PLANT SCIENCE BULLETIN

VOLUME 9   APRIL 1963   NUMBER 2

Drugs from Plants

H. B. MACPHILLAMY

CIBA Pharmaceutical Company

Tracing back man's first use of herbs for the treatment of his ailments is, of course, an impossible task. No records remain of the thousands of years of early human life, and we can only poorly speculate as to prehistoric activities. Recognition of the medicinal value of certain plants seems to have occurred very early in the development of all known peoples. Certainly it was a discovery which long preceded the art of writing. In order to have some idea of the history of plant drugs, we must follow the evolution of medicine itself. Primitive man did not admit the existence of disease from what we would call natural causes. Since he did not understand disease, he viewed it as the result of malevolent influence exercised by a god, or supernatural being, or by another human being, alive or dead. Disease was, there-fore, a magical or magico-religious, rather than a natural, phenomenon.

It may have been that during early man's constant search for food, he ate certain plants which caused marked and unexpected physiological effects. They could have produced a very bitter taste, or vomiting, or defecation, or headache, or hallucinations, or even death. All of these drug actions would have been interpreted as a means of expelling the demon responsible for the disease. It may also have been that man, like the animals, had a natural defense in the instinctive quest for healing. A dog will eat grasses or other plants when he is sick, and man may well have had a similar instinct, or at least he may have learned the medical value of herbs from observing the animals.

Whatever the origins of man's medico-botanical knowledge, there is positive evidence that by 3000 B.C. he had developed a substantial lore of botanical drugs in China, Sumeria, India, and Egypt. The Chinese Emperor Shen Nung compiled a pharmacopoeia about 2760 B.C. which lists several hundred plant species; a Sumerian tablet (about 2200 B.C.) gives prescriptions using botanical materials; the Indian Rem Veda (before 1600 B.C.) makes mention of numerous plant remedies; but the most complete early reference is the Egyptian Ebers Papyrus (about 1600 B.C.). It describes more than seven hundred herbal remedies, including, among others, poppy, castor oil, squill, aloes, and caraway.

Many of the medicinal herbs of the Egyptians seem to have been chosen primarily for their aromatic properties. Pleasant smells were believed to ward off the vapors of disease. No doubt they were also favored because of their ability to overcome the disagreeable odors which frequently accompany many illnesses. The reliance on aromatic sub-stances has persisted throughout the history of medicine, and is probably the origin of the custom in medieval times of physicians carrying a nosegay of sweet-smelling flowers. Apart from the aromatic herbs, the Egyptians were undoubtedly familiar with several plants now known to have real therapeutic value. For example, the soporific effects of poppy preparations were evidently known to them, but it is doubtful whether they made use of their pain-killing properties in surgical operations.

Modern medicine is generally considered to date from Hippocrates in classical Greek times (460–361 B.C.). His great contribution to medicine was to sweep away much of the mysticism which unfortunately crept back in later times. Hippocrates stressed the importance of the careful observation of the symptoms of the individual patient, and it was on this, rather than on the haphazard methods of his predecessors, that he based his treatments. From writings attributed to him it appears that he made use of three to four hundred drugs, the majority of which were of plant origin. The first Greek herbal was compiled in the fourth century B.C., but no copy is now known. Theophrastus (372–285 B.C.) included in his writings the Historica Plantarum which listed some five hundred plants that were probably originally compiled by Aristotle.

The Greek teachings were carried on in Rome by Galen (IO3–193 A.D.), and his ideas together with those of Hippocrates dominated European medicine for some fifteen centuries. However, in the absence of original thinkers and experimenters, their teachings were allowed to turn to dogma and, with the passing of time, became distorted and misunderstood.

Another great and influential figure of the first century A.D. was Pliny the Elder. Although he knew little medicine, his reputation was so great in other respects that his opinions on this subject were widely accepted for many centuries. In dealing with medicinal plants he put forward the so-called Doctrine of the Signatures which held that for every disease there was an appropriate herbal remedy, if only it could be found by the careful examination of botanical specimens. For example, plants with yellow flowers were used for jaundice; the root of Bryonia resembles a swollen foot and was used for dropsy; plants with red roots were obviously to he used for blood disease; leaves of lung-wort are lobed and spotted and thus resemble lungs, an association which has carried over to the generic name

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Pulmonaria; the shimmer and shaking of poplar leaves in the breeze was the basis for the name "quaking aspen" and for their use in palsy. One of the strongest associations which developed at a later date was connected with the European mandrake (Mandragora). The root of this plant frequently resembled the complete human body and, there-fore, was almost a universal cure. The vendors fostered the story that when the root was pulled from the ground it emitted a piercing shriek, immediately fatal to the hearer. The sellers of the roots were supposed to harvest them by tying a dog to the plant, and after stopping their ears and retiring to a safe distance, they called the animal. In answering the call, the dog pulled out the root but of course died in the process, thus justifying the high cost of the herb. From these examples it is obvious that this Doctrine considerably set back the use of plants in medicine based on their real therapeutic effect. However, what was lost by medicine was gained by botany for the Doctrine encouraged an intensive study of plant morphology.

The progress of medicine was further retarded by the Dark Ages. The barbarian hordes that overran Rome held primitive and blood-thirsty religious beliefs, and their medical practices were mixed up with sacrificial rites. The devils and demons who caused ill health were expelled with herbs, charms, and religious incantations similar to those of ancient times but with a medieval dress. However, the progressive medical traditions of Greece and Rome were kept alive by the Arabs. The Arabian pharmacists were able to add to the large number of tried and tested herbal remedies of the Greeks from the large abundance of plants in the gardens of the East. The perfumes and spices of the Orient were skillfully blended to serve the healing art. Over fourteen hundred herbs were classified and studied, and thus provided a basis for the beginnings of alchemy. Nevertheless, Arabian physicians, like their colleagues all over Europe, were as much conjurers and magicians as doctors.

Herbal medicine progressed only slowly through the Middle Ages, but by the sixteenth century, it was firmly established. The remedies of many peoples and many centuries had, by then, been recorded in a fairly accessible form, thanks to the invention of the process of printing in 1450. Valuable additions also came from explorations in the New World. Though the grain was scarcely separated from the chaff, the time was about ripe for herbalism to become an effective weapon for fighting disease. Gerarde, for example, the author of a very famous herbal, cultivated an extensive herb garden in England, and his catalogue published in 1596 listed over one thousand plants. The methods described in his herbal are quite similar to those used in the pharmacy of today. As might be expected from the circumstances of their origin, many of these remedies were valueless, but mixed in with them are many that have stood the test of time. The sixteenth and seventeenth centuries really mark the transition between the old medieval herbalism with its superstition and the modern use of herbs based on careful observation and controlled experiment. Nevertheless, the older methods die hard. Even today worthless herbal remedies enjoy a considerable vogue among the superstitious and the uninformed, especially as home folklore medicines.

Progress came only with a return to the scientific method based on observation and experiment recommended to physicians by Hippocrates more than two thousand years previously. By carefully observing the effects of various drugs in the course of a disease, it was gradually possible to sort out many of those preparations which were genuinely beneficial. A number of these were remarkably complex in their composition. Many of the ingredients were added for reasons of superstition or in the belief that they could do no harm. Nevertheless, because they did include some drugs of real value, a number of these elaborate formulas were effective. Gradually, by trial and error, useful plants were distinguished from those to which even today no definite therapeutic value can be attached.

By the eighteenth century chemistry and pharmacy were overlapping to a considerable extent. This joining of the two sciences had a great influence on the development of both. To a considerable extent the pharmacists had been able to separate the useful plants from the useless. Now with the help of the chemist it became possible to eliminate the inactive parts of medically valuable plants. For example, just before the end of the eighteenth century, it had been possible to obtain crude crystalline quinine from cinchona bark, and many more drugs were isolated in the early part of the nineteenth century, as can he seen from the dates given in the list mentioned later. This process of extracting and purifying the active principles of natural drugs was greatly extended during this period and today is an important branch of chemistry that will be discussed in more detail later.

Of all the herbs used by the ancients, and even of the hundreds mentioned in modern encyclopedias of botanical

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drugs, very few can actually be considered as playing a real part in the modern doctor's armamentarium against disease. Some of the more important ones are the following: Ephedra equisetina and E. sinica (Chinese Ma Huang, 3000 B.C.)

The active alkaloid is ephedrine (1887) which is used for allergic disorders, as a stimulant, and in the treatment of low blood pressure.

Pa paver soznniferuzn (Sumerian and early Egyptian, 'Goo B.C.)

The well-known opium alkaloids, morphine (1804) and codeine (1832), still have considerable value for the relief of pain, in spite of their addicting properties. Another sub-stance from the same plant, papaverine (1848), is an anti-spasmodic.

Colchicum autumnale (Greek, 8o A.D.; Arabian, boo A.D.)

The alkaloid colchicine (1819) has quite recently found use as an antimitotic in the study of plant genetics. Digitalis purpurea (Welsh, circa 900 A.D.)

The cardiac glycosides found in this plant are still important in the treatment of certain cardiac conditions. Digitoxin (1875).

Co flea arainca, Thai sinensis

These ancient beverage plants contain the alkaloid caffeine (182o) which is used as a stimulant and diuretic. Atropa belladonna (1500 A.D.), Hyoscyamus muticus (50 A.D.), and Datura stramonium (1600 A.D.)

These solanaceous plants have been used by various peoples for centuries. They contain the alkaloids atropine (1819) and hyoscyamine (1819) which are parasympatholytic agents.

Cinchona remijia (Peruvian Indians, pre-Columbian)

The use of this plant in the treatment of malaria was discovered by the Spanish about 1600. It is doubtful that it was used for this purpose by the natives. Quinine (1820) has now been largely supplanted by better synthetic drugs, but the other main alkaloid, quinidine (1833), still has considerable use in cardiac arrythmias.

Erythroxylum coca (Peru, 1688)

The active alkaloid, cocaine (186o), is a powerful local anesthetic and has been the prototype of many synthetic compounds.

Veratrum viride (North American Indian)

The alkaloids of this plant have been frequently pre-scribed for hypertension. Protoveratrine-A (1890). Chondrodendron tomentosum (South American Arrow Poison—Curare)

The alkaloid present in this plant, d-tubocurarine (1948), is used as a muscle relaxant in surgery.

Rauwolfia serpentina (Ayurvedic medicine of India, 700 B.C.)

The crude drug and its active alkaloid, reserpine (1952), are used extensively today in the treatment of high blood pressure and as a tranquilizer, a use mentioned by the ancients.

The outstanding economic success of two plants has been largely responsible for the greatly increased interest in medicinal herbs during the last ten years. The first, Rauwolfia, mentioned above, has yielded a medically important product, which at its height had sales in this country alone of more than $20,000,000 a year. This adequately demonstrated that at least one of the ancient remedies had merit. The other plant, Dioscorea, does not yield a drug itself, but it does provide a basic starting material for today's production of an important number of the steroid pharmaceuticals, such as testosterone, the male hormone, and the many cortical hormones related to cortisone.

As a result of this stimulus, practically every pharmaceutical company in the country is engaged in some form of plant drug research in the hope of finding another Rauwolfia, or at least some new product which will be of use to the medical profession. It is well recognized that the chances of success are probably not as great as they are through the synthetic approach, but it is a gamble well worth taking. Consequently, plant collecting expeditions are being financed to all parts of the world, especially in the prolific tropical regions. Witch doctors and medicine men are being consulted. Folklore remedies are being reinvestigated, but now with the tools and highly critical attitude of mod-ern research. Very few plants withstand the test, and this is not surprising. Modern jungle doctors are no better in-formed about the diseases they treat than were their earlier predecessors, and their drug concoctions are largely chosen for the same reasons.

What, then, is the justification for this approach to the collection of plants for present-day screening programs? First of all, it provides a basis, sound or otherwise, for getting plants into the scientific laboratories for investigation, and this is the most important consideration of all. The medicinal value of a plant will obviously never be discovered unless it reaches a laboratory. Second, the natural selection of folklore herbs which has gone on over the centuries must have increased, if only slightly, their chances of yielding useful products. For example, it has already been mentioned that bitterness was, and it still is, a criterion for the choice of an herb by medicine men. Alkaloids are one of the more prevalent bitter substances in plants, and they have been the chief useful class of plant-derived medicinals. Certainly, testing for their presence in a plant by taste, or much better by a chemical method, is a very valid and frequently used procedure in the field.

Another approach, and one which would seem to be much more scientific, is the collection of specific plants on the basis of their botanical relationship. For instance, it is known that certain plant families produce alkaloids more abundantly than others. Therefore, unexplored genera of these families should be investigated. Also, if one tabulates the plant families that have been well investigated according to a botanical system of classification, it becomes obvious that many families have not been touched, and another basis for selection becomes available. It may be question-able, however, whether this approach is any more productive of active extracts than the other, but at least it is systematic. It is probable that this search for plant drugs will

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have to be based mainly on empiricism.

The investigation of specific plants also has a difficulty. Whereas the collection of native herbs can be done by any good "bush man" who can adequately prepare herbarium vouchers, the identification of botanical material in the field can only be done by professional botanists. In many of the more remote parts of the world, where unfortunately the flora is most varied, competent botanists are a rarity. This difficulty, of course, can be overcome by sending well-equipped expeditions into the tropics, or more simply, by investigating the great number of unexplored plants which grow essentially in our own backyards and are thus near capable botanical advice.

With an accurate botanical name associated with each test specimen, the investigator is in a position to make a search of the literature concerning the particular genus involved. To the chemist the most important source of in-formation is Chemical Abstracts, where plants are listed under their generic name or cross-referenced with the common name. Such a search brings to light all that is already known about the plant, both as to its chemistry and its biological properties. Even if a plant has been already quite thoroughly investigated, it cannot always be automatically eliminated because it may not have been considered in the light of new biological interest and emphasis. Furthermore, other species of the genus and even similar samples of the same species obtained from different geographical areas often have properties other than those already reported.

The usual procedure for the evaluation of the biological properties of plant material is to prepare an extract of the ground, dried, plant part. In a way this presents a dilemma. The active ingredient, if present, usually exists in only a small amount and may he completely hidden by a mass of inactive constituents. Since at this stage its chemical and physical properties are as yet unknown, it is impossible to devise a selective extraction procedure. One possibility is to use a series of selected solvents designed to remove sub-stances based on their different solubility properties. Such a scheme starts with a fat solvent such as hexane, and is followed by increasingly polar ones until the final extract is made with water, either alone or with added acid or base. The objection to this method is that it necessitates the testing of a minimum of five or six fractions for each plant sample and would consequently overload completely the usual testing facilities of the biologists. As a compromise, the common practice it to make a cold and a hot extraction with methanol and then with water. These are combined and evaporated to dryness in a vacuum at a temperature not exceeding 4o°C. This requires the biological evaluation of only one sample, but it is completely recognized that activities present in only trace amounts will be missed altogether.

Plant extracts are biologically screened in essentially the same systems as are synthetic compounds. They are tested in as many varied ways as material, time, and personnel permit, regardless of the nature of the activity for which the plant may originally have been obtained. Frequently, an activity, if found at all, bears little or no relation to that which the plant is reputed to contain. The first step in the biological screening of an extract is usually to administer it parenterally in a relatively high dose to a small laboratory animal such as a mouse. The chances are that if it produces no effect, it does not contain a potential drug and thus may be eliminated. If symptoms are produced, observation of them together with the results of an autopsy may give clues for further investigation along specific lines. These include a study of the effect of the extract on the circulatory system, on the central nervous system, on various isolated tissues including the heart, in selected endocrinological situations, on blood sugar and blood cholesterol levels, and so forth. In the field of microbiology the effect of the extract on various bacteria, molds and other fungi, parasites, vi-ruses, sarcomas, and so forth, are evaluated. Thus, as far as is feasible, each extract is thoroughly investigated for any activity which may be of medicinal interest. Unfortunately, very few give positive results.

When activity is found, it is then the chemist's task to isolate the chemical individual responsible for this particular effect. This is highly desirable for a number of reasons. The use of medicinal plants in their natural state, or as crude extracts, presents several difficulties. The actual content of the drug may vary with both the locality and the season in which the plant is gathered. As the active principles of many plants are powerful poisons when taken in excess, the dangers of prescribing drugs of uncertain origin are obvious. Equally, the patient may suffer if the drug is of lower activity than usual. Then too, the plant may contain variable amounts of other substances which have only harmful effects. These difficulties can, of course, be overcome by means of suitable biological control tests, but they have the disadvantage that they are rarely capable of high ac-curacy and are usually time-consuming and expensive.

All plants contain a great number of inactive substances, and it is the chemist's problem to separate the active ingredient from these materials by taking advantage of some unique physical or chemical property of the drug. For example, water-soluble substances can be removed from those predominately soluble in fat solvents by shaking the extract in a mixture of the two appropriate solvents. The two liquids, each containing those substances predominately soluble in them, form into distinct layers and thus can he mechanically separated. The ultimate of this process is the countercurrent distribution technique in which even slight differences in the solubility of various components of a mixture with reference to appropriately chosen solvent pairs is employed. If the active material is acidic or basic in nature, it can be readily removed from the many inert neutral compounds present by making use of this property. Differences in absorbability on inert substances can be used in the many chromatographic separation methods which are now avail-able. It should be kept in mind, however, that no matter what procedure or combination of procedures is used for the ultimate isolation, every fractionation step must be carefully followed with biological tests until such time as the chemical

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properties of the drug are ascertained with certainty. Only then can a chemical assay be substituted without fear of being misled.

With the pure material available, extended biological tests can be performed in a more meaningful manner, and the efficacy of the drug evaluated under more critical conditions. Its chronic and acute toxicity is measured, its side effects determined, and so forth, so that finally a decision can be made as to whether human clinical studies would be safe and warranted. The introduction of a new drug, whether of botanical or synthetic origin, depends upon the results of hundreds of carefully controlled clinical cases. This is the ultimate test, and of the small number of compounds that actually reach this stage, few survive. It usually takes at least two years from the time the first plant extract is pre-pared until the pure substance has passed all of the many rigid requirements necessary for marketing. It also involves the work of many scientists and the expenditure of considerable sums of money. Although discouragingly few of the thousands of plants investigated ever result in a useful product, it is still worthwhle doing if but only one of this number succeeds in aiding in the treatment of disease.

For scientific as well as for practical reasons, it is desirable to know the exact chemical constitution of any new drug. This problem of structure elucidation is one of the most interesting and challenging to the chemist. An elemental analysis yields data from which an empirical formula is first calculated. The nature of the ultraviolet and infrared absorption of the substance gives valuable information as to the structure and functional groups of the compound. Degradation studies break the molecule down by controlled methods into recognizable pieces from which an original structure can be reconstituted in such a way that it con-forms with all of the known chemical and physical properties of the new drug. The ultimate confirmation of the structural proposal is its synthesis by an unambiguous route. This also frequently provides a more economical method for the preparation of the product as witnessed by the fact that practically all plant derived drugs are now made synthetically.

The knowledge of the chemical structure permits the chemist to prepare modifications of the original drug and to synthesize related substances so that the important relationship between activity and chemical structure can be studied. Frequently, it is possible in this way to accentuate certain desirable biological properties of the substance and at the same time to de-emphasize some of the compound's unwanted side reactions. The net result of these chemical transformations is often a more efficacious drug which has increased usefulness in a greater number of patients. Plant derived drugs have long provided many of the fundamental stimuli for new synthetic medicinals, cocaine and morphine being examples. Actually, the most widely-used drug of all, aspirin, was modeled on the natural product salicin derived from the bark of willow and poplar trees and long-used for the relief of rheumatic and neuralgic pains.

Research on medicinal plants has still a long way to go. Estimates indicate there are some 350,000 species, and many of them may produce useful substances. So far, relatively few plants have been thoroughly explored for therapeutic possibilities. Plant extracts have just begun to be screened during the last few years in two of the most important areas of medicine, viral infections and, what may be related, cancer. Already some promising results have been reported as illustrated by the action of some of the alkaloids of Vinca rosea in the treatment of certain leukemias. It is to be hoped that plant drugs may succeed where synthetic medicinals have as yet failed.

GENERAL REFERENCES

LEDERER, E., AND M. LEDERER. 1955. Chromatography. Elsevier Publishing Co. New York.

MERCK AND COMPANY. 1960. The Merck index. 7th ed. Merck and Co. Rahway, New Jersey.

PENICK, S. B., JR. 1962. The search for natural sources of pharmaceutical

materials. Jour. Indiana State Med. Assoc. 55: I040—1043. RAFFAUF, R. F. 1960. Plants as sources of new drugs. Econ. Botany 14:

276-279.

SVOBODA, G. H., I. S. JOHNSON, M. GORMAN, AND N. NEUSS. 1962. Current

status of research on the alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don). Jour. Pharmaceutical Sci. 51: 707—720.

WALL, M. E. 196o. Dioscorea—Steroidal sapugenins and derived steroidal hormones. Amer. Perfumer Aromat. 75: 63-73.

WEISIGER, J. R. 1954. Countercurrent distribution In: Organic analysis, II. Intcrscience Publishers. New York.

WOODSON, R. a, H. W. YOUNGKEN, E. SCHLIITLER, AND J. A. SCHNEIDER.

1957. Rauwolfia: Botany, pharmacognosy, chemistry and pharmacology. Little, Brown and Co. Boston.

Book Reviews

Plant life of Palestine. MICHAEL ZOHARY. i–vi + 262 pp. 1962. The Ronald Press Company, New York. $8.00.

Palestine, if set down in southern California, would cover the area extending from Yuma to Santa Barbara, in its long direction, and from San Diego to the Joshua Tree National Monument in the other dimension. Oriented more properly, and set in its appropriate latitudinal position, Palestine would lie between Oceanside, California on the north, and Vizcaino Bay, Baja California on the south. This comparison makes a fairly good point of reference for us relative to the vegetation and climate of Palestine which range from extreme desert in the south and southeast to broad-leafed evergreen oak forest in the north and northwest. The chaparral of California would appear to be more extensive than its counterpart, the garrigue, or sclerophyllous shrub vegetation of Palestine, and the evergreen oak forests correspondingly more extensive. Climatically, of course, there is a strong parallel, with wet winters and dry summers, with rainfall (strongly influenced by altitude) decreasing southward and eastward.

In certain respects one can go further into comparisons with southern California plant life. There is a remarkable similarity between the principal evergreen oak of Palestine. Quercus calliprinos, and the live oaks of California. The presence of various common genera—Cupressus, Rhamnus, Arbutus, Salvia, Prosopis—would help to make the California botanist feel at home there. On the other hand, the common dominance of genera such as Pistacia immediately brings out the decided and expected floristic distinction.

To the botanist who, like the reviewer, has only a passing

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acquaintance with the vegetation of California, the descriptions and illustrations in Dr. Zohary's book constantly bring up familiar pictures: from live oak woodlands, open deciduous oak (Quercus ithaburensis) woods, open pine (Pinus halapensis) stands, and brush land to barren desert hammadas of desert pavement with desert shrubs and small trees in the draws. The book covers soils, climate, flora, vegetation, ecology of desert plants, and man's relation to vegetation. Unfortunately there is no glossary.

The flora is discussed first from the point of view of phytogeographical elements: the Mediterranean element, the Saharo-Sindian element, the Irano-Turanian element, the Eurosiberian element, and the Sudanean element. Then the phytogeographical territories of Palestine, largely based on these, are presented and shown on a map. Endemics, vicariism, ecotypic variation, and disjunct areas are considered. The history of the flora is described in the same straightforward, scholarly fashion as the rest of the book. Either the history of the Palestinian flora is not as well known, or as exiting as the history of the southern California flora, or perhaps Dr. Zohary lacks the imagination and flair for paleobotanical writing characteristic of some of our California botanists.

The chapters on vegetation are descriptive, but so much depends on the reader's knowledge of the flora that the average reader (botanist) will find himself frequently swamped with species names. Vegetation is nicely classified into orders, alliances, and associations, usually with their proper endings according to the Braun-Blanquet system, something we mostly refuse to do in this country.

The book is a scholarly work resulting from the gathering together of Dr. Zohary's own field research and that of other botanists who have worked in Palestine. As his last chapter so admirably makes clear, man has so influenced the native vegetation of the region for so many years that it is now quite fragmentary. It is fortunate that Dr. Zohary has pieced together the remaining parts and has put the results in print to perpetuate the record.—MURRAY F. BUELL, Rutgers-The State University.

Morphology and evolution of fossil plants. THEODORE DELEVORYAS. 1-1X + 189 pp. illus. 1962. Holt, Rinehart and Winston, New York. $4.50.

This small book is one of a series being published under the heading of Biology Studies. Each book, as the publisher states, is not intended to be a treatise, but rather will undertake the task of very briefly summarizing significant information in a given field, and interpreting it in light of current research.

The author has succeeded in preparing a brief and extremely useful survey of paleobotanical contributions to the understanding of plant evolution and morphology. Admittedly the brevity has necessitated the omission of references to many genera and species. However, the genera which are discussed are well chosen, concisely described, and, in most cases, illustrated with photographs or excellent drawings. The subject matter is presented in thirteen chapters that vary from 3 to 41 pages in length.

In chapter one, "Introduction," the forms of preservation of plant material, the conditions for fossilization, and the techniques used in the preparation of material for study are defined and discussed. Literature citations at the end of the chapter direct the reader to important publications wherein procedures used in the various paleobotanical techniques are given in detail. A geologic timetable is also incorporated in this chapter for convenient use when references to geologic periods are made in succeeding chapters.

In chapter two, "Nonvascular plants," the author clearly points out that on the basis of the fossil record little can be concluded concerning evolution within this group of plants, for most of the fossil forms show little difference in morphological types when compared with extant forms. The lead sentence in the discussion of the Chlorophyta, i.e., "The green algae, the group from which the higher green plants originated ...," is perhaps too dogmatic. It should be qualified in order to conform with chapter three, and the third paragraph in chapter thirteen, where it is made clear that the Chlorophyta are chosen as the most likely source from which land vascular plants arose. The concept of the monophyletic origin of land vascular plants is well presented, and the supporting arguments are outlined in chap-ter three which is accordingly titled, "The appearance of land vascular plants."

In the chapters that follow, the members of the Division Tracheophyta are treated in the systematic order usually encountered in morphology texts. Characteristics of typical as well as atypical members of the Psilophytales are summarized in chapter four, "Subdivision Psilopsida," and an excellent point is made of the heterogeneity of this group. The Lycopsida and Sphenopsida, chapters five and six respectively, receive an excellent coverage in the limited space devoted to them. Chapters seven through ten represent over one-third of the text. They deal in sequence with the Class Pterophyta, the various avenues of evolution of the seed-habit, the Class Cycadophyta, and the problematical cycadophytes. The author's interest in the Pterophyta and Cycadophyta is well known through his several publications on members of these groups. This interest, coupled with the fact that a large part of paleobotanical research has dealt with intensive studies of these groups, results in a discourse that would appear to he rather lengthy for a text of this size. However, the space is justifiably and excellently used. The Class Coniferophyta is treated in a little over twice the space devoted to the Class Angiospermophyta. This difference reflects the status of our knowledge of morphological trends in these important groups. Though the origins of both the coniferophytes and the angiosperms are still unknown, the fossil record has yielded better evidence of evolutionary trends in the conifers than it has for the angiosperms. The evolution of the reproductive structures in the Coniferales is well summarized by the author, and is based largely upon the classical works of Rudolf Florin. The final chapter, "Summary and conclusions," contains a remarkably good condensation of present day concepts held by most paleobotanists concerning the evolution of a land flora and the evolution of single elements within the flora.

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Each chapter, excepting the last, is followed by references which will lead the reader to more detailed descriptions of the plants discussed in the text. Among the references, too, are papers dealing with the concepts of evolution of various floras. The book is well indexed.

This book is to be highly commended as supplemental reading material for courses in plant morphology, as a book for the student of evolution, and as an example of the author's consistent high quality of work.—FRANCIS M. HUEBER, Smithsonian Institution.

Letters to the Editor

Dear Sir:

I am distressed by the inadequate preparation of students, mostly graduates of biology and botany departments, who arrive in graduate school with the desire to study plant physiology or plant biochemistry, but without an adequate background in mathematics, physics, and chemistry. Some readers of the Plant Science Bulletin may be able to help correct this lamentable hiatus in undergraduate education.

To move freely along the highway of modern plant physiology, students need a solid understanding of physical chemistry. For the student who knows he is heading for graduate study in physiology or biochemistry, physical chemistry should obviously be taken as an undergraduate. But the principal problem lies in the advising of students only generally oriented toward botanical or biological sciences. In many otherwise reputable institutions a student may earn a B. A. or even an M. A. in botany without having a single course in college mathematics or physics. Such a student, wishing later to enter physiology, would require no less than three consecutive years making up undergraduate courses.

I am not suggesting that every taxonomist should take advanced organic and every morphologist, thermodynamics, but a college catalog is misleading when a curriculum that does not include calculus is labelled "botany." The student following a curriculum without calculus, without physics, or without organic chemistry, is not preparing for work in physiology or biochemistry. The curriculum may adequately prepare him for specialized areas of botany, but not for botany as a general field.

There appear to be two solutions to this problem in operation in American colleges: one is to train all undergraduate biologists for molecular biology. The other is to pro-vide two tracks in undergraduate biology: one more descriptive and one more quantitative. In a leading Eastern institution adoption of a two-track biology curriculum was followed by a doubling of the number of undergraduate biology majors.

At the very least, advisers should recognize the serious disservice done to students when they are not advised of the requirements for study in the quantitative and functional areas of the plant sciences.—C. A. PRICE, Rutgers—The State University.

Obituaries

JOSEPH F. ROCK
1884–1962
AN APPRECIATION

Dr. Joseph Francis Rock, the well known plant explorer, died in Honolulu on December 7, 1962, at the age of 79. He was the last of the many Western plant explorers who have brought back such a wealth of scientific treasures from China and adjacent Tibet. He will be remembered the world over for his many contributions, not only in botany, but also in linguistics, philology, history, geography, and anthropology—for he was a man of wide interests, great talents, and broad vision, and was widely known in many countries.

It is not the purpose of this brief note to sketch the life of this outstanding botanist, explorer, and interpreter of a vanished culture. That has been ably done in the News-letter of the Hawaiian Botanical Society (z(I) :19631, in an obituary by Alvin K. Chock, which will be republished in an early issue of Taxon. Rather, it is my purpose here to pay tribute to this unusual person, whom it has been my privilege to know since the 'zo's, because of our common interest in the botany of China.

Rock's most outstanding characteristic was his breadth of vision. His labors were for the fullness of his projects, not for their adaptation to his needs or to the needs of the moment. Thus he built for the future, whether he was creating a herbarium in Hawaii, or gathering rare manuscripts in the distant parts of China, or preparing bird skins for the U. S. National Museum. His work was thorough and unstinting, and was performed with far-seeing objectives. He had no patience with trivial things or limited goals and was intolerant of pettiness, meanness and arrogance. For these reasons he was considered by many to be too impatient and impulsive. But his record of accomplishment on his numerous difficult explorations attests to a fine balance between contempt for trivial obstacles and unbounded patience and determination in the face of major ones. Who, without patience, for example, could conquer the pictorially recorded Na-ki language, almost unrelated to any other language on earth, and complete a dictionary, really a veritable encyclopedia, of this tongue—his last literary contribution before his death?

His writings, which will be fully listed by Alvin Chock, are basic and enduring, even those which appeared in the National Geographic Magazine. In the botanical field his greatest production concerned his first and last field of endeavor, Hawaii. Although he aspired to see a full comprehensive flora of that region, he only set the standard by making two contributions to such a work. His other writings there were on other aspects of botany, such as the trees, always with examples of his superb photographs. He pre-fenced the ficads and forests to the writing table. In China his great botanical contribution was through collecting plant specimens, seconded by his marvelous photographs. This activity, however, gradually gave way, in part, at least, to linguistic, historical, and cultural studies of the neglected

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Na-ki kingdom of Yunnan and its people. He knew this culture and language was doomed to vanish and it was his objective to preserve its record for posterity in the form of the numerous priceless original Na-ki manuscripts now in the Library of Congress. Even when he was forced by the adversities of war to leave, and his manuscript of twelve years' preparation was lost, he returned to do it over again, only to be driven out a second time a few years later by the Communists. He never returned.

Another of Dr. Rock's great characteristics was his generosity and the extent of his humanity. These must have been the foundations of the success of his journeys in distant places full of great hazard, where he was dependent on local officials, guides, carriers, and helpers. These people do not bring the small, petty, and unkind traveler through hardships and dangers which they all share, and not only once, but a second time a few years later. He held the infant Dalai Lama on his knee—one of his many fond memories. He suffered for the people, especially the Na-id

people, who helped and protected him when they were op-pressed by their Chinese overlords. He was a trial and a tribulation to many officials who had to supply his needs in the field, and who, through lack of imagination or of knowledge of the conditions he faced and through their adherence to customary ways of procedure, put obstacles in his way. His independence of mind and lone-eagle tendencies often made him part company with officialdom.

Rock's love of the wilderness, the freedom, and the grandeur of the mountains of western China made him once wish to die with his eyes on the Lichiang Snow Range in Yunnan. This he doubtless would have done, with the aid of the Na-ki friends, but for the changes in China which forced him out in 1949. In recent years he spent his summers in Europe and his winters in the States, or, after 1955, in Honolulu, steadily at work recording and publishing for posterity from his storehouse of unique information. As noted, these writings were always of a permanent character. Al-though he long considered a book of personal anecdotes and experiences, which we called his "funnybook," he never could be prevailed upon to write it. That was always some-thing for the future. His last Christmas card, received shortly before word of his death, told of the completion of his dictionary and of his expectation to return next summer to Germany on invitation of the government there.

In his many works and in the warm place which he created in the hearts of those who knew him, Joseph Francis Rock has left much for those of us who remain, and for others who will come after US.—EGBERT H. WALKER, Takoma Park, Maryland.

ARTHUR H. GRAVES

Arthur H. Graves of Wallingford, Connecticut, Curator Emeritus of the Brooklyn Botanic Garden and consultant to The Connecticut Agricultural Experiment Station on the chestnut blight disease, died on December 31, 1962 in Meriden, Connecticut. Dr. Graves was 83. A native of New Haven, he graduated from Yale in 1900 and received his Ph.D. degree there in 1907. After teaching at Yale and at Connecticut College, he became in 1921 Curator of Public Instruction at the Brooklyn Botanic Garden. When he became consultant at the Connecticut Experiment Station in 1947 he also continued his association with the U. S. Department of Agriculture, which he served in varying capacities over a period of 50 years.

He wrote more than 200 papers on botanical subjects including an excellent book titled, "Illustrated guide to trees and shrubs." In recent years many of his papers dealt with breeding disease-resistant chestnut trees. Of the American chestnut he wrote in 1914: "The most hopeful indications for chestnut in North America in the future lie along the lines of breeding experiments. . . Work of this kind is extremely valuable and, although slow in yielding results, may eventually prove to be the only means of continuing the existence in our land of a greatly esteemed tree."

In 1930, Dr. Graves undertook the line of work he had suggested 16 years earlier. Writing in Horticulture in October, 1962, he reported that he and his associates had made more than 250 interspecific combinations of chestnuts. A few of these combinations with desired characteristics have now withstood blight inoculations for about 25 years and will soon be released for commercial propagation. Thus, although seemingly "slow in yielding results," the work envisioned by Dr. Graves in 1914 gives promise of continuing the existence, in modified form, of a greatly esteemed tree.

All of us who knew Dr. Graves will sorely miss this kindly gentleman. He was a botanist in the broadest sense of the word. His unquenchable thirst for knowledge and insatiable enthusiasm for all that was new or unexplored was a constant inspiration to those about him. He had served as an editor for Biological Abstracts since 1922, was President of the Torrey Botanical Club in 1939, and was a member of the American Association for the Advancement of Science, Botanical Society of America, and Phytopathological Society.—RICHARD A. JAYNES, The Connecticut Agricultural Experiment Station.

WENDELL H. CAMP

Dr. Wendell Holmes Camp, Professor of Botany and Head of the Department of Botany at the University of Connecticut, died at his home after an illness of several months on February 4, 1963. His death terminates a career of outstanding public service and widely-recognized pioneering contributions to botany.

Dr. Camp was born in Dayton, Ohio, 22 February 1904. He received his early training as a biologist and geologist at Otterbein College. His advanced botanical training was conducted at Ohio State University where he obtained the doctorate in 1932. His professional career was unusually varied and marked by a sensitivity and devotion to the development of both the theoretical and the applied aspects of botany. Dr. Camp had held teaching and advisory positions at Otterbein College, Ohio State University, East-ern Illinois State Teachers College, Columbia University,

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University of Pennsylvania, and, since 1954, was Head of the Department of Botany at the University of Connecticut. He held important positions at the New York Botanical Garden, was Curator of Experimental Botany and Horticulture at the Academy of Natural Sciences in Philadelphia from 1949 to 1954 and Director of the Taylor Memorial Arboretum from 1951 to 1954. His researches on the Ericaceae brought him world-wide recognition among botanists. As a result of his studies, he was honored in 1957 by an invitation to address the London Conference marking the centenary of the publication at Charles Dar-win's "Origin of species." During World War II, Dr. Camp directed government sponsored investigations in Haiti where he developed emergency rubber plantations. Later he was sent to Ecuador as a Special Agent of the U.S.D.A. to search for native sources of quinine to replace Asian supplies cut off by the war. He contributed his specialized knowledge to such diverse projects as the breeding of blueberries, azaleas, and rhodendrons, the commercial production of various drug plants, and the toxicity of industrial wastes in irrigation waters.

Dr. Camp's many publications confirm his devotion to public service and to his profession. Not only had he published over 70 technical papers in botany, but he made numerous contributions toward a better understanding of plants by the public. He was co-author of the National Geographic Society book "The world is your garden," he wrote for the Encyclopedia Britannica, and published many articles for popular and semi-technical journals. Dr. Camp served in administrative, advisory, and editorial capacities for International Botanical Congresses and for several botanical societies. He was a past-president of the Torrey Botanical Club and the American Society of Plant Taxonomists, and founder-editor of The taxonomic index. Special recognition of his public service came first in 1951 when he was awarded the honorary degree of Doctor of Science by Otterhein College, and later in 1962, he was presented with the Distinguished Service Award of the New York Botanical Garden.

Many of us will remember "Red" Camp for the fellow-ship we enjoyed with him, and the many stimulating and often heated discussions held in his company. Wendell Camp was one of the most colorful botanical personages of the last decades, and those of us who knew him will sorely miss his continuing friendship.

News and Notes

ANNOUNCEMENTS

The AMERICAN SOCIETY OF PLANT TAXONOMISTS has elect-

ed Ira L. Wiggins of Stanford University, President for 1963, and Arthur Cronquist of the New York Botanical Garden has been elected to serve a seven-year term on the Council of the Society. Officers appointed by the Council are: Charles B. Heiser, Jr. (Indiana University), Chairman of the Council; Lawrence R. Heckard (University of California, Berkeley), Secretary; Richard W. Pohl (Iowa State University), Treasurer.

The Council also appointed Peter H. Raven (Stanford University), Editor-in-Chief of Brittonia; H. W. Rickett (New York Botanical Garden), Managing Editor of Brittonia; Constantine J. Alexopoulos (University of Texas) and Cornelius H. Muller (University of California, Santa Barbara), to serve on the editorial board of Brittonia; A. E. Radford (University of North Carolina), Representative of the Society on the editorial board of the American Journal of Botany; Richard S. Cowan (U. S. National Museum) and A. C. Smith (U. S. National Museum), Representatives of the Society on the Council of the AAAS; Reed C. Rollins (Harvard University), Representative of the Society on the Governing Board of the AIBS; David D. Keck (National Science Foundation), Representative of the Society on the National Research Council.

The SOCIEDAD BOTANICA DE MEXICO announces that its Second Mexican Botanical Congress will be held September 17-20, 1963 at the Universidad Aut6noma de San Luis Potosi in the city of San Luis Potosi, Mexico. The Society will welcome attendance and participation by anyone interested in the botany of Mexico. There will be one or more field trips accompanying the meetings. Further information may be obtained from the secretary, Biol. Fernando Medellin, II Congresso Mexicano de Botānica, Apartado Postal No. 458, San Luis Potosi, S. L. P., Mexico.

THE PALYNOLOGICAL SERVICE of the Swedish Natural

Science Research Council is associated with the Palynological Laboratory, Nybodagatan 5, Solna, Sweden. This service was established to assist scientists and scientific institutions concerned with pollen slides, diagnoses of pollen grains and spores, photomicrography, and microtechnicalpalynological questions. Pollen slides are for sale at rates varying between 2 and lc) Swedish crowns in Scandinavia, and 4 and 20 Swedish crowns outside of Scandinavia. Charges for photomicrography and other services depend upon the circumstances in each special case. Ordinary pollen analyses are not regularly carried out, but help may be given in the identification of pollen grains and spores.

THE Fossil, FLORAS OF ANTARCTICA by Edna Plumstead was published in December 1962. Orders or inquiries for this illustrated volume may be sent to Sir Vivian E. Fuchs, The Trans-Antarctic Expedition, 22 Gayfere Street, London S. W. 1, England.

Herbarium specimens from the GREENE AND NIEUWLAND HERBARIA of the University of Notre Dame are now avail-able on loan to botanists. The usual period of loan is six months, subject to renewal upon request. Dr. Robert P. Mc-Intosh, Curator, has noted that loans will normally be made to any research investigator. Students requiring loans for research will need to apply through the director of their research, the curator of an affiliated herbarium, or a responsible staff member of their institution.

The ANNUAL SUMMER CONFERENCE OF THE BIOLOGY DEPARTMENT OF BROOKHAVEN NATIONAL LABORATORY will take place June 3-5, 1963 and will be devoted to the topic,

MERISTEMS AND DIFFERENTIATION. Those planning to attend should notify Dr. J. P. Miksche by May io, 1963 addressing

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him at the Department of Biology, Brookhaven National Laboratory, Upton, L. I., New York.

A newly created BONSAI SOCIETY OF GREATER NEW YORK

has been established at the New York Botanical Garden. Presently, membership is open only to residents of metropolitan New York City, but future plans call for forming a national and eventually international organization. In-formation may be secured by writing to the Society at the Garden, Bronx Park, New York 58, New York.

The committee on the DARBARER PRIZE OF THE BOTANICAL SOCIETY OF AMERICA will accept nominations for an award to he announced at the annual meeting of the Society at Amherst, Massachusetts, in 1963. Under the terms of the bequest, the award is to be made for "meritorious work in the study of the algae." Persons not members of the Botanical Society are also eligible for the award, but at present, the award will be limited to residents of North America. The committee will base its judgment primarily on the papers published by the nominee during the last two full calendar years previous to the closing date for nominations. Only papers published in the English language will be considered. Nominations for the 1963 award accompanied by a statement of the merits of the case and by reprints of the publications supporting the candidacy should be sent to the Chairman of the Committee, Dr. Jack E. Myers at the University of Texas, in order to be received by June 1, 1963. The value of the Prize for 1963 will depend on the income from the trust fund, but is expected to be about $250.00.

PERSONALIA

DR. OSWALD Tippo, Provost of the University of Colorado, has been appointed Executive Dean at New York University effective June 1, 1963. Dr. Tippo, a past-president of the Botanical Society and former editor of the American Journal of Botany, will have charge of the Washington Square College of Arts and Sciences, the College of Arts and Sciences at University Heights, and the Graduate School of Arts and Sciences. He will also be a professor of biology. Tippo will spend the first few months in his new position as assistant to Chancellor George D. Stoddard before assuming the newly created post of Executive Dean in September.

During the past year, PROFESSOR CARL L. WITHNER, Brooklyn College and Brooklyn Botanic Garden, was on' sabbatical leave as a Guggenheim Fellow. He has returned from three months traveling in South America where he collected orchids, and visited a variety of orchid collections in Venezuela, Brazil, Peru, Ecuador, and Colombia. During July, 1962, Professor Withner also spent three weeks in Mexico. Presently, Professor Withner is on leave from Brooklyn College to teach plant physiology and general biology at Stanford University. He has recently been promoted to full professor at Brooklyn College.

DR. EDMUND H. FULLING was awarded the Mary Soper Pope Medal at recent meetings of the AAAS in Philadelphia. The Medal is awarded from time to time "._for noteworthy and distinguished accomplishment in the field of plant sciences." It is administered by the Trustees of the Cranbrook Institute of Science. The citation to Dr. Fulling reads, "This year, 1962, it is our privilege to designate Dr. Edmund Henry Fulling, editor of The Botanical Review, and to draw the attention of our colleagues in science to the career of a dedicated and perceptive man who has served the scientists of his time in an exceptional manner." Dr. Fulling is Honorary Curator at the New York Botanical Garden, and founder of both The Botanical Review and Economic Botany.

During February and March, the EDITOR, in company with DR. RICHARD H. EYDE and MR. EDWARD S. AYENSU of the Division of Plant Anatomy, Smithsonian Institution, spent six weeks in Panama collecting specimens of petrified woods from Tertiary deposits on the Azuero Peninsula. Besides fossils, conventional botanical specimens were gathered together with wood samples for deposit in the National Collections.

DR. EDWARD F. ANDERSON of Whitman College has been awarded a grant-in-aid for study of the taxonomy of desert plants by the Henry E. Huntington Library and Art Gallery.