The story of drugs; a popular exposition of their origin, preparation and commercial importance

Front matter

Glass Book

COPYRIGHT DEPOSIT

IN THE DRUG COUNTRY A Characteristic Detail in the Piedmont

Contents

CHAPTER PAGE

I What Drugs Are and Where They Come From . . 3

II Beginnings and Accomplishments of the Medicine

Chapter I What Drugs Abe And Where They Come From

The public has always shown considerable interest and curiosity about drugs and medicines. This is partly due to the shroud of mystery with which the family doctor and the corner druggist have veiled the character of the contents of bottles and powders that have found their way to the bedsides of almost all of us at sometime or other in our lives. The American people are keen for anything suggestive of a riddle, and the hieroglyphics with which a physician covers the face of a little slip of paper, later to be translated into a bottle of cough syrup or headache powder by the druggist, stir our imagination. We read with avidity any article dealing with the subject of patent medicines, regardless of its inaccuracy. We relegate for later consideration such subjects as the tariff and the latest revolution, while we peruse the column of the morning paper describing the dozen or so inebriates who have been captured the night before — sadly the worse, so the account goes, because of too intimate association with this "tonic" -and that "hair wash";

and no daily paper is now complete without a section devoted to what Dr. Blank says.

The popular interest in drugs has of late years been stimulated by several factors, and more particularly by two, one of which was the publication of Mrs. Gene Stratton Porter's book, "The Harvester/ ' the other the outbreak of the war in Europe. For most of us, the idea of obtaining anything from woods and fields and subduing it to cultivation has a keen fascination, and in the minds of many persons those drugs and medicines that do not come from "coal-tar" come from the forest. In the demoralization of ocean traffic that came with the war, the fact that the continued supply of many important drug commodities was seriously menaced became a matter of daily mention in the newspapers ; and interest in the subject became almost universal. It possessed a certain element of romance, made excellent dinner conversation, and was discussed at almost any gathering where two or more people were assembled, much the same as prohibition later became the popular topic. Few persons, however, really knew enough about the subject to discuss it intelligently, and it was not uncommon for people to ask if aspirin grew on a bush, or to inquire how drugs could be grown in America when it was understood that Germany had them all patented.

The term "drug, ,, to some people, carries with it the idea of a narcotic — something taken to relieve pain or to put one to sleep — to be spoken of in an undertone, with a shrug of the shoulders. To others it means an individual chemical or a crude product that is used in preparing a medicine or in compounding a

DRYING A LEAF DRUG IN THE SUN Coca Being Prepared for Market in Peru.

Photograph by O. F. Cook. Courtesy and copyright by National Geographic Society, Washington. DC.

DRYING HOUSE WITH TRAYS FOR CUR- ING DRUGS BY ARTIFICIAL HEAT

COMMERCIAL PACKAGES OF CRUDE DRUGS AS THEY OCCUR ON THE MARKET monium sui.mm-F£RTiuz[iti

THE COAL TA

FAMILY TREE

COAL TAR" DRUGS AND THEIR ANCESTRY prescription. To still others it means any medicine ; and this comes nearer to being a true definition of what a drug really is, for it is any substance or mixture of substances used as a medicine, or that enters into the composition of a remedial agent.

Before discussing the different classes of drugs, it will be expedient to note a few general points concerning the localities in which they originate, to counteract the popular notion that the United States is entirely dependent on foreign sources for its supplies. At the outbreak of the war the prevailing opinion seemed to be that Germany furnished us with the majority of our drug supplies. As a matter of fact, the Central Empires produced comparatively few individual staples ; though the commerce in drugs that were collected or produced in northern Europe and Asia, and to a certain extent in Africa and South America, was centered in Hamburg. In other words, we depended on Germany for drugs to a considerable degree, not because they were produced there, but because they were brought there from all parts of the world, with Hamburg as the center of the export trade. Triest, also, was an important center for the articles collected in southern Europe and northern Africa. Therefore, when the ports of the Central Empires were blockaded, and supplies that had been coming here uninterruptedly for many years were suddenly shut off, it became necessary for American importers to make connections with dealers at the ports of origin.

An example of the control formerly exercised by the Germans is illustrated by the case of santonin, a popular remedy. This substance is a chemical individual, the active principle of the levant wormseed or santonica. The plant producing the levant wormseed grows in the wildest parts of the Russian steppes, far from any seaport or commercial center, and this is the only place where it has grown profusely enough to be commercially important. Its value was long ago recognized by the Russian government, and so zealously did it guard its monopoly that no plants or viable seeds were permitted to leave that country. The plant is a species of artemisia, closely related to wormwood, or absinthe, and to the numerous species of artemisias that run wild on our Western plains and mountain-sides, but it is the only artemisia that contains santonin. The so-called " levant wormseed' ' is not a seed at all, but the immature flower or bud, about the size of a large mustard seed, and it is gathered before it expands. The concession to gather this "seed," and to extract the santonin from it, was formerly sold annually by the Russian government; and for years the Germans bought the rights, thus controlling the traffic.

Since 1914 London has to a large degree succeeded Hamburg as a drug center, and Marseilles also has become an important port of collection and shipment. Amsterdam has always been a drug center, partly because for many years the Dutch have controlled the trade in cinchona bark, the source of quinin, the value and volume of business of which is probably greater than that of any other individual drug, with the possible exception of opium.

There was another reason for the popular conception of Germany's monopoly of the drug field. Some two decades ago there began to pour out of that country a great variety of so-called coal-tar products, some of which were of considerable merit as remedial agents, and are still extensively used. The development of substances of this nature was due to the fact that the German universities were specializing in chemical research and the problem of synthesizing quinin was receiving a great deal of attention.

In the course of this experimental work many new substances were produced, among them several well known chemical individuals, such as antipyrin, antifebrin, phenacetin, and aspirin. The commercial production of these coal-tar products was fostered by the Germans by means of the cooperation existing between certain basic industries of that country — namely, those concerned with the manufacture of dyes, explosives, and alcohol. In this cooperation for the advancement of German industry and trade as a whole, the new substances, as fast as they were evolved, were protected by patents at home and abroad, thus establishing the monopoly in their trade.

The commodities used as remedial agents, and which enter into the composition of the vast number of complex formulas dispensed by the physician and sold at the apothecary's, are divided into several different classes, belonging to two large orders familiarly known as inorganic and organic. There are metals, salts, and similar chemicals which in chemical language we refer to as inorganic substances, and which are represented by mercury, iodine, sulphur, iodide of potash, chlorate of potash, the bromides, sodium phosphate, calomel (a salt of mercury), bichloride of mercury, hydrogen peroxide, bismuth salts, boracic acid, carbonate of iron (used in Blaud's mass), magnesium sulphate (epsom salts), ammonium chloride, and many others, all of which have been manufactured in this country for many years.

Then, there is a large class of drugs composed of the three elements carbon, hydrogen, and oxygen, united in different ways, the nature of which is very complicated, and others containing those three elements together with nitrogen, which as a general proposition do not occur naturally, but are manufactured, and are therefore usually spoken of as synthetics. These belong to the great order of chemical individuals known as the organic series. (It might be said, in passing, that numerically by far the larger proportion of all crude drugs and active principles used in medicine belong to this order.) Some though by no means all of these are the " coal-tar derivatives ' ' to which reference has already been made. Among the organic compounds should be mentioned glycerin, novocain, carbolic acid, antipyrin, phenacetin, salvarsan, chloroform, chloral, iodoform, and aristol, though the four latter substances contain in their make-up certain elements — namely, chlorine in the first two, and iodine in the latter — which are, strictly speaking, elements of the inorganic branch of the family. Most of these substances were being made in this country prior to our entry into the World War.

Another large and very important group embraces the products of the vegetable kingdom which are themselves used as drugs, or which contain valuable principles that may be extracted and purified. The parts of the different plants entering the trade may be leaves, roots, barks, seeds, juices, resins, gums, the whole herbs themselves, or fungous growths that live on the plants. Thus we have the leaves of the belladonna, digitalis, coca, and senna; the roots of mandrake, aconite, rhubarb, sarsaparilla, and gentian; the barks of the cinchona and cascara; the seeds of nux vomica ; the juices of the aloes and of the poppy, the latter being known as opium ; the resin of Canada balsam, guaiac, and asaf etida ; the balsams of the tropical trees known as Peru and tolu ; the gum of acacia ; the whole herb of bone set ; and the fungus of the rye head, known as ergot.

The valuable principles yielded by these botanical drugs all belong to the organic order of chemicals. Some of the more important active principles are strychnin, which comes from nux vomica; morphin from opium; atropin from belladonna; cocain, from coca; and quinin, from cinchona. CafTein is another valuable medicine extracted from a vegetable substance, in this case tea dust or sweepings being the crude material. It is brought here from China by the shipload, and the cafTein extracted therefrom goes into headache mixtures and the ever-increasing popular beverage, Coca Cola and similar soda-fountain drinks. Camphor is obtained from the branches and twigs of the camphor-laurel, a large tree growing in southern China and Japan ; and menthol is frozen out of peppermint oil, the latter being distilled from a variety of the herb indigenous to Japan.

Mention should also be made of castor oil, which is expressed from the seed of the castor-bean. Several large firms devoted to this industry are within our boundaries. The seeds are gathered in India and sent to America by the shipload. Between 1860 and 1890 the castor-bean was an important crop in some of our Southwestern States, but in recent years, except for a brief period during the war, its cultivation has been virtually abandoned. During the war there was a great demand for castor oil as a lubricant for air-plane motors. Chaulmoogra oil, which has been used for some time, though only recently featured as a remedy for leprosy, is a butter-like substance expressed from the seeds of certain trees growing in Burma and adjacent territory. The extraction and purification of most of the active principles just mentioned has been carried out in this country for a great many years.

A few important medicinal agents are derived from the animal kingdom, notably cod-liver oil, pepsin, adrenalin, diphtheria antitoxin, and vaccine.

An attempt has been made to classify the staple drugs with which most of us are acquainted. A large proportion of the trade in medicines is concerned with those named or with preparations containing them. There are thousands of others that might be noted. Certain firms making specialties consume enormous quantities of some one commodity which may be but a small factor in the business of all the other firms in the trade. Ginseng, which is produced in great volume in this country, is used here scarcely at all, most of it being shipped to China and other Oriental countries.

It will be interesting to make a brief survey of the

WHAT DEUGS ARE 11

geographical sources of some of the drugs. As has been observed, we draw our supplies from all of the natural kingdoms, animal, vegetable, and mineral, and the basic products or crude materials are taken to the collection centers and refining establishments from the mines, from the prairies and forests, from the seashore, and from packing plants and slaughter-houses. The supplies of bismuth, a brilliant, shiny, and very heavy metal which eventually is converted into the well known salts of that metal, the subcarbonate and subnitrate, are all obtained from vast mineral deposits in widely separated localities, one of which is in Austria and the other in Ecuador. The commerce in this metal has been monopolized for many years, and the group controlling the mines has until very recently successfully prevented any competition, arbitrarily raising or lowering the price of bismuth, and in consequence its salts. Within the past decade, however, the recovery of bismuth as a by-product in the lead refineries of our Middle Western States has opened up a new source of supply of this metal, and the monopoly so long enjoyed by the foreign syndicate has been seriously menaced.

Almost as complete as was the bismuth monopoly has been the monopoly in the trade of iodine, which is the basic element used in the manufacture of the iodides, iodoform, tincture of iodine, and the many hundreds of medicinal preparations depending on some form of iodine as one of the essential ingredients. Iodine occurs in the salt deposits of Chile in the form of its sodium or potassium salt, the latter being separated out when the nitrate (saltpeter) is refined. From this crude sodium or potassium salt the element iodine is prepared. The only competition has been the iodine manufactured from the enormous acreages of giant kelp, a seaweed growing profusely in the vicinity of Japan and the British Isles. The burning of kelp and the subsequent recovery of iodine has not been a large factor in British industry for some time, but the Japanese product has been an important element in the trade, and though the Chilean iodine might be marketed at a price that would be less than the cost of the manufacture of the seaweed product, the controlling interests in the Chilean iodine have usually kept the price at a figure that was high enough to allow the Japanese to sell at a fair profit. The business in the sale of both bismuth and iodine has for years centered in London.

Mercury, the metallic element of calomel and bichloride, and one of the heaviest known substances, is a liquid that is smelted out of the cinnabar ores mined in California, Texas, and Sicily. Antimony, one of the basic components of tartar emetic, is mined in China, and from there shipped to this country in the form of black needles of antimony sulphide. Arsenic, which as the white oxide enters into the composition of pills of iron, arsenic and strychnin, and many hundreds of other formulas, as well as Fowler *s solution, is now a by-product in the smelting of copper, gold, and silver. Large and increasing quantities, more than sufficient for our entire needs in medicine, are produced in the United States. Boracic acid is prepared from the crude borax which is hauled out of Death Valley by the justly famous "Twenty-Mule

"HE ALCOHOL \ FAMILY TRLi

ALCOHOL

THE RELATION OF ALCOHOL TO THE MEDICINE INDUSTRY

A FIELD OF THE OPIUM POPPY

BOW FOREIGN DKUGS ABB SHIPPED

Bales of Sarsaparilla from Honduras

Team" and is therefore a product of domestic manufacture.

Dolomite, the mineral from which epsom salt is made, occurs in huge quantities in several of our States. The drug is now practically a by-product of the manufacture of carbon dioxide for the soda-water trade.

From coal-tar, which, as we all know, is a by-product of the manufacture of illuminating gas and coke, is recovered benzol and carbolic acid, the former the source of phenacetin and acetanilid, and the latter of salicylic acid and aspirin, and itself used as an antiseptic. The fractionating of coal-tar has been carried out in this country for many years.

Turning now to the vegetable kingdom, which yields some of the most interesting and important drugs, we find that the world's supply of cinchona, or Peruvian bark, comes almost entirely from Java. The forests of South America, up to 1850, were the only producing areas; but the threatened destruction of the species producing the drug led to commercial propagation in India, Ceylon, and Java. Recently the reported discovery of new forests in South America has opened up the possibility of this country again becoming a factor in the industry.

Asiatic Turkey and Persia are the chief sources of medicinal opium. India and China were formerly large producers of the drug used in making smoking opium, but the traffic is now rigidly restricted in India and is supposed to be suppressed in China.

Coca leaves, from which cocain is extracted, come from Peru, where the plant has been cultivated since before the dawn of history. Java will probably be an important source of supply in the future, since large plantations are being developed.

Licorice root, which in quantity is one of our largest drug imports, is obtained from Asia Minor, the Levant, and southern Europe. Only about 10 per cent, of this drug is used in the medicine industry, the rest being extracted and made into licorice paste, which is incorporated into chewing tobacco.

The leaf and the root of the belladonna plant, popularly called deadly nightshade (not the herb that grows in this country, commonly known as the deadly nightshade), are gathered in large quantities in southern Europe, and Austria especially, where the plant flourishes in the wild state. Belladonna itself is not used as a remedy for the eyes, as many persons suppose, but in the form of the extract (which is described in the next chapter), it enters into the composition of a great number of formulas of laxative pills and tablets and into belladonna plasters. Atropin, a chemical individual belonging to a group of complex organic substances known as alkaloids, is one of the constituents of belladonna, and this alkaloid is separated from the crude drug and yields the medicating agent used by the eye doctor. At the beginning of the war there was a shortage of belladonna, but rapid cultivation of the plant in the United States soon provided an adequate supply for our own use, and it was hoped that a permanent industry had been established. Since the cessation of hostilities the foreign supplies have again flooded the market, and at the present writing it is doubtful whether the belladonna-growers in this country can meet the competition of the cheaper and inferior drug.

Digitalis, the purple fox-glove, an indispensable heart remedy, formerly came from southern and central Europe and the British Isles. Large quantities of the leaf were gathered in the Vosges, and importations of another species, not the purple fox-glove, were received from Spain. The war shut off the foreign supplies, and it has been reported that military operations virtually exterminated the plant in the Vosges district. Digitalis is indigenous in the States of Washington and Oregon, and desultory attempts have been made to establish its collection there, with moderate success. Cultivation of the leaf was aggressively prosecuted in Virginia and Minnesota, and, as the drug produced was superior to that obtained from the wild state, it jumped into immediate popularity, and with a certain class of trade is preferred even now to the cheaper drug that is again coming from Europe.

For many years the world's supply of camphor came from Japan, and that country is still a dominant factor in the trade; but artificial camphor is now an article of commerce. Within recent years, also, plantations of camphor-trees have been established in Florida. Camphor imported into the United States averages 3,000,000 pounds annually, a large part of which is used in the manufacture of celluloid and moving-picture films.

Aloes, the bitter juice that exudes from a pricklyleaved tropical shrub, is imported from several sources, the most common variety coming from Curacao in the Dutch West Indies. It is also produced in northwestern -and southern Africa. This drug is often collected and dried in monkey-skins.

Referring briefly to some of the other staple crude botanical drugs, ergot is produced in Spain and Russia ; gentian in the mountainous region of southern Europe; sarsaparilla and ipecac in southern tropical America ; nux vomica in India and Cochin-China ; rhubarb in China : and senna in Egypt and India.

Of our American botanicals, attention has been called to ginseng, one of our indigenous plants. Mandrake root, yielded by the May-apple, is gathered in enormous quantities in the Central and Eastern States, sufficient for our own consumption and for export. Cascara sagrada is collected on the Pacific slope, and is used extensively here as well as large quantities shipped abroad. Hydrastis, or golden-seal root, formerly abundant in the wild state in the Ohio Valley, but now approaching extinction, is cultivated on numerous small plantations in the United States, and the supplies gathered furnish the world's demand. Wild cherry bark for cough syrups and lozenges is collected on the Southern mountain slopes.

Suprarenal glands, the crude material for that valuable hemostatic adrenalin, now being universally employed in surgery and dental practice for the control of hemorrhage, are obtained from the large packing establishments engaged in the slaughtering of sheep. The same industry supplies the countless hog stomachs that yield the pepsin so necessary for indigestion, a characteristic ailment of our strenuous population. The fishing industry of Norway and Newfoundland is responsible for our supplies of cod-liver oil, which is pressed out in tank-car quantities from the fish livers, stripped from the fish as they are tumbled out of the dories.

Thus it will be observed that the substances used by the medicine manufacturer and the doctor are drawn from all of the natural kingdoms, and that they come from all parts of the globe. Our own country produces many crude drugs and basic elements, and, because of its wide divergence of topography and climate, is admirably adapted to support the production of many botanical drugs, should conditions develop tc prevent the importation of foreign supplies, as was the case with belladonna and other foreign species, not requiring the nurturing of a wholly tropical atmosphere. Furthermore, some of our younger and more aggressive and progressive dealers in crude drugs are establishing connections with the initial sources of the commodities in which they are interested, and are thereby no longer dependent on the collectors and exporters of the Middle European nations.

Chapter II Beginnings And Accomplishments Of The Medicine Industry

In the state of society that existed in the periods prior to that which we recognize as possessing a consecutive history,when tribal customs prevailed, the sick in a community received aid from the headmen and the representatives of the religious orders. These leaders were simply those who possessed the superior intellect and physical characteristics, and who appreciated the credulity of the rank and file of their associates.

A knowledge of drugs and their uses was possessed by the ancient Chinese. Certain remedies, as exemplified by ginseng, were accorded almost superstitious reverence. The inroads made in the native supplies of this drug led to its practical extermination in Asia, and its cultivation was undertaken in Korea and Manchuria. Fortunately for the Chinese, the discovery of virgin stands of ginseng in the forests of the North American continent provided an unlimited supply of the drug for many years to come.

In prehistoric Peru coca was known as the divine plant of the Incas. The leaf of the shrub was in general use by the inhabitants, and no Inca was sent to his eternal rest without being provided with a bag of the drug. These little parcels of coca, in a remarkable state of preservation, have been brought to light by exploring parties who have penetrated the ancient burial-places. The bags are often of beautiful design and show a high perfection of handiwork.

The ancient Greeks were familiar with the use of drugs before the days of Homer, who sings about iEsculapius, a Thessalian, deified as the god of healing. Temples were dedicated to their hero, and his disciples were called ^Esculapiads. Greek medicine seems to have occupied a superior sphere of its own, and was not subordinate to religion, as was the case in ancient Egypt and India.

In the age of Pericles flourished the great teacher and physician Hippocrates (b. c. 460-377), known as the father of physic. The influence and teaching of this personage extended through the ensuing ages, and medical art as now practised dates from his time. The conquests of Alexander diffused the knowledge of Greek science. The development of Hippocratic medicine continued in Alexandria, and the study of anatomy was a feature of the Alexandrian school.

The development of medicine when Rome dominated the history of the world was due to the influence of Greek culture. The Eomans did not possess an independent school of medicine. When medical science appeared it was an importation from Greece.

The most renowned of the Greek physicians at Rome was Asclepias, who was born b. c. 124. In a. d. 77-78 Dioscorides wrote a book on materia medica, 1 enumer-

i Materia medica is a term employed in a collective sense for all the various drugs and medicines used for the cure or mitigation of disease.

ating some four hundred plants and drugs. This work still remains the most important contribution on the remedies employed in ancient times. About a hundred years later Galen, the imperial physician at Rome, added some two hundred more plants. The three names just mentioned are not only outstanding lights in the development of medicine and pharmacy, but two of them are commemorated in Dioscorea villosa, the wild yam, the root of which is used in the treatment of dropsy, and Asclepias tuberosa, the butterfly-weed, or orange milk-weed, familiarly known as pleurisy-root; while Galen 's name is responsible for the word galenical, which designates the pharmaceutical preparations of the natural vegetable drugs.

The hordes that overspread Europe following the decline of the Roman influence disseminated a knowledge of medicine and pharmacy that had been gradually accumulating from the earliest periods of the world's history. Among these people the dispensing of drugs had been practised by a special class of the priesthood. Egyptian inscriptions reveal how the physician-priests had sent their prescriptions to be filled by the priests of Isis. Papyrus records going back to b. c. 3300 contain references to the art of prescription-writing.

Many new drugs were now introduced into the materia medica. The knowledge acquired by the Romans from the Greeks, and augmented by the work of the philosophers who flourished when Rome was at the height of her glory, asserted its superior qualities over that of the Eastern conquerors. As it be-

HIPPOCRATES

GALEN

AN EXAMPLE OF PREHISTORIC SURGERY WITH FLINT TREPHINING INSTRUMENT

EMPLOYED came absorbed and appreciated, and when peaceful conditions began to prevail, schools of pharmacy and medicine were established at Damascus and Bagdad, the chief seats of the Moslem power.

During this period we have the first records of the use of some of the remedies used in modern practice. In the sixth century Alexander of Tralles used colchicum for gout, iron for anemia, and rhubarb for dysentery and liver cojmplaints. Diachylon or lead plaster had already been invented by Menecrates, a. d. 1, and was used by him for the same purposes as it is employed to-day. Under the Moslem influence the first apothecary shops were established and the first pharmacopoeia, or set of drug standards, was produced. The separation of the practice of pharmacy was recognized in the eighth century and legalized in the eleventh.

Frederick II in 1233, by edict, divided the pharmacists into two classes: the stationarii, who sold the crude drugs ; and the covifectionarii, who dispensed the prescriptions of the medical men.

The supremacy of the Mohammedan influence over medicine and pharmacy continued through the Middle Ages, but during the monastic period pharmacy was largely under the control of the religious orders, particularly the Benedictines. The monks were forbidden to shed blood, so the practice of surgery was turned over to the barbers. The familiar barber's pole, with its spiral decoration, is a survival of those times when the barbers advertised their calling by a device representing the application of bandages.

Ancient and medieval surgery was barbarous in the extreme. Ether and chloroform had not been discovered, and the use of local anesthetics was unknown. The operator utilized the crude instruments of the time, and his assistants held the head and extremities of the patient to prevent his struggles from interfering with the operation. Hemmorrhage was stopped by the application of a red-hot iron. This served a double purpose, though not appreciated at the time, for the heat destroyed the microorganisms that otherwise would have infected the wound and possibly set up blood-poisoning.