Part 17

About the same time the woman Tofana was selling her Aquetta di Napoli in Italy, but she was not brought to justice until 1709, when she confessed to the Pope and the Emperor Charles VI that her drops contained arsenic, and that by them she had caused the deaths of more than six hundred persons. The Emperor repeated her story to his physician, Garelli, by whom it was communicated to Hoffmann, who published it in his “Rational Medicine.” She preferred to prepare her drops by rubbing arsenic into the broken joints of a hog just killed and then collecting the juice. Tofana took refuge in a convent and lived for some twenty years after her condemnation. A letter from the English Secretary of State to the Commissioners of Customs, dated July 29, 1717, is on record, cautioning them against admitting a liqueur called Aqua Tufania from Italy, as accounts of its dangerous character had been received from the British envoys at Naples and Genoa.

THE CHAMBRE ARDENTE.

After the execution of the Marchioness of Brinvilliers, secret poisoning, far from being suppressed, appears to have become almost fashionable. The Government at least pretended to believe in widespread conspiracies. It may have been a political trick, as has been alleged, to get rid of some inconvenient opponents; but, however this may have been, a special commission was appointed by the French Government to inquire into the truth of certain rumours, and this commission acquired the title of the Chambre de Poisons, or Chambre Ardente. Louis XIV consented to the institution of this special court on learning that the notorious Ste. Croix, the coadjutor of Mme. de Brinvilliers, had at one time nearly secured the position of maître d’hôtel in his palace at Versailles. It principally concerned itself with the revelations made by two women who called themselves La Voisin and La Vigoureux, who with an unfrocked priest, who had assumed the name of Le Sage, had carried on a fortune-telling business of enormous extent in the city. They claimed the power of exhibiting the devil to their clients, and it was charged against them that they had sold a powder of succession to those who would pay for it. Many highly connected aristocrats were implicated, and some faced the commission while others left the country rather than expose themselves to the shame of exposure. La Voisin had kept records of her business, but those which were produced displayed rather the ridiculous than the criminal side of the conspiracy. The Duchesse de Foix had come to her for bosoms; Madame de Varsi wanted hips. Others had paid her fancy prices for petitions written with a special ink guaranteed to make them loved by the king. La Voisin was extremely insolent to her judges, and apparently she and her accomplices were all sentenced to be burned. According to Voltaire the sentence was executed in the case of all of them; but the account given by Madame de Sévigné, and by historians who lived nearer the period, go to show that the death punishment was only inflicted on La Voisin.

NEGRO CÆSAR’S ANTIDOTE.

In Prestwich’s “Dissertation on Poisons” (1775) an extract is given from the “Carolina Gazette” of May 9, 1750 stating that the General Assembly, the governing body of the colony, had authorised the publication of “Negro Cæsar’s Cure for Poison.” The General Assembly had purchased Negro Cæsar’s freedom, and granted him £100 a year for life as the price of this formula. It consisted of roots of plantain and wild horehound (? of each) 3 oz. boiled together in two quarts of water down to 1 quart and strained. Of this the patient was to drink one-third every morning fasting for three consecutive mornings. Certain conditions of diet were laid down, and it was quaintly added that if after the three days’ treatment no benefit had resulted it was “a sign that the patient has either not been poisoned, or has been by such poison as Cæsar’s antidote will not remedy.”

ARSENIC EATING.

About the middle of the 19th century some discussion took place in various popular and medical journals in reference to the alleged practice of eating arsenic in Styria and the neighbouring countries. Drs. Christison, Swaine Taylor, and Pereira were somewhat more than sceptical, but several doctors and others wrote confirming the statements from their personal knowledge. One of the most notable testimonies was contributed by Dr. Craig Maclagan of Edinburgh in the “Edinburgh Medical Journal” (1865). Dr. Maclagan had visited Styria and had introductions to several doctors in that country who had reported cases known to them. Two men were brought to Dr. Maclagan at the village of Liegist in Middle Styria, and in his presence took, one about 4½ and the other 6 grains of white arsenic. Dr. Maclagan brought home some of the substance which the Styrian doctor had given to these men, and on testing it found it to be genuine white arsenic. He also brought back some samples of the urine voided by the men some time after eating the arsenic, and found in it distinct evidence of the presence of the poison. The arsenic was taken by the men on a piece of bread, and in one case was washed down with a draught of water. How extensive was the habit, Dr. Maclagan could not say. The peasants called it Hydrach or Huttereich; the correct word was said to be hutten-rauch, furnace smoke. One of the men took his dose about twice a week, the other generally once a week. They had of course begun with doses of less than a grain. It was understood to be a tonic and stimulant, and to aid the respiration in climbing. It was also believed to promote sexual desire. Having acquired the habit the occasional dose was much missed if omitted for long.

IMMUNITY.

The modern employment of serums in the treatment of zymotic diseases goes a long way towards explaining the fact of the immunity of individuals in respect to bacterial poisons. But the possibility of immunity against such poisons as arsenic, opium, or serpent venom appears to rest on a different basis. In 1896 Professor (now Sir) Thomas R. Fraser, M.D., F.R.S., reported to the Royal Institution a long investigation dealing with the alleged resistant power of certain tribes or sects in India, Africa, &c., who can suffer the bites of unquestionably venomous snakes without becoming seriously affected. After quoting numerous reports from old and recent works showing that this immunity is an actual fact, Professor Fraser described a long series of experiments extending over many years with venom which he had obtained from India, America, Africa, and Australia. The venom, he stated, is a complex substance and is not a ferment. Ascertaining the minimum lethal dose for each animal he experimented on frogs, cats, rabbits, guinea pigs, and other animals, and beginning with one-tenth, one-fifth, or one-half of that dose, and gradually increasing it, he found it possible to administer four or five times, and in the case of rabbits up to even fifty times the lethal dose. From the immunised animal a serum was prepared which was antidotal in very minute quantities if mixed with the venom, but if administered separately by hypodermic injection, though at the same moment with the venom, some twelve and a half times as much was found to be necessary, and it was estimated for a normal bite of an average man no less than 11½ ounces would have to be administered hypodermically soon after the bite to prevent probably a fatal result. The most interesting observation was that the poison taken into the stomach was almost innocuous, and yet exercised a protective effect. In many of the narratives given by travellers describing the feats of the snake charmers it has been related that they will squeeze the venom from the serpent’s mouth and swallow it. This would evidently be one of their methods of rendering themselves proof against the poison when injected by a bite. Professor Fraser’s paper is published in full in “Nature” April 16 and 23, 1896. The author gives his reasons for believing that the action of the antidote is chemical.

MODERN TOXICOLOGY.

Systematic and scientific investigation of alleged poisoning was scarcely known before the end of the eighteenth or the beginning of the nineteenth centuries. The advance of chemical and physiological knowledge, however, was soon applied to the more certain detection of the criminal use of toxic agents. Orfila’s “Traité de Toxicologie,” published in 1814, the result of a multitude of experiments, was the work which led the way in the establishment of exact tests. Dr. Swaine Taylor in England, Sir Robert Christison in Scotland, Casper in Germany, and a host of other medical chemists pursued the subject, and gradually toxicology reached an assured position. How slow was this attainment may be gathered from the testimony of an expert in a French murder trial in 1823 that globules of fatty mutton had been mistaken for white arsenic.

To Marsh’s arsenic test, made known in 1836, may be traced the practical fall of the poison which for so many centuries had reigned supreme among the deadly agents employed by the most cowardly but most dreaded of the tribe of assassins. The power of proving the presence of the metal which was afforded by the method then set forth brought out the chemical expert, and led to angry controversies. The skilled experimenter was apt to be very confident of his results, and naturally others who claimed to be as skilful as himself disputed his conclusions. Theories of the almost universal diffusion of arsenic were vigorously maintained, and on one occasion in France, in 1839, when Orfila had demonstrated the presence of arsenic extracted from the organs of the person supposed to have been poisoned, Raspail undertook to extract as much from the judge’s armchair.

Meantime the resources of the poisoners had been vastly extended by the discovery of the alkaloids. Many of these substances possessed extreme toxic power, and the invention of the means of detecting them was necessarily a gradual process. It was attained, though; and it may be asserted that at present either by chemical or physiological tests the recognition of the administration of any of the dangerous alkaloids is as certain as is that of the metallic poisons.

About the year 1870 a new complication occurred when an Italian chemist named Dr. Selmi proved that putrefactive animal matter and certain bacteria yielded alkaloidal products, often poisonous, to which the name of ptomaines was given. Selmi was engaged as an expert in the investigation of a case in which it was suspected that an individual had been poisoned. A product was obtained, apparently an alkaloid, but which Selmi could not identify with any known vegetable substance. He came to the conclusion that it was of animal origin, and after a long series of experiments he proved his theory. Several eminent toxicologists at first asserted that ptomaines could be distinguished from vegetable alkaloids by the property of yielding Prussian blue with ferric salts. This test, however, proved fallacious as several series of vegetable alkaloids, notably the pyridic and the allylic, gave the same reaction. The distinction between animal and vegetable alkaloids is a delicate one, and has to be established by an accumulation of chemical evidence.

Leucomaines, which are also alkaloidal products, are distinguished from ptomaines by being formed in the body from living tissues, as a result of their activity. These were first separated by Armand Gautier in 1886. Their constitution is more complex than is that of the ptomaines, but they are not generally of a poisonous character.

XXIII

PHARMACY IN THE NINETEENTH CENTURY

“The advance in every section of chemistry during this century (the 19th), and especially during the latter half of it, has literally been by leaps and bounds. Although practically a creation of our own time, no branch has been more fruitful in result, in suggestion, or in possibility, than that of organic analysis.” (SIR THOMAS E. THORPE:--“Essays in Historical Chemistry,” 1894.)

Three great achievements characterise the pharmacy of the nineteenth century, namely, the discovery of alkaloids in its early years, of anæsthetics in the middle period, and of synthetic organic products in its later years.

ALKALOIDS.

The alkaloids extracted from vegetables are the ideal quintessences which the alchemical pharmacists of the sixteenth and seventeenth centuries sought so eagerly to obtain. Their characteristic property is that they are basic, that is, that definite salts can be formed from them by combination with acids. They all contain nitrogen, and have an alkaline reaction.

Of all the popular vegetable drugs opium was the one more than any other tortured to yield up its essence. The early laudanums and extracts of opium aimed at this result, and preparations, such as the Magisterium Opii of Ludovici of Weimar (born about 1625, and author of “Dissertations on Pharmacy”), were used in the belief that the quintessence had been in some degree secured. Robert Boyle experimented with opium with the object of extracting its essential principle. The process he adopted was first to treat the drug with calcined tartar (salt of tartar), and then extract with spirit of wine. By this means he obtained a solution which would be principally one of morphine.

In 1803 a French manufacturing chemist, working on an idea suggested by Vauquelin, produced a crystallisable salt which was at first supposed to be the active ingredient of opium. Experiments on animals seemed to confirm this opinion, and the salt of opium, or “sel narcotique de Derosne,” was believed to have solved the long-standing problem. The product was described in the “Annales de Chimie” of February, 1804. It was the substance now known as narcotine. Sertürner regarded it as meconate of morphium, a misapprehension which was corrected by Robiquet.

In December, 1804, Seguin, a chemist who had been a demonstrator under Fourcroy, and who subsequently got into trouble with Napoleon’s Government on charges of having enriched himself out of drug supplies to the Republican armies, read a paper to the Institute in which he described a process which would yield morphine. For some unexplained reason that paper was not published until 1814. Meanwhile Friedrich Wilhelm Adam Sertürner, a pharmacist of Eimbeck, in Hanover, had been working on Derosne’s salt, and had investigated more accurately than anyone before him the composition of opium. His first report was published in 1806, and in that he announced the discovery of “opium-säure” (opium acid), but in 1816 he named this product “meconic acid,” and explained how it was combined with an alkaline base which he called “Morphium.” He described this as analogous to ammonia, and prepared several salts from it. He came near to losing his life in the course of his experiments as, misled by the comparative harmlessness of Derosne’s salt, he had ventured on dangerous doses of his own product. Consequently he was able to determine very accurately the therapeutics of morphine at the same time that he announced its discovery.

“I flatter myself,” wrote Sertürner in 1816, “that chemists and physicians will find that my observations have explained to a considerable extent the constitution of opium, and that I have enriched chemistry with a new acid (meconic) and with a new alkaline base (morphium), a remarkable substance which shows much analogy with ammonia.”

Sertürner’s discovery excited much interest and emulation, and its importance was fully endorsed when, in 1831, the French Institute awarded to him a prize of 2,000 francs “for having opened the way to important medical discoveries by his isolation of morphine and his exposition of its character.”

Before Sertürner had definitely established the nature of alkaloids, Vauquelin had separated from tobacco a substance which he regarded as its active principle, and which was undoubtedly an impure nicotine. This was in 1809. The alkaloidal character of this extract was not, however, recognised until 1828, when Posselt and Reimann produced it in a pure form.

Vauquelin had in 1812 extracted daphnine from mezereon root, and in describing his experiments had alluded to its alkaline character. For this reason the credit of having been the first to have discovered an organic alkali has been attributed to him; and when in 1818 Pelletier and Caventou discovered an alkaloid in St. Ignatius’s beans, to which they gave the name of strychnine, they stated that it had been their original intention to designate the substance Vauqueline in honour of the celebrated chemist who had first established the existence of an organic alkali. It had, however, been pointed out to them by distinguished members of the Academy that it would have been a doubtful compliment to associate such an honoured name as that of Vauquelin with such an evil (_malfaisant_) substance as this new product.

A number of chemists narrowly missed the discovery of quinine. As early as 1746 Count Claude de la Garaye obtained from cinchona bark a crystalline salt which he termed sel essentiel de quinquina. Two other French chemists, Buquet and Cornette, subsequently introduced another sel essentiel de quinquina. Both these products were simply kinate of lime. A Swedish physician named Westerling announced in 1782 that he had discovered the active principle of cinchona, and he gave it the designation of vis coriaria. His product was in fact cinchotannic acid. Seguin perhaps made the worst mistake of all the investigators in coming to the conclusion that what was precipitated by tannin was the essence of cinchona from a medicinal point of view, and he actually recommended that gelatin should be substituted for cinchona in cases when price was an object. Fourcroy made several attempts to ascertain the true chemical constitution of the bark. In 1790 he separated a resinous principle, mixed with some colouring matter, since called cinchonic red. This he at first supposed was the essential medical constituent of the bark. Vauquelin later adopted this erroneous theory, and so missed his way. In 1792 Fourcroy got nearer to the truth when he observed incidentally that the water in which the bark had been macerated turned litmus paper green; and he also remarked that lime water caused a greenish precipitate in the infusion. He did not pursue the investigation, but his comment on what he had stated is noteworthy. “These researches,” he said, “will no doubt lead to the discovery one day of an anti-periodic febrifuge, which once known may be extracted from various vegetables.” Berthollet followed on Fourcroy’s lines, but came to the conclusion that the precipitate which lime water gave with decoctions of cinchona was magnesia, which he believed was a constituent of the bark in combination with hydrochloric acid.

In 1811 Gomez, of Lisbon, described a crystalline substance which Dr. Duncan, of Edinburgh, had obtained from certain species of cinchona, and gave to this product the name of cinchonine. Lambert later prepared it in a state of considerable purity. But neither of these chemists suspected its alkaline nature. In 1820 Pelletier and Caventou studied the whole chemistry of cinchona and succeeded in showing that the cinchonine of Gomez was a mixture of two alkaloids, to the second of which they gave the name of quinine. Quinidine was isolated by Henry and Delondre in 1833, and cinchonidine by Winckler in 1844, but the name of the latter was given by Pasteur in 1853. Pasteur also produced the alkaloidal derivatives cinchonicine and quinicine.

Robiquet had the idea that as the coffee plant belongs to the same family of plants as the cinchonas it might be possible to find quinine in coffee. In searching for it he isolated caffeine. This was in 1821. In 1827 Oudry found an alkaloid in tea and called it theine. Jobst and Mulder in 1838 proved that these alkaloids are identical. It is now recognised that the alkaloids of cocoa, of guarana, and of Paraguay tea are all the same substance, or closely related.

Pelletier and Caventou isolated strychnine from the St. Ignatius beans in 1818, and brucine from false angostura bark (_Brucæa anti-dysenterica_) in 1819; in the same years they obtained veratrine from cevadilla seeds and white hellebore root; but it would appear that in their investigation of cevadilla seeds, which was the first to yield the alkaloid, they were preceded by a very short time by Meissner. Pelletier and Magendie produced emetine from ipecacuanha in 1817, and Pelletier alone is credited with narceine in 1832. Codeine was discovered by Robiquet in 1821 when he was examining a new process for obtaining morphine which had been suggested by Dr. William Gregory, of Edinburgh. Belladonna had been studied by Vauquelin and many chemists after him, but it was not until 1833 that atropine in a state of purity was isolated from it. This was accomplished simultaneously by Geiger and Hess, two German chemists, and by Mein, a German pharmacist.

ANÆSTHETICS.

The greatest triumph achieved in any department of medicine, and worthy, perhaps, to be described as almost, if not quite, the most beneficent discovery in the world’s history, is that of the successful employment of anæsthetics. This great glory belongs to the nineteenth century. Indian hemp had been employed for centuries in the East, mandragora had a classical reputation, and from time to time the possibilities of hypnotism had been expounded by one or another of its professors. But it is only within the past sixty years that the terrible anxiety and suffering associated with surgical operations have been so far mitigated as largely to increase the prospects of success, and to annihilate the pain. To Sir Humphry Davy is due the credit of first suggesting the line of advance towards this precious goal by describing his experiences of the inhalation of nitrous oxide gas which he found had the effect of relieving toothache and other pains; “uneasiness swallowed up for a few minutes by pleasure,” were his own words; and he foresaw the possibility of this agent being employed as an inhalation “in such surgical operations as involved no great effusion of blood.” That was in the year 1800. About 1830 Faraday observed and noted the effect of ether on the nervous system, which he stated was similar to that of nitrous oxide gas.