The adoption of this view of the causation of rheumatic fever opened up a new field of therapeutic research—and a hopeful one too; for of all diseases malarial fever is that over which drugs exer cise most control. Quinine cures ague. That is one of the best es tablished facts in the practice of medicine. Rheumatic fever being similar in nature and mode of production, there might, nay there ought to, be some drug capable of arresting its course as quinine arrests the course of an ague. That is the line of therapeutic research which the miasmatic theory of rheumatism opened up.
A striking fact in the natural history of the malarial fevers is that the trees which provide their cure grow best in countries and locali ties in which these fevers most prevail; nature seeming to produce the remedy under climatic conditions similar to those which produce the disease.
In rheumatism a low-lying, damp locality and a temperate climate present the conditions most favorable to its ()eminence. Looking about for a plant or tree which most flourishes under such conditions, that which most naturally presented itself was the willow—the various species of salix. Among the Salicacem, therefore, a remedy for rheu matism was sought. The bark of most willows contains a bitter prin ciple called salicin. This seemed exactly what was wanted. If the miasmatic theory of rheumatism were correct it seemed not improb able that salicin might exercise on the rheumatic poison the same destructive action that quinine exercises on the poison of ague, and might thus cut short the course of rheumatic fever. It was accord ingly tried. The results exceeded all expectation. It was in 1874 that the observations were begun; and early in 1876 the results were given to the profession. They were thus summed up : "1. We have in salicin a valuable remedy in the treatment of acute rheumatism.
"2. The more acute the case, the more marked the benefit produced.
"3. In acute cases its beneficial action is generally apparent within twenty-four, always within forty-eight, hours of its- administration in sufficient dose.
"4. Given thus at the commencement of the attack, it seems some times to arrest the course of the malady as effectively as quinine cures an ague, or ipecacuanha a dysentery.
"5. Relief of pain is always one of the earliest effects produced. " 6. In acute cases, relief of pain and a fall of temperature gener ally occur simultaneously" (Maclagan).
While these observations on salicin were being made, Kolbe, hav ing discovered a method of manufacturing salicylic acid (originally prepared from salicin) from carbolic acid, was bent on finding some use for it. First tried by surgeons as an antiseptic, it was also freely
experimented with by physicians in all sorts of diseases, but chiefly in those attended by fever. Its febrifuge properties were soon recog nized, and much that was favorable hoped from, and reported of, its action in typhoid fever, diphtheria, erysipelas, pymmia, etc. But it was soon seen that the disease in which it did most good was acute rheumatism.
Early in 1876, Stricker and Riess published a most favorable ac count of their experience of its employment in that disease. Their results were quite in accordance with those got from salicin.
The conclusions at which he had arrived are thus formulated by Stricker : "1. Salicylic acid appears to be a rapid and radical remedy in recent cases of genuine acute rheumatism of the joints.
"2. It is not injurious to the human organism when administered every hour in doses varying from 7,1 to 15 grains.
"3. It can be given in these doses for a longer time to young and strong individuals than to the old and feeble.
"4. In the latter it produces toxic symptoms more readily than in the former.
"5. The toxic symptoms vary in degree.
" 6. Those most commonly met with are noises in the ears, diffi culty of hearing, and diaphoresis; when these occur the administra tion of the medicine should be discontinued.
" 7. If salicylic acid be found to fully answer the expectations entertained regarding it, the internal administration of a certain quantity may be expected to prevent the occurrence of fresh attacks in hitherto unaffected joints, and also secondary inflammation of serous membranes, especially the endocardium.
"S. To prevent relapse, the medicine must be continued in smaller doses for some days after the termination of the main treatment.
"9. Salicylic acid is of doubtful utility in chronic articular rheu matism.
"10. It is not likely to be of use in gonorrhoeal or diarrliceal rheumatism, or in the polyarthritis attending septiccemia." Results so striking could not fail to attract attention. The new drugs were eagerly tried; observations were made on all hands; the journals in England, Germany, France, and America contained nu merous reports of cases of acute rheumatism treated by salicin and salicylic acid, and very soon it. became a matter of general acknowl edgment that these drugs possessed in a remarkable manner the power of shortening the duration and controlling the course of that disease.