SCOPE AND PROBLEMS Scientific and applied pharmagognosy

SCOPE AND PROBLEMS

PHARMACOGNOSY is essentially the study of raw materials and the products manufactured from them. While the origin of this science dates back more than a century in the Old World, it is only within the last twenty years that the subject has received any serious attention in this country. During this time much has been done to make pharmacognosy and chemistry the fundamental sciences in pharmacy.

In a narrow sense pharmacognosy embraces the study of medicinal plants and their crude products commonly designated as drugs. It has, however, many-ramifications and its branches extend into nearly all of the industries, requiring the consideration of a very great number of economic plants and their products. The divisions extend into the drug business, the spice trade, cereals and food products, the gums yielding varnishes, the origin of vegetable dyes, the properties of woods, the nature of fibers, papers and fabrics, etc., so that, in short, pharmacognosy deals with the properties, identification, sources, and nature of raw materials and their products.

Use of Microscope. Inasmuch as pharmacognosy requires that one shall be expert in the use of the microscope it might be said to be equivalent to technical microscopy or microscopical technology, meaning thereby the use of the microscope for the identification of, or confirmation of analytical data obtained in the examination of any natural or commercial product. An excellent illustration of the value of the microscope in the examination of a commercial product is in the case of a seizure of apple jelly many years ago. The price was such that at once the health authorities suspected that itwasanartificialproduct. As the nature of it could not chemically be detected, it occurred to someone to examine it under the micro-scope and it was found to contain the skeletons of certain specific diatoms. Intracing the habitat of these organisms it was ascertained that they grew upon certain seaweeds in the Pacific ocean, especially in the vicinity of the Japan Sea. This led to the discovery that agar-agar, now a common commercial article, had been employed in the making of the jelly.

Aim of Pharmacognosy. The ultimate aim of the science of pharmacognosy is to obtain a knowledge of the chemical nature and the properties of all commercial products, from their origin in nature to the final changes produced in their manufacture. To attain this object requires that the student in pharmacognosy should be well-trained in chemistry.

The term pharmacognosy was introduced by Seydler in 1815, and is formed from two Greek words, medicine, and Yvoiois, knowledge; and literally means the science or sumof knowl- of 1 The most edge drugs. idea of the of scope pharcomprehensive

macognosy has been given to us by Fliickiger, who states that it "is the simultaneous application of various scientific disciplines with the object of acquiring the knowledge of drugs from every point of view." The subject was unusually well expounded by Martius,"

Grundriss der Pharmakognosie des Pflanzenreiches," and may be regarded as a great pioneer in pharmacognosy.

Historical. Tschirch has well said that pharmacognosy dates back further than any of the departments of pharmacy. He rightly states that the old herbalists (rhizotomists) were really the first pharmacognocists, and he considers that Dioscorides, by reason of his writings on medicinal plants, was the first teacher in pharmacognosy. One is sometimes tempted to draw a narrow line and say that the history of the subject begins with the work of Martius.

While it is true that Martius appreciated the significance of the word " we must not pharmacognosy," who, in 1825, published a work entitled forget century and even much later it was usual for people to get their drugs directly from the living plants. Up until comparatively recently the identification of drugs was based on a study of living plants, and it was necessary, therefore, not so much to distinguish between the substances which were brought to market as it was for those who gathered medicinal plants to identify them in the field.

The work of the herbalists and systematists of earlier times gradually merges with that of the morphologists of more recent years. There has been a growing tendency to study not only the portions of living plants furnishing the drugs of commerce, but the entire plant. This is necessary, if we would understand the real significance of the characteristics of drugs. Fortunately, also, plants are being studied at close range and under conditions of cultivation, so that there will be less misapprehension in regard to the authenticity of the material sentering commerce. Informer years a number of mistakes have been made in describing drugs which might have been avoided had the identity of the material been first deter- mined and the foundation studies made upon the living plant.

Histological Pharmacognosy. The development of modern pharmacognosy may be said to date from the initial studies on the inner morphology or the anatomy of plants. All of these studies show that in the cellular structure of plants we find the plant unit. The importance of this discovery will be at once apparent when we recall that very many plants, as well as drugs, may resemble each other very closely when viewed macroscopically, but when we come to examine their cellular structure we find that the nature of the cells and their contents or their arrangement is constant for the most part for the same drug, and vary in different plants or drugs.

This advance in the study of plants is largely due to Schleiden, who, in 1838, announced that the cell is the fundamental unit in plants and showed that all the different tissues are combinations of cells. Schleiden not only contributed very largely to the knowledge of the structure of plants, but was among the first to recognize that drugs of different origin might be determined by their cellular differences. Without having any knowledge, for instance, that the several commercial sarsaparillas were obtained from different species of Smilax, he showed by reason of certain differences in the cells of the hypodermis and endodermis that they must be obtained from different species, which has since been proven to be the case.

Schleiden early saw that pharmacognosy was to be a distinct science. He designated pharmacognosy as a botanical discipline, indeed he said: "Pharmacognosy is the mother of all scientific When Schleiden said this he no doubt had in mind the difficulties attending pharmacognostical work and recognized the value of the training required in this study. For the pharmacognocist working upon dried materials must have in mind the relationship between the fragments of the drug he is examining and the growing plant.

Adulteration in Drugs. By adult eration we mean the deterioration or deficiency in quality of a commercial product, (no matter what this may be due to) , It may be due to a variety of causes such as aging, lack of care in preparation, substitution, extraction of important constituents, or the addition of other substances which maybeeitherharmlessorharmful. Adult eration may occurina great variety of forms. The following may be mentioned as giving some idea of not unusual occurrence:

Large pieces of iron may be used to increase weight, as in Burgundy Pitch ; pieces of lead pipe may be inserted in the fresh root as in Ginseng; bullets are occasionally found in the masses of opium; pebbles and rocks admixed with a safcetida; large quantities of dirt may be left in the middle of the bundles of sarsaparilla ; the substitution for a proximate principle, as papain by bread; admixture or even substitution by other species as apocynum, hyoscyamus and scammony, in which occur closely related forms; the substitution by widely separated genera as Mountain maple bark for Viburnum Opulus; in still other cases toxic drugs may be substituted for the genuine, as spurious cubebs for true cubebs, belladonna for inula.

Micro-chemistry. During the past fifteen or twenty years there has been a growing interest in the study of plant constituents by the application of chemical reagents to microscopic sections.

Up until recently we have been largely concerned in the identi- fication of raw materials and have been quite content to be able to distinguish the genuine article from spurious substances. This work has been based largely upon the forms of cells and composi- tion and structure of the cell wall. In some instances the study of some of the cell contents, as of starch grains and crystals of calcium oxalate, has afforded an important clue to the identity of the product under examination. As our interest in the study of the quality of the drugs increases, and this is based upon the constituents or those principles called active principles, it is very important that these constituents be studied in the cells of the plants and drugs.

A careful perusal of the literature will show that very many observations have been made showing the separation out in microscopic sections of definite crystalline substances. In some cases these occur even upon the outside of the drug, as the coumarin crystals on tonka beans and vanillin crystals on vanilla pods.

Again, these crystals may be formed upon heating the material, as in

benzoin and other 1 substances many drugs. Again, crystalline separate upon the addition of mineral acids, as when nitric or sulphuric acid is added to sections of hydrastis. Cognizance of these crystals is being taken to some extent in all of the progressive pharmacopoeias, and while the subject is in a more or less chaotic condition at present, yet the interest in this method of analysis is growing

to such an extent that we may expect before long that the crystal-lographic methods of analysis will play quite as important a part in the work of the pharmacognocist as the anatomical or histological methods have up until this time.

Problems of Pharmacognosy. Pharmacognosy has for its object the study of drug sand the plants  yielding them. The main object is not only to determine the identity of the drug and its origin, but the study of its constituents and the factors influencing their variation in the living plant as well as after collection. In the pursuit of pharmacognosy we examine drugs which for the most part consist of broken fragments, and from these pieces, frequently microscopic in size, the plants from which they are derived must be determined. Again, particles which resemble each other or are obtained from very closely related species must be separated. Part so fother plants growing with them in the soil must be distinguished and standards established showing how much of this extraneous material is permissible, and these standards must be so framed that drugs collected at widely separated points will be of uniform quality and efficiency.

The problems of pharmacognosy take us at once into the field where the origin of the drug scan best udiedatfirsthand. A second phase of the subject are the studies of pure morphology dealing with the development of certain structures as the stipes in cubeb, or the origin of tissues in seeds, and scars or markings in roots and rhizomes. The difference in constituents of different parts of the same plant, as the oils in the leaves and bark of cinnamon or difference in the proportion of alkaloids in the different kinds of cinchona, offers a most fertile opportunity for the application of physiological studies. Further-more, when we approach the subject of the cultivation of medicinal plants we are confronted with the problems of hybridization and mutation. We may further expect those who have had special training in the literature and language are likely to become interested in the historical study of drugs and in the nomenclature employed in designating them in commerce. In the historical study of drugs such phases are considered as the origin of their introduction into medicine, the dissemination of information concerning their uses among other nations, the official recognition by some, of the more important pharmacopoeias, and finally the facts regarding their real usefulness as supplied by modern pharmacological investigations and clinical experience.

The study of synonyms is one of the most important departments of pharmacognosy. While there have been some attempt stotreat of the synonyms of drug names and their derivation, nothing has been written which is adequate to the needs of this subject. It is one of the most difficult phases of pharmacognosy, and requires that the student shall be acquainted not only with the principles of scientific nomenclature, but that he shall be familiar with the several languages and the historical development of pharmacognosy. Tschirch has designated this department of pharmacognosy, pharmacoetymology.

Finally, there is a phase of pharmacognostical work that is receiving greater attention each year, and this is the division which relates to the study of drugs from the time they are shipped by the collector until they reach the retail pharmacist or even the consumer. This subject can not beignored, for it involves the study of the packing of drugs, the conditions of storage, and the changes in the quality of drugs in passing from hand to hand. While some few drugs remain more or less unaltered, or even may be improved on storing for a limited time, a large number of the more valuable of them require that they be kept under special conditions and for a very limited period of time. As indicating the importance of the subject the various pharmacopoeias are giving very explicit directions regarding the manner in which certain drugs shall be kept and how long they will retain their active constituents. This study requires an intimate acquaintance on the part of the pharmacognocist with the collector, the appraiser's stores, the wholesale warehouse, and the retail drug store.

It should also be stated that in practice we have a scientific pharmacognosy and a practical one. The problems of these two departments of pharmacognosy may be the same, as may also be the results, but the objects in view are very different. In the one, investigations are carried on that our knowledge of drugs may be made more complete and the investigator considers neither the cost nor the time. In the other the expert proceeds so far in the search for this knowledge as the problem in hand permits. The results of the scientific investigator will be published, whereas the results of the practical expert are usually withheld.

To a scientific mind the practices of commercial life are enigmatical, especially as they relate to the sale of foods and drugs. The scientist is familiar with the great variation of commercial products and has been publishing for many years the results of his studies with the view of benefiting mankind. So engrossed she in his search for the truth that he can hardly conceive that others are not working toward this same end. One can imagine his disappointment in finding that the motive of the manufacturer, in practice at least, works out quite to the contrary.

There are several reasons that may be given for the conditions that have prevailed in commercial life up until very recently. In the first place the public could not distinguish whether the commodities they were buying were pure or adulterated. Then price the process of purification, and this was but a step leading to the addition of more or less harmless substances until finally harmful foods and inert drugs were generally exploited. A third factor was the lack of knowledge on the part of the manufacturers and dealers to distinguish genuine foods and drugs from those which were adul-terated, spurious or worthless. This condition was remedied so soon as analytical data concerning the composition of foods and drugs were published in the scientific journals and some of the State Boards of Health employed analysts who published reports from time to time on market conditions.

These published results were rather startling, as up to within "fifteen years ago it was stated that of the whole food supply of the country one-seventh is adulterated." One can readily obtain figures in any of the pharmaceutical journals during the past ten years showing that something like 50 per cent of the powdered drugs upon the market were adulterated. The trade in spices was even worse, for we read that " the adulteration of spices is a practice so common that we would really be surprised to find goods pass through the grocery trade that are absolute lypure." This condition, of course, could not continue indefinitely, and fortunately a few manufacturers, who valued the reputation of their products even more than the money they could make out of them, lent support to National and State legislation which should fix standards of purity for foods and drugs. This finally ended in the passage of the Food and Drugs Act in 1906, which was followed by co-operative legislation in the various states.

The Microscope has been employed in the examination of drugs since 1847, when Schleiden used it in the examination of the sarsa-

In 1853 Schacht showed its value in the examination of textile fibers. The earliest reference in English to the use of the microscope as a means of detecting the admixture or adulteration of drugs is the statement of Professor Pereira in his introductory lecture before the Pharmaceutical Society of Great Britain in 1851, when he said: " You are doubtless conversant with the recent very extensive employment of the microscope for disclosing the adultera tion of food. No less useful no less powerful is it in disclosing the contamination of drugs; and I cannot too strenuously recommend you to employ it."

The investigations of Pereira, Hassal and others showed even at that time not only that the microscope had unlimited valuable practical applications, but that it was the only means which had been discovered to detect the admixture or adulteration of non-crystalline organic substances. An article published in the American Journal of Pharmacy in 1853 (pp. 45-48) on the use of the microscope in the examination of drugs shows that in spite of the fact that it has only recently come into general use its value was very early appreciated.

Some years ago a pharmacist, who had made a specialty of spices and endeavored to purchase only the purest available, became suspicious upon opening one keg of ground black pepper and finding alarge fragment of apodofcayennepepper. Asubsequent examination of the powder showed that it was an artificial product which was very common some years ago, the strength being reinforced by the use of cayenne pepper.

Very many instances could be given showing the value of the microscope in the examination of commercial products and the detection of adulteration as the presence of poke-root in belladonna root, or the substitution of ruellia for spigelia, foreign starches in cacao, presence of capsicum in ground ginger, the endocarp of olive (commonly called olive pits) in ground pepper and other spices as well as in powdered drugs, the presence of wheat middlings in ground mustard as well as in ground spices and drugs, and even to the detection of organic or inorganic crystalline substances in complex preparations. The use of the microscope is not only valuable in analytical work, but it is also valuable in synthetic work, as in determining the composition of cattle powders, medicinal teas, flavoring mixtures and practically all artificial combinations.

Those who are especially interested in this subject and are considering the advisability of preparing themselves for this work may ask for a definite statement as to the subjects that one should be proficient in in order to be a successful pharmacognocist. Taking it for granted that this inquiry is being made by the student who has his whole future ahead of him and who, it is presumed, can take the necessary time to qualify, we may say that the pharmacognocist of the future should have as a foundation rather thorough laboratory instruction in botany, chemistry, physics and crystallography. Not one of these branches can he afford to neglect, and the amount of instruction should be at least the equivalent of that given in these various subjects in the undergraduate courses of any of the best American universities.

On the other hand, no amount of reading or scientific training will quite take the place of a real interest in the subject. This interest can be acquired not only in the drug store or large warehouse, but in college laboratories with their extensive collections.

Soure: Scientific and applied pharmagognosy by Henry Kraemer, New York, John Wiley & Sons, Inc. London: Chapman & Hall, Limited 1920