CHAPTER XXXI. Chemistry and Experimental Pharmacology

CHEMISTRY AND EXPERIMENTAL PHARMACOLOGY

The experiments which were carried out by Antonius Musa Brassavola, in the early part of the sixteenth century, upon animals and criminals, for the purpose of learning the effects produced by certain drugs when administered internally, afford one of the earliest instances of a genuine experimental pharmacology. The account of these experiments, which was published at Rome, in 1536, under the title “Examen omnium simplicium, quorum usus est in publicis officinis,” deserves honorable mention. An even more remarkable evidence of the research spirit which was abroad at that period is to be found in the work done by Fortunatus Fedelis, a native of Palermo, Sicily, and an ardent champion of the direct method of observation as applied to therapeutics.

Van Helmont, of whose life and contributions to the science of medicine I now propose to furnish a sketch, represents in a certain sense Paracelsus’ successor; and, as a matter of fact, he was even more closely associated with the development of chemistry as an independent science than was his predecessor.

Jean Baptiste Van Helmont was born at Brussels in 1577. His parents, who belonged to the nobility, possessed ample financial means and were therefore able to give their son every opportunity to secure a liberal education. While still a lad he enrolled himself among the students of the University of Louvain, and advanced so rapidly in his studies that, already at the early age of seventeen, he had passed all the examinations required of applicants for the degree of Master of Philosophy. He was not willing, however, to receive this honor at that time, feeling that he had not acquired sufficient knowledge to justify such acceptance; and from that date forward he turned his attention to the study of other branches of learning. Finally, in 1599, he accepted from the same university the degree of Doctor of Medicine, and soon afterward left Belgium with a large party of his friends to make an extensive tour through the Alps of Switzerland and Savoy. After his return home in 1602 he devoted his attention chiefly to chemical researches; but in a very short time he started off again on a journey to Spain and France, and eventually to England, where he spent nearly a year in the city of London, returning to Belgium in 1605. He married, about this time, a rich heiress of Wilworde, in the neighborhood of Brussels, and resumed with great zest his labors in chemistry and alchemy. He was thus enabled to manufacture many remarkable remedies with which--as he himself declared--he succeeded in curing myriads of patients who had failed to receive any benefit whatever from the ordinary resources of medical science. He died on December 30, 1644.

I do not feel equal to the task of expounding Van Helmont’s often very obscure theories regarding the physical and psychological processes that take place in the human being; regarding the distinctions which he makes between the “archaeus influus”--the regulating principle which governs all the psychical and physiological processes in the body--and the “archaeus insitus”--the subsidiary power which resides in each individual part of the body, but which at the same time is under the control of the “archaeus influus”; and regarding the doctrine that disease is the result of an “idea morbosa” of the “archaeus influus.” August Hirsch says that in developing these theories Van Helmont puts forward many bright ideas, which unfortunately lead one into a wilderness of fantastic, theosophic concepts. If sufficient time and space were at my command it might be interesting to separate some of these bright thoughts from the extravagances in which they are buried, and thus demonstrate the truth of the statements made by both Hirsch and Dezeimeris to the effect that Van Helmont, in matters relating to physiology and pathology, was unquestionably a precise and critical observer, a sound thinker, and a correct interpreter; but the plan of the present work will not permit me to enter into all these details. I can only quote a few of the teachings or sayings to which Hirsch refers:--

Digestion does not, as Galen maintains, depend upon heat, but upon a certain ferment existing in the gastric juice.

Heat is not, as has hitherto been taught, the cause of life, but rather one of its products.

The final cause of the sensory phenomena of life is the archaeus influus, which, while it is inseparably united with matter, nevertheless does not represent the soul itself, but rather the organ of the soul, and is seated in the “duumvirate” of the spleen and the stomach.

Disease, in order to acquire sufficient power to antagonize life effectively, must unite its forces with the archaeus influus.

It is claimed that Van Helmont, more than any other teacher of medicine, was instrumental in giving the deathblow to the practice--which prevailed in all the medical schools of that day--of teaching the obsolescent Galenic doctrines, and that for this valuable service alone he deserves full recognition at the hands of the medical profession of to-day. But, as we learn from Ernest von Meyer’s history of chemistry, Van Helmont has a much stronger claim for recognition in the fact that he made many important contributions to iatrochemistry and also to fundamental or pure chemistry. Taking one thing with another, says von Meyer, we may safely assert that Van Helmont’s useful contributions to the medical and chemical sciences by far outweigh those which are of a fantastic or useless nature. It was he, for example, who materially increased our knowledge of the nature of carbonic acid. He demonstrated how it may be extracted from limestone or from potash by the aid of acids, from burning coal, and from wine and beer while they are undergoing fermentation. He also showed that it is present in the stomach, in various mineral waters, and in hollows in the earth. He gave it the name of “gas sylvestre.” He would doubtless have carried his discoveries much farther along if he had possessed the apparatus which is required for such researches. However, despite the lack of these facilities, he was able to describe hydrogen and marsh gas as special varieties which do not possess the same composition as ordinary air. Finally, in his treatise entitled “Pharmacopolium ac dispensatorium modernum” will be found a goodly number of useful instructions as to the proper manner of preparing drugs.

A complete collection of his writings was published at Amsterdam by his son, in 1648, under the title “Ortus medicinae vel opera et opuscula omnia.”

Theophrast von Hohenheim--who is known everywhere throughout the world as “Paracelsus”--was the son of Wilhelm Bombast von Hohenheim, a physician who belonged to one of the noble families of the Duchy of Württemberg. He was born in 1493 at a spot called “Das Hohe Nest” (the lofty nest) in the Canton of Schwyz, about one hour’s distance from the celebrated monastery or cloister of Einsiedeln, of which institution his father was the official physician. Switzerland, therefore, has a right to claim Paracelsus as one of her sons. In 1502 his father transferred his home to Villach, in Carinthia (to the east of Tyrol), and continued to live there up to the time of his death in 1534. It is not known where the son obtained his degree of Doctor of Medicine. It is a well-established fact, however, that he received the first part of his training as a chemist from Johann Trietheim, the Prior of Sponheim, and his subsequent education in the laboratory of Sigmund Fugger, the cultivated owner of wines at Schwatz in the Tyrol. He traveled all over Europe, going from one university to another and making the acquaintance of people who were well informed in matters relating to natural history, chemistry and metallurgy; and during all this time he appears to have absorbed a great deal of information relating to almost every department of human knowledge. Finally in 1526, soon after he had returned to Switzerland, he received, through the aid of certain influential citizens, two important official positions in Basel,--that of City Physician and that of Professor of Medicine and Surgery in the University. To the surprise of all, and contrary to long-established custom, he delivered his lectures in German and not in Latin. This action on his part called forth bitter criticism from the university authorities, but at first it met with the approval of the students. During the following two years, however, he gradually became unpopular with all classes of the community, and was finally obliged to leave Basel. Haeser attributes this unpopularity to Paracelsus’ rough manners, to his intolerance of the opinions of his colleagues, and to his tirades against the apothecaries for their excessive charges. It is very difficult to determine how far jealousy was responsible for the state of affairs which I have just described. Cabanès, the author of an admirable biography of Paracelsus (Revue Scientifique, Paris, May 19, 1894), gives his own estimate of this remarkable man’s character in the following terms: “Poor, miserable, and persecuted during his lifetime, he was misunderstood even after his death, and was calumniated by history.” Paracelsus evidently believed it to be his bounden duty to destroy the then prevailing cult of Aristotle, Galen and Avicenna as the great teachers in medicine; and, filled with this idea, he prophesied the growth of a new science of medicine on the ruins of their teachings. It is stated that the students, after one of these excited lectures, made a bonfire and burned a number of copies of the works of these famous authors, thus showing that Paracelsus was sufficiently eloquent to infuse some of his own reforming spirit into the minds of his auditors. He made a great mistake, however, when he attacked in a similarly violent manner the shortcomings of many of his contemporaries. “The medical profession,” he said, “has become a mere money-making business.” As a natural result of such tirades, Paracelsus was forced to leave Basel. He fled first to Colmar in Alsace and at a later date took refuge in St. Gall, Switzerland; and it was while he resided in that city that he published three books of his “Paramirum.” Then in 1535 he once more resumed his wandering life, in the course of which he visited Poland, Lithuania, Illyria, etc. On reaching Salzburg, in Austria, he fell ill and died on September 24, 1541, at the age of forty-eight.

Paracelsus was a prolific writer. To all the treatises which he published he gave extravagant titles. To his principal work, for example, he gave that of “Paramirum”--The Surprising Marvel; to another, that of “Paragranum”--Grain of Superior Quality; and to a third, that of “Archidoxia,”--Transcendental Science. He wrote treatises on syphilis, on the plague, on epidemics, on the diseases of grave-diggers, on ore-smelters, etc. It is admitted by all his critics that he devoted altogether too much time and thought to alchemy, demonology, necromancy, etc. Cabanès quotes Cruveilhier as saying that Paracelsus believed in the reality of beings of a fantastic nature, but attached little or no importance to them. Then Cabanès himself adds: “The thing which more than anything else absorbed his thoughts was the irresistible desire to overthrow the Galenic idol and substitute for it the science of experience, of observation pure and simple.” Bordes-Pagès, another distinguished French physician, says of this extraordinary man: “The great glory of Paracelsus is to be found in the facts that he cast off the yoke of a former epoch, more speculative than practical; that he summoned physicians to resume their allegiance to experience; and that he opened a long career for the alchemists, upon whom he urged the duty thenceforward of making new remedies the principal object of their researches.... He simplified and spiritualized therapeutics.” Some of Paracelsus’ own sayings are worth preserving: “Without air all living creatures would perish from suffocation.” “Man is the supreme animal, the one last created.” “Alterius non sit, qui suus esse potest” [He who is able to be his own master should not allow himself to be led blindly by another]. When he was accused of being coarse-grained and of deceiving the people, he replied: “By nature and also owing to the kind of people with whom I associated in my youth I am not of a finely-spun texture.... We were not nourished with figs and white bread, but with cheese, milk and black bread-food that does not make delicate lads.... They say of me that I lead the people astray, that I am possessed of a devil, that I am a sorcerer, and that I am a magician. Whatever truth there may be in these charges, one thing is certain: You are all of you unworthy to unloose the latchets of my shoes.” (From Paragranum, II., 120.)

Oporinus, who acted for a long time as Paracelsus’ assistant, made the following statements with regard to some of the methods of his former master:--

He always kept several preparations stewing on his furnace--as, for example, a sublimate of oil or of arsenic, a mixture of saffron and iron, or his marvelous Opedeldoch. He never prescribed a special diet nor any hygienic measures. As a purge he gave a precipitate of theriaca or of mithridate, or simply the juice of cherries or grapes, in the form of granules (about the size of the droppings of mice), and he was careful always to give them in uneven numbers (1, 3, or 5). He was bitterly opposed to the polypharmacy which prevailed so widely in his day.

Cabanès says that we probably owe to Paracelsus an increased knowledge of the virtues possessed by the different preparations of antimony, mercury and iron, and by salines. It was he who created the distinction between officinal and magistral preparations. To our list of pharmaceutical preparations, he added tincture of hellebore, compound tincture of aloes, digestive ointment, the tincture of metals (“Lilium” of Paracelsus), the “Saffron of Mars,” etc. He was the inventor of the precious preparation known as “la mumie,” a preparation which was popularly believed to possess marvelous healing powers. Ambroise Paré, toward the end of his career, was greatly blamed because he did not employ this remedy, and he was finally compelled in self-defense to write a pamphlet on the subject. (The text is reprinted in Malgaigne’s “Ambroise Paré,” under the title of “Traité de la mumie et de la licorne.”)

Adolphe Gubler of Paris credits Paracelsus with the distinction of having been the first physician to give an impetus to the movement which had for its object the application of chemistry to the perfection of medicinal preparations. He also maintains that Paracelsus should be looked upon as in a large degree the originator of specific remedies, and that he is justly entitled to the distinction of having been the first publicly to announce the “quintessences”--that is, the active principles (vegetable alkaloids)--of drugs. According to this claim it is understood that Paracelsus taught that each drug contained a specially active elementary body which it was possible to extract as a separate substance. Acting upon this belief Paracelsus did not hesitate to give the preference to the pharmaceutical preparations known as “tinctures”--that is, alcoholic extracts. Great credit is also due to Paracelsus for his rejection of the doctrine that guaiac is an efficient remedy against syphilis, and for his insistence that mercury is the only useful agent in curing that disease. Tartar emetic (potassium antimonyl tartrate) is one of the drugs the introduction of which into our pharmacopoeia should be credited to Paracelsus.

One of the earliest references to genuine diphtheria is to be found in the writings of Paracelsus, who speaks of the disease in the following terms:--

When this disease is located in an external wound it not infrequently spreads to the muscles of the larynx; and, vice versa, when a person has the disease in his throat, and at the same time happens to have an external wound, the malady is likely to spread to the wound.

Paracelsus’ idea of the existence of an “archaeus,” a power which presides over all physiological actions as well as over all the operations of medicinal drugs, resembles very closely the “vital force,” or “animism” so strongly championed by Stahl in the seventeenth century.

From all that I have said above regarding the excitable nature of Paracelsus it seems almost a waste of time to tell our readers that his contributions to the science of surgery were of very slight value. He despised the study of anatomy, claiming that a knowledge of this branch of medical science was not essential to a proper acquaintance with the human body. “To dissect,” he once remarked, “was a peasant’s manner of procedure.” (Cabanès.) His surgery, as one may imagine, showed clearly the bad effects of such beliefs.

During the latter part of the nineteenth century there developed among the leading men of the medical profession a sentiment in favor of honoring the memory of Paracelsus by the erection of a suitable monument at Basel, Switzerland, the city in which he made his first public appearance. The project met with a favorable reception and the statue is now an accomplished fact. This is a remarkable instance of tardy justice being rendered to the memory of a physician who, for three hundred years, was almost universally looked upon as a vain, half-crazy man.

The next advances of any special importance in the department of chemistry were made in Great Britain by Robert Boyle, who was born at Lismore, County of Cork, Ireland, on January 25, 1626. He was the fourteenth child of the Earl of Cork. His early training was obtained at Eton, and then afterward he spent two years at Geneva, Switzerland, in prosecuting his scientific studies. In 1654 he entered Oxford University and became intimately acquainted with some of the most learned men of that day. While he was a student at the university he became a member of what was known as “The Invisible College,” a society which was influential in bringing about the founding of “The Royal Society,” of which organization he was president from the year 1680 to the time of his death in 1691.

Boyle was endowed with a noble character--modest, religious and generous. He gained distinction as a chemist in several departments. Applied chemistry is indebted to him for a number of important contributions; he added to our knowledge of chemical combinations and to the methods of analyzing them; he enriched the chemistry of gases and also pharmacology; and he gave a clear and easily intelligible definition of what a “chemical element” is. He laid stress upon the doctrine that a chemical combination represents the union of two component elements, and that this combination possesses characteristics quite different from those possessed by either of the two component elements. Before his day there was practically no such thing as analytical chemistry, and it is to Boyle that we owe the establishment of a clear conception of what the terms “chemical reaction” and “chemical analysis” signify. The part played by atmospheric air in combustion was made by him the subject of numerous experiments which proved later to be of great assistance in the final solution of the problem.

In one of his writings Boyle says in substance that if men would devote their energies to carrying out experiments and collecting observations, rather than to the constructing of theories without having previously tested with thoroughness the grounds upon which they believe them to be based, the world would be greatly the gainer. The promulgation and insistence upon the importance of this doctrine for the growth of the science of chemistry constitute--so those competent to judge claim--Boyle’s greatest merit in scientific work and his most important contribution to chemistry.

Among the chemical treatises which Boyle wrote and published the following deserve to receive special mention: “Sceptical Chymist,” 1661; “Tentamina quaedam physiologica,” 1661; “Experimenta et considerationes de coloribus,” 1663; and “Medical Experiments,” 1692–1698. Although Boyle was not an avowed follower of Bacon, he carried out thoroughly the principles which the latter taught.

Raymond Minderer, a practicing physician in Augsburg, Germany (1570–1621), deserves the credit of having added to our stock of remedies the acetate of ammonia (liquor ammonii acetatis). Diluted with an equal quantity of water it is still employed to-day as a remedy under the name of “Spirit of Mindererus.” He was the compiler, in 1613, of the Augsburg Pharmacopoeia.

General Therapeutics.--Transfusion.--The Discovery of Cinchona and Ipecacuanha.--In the department of general therapeutics, as we learn from Berendes, several important new measures were brought forward during the seventeenth century; and among these the following deserve to receive brief mention in this place: the operation of transfusing blood from a healthy individual to one who is ill; the introduction of cinchona into the European pharmacopoeia as an efficient remedy in the treatment of certain fevers; the similar introduction of another South American drug--viz., ipecacuanha; and the invention of many medico-chemical products and the improvement of others that were already in common use.

As regards the operation of transfusion, from which great things were expected, Sir Christopher Wren (1632–1723), the famous architect and astronomer of London, is reported to have been the first person to urge a trial of this procedure. On the other hand, Robert Boyle, the chemist, actually performed the operation on animals. He followed the method suggested by Richard Lower (1631–1691) of England, viz., by allowing the blood to flow from the carotid artery of one animal into the jugular vein of a second animal; while Edmund King adopted the plan of allowing the blood to pass from the jugular vein of one animal into the corresponding vein of a second animal. Upon a human being the operation was probably performed for the first time (in 1666) by Denys, Professor of Philosophy and Mathematics in Paris. Repetitions of the operation were made, two or three years later, in London and in Rome, but they produced no good effects and in some instances they terminated in the death of the individual for whose benefit the operation had been performed. In 1668 the French Parliament and the Papal Government forbade a repetition of the operation.

In 1638--so the story runs--the wife of Count Cinchon, Viceroy of Peru, was cured of a stubborn intermittent fever by the native physicians, who employed, in their treatment of the malady, the bark of the tree now universally known by the name of “Cinchona.” In 1640 Juan del Vego, the regular medical attendant of Count Cinchon, introduced the new remedy into Spain, but it was not until after the lapse of about fourteen years that the drug found its way into England and Central Europe. The price at which it could be purchased was at first very high; it was almost literally “worth its weight in gold.” Even as late as 1680 the bark sold in England for £8 sterling per pound. Notwithstanding the generally recognized value of the drug in the treatment of certain fevers there were not a few men who continued for many years to oppose its use. Thus, Johann Kanold, a practitioner of medicine in Breslau, Germany, is reported to have said, on his death-bed in 1729, that he would rather die than be cured by a remedy the action of which was so opposed to all the principles which he considered right in therapeutics.

Ipecacuanha, another very important drug, was added to our stock of remedial agents toward the end of the seventeenth century. It was brought into France from Brazil, in 1672, by a French physician named Le Gras, but its value as a remedy for the cure of dysentery did not begin to be appreciated until after Helvetius, a semi-quack, had sold to Louis the Fourteenth, for one thousand louis-d’or (about $4000), the formula for the preparation which he (Helvetius) had been using with great success during the recent epidemic of that disease, and which moreover had effected a remarkably rapid cure in the case of the King’s own son--the Dauphin. After the purchase had been made by Louis the Fourteenth, in the interest of the French people in general, it was ascertained that the only active reagent among the ingredients of the formula was ipecac, a drug with which the Paris physicians had long been more or less familiar. Ipecac, it will also doubtless be remembered, constitutes the important element in what is known as the East Indian treatment of dysentery.

Probably the earliest modern treatise on matters connected with pharmacy is that which bears the title “Onomasticon Latino-Germanico-Polonicum rerum ad artem pharmaceuticam pertinentium.” It was published about the year 1600, and its author was Paul Guldinus.

One of the most important iatrochemical authorities of the seventeenth century was Johann Rudolf Glauber (1604–1668), to whom we are indebted for the invention or improvement of a large number of medico-chemical products. The well-known “Glauber’s salt” may be named as one of these products, and chloride of iron as another.