irratation. “In such we find cinchona improves the appetite, promotes the digestive functions, and increases the strength of the pulse. The muscular system acquires more power, and the individual is capable of making greater exertion, both mental and bodily, than before; the tissues acquire more firmness to the touch, and lose their previous flabbiness; moreover, it has been asserted, and with great probability of truth, that the quality of the blood improves.”

It often proves valuable in arresting profuse and debilitating night-sweats and other profuse discharges arising from debility, particularly in the convalescent stages of fever. It is also important in the advanced stages of continued fevers as a tonic, when there is great debility, provided no symptoms of delebral inflammation, or inflammation of the digestive or other vital organs be present.

The cinchona, or some of its preparations, is extensively used in the treatment of intermittent fever; and it rarely fails to arrest it, if judiciously adminstered. Some prescribe it not only during the intermission, but also throughout the whole period of excitement; and some premise with emeties of cathartics, while other usually omit all evacuants.

Although it may be employed in many cases during the pyrexial stage with advantage, yet we deem it most beneficial, as a general rule, during the period of apyrexia, especially if fisceral congestion or local inflammation exist. If administered during the stage of excitement, the quantity necessary to moderate it is so great, that it proves irritating an doppressive to the stomach, and might increase the intensity of the fever, instead of diminishing it. The same objections are not obnoxious to the use of the sulphate of quinine, and consequently, if their is used, the sale is preferable.

1887: Scudder: QUININE
The active principle of Peruvian bark is the remedy that is principally used by all classes of physicians to arrest periodic disease. It has been used many times without either reason or common sense, and in combination with many deleterious medicines, and hence, in many sections of the country, it has fallen into disrepute. In my practice, in not one case out of a hundred dose produce any unpleasant symptom, not even ringing in the ears. The patient is always prepared for its use by getting the stomach and bowels in good condition, and arresting the excitation of the vascular system by sedatives, and means to promote secretion from the skin and kidneys. Employed in this way, its action is certain as mild as any other agent, and it has entirely passed from the system in twenty-four hours.

As before remarked, diseases which manifest periodicity, are those in which it is indicated, and in which it proves a specific – as ague, bilious fever, intermittent neuralgia, and similar affections. As a general rule, the system being prepared for its administration, from twelve to fiteen grains will arrest the disease.

In the fevers of children, and typhoid fever, we employ it in small doses, after the action of the sedative, in order to stimulate the nervous system. Take quinine, five grains; aromatic sulphuric acid, twenty drops; simple syrup, two ounces: the dose being a teaspoonful every three hours to a child two years old.

1895: Watkins: CINCHONA CAL , SP MED:
Anaemia resulting from chronic suppuration, empyema, afternoon pyrexia, paleness, weakness, loss of appetite and strength, deficient recuperative energy. One drachm to four ounces water; teaspoonful every four hours.

1901 : Harvey W Felter (Tonics) – CINCHONA – PERUVIAN BARK
BOTANICAL ORIGIN – The bark of Cinchona calisaya , Weddell; Cinchona officinalis, Linne; and of hybrids of these and of other species of Cinchona, containing not less than five per cent of total alkaloids and at least 2.5 per cent of Quinine (U.S.P.); Nat. Ord., Rubiacea. South America, also cultivated to some extent in Java , India and Jamaica . There are several grades of the bark, the chief varieties being the Yellow Cinchona and the Red Cinchona.

CHIEF ACTIVE CONSTITUENTS. – Quinine, Quinidine, Cinchonine and Cinchonidine.

1901 : Harvey W Felter (Tonics) – QUININAE SULPHAS – QUNININE SULPHATE
DESCRIPTION -A very light compressible mass of fine, silky, white, needle crystals, somewhat flexible and yet easily broken and having no odor but a very persistent bitter taste. It effloresces superficially when exposed to air, losing its lustre. Exposed to warm air it loses water, but in a damp atmosphere it absorbs it again. Light causes it to become colored, therefore, it should be kept in the dark, in well closed bottles. Soluble in cold water (740), boiling water (30), cold alcohol (65), boiling alcohol (3) glycerin (40), chloroform (680), and readily in acids.

1901 : Harvey W Felter (Tonics) – CINCHONIDINAE SULPHAS – CINCHONIDINE SULPHATE
DESCRIPTION – This salt occurs in silky, white needles, odorless, but very bitter in taste. On exposure to air they effloresce slightly. Soluble in cold water (70), boiling water (1.42), cold alcohol (66), boiling alcohol (8), chloroform (1316), and nearly soluble in ether.

SPECIFIC CINCHONA This is made of yellow Cinchona, the Quinine alkaloid yielding bark. This is the most valuable of Cinchona barks and should be used in high grade preparations. It precipitates portions of red tannates when mixed with water.

This is the very best tonic to use. It is the bark of the Cinchona trees, which grow in great abundance in South America . These trees form immense forests forty or fifty miles in width, extending through several degrees of latitude. In the market Cinchona comes in the form of flat or quilled pieces. It is red, yellow or brown in color, having an aromatic odor and a very bitter taste. The size of the pieces depends upon the size of the tree from which they are obtained. The fine bark comes form the small twigs and branches, and the large pieces from the trunk and large limbs. There are several varieties of this bark, of which the gray, red and yellow are used in medicine. The pale or gray bark is more astringent than bitter and contains more Cinchonine than Quinine. The yellow is more bitter and very rich in Quinine, while the red or brownish red bark, is both bitter and astringent, and contains a very large amount of Quinine.

The most important alkaloids of this bark are Quinine, Quinidine, Cinchonine, and Cinchonidine. They abound in varying proportions in the barks, the red and yellow containing about equal amounts. Cinchona derives its name from the Countess of Cinchon of Peru, who was cured of a fever by its agency. The Peruvians made known its great virtues to the Jesuits, who introduced it into Europe , giving it to the poor who were sick of fevers. The medical men of the day opposed its use because it was introduced by the clergy, and Protestants opposed it because it was introduced by the Catholics. But on account of its great medicinal value it rapidly came into general use.

Quinine is the most important alkaloid of Cinchona and this is generally employed in the form of the sulphate. Given in doses of one or two grains five or six times a day it is tonic, increasing the strength of the appetite, digestion and circulation. The temperature is slightly increased and all the functions of the body are improved, but if there is irritability of the stomach and digestive organs Quinine increases it. In doses of from fifteen to twenty grains daily for several days it produces headache, confusion of thought, ringing in the ears, fullness and throbbing of the head, suffusion of the face, and an excited condition of the nervous system. In doses of from thirty to forty grains daily for several days the sight is impaired, the pupils dilated, the muscles become feeble, and the limbs tremulous. In still larger doses it produces loss of consciousness, great debility, loss of motion and collapse. Some persons are very easily influenced by Quinine and Cinchonism is the name given to the condition induced by its excessive use. If its use is not continued after this is produced its effects gradually become less until finally they pass off entirely. The deafness and loss of vision gradually pass away and are seldom permanent unless the drug is very long continued. Delirium and convulsions may supervene as if the patient were under the effects of alcohol.

The effect of Quinine on the digestive organs is that of a local stimulant. If the stomach is irritable it will increase the irritability. In small doses it produces constipation; in large doses diarrhoea. When taken into the stomach it is absorbed into the circulation and is in part eliminated by way of the kidneys. As long as the system is under its influence its presence may be detected in the urine, the amount so found depending upon the amount of the drug taken. Full doses of Quinine reduce temperature by interfering with the oxidation of the blood.

In acute inflammation of the urinary organs this drug increases the difficulty, and may give rise to complete retention of urine. The trouble with Quinine is that it is so rapidly eliminated that its influence is correspondingly temporary. As a rule it remains in the system only twelve hours and it may be eliminated in six hours. In some cases Quinine given three or four days previously has been detected in the urine.

In small doses it slightly increases the temperature, or it may not affect it at all. In large doses it is a great antiperiodic, and as such it is largely used in the treatment of malarial fevers and allied disorders. In these malarial diseases the poison comes from a low form of organic life which enters the blood and exerts its influence upon it. Quinine prevents the multiplication of and destroys these micro-organisms, and aids in their elimination.

In small doses Quinine favorably influences the digestive organs, and is a good remedy in dyspepsia. In large doses it irritates the stomach and produces nausea and vomiting. The blood pressure is diminished and nerve centres are paralyzed by Quinine. The vagus nerve is partially paralyzed under its influence. In small doses it is tonic to the heart and the condition of the blood and digestion is improved, the pulse becomes stronger, and the brain is gently stimulated.

Cinchona differs from the simple bitters in being stimulant to the brain and nervous system. When given in moderate doses, if not contra-indicated, it never produces any bad results, but given in too large doses congestion of the brain and great prostration will probably ensue. After the stage of excitement has passed in such a case give stimulants and coffee.

The alkaloids of Cinchona are very valuable, but they do not represent fully all the properties of the bark. The latter possesses astringent properties not possessed by the alkaloids. So if at any time this astringent effect is desired the bark is best to use. When it tonic influence is desired and an antiperiodic is not needed the bark is the best to use. In putrid fevers use the bark with wine and iron. In many chronic periodic diseases the bark cures when Quinine fails. In chronic ague an emetic is many times the thing needed. It is wonderful what a change may be produced by a good thorough emetic given every day for three or four days, and then followed by Quinine. In the treatment of intermittent fevers Quinine is specific, acting with great certainty. When it fails in recent cases it is because of some unlooked for complications, which may be of the stomach, liver, or spleen. Remove the complications and Quinine will do its work. So in recent uncomplicated ague Quinine is an absolute specific.

The next thing is how to administer it, when and how much?

As a rule from fifteen to thirty grains in broken doses is sufficient, depending upon the condition of the patient. Give five grains at a time during the intermission every three hours so that the last dose may be taken one hour before chill time. Dont give it when the chill is on; it only increases it, and in the sweating stage it is unnecessary. This treatment usually breaks the ague, but is some cases breaking it does not cure, and in a few days it comes on again, but generally in recent cases breaking it cures it. In order to be sure of its cure give five grains of Quinine every day, or if administered only once a week, give it on the sixth day in one dose of fifteen grains until twenty-one days have passed. See that the patients stomach, liver, and spleen are in the meanwhile kept in good condition. If the patient is anaemic give Quinine with some preparation of iron. A solution is the best preparation of Quinine to use:
R. Quinine Sulphate, 3 j
Dil. Hydrochloric Acid, Gtt, xxx
Aua, fl 3 ij.

Sig.- Give a teaspoonful every three hours

Each dose contains four grains of Quinine. If it is desired to cover the taste combine it with Licorice;
R. Quinine Sulphate, 3ss.
Fld. Ext. Licorice, fl 3ss
Simple Syrup, fl 3 ss

Sig.- Dose, a teaspoonful.

Each dose contains two grains of Quinine. For children give half teaspoonful doses.

In congestive chill Quinine is the very best remedy we can use. If it is absorbed it will almost surely cure. Again in malignant intermittent fever Quinine is the very best remedy. Many times in these cases the stomach is not able to absorb any remedy. In such cases give Capsicum and Quinine and apply a sinapism to the epigastric region. Here we must give large doses; twenty grains will not cure here. Give from forty to sixty grains in broken doses of from ten to twenty grains. In this trouble there is no choice of time, but the remedy should be given just as soon as you know what you are dealing with. This treatment usually saves the patient. In remittent fevers, with well marked remission, this agent is just as good as in the case above mentioned. Give it during the remission, and if the disease is malignant give the large dose.

Some recommend Quinine in typhoid fever, but, as a rule, we do not regard it as a good remedy for this disease. If given here at all let it be administered with the mineral acids, and give it in small doses of one or two grains four times a day. The conditions here are a moist skin and tongue, a small, feeble pulse, and periodicity. If given here in large doses, as it sometimes is, to bring down the temperature, it does more harm than good by its evil effects on the stomach and nervous system. In doses of one grain it is a good tonic to the nervous system. Again, it is a good remedy in intermittent neuralgia with intense pain. Use it here with Morphine. Triturate Quinine twenty grains with Sulphate of Morphine one grain; divide and put into ten capsules, and give one every three hours. This is very efficient in these cases, the pain being relieved by the combination more rapidly and permanently than if either were used alone. Quinine is a very good remedy in hay fever. Make a solution on one-half grain to one ounce of water and inject into the nostril.

Quinine has been recommended as a good uterine stimulant and is not abortive under all circumstances. If there are indications for its use give it even if the female be pregnant. Under these conditions it is indeed a good anti-abortive. As a stimulant to the uterus, some claim it to be equal to Ergot as a parturient. We regard it with less favour. If, however, Ergot is not at hand or undesirable, Quinine may serve the purpose. It acts best when given at a single dose of ten grains. This stimulates uterine contractions, though not so well as Ergot. It may be given in uterine inertia with post partum haemorrhage and inefficient uterine contraction. Quinine has the power of arresting or preventing fermentation. It destroys living germs and is a good antiseptic in septic diseases. In such cases give two grains five or six times a day, using it alone or with the mineral acids.

It is good prophylactic against malarial diseases. In this it has been thoroughly tested, and it will prevent or moderate the disease. Cinchona preparations are useful also as local applications. The powdered bark applied to ulcers promotes the healing process. A solution of Quinine applied with a spray apparatus is a very good agent in diptheria. For this solution use thirty grains to two ounces of water and add enough hydrochloric acid to make it easily soluble.

Quinine two drachms to alcohol one pint is useful to prevent profuse sweating, as of the feet. Sponge the parts with it.

Persons who have suffered considerably from ague are benefited in other diseases that may attach them by the use of Quinine. In rheumatism this is markedly true, or if the patient lives in a malarial district Quinine is a valuable adjunct to the treatment of other diseases. The same is true in diarrhoea and dysentery. Here us Ipecac and Quinine in combination.

Some troubles of the liver and spleen are much benefited by Quinine. It influence on the spleen is very powerful. Persons who have ague have an enlargement of this organ knows as the ague cake. Two or three grains three times a day relieves this. It is useful in erysipelas with great debility. For this purpose use the following:
R. Quinine Sulphate, grs. xx
Tinct. Chloride of Iron, fl 3 ij.
Syr. Simplex, fl 3 iv. M.

Sig.-Give of this a teaspoonful every three hours.

Quinine antagonizes the erysipelatous poison. It may be give in neuralgic affections following other diseases, as small-pox. Give from twenty to thirty grains in broken doses. In the colliquative sweating attending lung diseases use the following:
R. Quinine Sulphate, grs. xxx
Aromatic Sulphuric Acid, fl 3 ss.
Agau, fl 3 iv. M.

Sig.- Give a teaspoonful three times a day, the last dose being given at bedtime.

Quinine is indicated, or at least not contra-indicated, when there is soft, open pulse, moist skin and clean tongue, and absence of marked nervous irritability. Under these conditions it may be safely given. It is a good stimulant to the cerebro-spinal system in doses of from one to two grains. For restoring strength after server haemorrhage use ten drops of the tincture of the red bark every four hours. Quinine is generally given in a solution of hydrochloric or other acids; it is readily absorbed in this condition. but it is unpleasant. If it be taken with no acid the stomach furnishes all that is needed to render it soluble. Taken floating in water it is not so unpleasant, or its unpleasant taste may be concealed by triturating with equal quantities of ginger, or by rubbing thirty grains of it with three drachms of extract of Licorice root and adding enough simple syrup to make two ounces. Dose, a teaspoonful.

Another alkaloid of Cinchona is Sulphate of Cinchonidine. Its properties are the same as those of Quinine. Some think it is not so liable to produce cerebral disturbance and irritation of the stomach. We think there is little or no difference. These two agents may be used interchangeably. Cinchonine Sulphate is only half as strong as Quinine , and must be given in doses twice as large for the same effect. Sometimes this agent cures when Quinine fails, but they may generally be substituted the one for the other.

1905: Petersen (quinine)
Properties: Antiperiodic

The salt obtained from the bark of cinchona calisaya. Sulphate of quinine is the form mostly employed.

Physiological action: Quinine in large doses has produced permanent deafness and in some cases temporary blindness. In doses of from 4 to 6 grains taken 3 or 4 times a day, it produces very often engorgement of the brain, headache, throbbing in the head, ringing in the ears, impairment of hearing, nervous excitement and even confusion of the mind. If dose is increased and continued there will follow restlessness, sleeplessness, general debility, feeble pulse, dilated pupils, coolness of extremities, partial or complete loss of voice, hearing and sight. Large doses, often repeated, cause disturbance of the gastro-intestinal tract, dizziness, headache and even delirium. Quinine in very small doses is a tonic, in medium doses a stimulant and in large doses a depressant. It acts on the cerebro-spinal nervous system and on the heart through the ganglionic nervous system.

Indications: In diseases with periodicity. When skin is soft and inclined to moisture. Tongue moist and not dirty. Full, soft and open pulse.

Use: In all conditions where there is marked periodicity and where the secretory functions are in working condition, the use of quinine is not followed by any unpleasant results. For this reason in periodical fevers it should be given during intermission if it is indicated in the case. In small doses it stimulates; while in large doses it depresses. It acts on the derebro-spinal nervous system and the ganglionic nervous system of the heart. In congestive chills it should be given before the attack if possible, and stimulants given during the attack. Average dose is from 2 to 5 grains every 2 to 4 hours. In congestive chills 8 to 15 grains may be given before attack.

1909: Felter and Lloyd: CINCHONA (U.S.P.) – CINCHONA
History – As a therapeutical agent of inestimable value, cinchona, from its first introduction and use to the present day, stands pre-eminent. In fact, no article of the Materia Medica has borne so high and unwavering a reputation. It is an agent for which, notwithstanding the vast addition to the list of the Materia Medica, no other substance has been discovered in nature nor in the laboratory that could fully substitute its therapeutical value.

The period of the discovery of the medicinal properties of cinchona, is unknown. Some fabulous stories are mentioned concerning it, but we have no reliable information as to when, or how it was discovered. Some writers (Geoffroy, Ruiz, and Joseph de Jussieu), are of the opinion that the Indians were acquainted with its medicinal properties prior to the arrival of the Spaniards; but even this is doubtful, for La Condamine, who visited Peru in 1738, found the natives then unacquainted with it; and J. J. Caldas, pupil of the celebrated botanist, Mutis, who traveled from 1802 for many years in the mountains of Peru in order to examine the natural history and geographical distribution of the Cinchonas, states that the Indians who inhabit those regions, and among whom fever often makes sad inroads, will not use it, believing that it heats the blood and humors; and states that the heaviest chastisements are often inflicted to compel them to employ it as a remedy; he remarks that this prejudice is much aginst the fact of their ever having been acquainted with its use, as they cling with the greatest obstinacy to their inherited customs, vices, and prejudices. Ulloa, and Humboldt also express the opinion that the Indians were unacquainted with the use of cinchona.

The introduction of cinchona into Europe dates from the year 1639; it came to be known, it is said, from its having cured the lady of the Comte de Chinchon, at that time Viceroy of Peru, of a fever, and who, upon her return to Spain , carried some of the bark with her. For some time after its introduction, the Jesuits, who received the bark from their brethren in Peru, alone used it, and kept to themselves the secret of its origin; and it was through their use of it that its fame as a febrifuge so rapidly spread, and from which fact it derived the name which still clings to it, of “Jesuits’ bark.” The medical profession at first opposed its use, and it is recorded that it was not employed by them, until Sturum, of Antwerp , in 1639, and Bado, of Genoa , in 1663, advocated its employment and wrote in praise of its virtues. Notwithstanding the length of time that has elapsed since the discovery of the medicinal properties of cinchona bark, its botanical history is yet subject to discussion. A number of botanists have explored and described some of the sources of the barks of commerce, yet much remains to be accomplished. The barks that are recognized as official by the Pharmacopoeias, both of this country and Europe , are now chiefly cultivated. Much of the information we have concerning them is from the labors of M. Weddell, who accompanied a scientific expedition, under the patronage of the French government, to Brazil and Peru in 1843, and who continued his researches until 1848, since which others have written descriptions, as M. Guibourt, E. Rampon, A. Delondre, G. Planchon, etc. but they have not materially differed from Weddell. Prior to him was condamine, who first described the Cinchonas, Jussieu, Mutis, Ruiz, Pavon, Humboldt, and Bonpland. Weddell’s researches (modified) having been adopted by many as authority, we shall, in the following text, give in a somewhat condensed form his manner of collectin the bark (see Distribution and Collection), and some remarks upon the classification of barks into red, yellow, and pale barks, as adopted generally in works upon Materia Medica.

Previous to the year 1775, Loxa bark (most probably derived from Cinchona officinalis), was the only kind of cinchona known in commerce. It was not until 1772 that Mutis discovered the valuable tree in the neighborhood of Santa Fe de Bogota, and at this period Europe began to receive Cinchonas direct from the ports of New Granada, on the Atlantic . Some years later the authors of Flora Peruviana (Ruiz an dPavon), studied the species of lower Peru , to the north of Lima , and these were also introduced into commerce. The only species then, which botanically speaking, still remained unknown in Europe , were those growing in the vast extent of country extending southward. Notwithstanding the efforts of De Jussieu and the botanist, Thaddeus Haenke, little was added to the scientific knowledge of the Cinchonas by their travels. In the work by M. Weddell, he has made known the species observed by him in those regions during the years 1845, ’46, and’47. Frm his observations, this Cinchona (Calisaya) does not spring up again in the localities from which it has been cut, the circumstances peculiar to its growth being, as it were, altered, and a stunted growth, the variety Josephiana, is the only representative of the majestic C. Calisaya to be found in the localities which have been destroyed by the hands of the cascarilleros in a very ruinous and wasteful manner. To remedy the evil, at least as far as lay in its power, the government of Bolivia prohibited the cutting of the bark from the year 1851 for three years; this, together with a monopoly by the government of all the bark then cut in its territory, caused a rapid rise in the value of calisaya bark, and forced the manufacturers of uinine to use other barks in its preparation.

The immense commercial demands on the Cinchonas of these parts, tending to exhaust the forests, also rendered it necessary that new sources should be discovered. According to Wellcome’s report (Fluckiger, 1884), the forests of Loxa, for example, are now exhausted of their cinchona trees. To give some idea of the consumption of this bark, and the enormous drain upon the localities from which it was obtained, the company which had a monopoly of it exported at one time annually, more than 850,000 pounds of it. The great extent of the country, however, over which the Cinchonas are spread, excludes the idea, which has been entertained, that we shall every be deprived of this valuable drug, and the extensive Eastern cultivation now makes the contingency of its extinction next to impossible.

Action, Medical Uses, and Dosage - Cinchona bark is tonic, antiperiodic, slightly astringent, and topically antiseptic. When swallowed, a sensation of warmth is experienced at the stomach, which gradually spreads over the whole trunk; occasionally, it produces an unpleasant excitement of the stomach and bowels, with retching and emesis, more especially if the former be sensitive. In a little while after its administration the general system becomes more or less influenced, the pulse being fuller and more rapid, and a gentle stimulus imparted to the various organs of the body. With many persons it occasions symptoms which have been termed cinchonism, and which, some believe, are evidences that the remedy is exerting a favorable influence; but these symptoms should never be pushed too far. They are: Throbbing headache, and giddiness, of greater or less severity, tinnitus aurium, and imperfect hearing. Cinchona is valuable in functional derangement of the stomach, improving digestion, and invigorating the nervous and muscular systems in diseases of general debility, and in convalescence from exhausting diseases. Cinchona will be found useful in all febrile, eruptive, and inflammatory diseases, which manifest a degree of periodicity, in which it should be administered during the remissions; it is also valuable during the low and typhoid conditions of these diseases, and also in those cases, where, from an excessive and continued secretion of pus, the system becomes very much enfeebled and prostrated, in which it supports the powers of the constitution until all abnormal action is removed. It is likewise of much benefit in all chronic affections attended with periodicity, great feebleness, or nocturnal perspiration. When it occasions vomiting, its use should be suspended for a time. Its employment is contraindicated in acute inflammation, inflammatory fever, plethora, active hemorrhages, and in all nervous or vascular irritations.

Cinchona bark, however, exhibits its most important therapeutical powers as an antiperiodic, and in the consequent influence it exerts in almost in variably curing remittent and intermittent fevers, and the generality of diseases which are accompanied by sumptoms of marked periodicity, as neuralgia, hemicrania, dyspepsia, diarrhoea, and dysentery, when epidemic, etc. Its use should in most cases be preceded by a mild laxative, after the action of which the powder may be given in doses of 10 to 60 grains, and repeated, according to circumstances, every 1, 2, or 4 hours, until 1 or 2 ounces have been taken during the periods of intermission, and continue thus until a cure is effected, or the remedy is found insufficient for the cure of the disease. In the use of the barks, to obtain their antiperiodic influence, the red and yellow are considered superior to the pale, and of which the red is preferred. As a tonic, the pale bark is generally preferred, being less obnoxious to the stomach and intestines. Quinine, or its salts (see Quininae Sulphas), especially the sulphate, is usually employed as a tonic and antiperiodic in place of the bark itself, but there have been many instances in which the bark in powder has succeeded in effecting a cure, when its alkaloidal salts failed; the cause of this is not well understood. Still, it is often the case that the crude drug, which holds all associated principles, is more effective than its isolated alkaloid. In such cases, when the powder, from its bulk, or otherwise, offends th stomach, the infusion, decoction, tincture, or extract may be administered. Sometimes cinchona, or its preparations, occasion purging, which may be obviated by small portions of opium or laudanum. When a tonic effect only is desired, and periodicity is lacking, or when a tonic is indicated after exhaustive bleeding, the bark is preferably to the quinine salts, and, for some reason not well determined, the bark is sometimes preferably in chronic cases of ague. Cinchona is to be preferred when an astringent effect is desired.

Externally, a poultice of the bark has been found an excellent application to felons, fetid and gangrenous ulcers, etc.; also as an injection with opium, when the stomach rejects it; the powdered bark, placed between muslin, and held in place by sewing it in cross-bars, the same as in quilting, making medicated jackets, to be worn in contact with the body, has been of utility in obstinate intermittents. Dose of cinchona as an antiperiodic, from 1/2 to 1 drachm; as a tonic, from 10 to 60 grains; of the infusion or decoction, 2 fluid ounces, to be repeated 2 or 3 times a day; of the extract, from 5 to 30 grains; of the fluid extract, 10 to 60 drops; of specific cinchona, 5 to 30 drops.

Quinine, cinchonine, and quinidine appear to possess somewhat similar medicinal properties; their salts (as the sulphate) appear to be best adapted for medicinal use, principally on account of their ready solubility. Dose of either, from 1 to 5 grains, 3 times a day, or oftener, if required; in severe intermittents as high as 10 grains may be administered for a dose.

Specific Inidcations and Uses – Periodicity and, like quinine, effective when the pulse is soft and open, the tongue moist and cleaning, the skin soft and most, and the nervous system free from irritation. If opposite conditions prevail, cinchona will be likely to aggravate. Empyema; gastric debility; anemia and debility from chronic suppuration; afternoon febrile conditions; weakness, with pale surface, loss of appetite, feeble digestion, and deficient recuperative powers.

1909: Felter and Lloyd: CHINOLINA – QUINOLINE
Action, Medical Uses, and Dosage – This agent has not fulfilled the claims made for it when introduced into medicine. While it has some antiperiodic and antipyretic properties, rendering it occasionally successful in periodical fevers, its bad effects upon the stomach – nausea, vomiting, and disordered digestion – more than offset any of its better qualities. A 5 per cent solution has been used with asserted success as a solvent for the false membrane of diphtheria, but the preparation has now fallen into disuse for this purpose. The tartrate and salicylate are given in doses of from 7 to 15 grains. Quinoline preserves anatomical specimens, though it extracts all the coloring matter. The following preparation is suggested: Quinoline 5 parts, common salt 6 parts, glycerin 100 parts, water 900 parts.

1911: Fyfe
Periodicity, and all other symptoms indicating quinine. Cinchona is sued somewhat extensively as a substitute for quinine sulphate, especially in the treatment of children, on account of its being almost free from bitterness. Its action is similar to that of quinine sulphate, but it should be given in slightly larger doses.

Periodicity, convalescance from exhausting diseases, low and typhoid conditions, prostration caused by an excessive and long continued secretion of pus; chronic affections attended with periodicity, great feebleness, or nocturnal perspiration. Cinchona calisaya is contra-indicated in acute inflamatory disease, plethora, active hemorrhages, and all vascular nervous irritations. When indicated it is a good tonic, and in many gastric derangements it is a remedy of merit. It is used topically as a gentle stimulant and antispetic.

1911: LLOYD
Tradition states that the medicinal qualities of cinchona (Cinchona calisaya) were known to the aborigines of South America from the earliest times. Arrot (Philosophical Transactions, xl, 1737-8, p.48) states that the qualities and uses of the bark of cinchona were known to the Indians before the days of the Spanish Conquest. Others declare that the Peruvians distrusted the drug, considering it dangerous; Markham (406) asserting that the native doctors did not employ it. Preceding 1739, a Jesuit missionary, however, was cured of fever by the bark, administered to him by an Indian; a like incident being recorded concerning the Spanish corregidor of Loxa, in 1630. In 1638, the wife of the Viceroy of Peru, the fourth Count of Chinchon, being attacked by a fever, was cured with the powdered bark, which being commended by her, gave it the name, “The Countess Powder,” or cinchona. Introduced into Spain under the name Jesuit bark, or powder, as well as cinchona, it passed thence into other European countries, being largely distributed by the Jesuit Fathers.

Acrimonious discussions, too numerous and too personal to attempt to record, followed the inroads of this once rankly empirical drug, which, however, was possessed of qualities sufficient to establish it finally in the favor of “regular medication”. It was introduced into England about 1656, commanding then a price many times above that of opium.

1919: Ellingwood: CINCHONA – CINCHONA CALISAYA
Synonyms – Peruvian bark.

Constituents – Quinine, Quinidine, Cinchonine, Chinchonidine, Quinamine, tannic acid; thirty-two natural and eight artificial alkaloids, resinoid, volatile oil, gum, sugar and wax.

Preparations – Extractum Cinchonae, Extract of Cinchona. Dose, one to five grains. Extractum Cinchonae Fluidum, Fluid Extract of Cinchona. Dose, ten to sixty minims. Specific Medicine Cinchona. Dose, one to thirty minims. 1921: Lloyd

CINCHONA *1 (Cinchona, Peruvian Bark)

Official in every edition of the U.S.P., from 1820, following. The species of cinchona official in 1910 are those derived from Cinchona Ledgeriana, Cinchona Calisaya, and of hybrids of these with other species of cinchona. Red cinchona is derived from Cinchona succirubra, or of its hybrids.

The Extra Pharmacopeia, Martindale and Westcott, Vol. I, 1920, describes the bark as follows: “The principal dried barks used for the production of the salts of the cinchona alkaloids are: red cinchona bark, from Cinchona succirubra; yellow cinchona bark, obtained from Cinchona Calisaya containing upwards of 6% of alkaloids (half of which is quinine); pale cinchona bark (crown or Loxa bark), from Cinchona officinalis (containing 5% alkaloids, of which 3 1/2% may be quinine); the bark of Cinchona lancifolia, Mutis; Colombian bark (containing about 2% alkaloids, of which only small proportion is quinine); and other species of cinchona; that of certain species of Remijia may also be used. The variety most used for making galenical preparations is the cultivated red cinchona.”

Possibly never before, surely never since, has a remedial agent of the vegetable world met vicissitudes such as were experienced by cinchona during the half-century following its discovery in the Peruvian wilds. To make a creditable summary thereof is a very difficult task. To condense into a short article merely the principal events of its voluminous record, with full references to publications regarding this South American bark, can not here be accomplished.

The mystery shrouding the discovery of cinchona has nevery been authoritatively cleared. In the light of its present supremacy and world-renowned importance, the discredit and odium cast upon it in the early records, when its only friends were laymen, charlatans and semi-professional empiricists, seem now almost incomprehensible. Past literature of more than half a century voices acridly the distractions bred in the ranks of the medical profession, as this strange bark, a gift of the mountain fastnesses of the Peruvian tropics, forced itself into prominence. The monstrous reports concerning its harmfulness, and the divisions in the profession itself as regards its usefulness, bespeak toleration today, as physicians and pharmacists now differ concerning fact, ideals, and ethics with other drugs.

INDIAN HISTORY: That the natives of Peru were not aware of the value of cinchona in fevers, is the opinion of many writers, including Humboldt, the explorer, and Ulloa. *2Humboldt (see Pharmacographia) states as follows: “At Loxa the natives would rather die than have recourse to what they consider so dangerous a remedy.” To this Fluckiger *3 adds, “The early native history of cinchona is lost in obscurity, but traditions are not wanting.” Markham , page 5, says, “It is mentioned neither by Inca Carcilasso de la Vega, *4 nor Acosta, *5 in their lists of Indian medicines.” To this Markham adds, “It seems probable, nevertheless, that the Indians in the neighborhood of Loxa, 230 miles south of quito, where its use was first made known to Europeans, were aware of the virtues of Peruvian bark, and the local name for the tree, quina-quina, ‘bark of barks’, indicates that it was believed to possess some special medicinal properties.”

Other writers, on evidence equally valid, assert that the bark of cinchona was undoubtedly employed in native Indian medication. An argument in favor of their view, and an explanation for the secrecy maintained by the natives, is that the cruel methods of the Spanish conquerors led the Indians to guard from the invaders all knowledge of this, their greatest treasure.

Jessieu *6 states that the firt knowledge of the efficacy of this bark was derived from the Indians of Malacotas, some leagues south of Loxa. Weddell’s History. *7

Ralph Irving, *8 1785, records current tradition of his day, as follows: “It has been generally supposed that the Indians were acquainted with the use of this bark as early as the year 1500. It has also been alleged that the discovery was due to the accident of a diseased Indian drinking from necessity some stagnant water wherein this tree had long macerated.” This traditional narrative is varied by others, who state that “the party cured was a Spanish soldier.” (Wellcome, page 829.) Irving , in answer to the question why for more than one hundred years no mention was made of this drug in early Spanish literature, says, page 125, “Such discoveries were indeed poor objects for a rapacious and illeterate army, whose every path was marked with cruelty and slaughter.” Joseph de Jussieu, who visited Loxa in 1739, reports that the bark was “first made known to a Jesuit missionary cured of a fever by an Indian priest of the Sun Worshippers,” Fluckiger. Perhaps the latest evidence on this phase of the cinchona subject is that contributed by Henry S. Wellcome *9, who in 1878-9 made an exploring trip to the cinchona sections of South America . Mr. Wellcome’s impromptu Address on the Cinchona Subject, accompanied by specimens of the bark and leaves taken by him from the cinchona trees, formed the leading feature of the meeting of the American Pharmaceutical Association in Indianapolis , 1879. (Proc. Am. Pharm. Assn., 1879, P. 830.) He accepted that the use of cinchona in fevers was known to the Indians, but that they were secretive concerning it, “as is frequently the case with primitive peoples, in all parts of the world.” He asks, “How is it that the term applied to cinchona bark by the Indians is quinia-quinia, which signifies ‘medicine bark?” He adds, “The Indians of Equador told me they regarded the bark as a specific in fever.”

Taking the evidence as a whole, one may accept either of the traditions that thread the story of cinchona, that the secret of the bark was imparted by the Indians to the Jesuits, or that a Jesuit himself discovered its virtues. To the writer it seems more than likely that the natives of those malarial tropical lands made the discovery, perhaps in times lost even to tradition, than that a casual explorer of the almost inaccessible valleys of the high Cordilleras should, from the multitude of herbs, shrubs and trees, with tropical forms of vegetation of every description before him, have experimented on himself and established the qualities of the bark of this one tree. To this we might add that the art of neglecting to credit the aborigines or the pioneer, is not wholly confined to times gone by.

INDIAN NAMES OF CINCHONA. Few historical writers disagree in that there were wide variations in the spelling of the original Indian name for cinchona, Quinia-quinia, among these being Quin-quinia, Quina-quina, Quinquinia and Quinaquinia. Markham , *10 p. 5, footnote, says, “In Quichua, when the name of a plant is duplicated, it almost invariably implies that it is possessed of some medicinal qualities.” Fluckiger says, P. 81, that Quina-quinia was “adopted by the Europeans, and that it became simplified into Quinia, Kina, or China .” The last term, China , is much employed in Homeopathic materia medicas. Among the references to cinchona treatises given by Markham , sixteen employ the name Quinquinia as the leading title.

Irving , p. 10, states that “The natives (location not given. -L.) are said to have known it by the name of Ganapride, Guananepide, Chinanepide, and Quananegine.” He adds, “We are not sufficiently acquainted with the language of those countries to understand the import of these names. It is probable, however, that some of them are derived from the known virtues of the remedy, and others from particular circumstances respecting its discovery and appearance.”

Relph* uses the term Quinquinia continuously, for example, P. 9, “Before the year 1730 no botanical history of the Quinquinia or Arbor Febrifuga Peruviana, as the Cinchona officinalis was then called, is found worthy of attention.”

The evidence presented, in our opinion, firmly establishes Quinia-quinia as the Indian name of cinchona, regardless of the spelling, in historical literature.

“JESUITS’ BARK.” It is generally accepted that cinchona owes its introduction to the Jesuit missionaries to South America , from whom it took the name “Jesuits’ Bark.” It also received the name “cinchona” from the Countess of Chinchon, who in Peru , through the agency of the Jesuits, had by its means been cured of a fever. It is, however, a subject of discussion, as previously stated, whether the Jesuit Father who, through the Corregidor of Loxa, introduced the drug to the physician who treated the Countess, obtained his knowledge of its virtues from the Indians. It is also a matter of discussion whether the “bark” was first brought into Europe by the Jesuits, or by the Countess of Chinchon. Let us present briefly the record.

Relph, 1794, states that “the ‘Peruvian bark’ was first brought to Spain in the year 1632, *11 and that its febrifuge power was recognized in that country from an actual trial of its success in 1639; *12 yet so prejudiced against it were the Spanish physicians, that, had not its use been promoted and zealously guarded by the Jesuits, the utility of this medicine might have been still unestablished.” He adds that Arrot’s “Account of the Peruvian or Jesuits’ Bark, read before the Royal Society in 1737, is the first in order of time which appears to claim any consideration.”

Dr. Thomas Sydenham, one of the fairest and least prejudiced authorities in medicine during the period of the cinchona controversy, uses the term Jesuits’ Bark freely. But he employs also the terms Peruvian bark and cinchona.

Fluckiger accepts practically that a Jesuit Father introduced the bark to the physician of the Countess of Chinchon, having obtained his knowledge of its virtues through the Spanish Corregidor of Loxa, Don Lopez de Canizares. He says, P. 82, “Here in the village of Malacatos , a traveling Jesuit is said to have been cured by a cacique (Indian priest) of a fever by means of cinchona, and to have extended a knowledge of the remedy.” In this village, the Spanish Corregidor of Loxa, Don Lopez de Canizares, was also cured of fever in 1630. This same Don Lopez, on learning of the illness of the Countess, in Lima , 1638, *13 sent the Jesuits’ bark to her physician, Dr. Juan de Vega, who cured her of the disease. In the opinion of the writer of these historical notes the chain seems complete, as follows: *14

An Indian “medicine man,” (priest), in Malacatos, near Loxa, taught a Jesuit missionary the use of the drug.

This missionary taught others, Canizares of Loxa thus learning of it.

Canizares sent the bark to Juan de Vega, the physician treating the Countess of Chinchon, wife of the Viceroy of Peru.

On her recovery, the Countess sent the bark to Europe .

This leads to the question of the European history of cinchona, and name of the drug.

THE EUROPEAN NAME. – CINCHONA or CHINCHONA. Peru was invaded and subjugated by the Spaniards in 1513. Enormous riches were obtained by them, but the knowledge of cinchona, most precious of all the gifts of Peru , lay dormant for more than one hundred years.

In 1628 the fourth Count of Chinchon was appointed Viceroy of Peru, and with his wife reached Lima in 1629. In 1638 the Countess was stricken with tertian fever, then a very prevalent and a very perplexing ailment, so far as treatment was concerned. Her physician, Dr. Juan de Vega, received from the Corregidor of Loxa a “new remedy,” the bark of a native tree, which he proceeded to administer to the Countess, who recovered. On her return to Spain , in 1640, the Countess brought with her supplies of the bark. This was used among the sick of her home locality, and became celebrated as a specific for fever and ague under the name “The Countess’ Powder.” “By this name it was long known to druggists, and in commerce.” ( Markham ). Her Peruvian physician, Dr. Juan de Vega, followed her to Spain , bringing large supplies of the bark, which he sold at 100 reals a pound. The name of the Countess of Chinchon was thus indelibly linked with this great discovery. Linnaeus, in recognition, attempted to honor her by naming after her the genus yielding the bark, but by error of spelling he omitted from the name one letter h, making the record cinchona, instead of chinchona. Spanish botanists discovered the error, but Linnaeus having died, the correction was not made. The mutilated name now stands authoritatively, the world over, though resisted unavailingly by many authorities, and had been adopted by our own Pharmacopeia. But regardless of the lost letter h, the Countess of Chinchon has not lost the gratitude of the world.

EUROPEAN HISTORY OF CINCHONA. Here we find, interwoven, the story of commercial greed, and the efforts of the self-sacrificing pioneer; antagonisms of religious sects, and rivalries of nations; distractions bred by medical ethics and personal hatred within professional ranks.

That the Countess of Chinchon took the drug to Spain in a spirit of pure service to humanity, is incontrovertible. That the Jesuit Fathers independently, perhaps simultaneously, made the same humane offering in Italy , is likewise accepted by this writer. As already recorded, Ralph Irving states, P. 14, that “It was known in Rome in the year 1639, and that, in the year following, John (Juan) de Viga, physician to a Vice Queen in Peru , established it in Spain at an hundred crowns a pound.” Since de Vigo (spelled elsewhere Vega) was the physician who treated the Countess, it is evident that he hastened to Spain with the new discovery. That the Jesuits were not less active is demonstrated by the fact that Cardinal de Lugo, *15 Attorney-General of the order of Jesuits ( Rome ), began “the distribution of cinchona to the indigent sick.” Thus, to use the words of Markham, P. 14, “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 favored by Roman Catholics.”

Came now another opportunity for conflict. Though long previously adopted by the physicians of Paris , Spain and Italy , cinchona did not appear in England until about 1655-58, and then as a popularly advertised “nostrum,” *16 under the title, “The excellent powder known by the name of the Jesuits’ Powder.” During the entire interval commercialism was rampant, sophistications were plentiful, and fortunes were made, as perhaps never before with a new drug. These facts became an opportunity for professional controversy, marked by much acridity. Thus the greatest gift of the botanical new world was, for half a century, praised by some, vilified by others; being made the basis of secret fever cures, it was ostracised and traduced, and narrowly escaped a total extinction by the profession.

Forty years after its introduction into England , Charles II, who reigned from 1660 to 1685, was cured of a fever by his physician, Talbor, who was knighted therefor. Talbor’s secret remedy was, in 1679, purchased by Louis XIV “for 2000 Louis-d’or, a large pension and a title.” ( Markham ). After the death of Talbor the formula was made public, its chief constituent proving to be the Jesuits’ Powder, or cinchona. From that time cinchona, under its various names, became an article of commerce throughout Europe .

CINCHONA CULTIVATION. Early in the cinchona period came the fear that within a reasonable time the native forests would be exterminated. Exportation of the plants was naturally opposed by the Peruvian government, which desired to retain the monopoly of so important a product, but, in 1743, La Condamine attempted to transport young plants down the Amazon and thence to Paris . The box containing these was washed overboard, but subsequent attempts were more successful, and cinchona groves were established in localities appropriate as regards climate, soil and elevation. Not only was the world thus saved as concerns this valuable drug, but the yield of alkaloids was enormously increased, and the price has much decreased. Markham thus describes his experience in collecting young cinchona plants for transportation:

“In different parts of this ridge we collected 124 young C. Calisaya plants, most of them root-shoots, and a few seedlings. There were also two young trees bearing capsules. The C. Calisaya plants were all growing out of moss which covered the rock to a thickness of eight inches or a foot.”

PROFESSIONAL HISTORY: Incomplete would be this brief history of cinchona, were no reference made to the many professional distractions connected therewith. Unbelievable, almost, were these. “The controversies that arose on the subject, between learned doctors, were long and acrimonious. Dr. Colmenero, a professor in the University of Salamanca , wrote a work in which he declared that ninety sudden deaths had been caused by its use in Madrid alone.” ( Markham ). Factional, as well as personal, were the disputes over its value or harmfulness. The two sides of the controversy can perhaps be no more forcibly presented, than in the disputants’ own words, as late as 1683, (Gideon Harvey), *17 and 1715, (Sydenham) *18:

Harvey , whose antipathy to cinchona was perhaps due to the fact that it was first introduced into England through newspaper advertisements by an apothecary, spares no words in attacking the apothecary who presumed to introduce the “Quack” remedy. Nor does he handle more kindly the physicians “who prostitute their calling by using a remedy thus introduced.” Let us quote:

“This Jesuits’ Powder is not a medicine newly found, but revived by a debauched Apothecaries’ Apprentice of Cambridge, in the application to all intermittent Feavors, and he in this empirical practice, is most diligently imitated by our most famous Physic Doctors, as their Esculapius and first master. (A hopeful tribe in the meantime that shall leave Sense, Reason, and Dogmata, to follow a Quack or Empirick).” *19

The opinion of Dr. Harvey concerning the “Fathers Jesuits whose name is put upon the parcel,” *20 is expressed as follows:

“However, I am of the opinion that the aforesaid drug is artificially prepared, the tree spoken of, or some other like it, affording nothing but wood, into which the bitter taste is immitted, by macerating it a convenient time in the juice of a certain Indian plant, to which that penetrating bitterness is peculiar.”

Harvey thus continues the discussion:

“After all, I could wish these Fathers had kept their Indian Bark to themselves, and sure I am, hundreds would be on this side the Grave, whose bones are now turned into the first element.”

In this sentence Harvey , rather gently, introduces his opinion of the effects of “this terrible scourge.” From his chapter bearing the heading, “Proving that the Jesuits’Powder never yet cured any remitting fever,” let us quote. *21

“That many Noblemen, and hundreds of others, within these few years, being seized with this popular feavor, and managed with the Jesuits’ Powder, have died, or more properly been manslaughtered by their physicians, needs no confirmation.” “They (the physicians using Jesuits’ Powder) have killed thousands, and never yet cured any one man, excepting possibly three or four among a million, whose robust natures neither Disease nor Remedy could destroy.” As a specific case Dr. Harvey cites a man “of illustrious extraction,” whose treatment, and result thereof, he gives, as follows: “By as much as the Cinchona abated the Paroxysms of his Tertian, in an equal scantling it augmented his continual Feavor into a burning, and at last by its frequent exhibition Jesuited him out of hsi being.”

Concerning the after effects of cinchona Harvey writes as follows: “Agues can not otherwise be termed cured by the Jesuits’ Bark, but only stopped. The fits upon some short interval do return. Worse diseases are engendered as Dropsy, Consumption, Scurvy, or twenty other Distempers that either render the party his whole lifetime extremely crazy or kill him outwright.”

Concerning the selection of a physician, Dr. Harvey says: “If you shall meet with a physician that can safely, and not over speedily Cure you, without giving the Jesuits’ Powder, never meddle with the Jesuit, with whom the less a man has to do either sick or well, its the better.” *22

In the closing chapter of his book Dr. Harvey viciously attacks “The Conclave of Physicians” *23 who change their methods of treating fever (examples given) as the years pass until finally “they fall into an empirical course, as exhibiting Jesuits’ Bark against all continual an dintermittent fever, which now (Jesuits’ Bark) by all men is judged to be more fatal than any of the former.

Quite different in tone, and more effective, is the argument of the staunch supporter of cinchona, Dr. Thomas Dydenham, in “The Whole Works,” 1715. *24 His moderation, “viewing a disease as a thing in itself”, is shown by the following passage from his Preface: “If any one should object here, that we had long ago a sufficient number of Specific Remedies, this very Man, if he will make diligent search, would soon be of another mind; for the Peruvian Bark is all the Specific we have.”

The formula of the ague remedy used by Sydenham in the epidemic of 1681, is as follows: “Take of the Jesuits’ Powder one Ounce, of the Conserve of Red Roses, two Ounces, mingle them.”

Space forbids his voluminous comments on ague and its treatment, but the following extract giving his views regarding purging an dbleeding in fevers, and summing up, without personalities, the prejudice against cinchona, will not be out of place:

“Therefore, whilst I considered how ineffectual this method was (the accepted course of treatment – L.) and also other evacuation, that is Bleeding and Purging, both whereof by relaxing the Tone of the Blood protract the Disease, the Peruvian Bark gave me the most certain hope; concerning which I can safely say, notwithstanding the prejudice of the common people, and of some of the Learned, I never saw, nor could so much as suspect any mischief would happen the Sick by the use of it. I should not doubt to give it the first place, among all the Medicines that are yet known.”

In explanation of the prejudice against cinchona Sydenham says: “But the said Bark has got an ill Name, I suppose for these reasons, chiefly; First, because all the dreadful Symptoms that attend an Ague, when it has tormented an Man a long time are imputed to the Bark, when he scarce has used it once.”

Sydenham makes the following historical contribution as regards the introduction of cinchona into England (p. 224):

“The Peruvian Bark which is commonly called the Jesuits’ Powder about twenty-five years ago, if I remember well, first became famous at London for curing Agues, and esxpecially Quartans, and indeed for the very good reasons, seeing these diseases were rarely cured before by any other Method or Medicine.”

With refreshing exactness Sydenham closes his remarkable work as follows (p. 453):

“And this is in manner the Sum of all, which I have hitherto known concerning the Cure of Diseases, viz. to the 29th of September, 1686.”

Notes:
*1 – Descriptions of the trees yielding cinchona bark, together with the processes of the natives in its collection are most interesting. But to include in this article a section devoted thereto is impracticable. The publications cited as authorities cover the ground to the fullest extent.
*2 – A celebrated mathematician and naval officer, born at Seville in Spain , 1716. He accompanied La Condamine, Gordin and other “Savants” in the historic expedition to South America to measure a degree of meridian of the equator, 1735. He gave particular attention to the cinchona subject, protesting to the Spanish government against the habit of destroying the trees to get the bark, advising that others be planted in their stead. “Though the trees are numerous, yet they have an end.”
*3 – When reference is made to Fluckiger personally, his illustrated, 101-page work, The Cinchona Bark, translation by Frederick B. Power, Ph.D., is intended. His contributions to Pharmacographia are embraced under the title of the book. Frederick August Fluckiger was born in Langenthal, Schuytz , Switzerland , May 15, 1828. One of the world’s foremost pharmacologists and teachers, he held the esteem of all who knew him either personally or through his contributions to science. To cite his publications is impossible in this note. His crowning efforts may be seen in The Cinchona Barks and Pharmacographic. The writer of this note may be excused, he hopes, for stating that he treasures a letter from Dr. Fluckiger, 1885, stating that he was using the article on aconite in his teaching, as well as other chapters of Drugs and Medicines of North America. Nor less to be prized is the honor of having been selected by Dr. Fluckiger to unite with him in the production of a Pharmacographia of North American Medicinal Plants, interrupted by the death of Dr. Fluckiger.
*4 – Garcilaso de la Vega. He was surnamed The Inca by reason of the fact that he was born in Peru , his mother beinga native Princess descendant of the Incas. He published a History of Peru and obtained a pension from Philip II. 1605 he wrote an account of the conquest of Florida by De Soto . See Prescott ‘s History of Conquest of Peru , Vol. I, book II.
*5 – Acosta, Joseph, Spanish Jesuit born in Medina Del Campo, about 1530. In 1571 became missionary to South America . On his return in 1588, he published Natural and Moral History of the Indes. Connecting himself afterwards with the University of Salamanca , and died in 1600.
*6 – Brother of Antoine and Bernard de Jessieu: a famous family of scientists. Hoseph, in 1735, visited Peru as Botanist, collecting specimens and general information, under an exploring expedition of the French and Spanish governments. In 1739 he visited Loxa in association with La Condamine in the first examination of the Loxa cinchona trees, remaining in South America after La Condamine’s departure. In all he spent thirty-four years in laborious, self-sacrificing pioneering research, to be at last robbed by a dishonest servant of his great collection of plants and specimens. In 1771 he returned to France , deprived of reason by the great loss.
*7 – Dr. H. A. Weddell is accepted as exceptional authority on the cinchona subject. In his voyage to Bolivia and Peru he made special studies of the cinchonas, published many treatises on this history and connected problems, the one issued in Paris (1849) being illustrated by 34 plates. His name occurs in all historical reviews of Peruvian bark.
*8 – Ralph Irving dedicated his 101-page dissertation to John Eliott, Esq., December 16, 1784. It comprised experiments and statistics on “Red and Quill” Peruvian Bark, the Dissertation being awarded first prize by the Harveian Society of Edinburg, 1784. The book was published in 1785.
*9 – Henry S. Wellcome is an American, connected, at the time he made the exploration of the cinchona regions of South America, with the New York firm of McKesson & Robbins, under whose auspices he made the journey. He removed to England and with Mr. Burroughs established the firm Burroughs, Wellcome & Co. The African traveler and explorer, Stanley, and Mr. Wellcome, were close friends, jointly introducing strophanthus, which see.
*10 – Clement Roberts Markham was a traveler and author. He was born at Stillingfleet, Yorkshire , England , July 20, 1830. His journeys were from the Arctic regions to the tropics, where (tropics) he became interested in cinchona. In Peru he made studies of the locations the trees occupied, and, collecting the young ones, introduced successfully cinchona to England . A pronounced champion for the correct spelling of the “Countess” name, he attacks the misspelled word cinchona, demanding that it be chinchona. His 550-page volume on the Peruvian barks, titled Chinchona, is a scholarly treatise by one acquainted with the subject by personal experience and literary research.
*11 – That was six years before the Countess was cured of fever, and eight years before she sent specimens of the bark to Europe . We have not been able elsewhere to verify the date 1632.
*12 – This date conforms to the accepted date of the Countess’ exportation.
*13 – If he sent the bark to Spain at once, the date given by Relph (1632) is tentatively verified, to the effect that cinchona as “Jesuits’ bark” was used in Spain seven years before the Countess was cured.
*14 – Needless is it to give references to numerous unmentioned prints that touch this subject. Authorities mentioned in the text are voluminous in themselves and all cite others that will keep one long busy if ultra-research in cinchona is desirable.
*15 – Cardinal de Lugo, a Spanish priest, was born at Madrid in 1583. He was made a Cardinal in Rome , 1643. His interest in cinchona was pronounced and served to further the term Jesuits’ bark. His free distribution of the new agent to cure malaria, as well as his authoritative influence in its commerce by apothecaries, gave to the powder the name Cardinal de Lugo Powder.
*16 – See Professional History, Harvey .
*17 – See note 1, page 76.
*18 – “The English Hippocrates,” whose work on fevers, published in 1666, gave cinchona a hearty welcome. This was naturally offensive to the anti-cinchona faction, as shown by the extracts on pages 75, 76.
*19 – To take from the world’s products, medicines as well as foods, introduced by parties engaged in commerce, would impoverish humanity. And yet the art of thoughtlessly sneering at the “Commercial” man is to some a pleasant pastime.
*20 – This is the only reference we have noticed concerning the method of distributing Jesuits’ Powder. Concerning the amount of the powder and the price, Harvey states, page 140, “a crown an ounce.”
*21 – Bear in mind that this is written by the “physician in ordinary to His Majesty,” nearly fifty years after cinchona’s introduction in Europe .
*22 – These rather coarse arguments (the more vicious not reproduced), might lead one to consider the author a mountebank. But his record, as given in Lippincott’s Biographical Dictionary, is as follows:
“Harvey (Gideon), an English physician and writer, born in Surrey , was medical attendant of Charles II in his exile, and was subsequently physician to William III. Died in 1700.”
*23 – Evidently the section of the Medical Profession with which he did not affiliate. Particularly vicious is he againt the “Paris Conclave” and the eminent English anatomist, Dr. Thomas Willis, to whom he devotes Chapter XVII, titled “Willis, his Hypothesis of Agues is Ridiculously Erroneous.”
*24 – The Translator’s Preface from the Latin edition (by John Peachey, M.D.) is dated 1711. The Author’s Preface, undated, follows. The Translator’s English volume is dated 1715. The Author’s final word (see page 78) makes the date of his last contribution September 29, 1686.
* John Relph, M.D., was physician to Guy’s Hospital in 1794. His 177-page volume see Bibliography following Cinchona) is devoted to “A new species of Peruvian bark lately imported into this country under the name yellow bark.”