an empirical law. Two of these intervening links were then described, first, the seat of the disease, and the seat of the action of the drug are the same; and second, the kind of action of both are the same. It was promised that a third link should be described by and bye. This third link has now been exhibited to you; it is the opposition of the action of the small dose to that of the large dose. These three links make plain to reason the connection between the links at each end. We have now a completed series of causation, and the law which was empirical becomes rational. The other simile was that of a triangular basis and a three-sided column erected upon it, with inscriptions on each side. This must now be enlarged into a hexagonal foundation and a six-sided pillar. The six sides have six principles engraved on them, to forget for the moment the historical order of their discovery, in the following succession:-On the first side "in poison there is physic." On the second side "identity of seat of action of disease and of drug." On the third identity of kind of action of disease and of large doses of the drug." On the fourth" similarity of the symptoms of disease and those of large doses of the remedy." On the fifth "contrariety of the action of small doses and large ones." And on the sixth "the dose of the remedy must always be within the limits of this contrary action." It may be asked, is there anything to guide our choice of a dose from among all those included within the range of the small dose action? This choice may be determined by reference : 1. To the drug, and its primary and subordinate actions, i.e. to the organs in which these actions take place. 2. To the disease, and its special nature and susceptibilities. For a drug to be a medicine it must have two actions in different doses: the action of the small dose must be contrary to the action of the large dose. This suggests the idea that for the virulent poisons -such as snake venom, arsenic, opium, &c., for which no antidotes are yet known, the best antidote may be very small doses of itself. The only opportunity I have yet had of putting this thought (an hypothesis in the useful sense) to a practical test is in respect to mercury. In a case of poisoning by this metal the third trituration of itself (the millionth part of a grain) was manifestly beneficial. The region of drugs as poisons in health, and as remedies in disease has been taken possession of. It is in part characterised by this-the hurtful action of drugs in health is perturbative; the curative action in disease is silent and peaceful. This is the geographical outline. The details are much "terra incognita within, which need to be explored. I am not prepared to enter into the investigation of the action of what are now familiarly known as infinitesimal doses. This part of the region is still mysterious. To a certain class of minds this mystery is its chief attraction. The haziness of its atmosphere renders it to them the valley of the enchantress, which has charms for such minds irresistibly attractive. But I will offer one observation. The action of really infinitesimal doses appears to be the converse of the action of the doses we have been occupied with to-day-one which is inappreciable in health, but perturbative, and sometimes curative in disease. My brethren, I ought to have concluded long ago. Suffer me to offer you my respectful thanks for your prolonged attention. If I have succeeded in carrying your minds along with mine, or if you shall hereafter be brought to view these objects in the light which has been attempted to be thrown upon them to-day, the time and attention will not have been unprofitably spent, and the day and the place will have become memorable to you. Farewell! June, 1873. Since this Essay was written I have received the 42nd Report of the British Association for the Advancement of Science' for the meeting at Brighton last year (1872), which contains a 'Report on the antagonism between the action of active substances, by Thos. R. Fraser, M.D., Secretary to the Committee consisting of Sir R. Christison, Bart., Dr. Laycock, and Dr. Fraser.' In this Report the results of experiments on the antidotal power of atropia (the active principle of belladonna) over the poisonous action of physostigma (Calabar bean) in rabbits and dogs are given. These results offer a confirmation to a certain extent of the conclusions drawn in this address as to the varied action of different ranges of doses of drugs. These experimenters found the limits within which sulphate of atropia can prevent the fatal effects of a lethal dose of physostigma. 0.005 gr. was too small, but "any dose ranging from 0.015 gr. to 5.2 grs." was sufficient. When the dose of physostigma was larger than the lethal dose, e.g. when twice the minimum lethal dose, the range was from 0.021 to 3.2 grs. When two and a half times the minimum, from 0.025 to 2.2 grs. When thrice the minimum, from 0.06 to 1.2 grs. And when three and a half times, from 0.1 to 0.2 gr. cessful antagonism could not be obtained above this dose." "Suc The conclusion of the Report contains an important statement: "An eminent authority in pharmacology has recently published the statement that the only method whereby the injurious action of a poison, absorbed into the blood, can be made to terminate is by the employment of such means as will cause or hasten the elimination of the poison. This statement, fortunately, does not accurately describe our remedial resources. The existence of so undoubted an example of physiological antagonism as that between atropia and physostigma shows that the toxic influence of a morbific agent may be directly opposed by a physiological antidote, and that recovery may be produced by influencing the abnormal conditions themselves, in such a manner as to cause their return to a normal state." July, 1873. |