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Rh the subject has more recently made rapid advances, due largely to the creation of new laboratories and the institution of new chairs devoted to pharmacological research. The chief impor- tance of the work lies in the application of the knowledge gained of the physiological action of drugs to the treatment of disease in man and animals; and, though there have been periods when this branch of therapy in spite of its antiquity and persistence has been suspect, recent research leading to new, more accurate, and more scientific use of drugs has placed the subject in a posi- tion so indubitable that the time is not in sight when the practice of medicine or surgery will be able to dispense with its services.

The main directions of recent advances in knowledge may be indicated. The action of familiar drugs becomes daily more ac- curately known, leading to a juster estimate of their value and greater precision in the use of them in disease. New remedies are being introduced and older remedies superseded. The enormous development of synthetic chemistry has furnished many potential remedies, all of which are now subjected to pharmacological in- vestigation before they are used on man. One relatively recent development which has proved fruitful in results of great practi- cal importance in the treatment of disease is that of experi- mental therapeutics, where the cure of disease artificially pro- duced in experimental animals is investigated. So far this has been most successful in the case of experimental trypanosomi- asis, largely owing to the ease with which a disease of this nature can be induced in laboratory animals and the constancy and certainty of its duration.

Here only such developments of pharmacology need be men- tioned as have already passed from the by-way of mere academic interest into the highroad of practical application.

Of the simpler saline compounds the familiar Epsom salts mag- nesium sulphate-^has been found to have more interesting actions than that for which it is generally used. When given as a purgative very little of it is absorbed into the blood, owing to the difficulty which both magnesium and sulphate ions experience in passing through membranes like the lining of the gut. But if injected hypodermically or intravenously in sufficient quantity it has a powerful action on the nervous system, causing a kind of motor paralysis and anaesthesia. This effect of magnesium for the sulphate ion takes no part in it has been utilized in the treatment of tetanus, in which condition magnesium salts have been injected intraspinally, with benefit in many cases in so far as the relief of symptoms is concerned. This depressant action of magnesium on the nervous system is antagonized in a dramatic way by calcium salts; an animal paralysed by magnesium being restored, in suit- able cases, to a normal condition in a few seconds by intravenous injection of a soluble calcium salt.

Of the heavy metals arsenic and antimony have in recent years claimed most attention. Both arsenic and antimony have been used empirically in the treatment of syphilis for over a century but with- out having any great vogue. When it was discovered that organisms of the trypanosome type are the cause of syphilis and of many tropi- cal diseases, and that arsenic is a powerful poison for such organisms, an experimental justification for the employment of this substance in the treatment of syphilis was furnished. The drawback to its use was that it is so poisonous to higher animals that it is difficult to get into the blood a concentration of arsenic sufficient to kill the para- sitic organisms there present without injuring the host. It was found, however, that certain organic compounds of arsenic could be made which were very much less poisonous for mammals though their toxicity for trypanosomes was retained or enhanced. Pursuing this line of investigation of a large number of arsenical compounds Ehrlich eventually discovered and recommended, as a result of animal experiments, salvarsan as a remedy for syphilis. The value of salvarsan and of nearly related compounds in the treatment of syphilis is now common knowledge. One interesting point in regard to this is that those unicellular organisms of that type which causes syphilis readily become immune to the action of arsenic. It is there- fore possible that, with the almost universal use of salvarsan now- adays, strains of syphilitic infection may be developed which are immune to arsenic ; and for people infected with syphilis from these sources arsenical compounds like salvarsan would no longer have any remedial value. The risk of this unfortunate sequel is small be- cause usually salvarsan treatment renders the patient no longer liable to infect other people and only in this way could an " arsenic- fast " infecting organism be produced, but the risk would seem to be not negligible. Fortunately no such immunity to mercury occurs.

The fact that antimony belongs to the same chemical group as arsenic suggested the possibility that it, too, might be valuable in these diseases and pharmacological investigation showed that antimony has for trypanosomes a toxicity superior even to that of arsenic. Though no organic compound of antimony has been dis-

covered comparable in advantageous properties with the salvarsan compound of arsenic, the familiar tartar emetic (potassio-tartrate of antimony) has been found, when administered intravenously, adequate for the treatment of two important diseases, Kala-Agar and Bilharzia diseases due to organisms different from trypano- somes and for which no other effective remedy is known. These dis- coveries have led to a revival of the use of antimony in medicine; in the I7th and i8th centuries especially, antimony was regarded almost as a panacea, but later it lost a prestige which it is now regaining.

One of the established pharmacological actions of lead is to stimu- late involuntary muscle of every kind, as exemplified in cases of industrial poisoning by the occurrence of colic caused by irregular and spasmodic contraction of the muscle of the bowel. While lead- poisoning tends to become less common, owing to trade precautions and earlier recognition of it, stress has been laid on the frequency with which lead is used, especially in industrial districts in the N. of England, to procure criminal abortion, which it tends to do -though only in poisonous quantities by the irritant action of lead on the muscle of the uterus. For this purpose lead plaster, which is easily procurable by the laity, is frequently used by ingestion.

Of the simpler derivatives of benzol, carbolic acid itself, which was first employed by Lister as an antiseptic now over half a century ago, has gone largely out of use, especially as a surgical antiseptic, though certain closely related compounds have important antiseptic uses. Thus benzoic acid and benzoates are very widely used as antiseptics in preserved foods and are, so far as careful experiments have shown, harmless in the quantities used for this purpose. Salicylic acid has come to be a favourite antiseptic for many infective skin diseases.

The group of antipyretic derivatives of benzol continue to be widely employed not so much for reducing febrile temperatures as for their action in relieving pain, which they effect by a paralysing action on that part of the brain which is responsible for the percep- tion of pain. A large number of new compounds of this type have been investigated but so far only one of them threatens to usurp the supremacy of the older phenacetin and antipyrine, namely aspirin. Aspirin is a compound of salicylic acid and acetic acid. Salicylic acid and its compounds have a very important, and partly specific, effect in rheumatic fever in which they relieve the pain and reduce the temperature; but aspirin is more effective in relieving non- rheumatic pain such as headache. It is a relatively harmless drug; but occasionally alarming, if not serious, symptoms are produced by it in people specially susceptible to its action, the most frequent symptom being oedematous swelling of the face, which, however, disappears when the drug is discontinued.

Though much new work has been done on the effect of moderate doses of alcohol, little has been added which was beyond the shrewd suspicion of those who have intelligently experienced its effects throughout the ages. That it has killed more than it has cured is more than probable; that, if the imperfection of human nature per- sists, alcohol, if it is banished, will be replaced by something worse is not unlikely. Numerous new artificial hypnotics have been inves- tigated, of which veronal, legitimately used, has proved safe and efficient. Unfortunately cases of veronal habit have become in- creasingly frequent, and deaths from overdosage, of which the lay papers have afforded numerous examples in recent years, must have served to warn the general public of its dangers.

Of the general anaesthetics ether has steadily gained in favour for routine purposes. To get rid of its irritant action on the lungs and bronchi, it has been administered in limited cases intravenously and by rectal injection, but experiments are in progress which may result in the discovery of an anaesthetic ether deprived even of the slight drawbacks which at present attach to it.

With regard to the great group of alkaloids, much light has been thrown in recent years both on their chemical constitution and their exact pharmacological actions, and no apology need be made for taking the alkaloids of opium first. These can be divided chemically into two groups, of which morphine is representative of the one and papaverine of the other. The two groups differ considerably in their actions, as might be expected. The papaverine group has a much more pronounced action than the morphine group in relieving spasmodic contraction of smooth muscle a pharmacological ex- planation of the clinically observed fact that preparations of opium, which contain a mixture of the alkaloids, are better for relieving colic, for example, than pure morphine. Preparations like tincture of opium have long been used for the relief of pain by external applica- tion, in spite of the fact that pharmacological evidence was against its having any action on the sensory nerve ends, but more recent and exact research has shown that some of the alkaloids have a distinct local anaesthetic action, apart from the effect they have in relieving pain by an action on the central nervous system.

The stimulant action of caffeine on the higher functions of the brain is recognized in the world-wide practice of consuming beverages, such as tea and coffee, which owe their stimulant action to the caffeine that they contain. But caffeine also stimulates the kidney and causes an increased flow of urine. Caffeine is chemically a tn- methyl-xanthine and two closely allied compounds, theobromine and theophylline dimethyl-xanthines are more powerful diuretics while having less effect on the central nervous system. They are used, in preference to caffeine, where diuretic action alone is desired.