Minimal Lethal Dose of various Toxic Substances. 327 



In proof of this, attention must be drawn to the fact that it is not always 

 the larger species which are more susceptible than the smaller species to 

 dosage proportional to their relative body surface, or even to their relative 

 body weight. Sometimes the conditions are reversed. Thus, as is well 

 known, a horse infected with tetanus may be found in apparently excellent 

 condition and as yet exhibiting no symptoms of the disease at a period when 

 its blood already contains enough tetanus toxin to kill a guinea pig injected 

 with only a few cubic centimetres of the horse's serum. Similarly in the 

 case of rats and guinea pigs, rodents of about the same size, the rat can resist 

 several hundred times the dose of diphtheria toxin which will be fatal to the 

 guinea pig within a few days. 



In the case of substances other than bacterial toxins similar examples 

 showing a greater resistance in the larger species than in the smaller can 

 readily be found, as for instance in the experiments of Meurice, already 

 referred to (9), in Bock's experiments (21) with cobalt compounds, in 

 Jodlbauer's paper on Tetramethyl ammonium chloride (22), in Eraser and 

 Elliott's experiments on Cobra venom and on Enhydrina venom (14), and 

 in many other pharmacological investigations. It follows that drug suscep- 

 tibility is by no means necessarily greater in the larger species than in the 

 smaller, but on the contrary it is frequently less. Accordingly, any general 

 explanation of drug action in different species of animals, which is based upon 

 the relative size of their surface, cannot be maintained. Only within one and 

 the same species of animal will the surface relation prove a l'eliable guide in 

 dosage. 



In this connection it is of some interest to consider briefly fornmk-e for 

 dosage in the human subject such as have been made use of or suggested by 

 various writers. For the sake of ease in calculation these have usually been 

 based on the age of the patient, and most of them appear to aim at giving 

 dosage in relation to the body weight. 



But in the case of the formula of Thomas Young, 1813, we meet the earliest 

 example of dosage calculated so as to give younger individuals a relatively 

 greater dose per unit of body weight than is given to adults. Young wrote 

 that " for children under twelve years old, the doses of most medicines must 

 be diminished in the proportion of the age to the age increased by twelve : 

 for example at two years old 1/7 = 2/(2 + 12). At twenty-one the full dose 

 may be given. Y." (23). 



We owe the exact reference to the kindness of Dr. A. J. Jex Blake ; but 

 how Young arrived at his formula, Age/(Age + 12), it has not been possible 

 to discover from his writings. However this may be, his formula actually 

 gives for all ages from about four or five to about 16 a dosage fairly 



VOL. LXXXVII. — B. ■ 2 B 



