Part 39

One of the most remarkable minds that has ever applied itself to medical problems was that of the Quaker physician Thomas Young (1773-1829). He was a man of immense learning, and is remembered for having been the first to decipher Egyptian hieroglyphics. Young explained the power of the eye to ‘accommodate’ for near vision. This faculty of ‘accommodation’ was, he showed, due to changes in the curvature of the crystalline lens (Fig. 132). In his memoir On the Mechanism of the Eye (1801), Young gave the first scientific account of Astigmatism. His theory of color vision and his doctrine that light is due to waves in the ether are still important. His ‘wave theory’ of light completely replaced the old view, the so-called ‘emission theory,’ that light is due to something material which goes forth from the luminous object. While we are referring to Young we may remind the reader that his work on ‘Energy’ lies at the back of all modern Physics, in the history of which he takes an extremely important place.

The operative treatment of the eye is of great antiquity. The most important operative procedure is that for ‘cataract,’ a condition caused by an opacity of the lens. ‘Couching’ for cataract, that is depressing the opaque lens, was practised by Alexandrian surgeons in the third century B.C. It is described by Celsus (p. 43) in the first and mentioned by Galen (p. 50) in the second Christian century. Contemporary with these authors are descriptions of the actual extraction of the lens affected with cataract.

In Imperial Roman times there were surgeons who devoted themselves exclusively to cataract operations. These were practised during the Middle Ages by the Arabs and to a less extent by the Westerns. For the most part the operations were performed by wandering quacks, who were, however, often very skilful. In the sixteenth century operations on the eye began to pass into the hands of recognized medical practitioners. The advances in the knowledge of the anatomy and physiology of the eye in the eighteenth century enabled the French surgeon Jacques Daviel (1696-1762) to explain the real nature of cataract, which is usually nothing but a senile change in the lens of the eye. His knowledge made it possible for him greatly to improve the operation for extraction, so that, over a large range of cases, he had only 11 per cent. of failures.

The modern era of ophthalmic surgery was ushered in by Donders (p. 319), von Helmholtz (pp. 213 and 319), and Albrecht von Graefe (1828-70). The last was a professor at Berlin who greatly improved the operation for cataract and introduced or improved many other important operations on the eye. He was one of the first to make important clinical observations with the ophthalmoscope, and he showed how the instrument may be made to yield information not only of the condition of the eye itself, but also of the brain and of its membranes, an application which has become of the greatest value in later medical developments. Though he died before the most important work of Pasteur and Lister had become generally accepted, von Graefe was yet practising a system of surgery which was not far from aseptic.

As with most departments of Medicine, so also with Ophthalmology, the most significant advances during the last generation have been in the direction of prevention rather than cure. Prominent among these measures are, firstly, school inspection with the consequent early detection and isolation of infectious cases of conjunctivitis; secondly, maternity welfare accompanied by prompt notification and treatment of the very dangerous and sight-destroying ‘Ophthalmia of the New-born’; thirdly, improved light regulation in factories and schools; and, fourthly, adequate provision of spectacles for school children with errors of vision.

The recognition of the infectious character of the very chronic and sight-destroying disease known as Trachoma, or ‘Granular Conjunctivitis,’ has been of great importance for the Public Health. The disease is common in the near East and in Eastern Europe and by no means rare in slum quarters in the West. A rigid system of inspection of immigrants, together with quarantine combined with treatment, has done much to diminish its ravages in the United States.

§ 20. Investigation of the Nature and Action of Drugs.

(a) Entry of Vegetable Drugs into the Pharmacopoeia.

An examination of the list of drugs that are in use at the present day--apart from those which have been introduced by the scientific movement of the last generation--yields some surprising results. Some thirty per cent. of the crude vegetable drugs in the modern official Pharmacopoeia were known in remote antiquity. The Egyptian medical papyri mention, among others, Aloes, Caraway, Castor Oil, Coriander, Dill, Fennel, Juniper, Mint, Myrrh, and Turpentine. Among Egyptian mineral remedies still in use are salts of copper and of lead. Assyrian medical tablets refer to most of the Egyptian drugs as well as to a number of others, among which are Almond Oil, Aniseed, Galbanum, and Liquorice. Among Assyrian mineral remedies that are used by us to this day are Alum and Bitumen. Early Indian medicine had a very copious pharmacopoeia. Cannabis indica, known as ‘Hashish’ or ‘Indian hemp’, Cardamoms, Cassia fistula, Datura stramonium, and Nux vomica are among the valuable Indian herbs now in use in scientific medicine, while Mercury preparations were perhaps ultimately of Indian origin.

The medical herb lore of the Greeks comes to us chiefly from Dioscorides (p. 43), who mentions about five hundred plants. A large number of these are still in our own Pharmacopoeia. Among these, besides those of Egyptian, Assyrian, and Indian origin, are Ammoniacum, Belladonna, Camomile, Catechu, Cinnamon, Colchicum, Colocynth, Crocus, Galls, Gentian, Ginger, Hyoscyamus, Lavender, Linseed, Male Fern, Mallow, Marjoram, Mustard, Poppy, Rhubarb, Sesame, Stavesacre, Storax, Terebinth, Tragacanth, and Wormwood. About thirty-seven per cent. of our Pharmacopoeia was known to the later Greeks. From them the Arabs derived, adding, however, enormously to their drug-lists, so that we may say that about fifty per cent. of our drugs were in use by the Arabic-speaking physicians of the Middle Ages. With the discovery of America further important additions were made. Of these we have already discussed the introduction of Cinchona, Ipecacuanha, and Tobacco (p. 95). Few important additions were made in the eighteenth century, though among them was Digitalis (p. 328).

(b) Active Principles.

One of the things that separate the practice of Medicine of our time from that of previous ages is our power to give drugs in ‘pure’ form. This means not only that we can secure drugs without adulteration, but also that the active substances in drugs can be chemically isolated and given without admixture. Most drugs used in Medicine are, in fact, of vegetable origin. The possibility of giving them in chemically pure form depends upon the discovery, early in the nineteenth century, that plants owe their poisonous and remedial properties to small quantities of Active Principles, which are susceptible of chemical extraction and isolation. Thus the science that deals with the action and nature of drugs, Pharmacology, really took its rise about a hundred years ago, though many had experimented with drugs at an earlier date.

Further progress in the same direction has been made by the so-called ‘synthetic’ preparation of drugs. Certain substances of vegetable origin do not readily yield their active principles and to extract them very complex chemical processes may be involved. There are special obstacles to the complete purification of other drugs, even when they have been obtained in a relatively pure state. These difficulties can sometimes be surmounted by the preparation of the drug from inorganic materials. This synthetic process of preparation is now possible for many substances that are of medical application. Furthermore, when a drug can be thus synthetically prepared, it is often possible to try chemical variants upon it, and thus to obtain a more effective preparation.

In former times a vast number of drugs were habitually employed by physicians, and they were often given in very complicated prescriptions. ‘Polypharmacy’, the giving of many drugs, is a vice from which Medicine has now in large part freed itself. The number of drugs given by scientific physicians is far fewer that it was. For this there are several reasons. Firstly, many drugs were found useless for the purpose for which they were administered, and were at times even dangerous. Secondly, since attention has been drawn to the active principles of drugs rather than to the crude natural drugs, it has been seen that, in fact, many of the drugs that were being given were merely duplicates one of another, and that often the administration of the active principle itself was more effective and more reliable than that of the source from which it was obtained.

What then is the nature of the drugs now being administered by scientific physicians? They fall into a number of classes. The nature and action of some of these is so simple that no prolonged discussion of them is necessary. There are, for instance, the inorganic acids and alkalis, the primary action of which, when taken internally, can be determined by a series of experiments on gastric juice in a test-tube kept at body temperature. Again, there are soluble inorganic salts, which are absorbed unchanged from the alimentary canal. These have the effect of increasing secretions. Their purgative effect is well known, though the physiological details of their action are not yet clear. There are yet other substances, such as metallic Mercury in ‘grey powder’ or Bismuth, which act mechanically, even when administered internally. Over and above these simpler substances, and in addition to the traditional vegetable substances which have been in use as medicines for centuries, there are others which have only been accessible during the last few generations. We have already discussed under separate headings the derivatives from animal glands, such as of the Thyroid (p. 305), of the Adrenals (p. 307), or of the Pancreas (p. 306), as well as the bacterial Vaccines (p. 261) and Antitoxins (p. 267). We now turn to pure chemical substances of vegetable origin. Of these mention may be made especially of the groups known as the Alkaloids and the Glucosides.

(c) The Alkaloids.

By ‘Alkaloid’ is understood a nitrogenous substance, usually of vegetable origin, which forms salts with acids. The alkaloids are mainly obtained from the dicotyledonous plants. Generally they occur in nature in combination with plant acids such as citric or tartaric acid. The alkaloid group contains some of the most important drugs that we possess. Among them are Morphine, Strychnine, Cocaine, Atropine, and Quinine.

The investigation of the alkaloids began with the nineteenth century. Morphine was isolated from Opium by the Parisian apothecary Charles Derosne (1780-1846) in 1803. He failed, however, to recognize its chemical affinities, which were first grasped by the German apothecary Adolf Sertürner (1783-1841). Their work, however, attracted but little notice until attention was drawn to it by the great French chemist Joseph Gay-Lussac (1778-1850), in 1817. The result was the concentration of much scientific ability on the alkaloids. Prominent among the early investigators were the French pharmacologists Pierre Joseph Pelletier (1788-1842) and Joseph Caventou (1795-1878). Between 1818 and 1820 they isolated from Cinchona (p. 95) certain alkaloids allied to Quinine, from Nux vomica the alkaloid Strychnine and certain of its allies, and from Coffee the alkaloid Caffeine. Pelletier in conjunction with the distinguished chemist Jean-Baptiste Dumas (1800-84) followed this by a quantitative examination of a number of alkaloids in 1823. The first alkaloid to be used as such in medicine was Strychnine. It was introduced in 1821 by the French physiologist François Magendie (1783-1855), the teacher of Claude Bernard.

In the thirties and forties of the nineteenth century Liebig, who had developed his doctrine of radicles (p. 206), attempted to determine the formula of alkaloids. He was followed by Wöhler (p. 206). Since then an immense amount of work has been done in investigating the chemical nature and physiological action of alkaloids. The general result has been to reveal the fact that each alkaloid-yielding plant contains not one but a number of alkaloids. Those from the same plant often have similar but not identical action upon the animal body. The differences in physiological action of allied alkaloids have occupied much of the attention of pharmacologists. The accurate knowledge of these differences has made possible a far greater finesse in the administration of alkaloid drugs than was previously possible. Some alkaloids can be prepared synthetically, but the process is mostly of theoretical rather than practical importance.

(d) The Glucosides.

The Glucosides are an ill-defined group which have in common the property of yielding a sugar-like substance--usually glucose itself--as a result of certain chemical processes. They are mostly of vegetable origin and the history of their investigation has been parallel with that of the alkaloids. The first glucoside to be isolated was Salicin, which was obtained from willows in 1819. It is the active principle of the very ancient remedy for rheumatism, ‘Oil of Wintergreen’. Salicylic acid was introduced into Internal Medicine in 1873 and its derivative, Aspirin, in 1899. Both drugs are of great importance, and many other derivatives of Salicin are in use. Salicin and its derivatives can be prepared synthetically, and the synthetic products are in use in Medicine.

Of all the glucoside-yielding plants, perhaps medically the most important is the Foxglove, Digitalis purpurea. The use of the plant was known to some of the medieval herbalists, and is, moreover, recommended in the German and English printed herbals of the sixteenth and seventeenth centuries. Foxglove is mentioned as a folk remedy in George Eliot’s Silas Marner, the story of which refers to a period round about 1750 before the Industrial Revolution, ‘when the spinning-wheels still hummed busily in the farm-houses’ (Fig. 89). It was introduced into scientific Medicine in 1785 by William Withering (1741-99) of Birmingham in his Account of the Foxglove, which gives details of numerous cases treated with it.

Digitalis long resisted the attempts to extract an active principle, but since the seventies it has yielded to investigators a whole series of glucosides. Digitalis and its derivatives have become of much importance, especially in the treatment of cardiac conditions. Despite the success in obtaining glucosides from the Foxglove, the extract of the plant itself continues in wide use.

(e) The Study of Pharmacology.

Since the middle of the nineteenth century the investigation of the physiological action of drugs has been mainly in German hands. The most prominent exponents of the method have been Karl Binz (1832-1912) and Oswald Schmiedeberg (1834-1921), both professors at Dorpat, where there has been a pharmacological laboratory since 1849. The first pharmacological laboratory in America, that at Ann Arbor established in 1893, and the first in England, that at University College, London, established in 1905, were successively occupied by A. R. Cushny (1866-1926). The work of these and of other pharmacologists has not tended to increase but to reduce the number of drugs. Nevertheless, some new drugs of great importance have been introduced by them. Of these, among the more valuable is Amyl nitrite, the inhalation of which was first recommended by T. Lauder Brunton (1844-1916) as early as 1867 as a remedy in certain cases of sudden heart seizure.

Improvements have been made not only in the drugs themselves but also in modes of administration. The ancient methods of inunction and inhalation, as well as other older methods, have been greatly elaborated in modern times, and are now of wider application than they were. No advance of this order compares in importance with the introduction of the Hypodermic Syringe by the ingenious French surgeon Charles Gabriel Pravaz (1791-1853). By means of this instrument various drugs can be injected directly into the subcutaneous tissues or into the veins. This mode of administration is more accurate and under better control than any other, and the action of the drug so injected is swifter and more sure.

(f) Chemotherapy.

During the twentieth century the outlook on drug treatment has been modified by the success obtained in the specific treatment of certain diseases, that is to say, treatment by remedies which strike at a particular disease and no other. Until quite recently scientific Medicine recognized very few specific remedies. It had been ascertained that Cinchona owes its value in Malaria to the alkaloid Quinine (p. 326), which acts as a specific exterminator of the malaria parasites, and not simply as a remedy for fever in general. It had also been ascertained that Ipecacuanha owes its value in tropical Dysentery to the alkaloid Emetine, which acts similarly as a specific exterminator of the protozoal organisms which are the infective agents. Quinine and its allied alkaloids and Emetine and its allied alkaloids were practically the only specifics the value of which had been scientifically proved, except Mercury for Syphilis.