306 Transactions. 



that received 10 mlgm. per kilo, one died, and both the others showed con- 

 vulsions and were very ill for more than twenty-four hours. Severe symp- 

 toms were also present with 9 mlgm. per kilo. It was noticed that frogs 

 experimented upon in the winter were more susceptible to the poison than 

 those used in the summer. 



The relatively high lethal dose of tutin in frogs may have some connection 

 wdth their mode of respiration. To a large extent this is cutaneous, and 

 therefore a drug such as tutin, which owes its lethal power largely to its in- 

 fluence on the respiratory centre, might a priori be expected to be less lethal 

 to these animals than to those that have only a lung-respiration. The fact 

 that lizards, which have a dry skin and presumably only a slight cutaneous 

 respiration, succumb to about one-third the lethal dose for frogs points in 

 this direction. 



Even with large doses the course of events in frogs is comparatively slow. 

 For example, in Exp. 54, where about 60 mlgm. per kilo was given, the 

 animal lived for an hour and a half. 



5. Action on Fishes. 

 (a.) General Action. 



There is an advantage in using small fishes to test the pharmacological 

 action of drugs, because large numbers can be dealt with, and thus the 

 factor of idiosyncrasy, which so often confuses results, is in great measure 

 eliminated. Moreover, fishes can be placed in a watery solution of the 

 drug, and the symptoms and time taken to kill easily noted. Eecently 

 SoUmann (26) has used funduli and sticklebacks in this way, and suggests 

 that the method might be used to study the antagonism of diaigs. 



In the first experiments of this kind undertaken by the present writer 

 young trout prociu'ed from a fish-hatchery were used. The fry were kept 

 till required in a trough with an overflow, placed beneath a running tap, and 

 were fed on fresh minced liver. The experiments were carried out in the 

 following way : 60 or 100 c.c. of tap-water, to which a solution of tutin had 

 been added in definite quantity, were placed in a small wide beaker, and 

 the fish transferred to it. Several beakers containing various strengths of 

 tutin, and one beaker containing tap-water only, as a control, were set on 

 together, and watched at intervals during the day. 



Symftoms. — The young trout were about 1 in. to 1^ in. long, and in 

 good condition. When first placed in the test-beakers they became very 

 excited if the tutin solution were strong. After a period of excitement, 

 during which rotatory movements on the long axis of the body were fre- 

 quently seen, they became quieter, and then it was noted that the gill- 

 movements were much exaggerated. After a time they lost their power of 

 maintaining equilibrium, and lay on one side gasping. From this position 

 they would frequently spring up and swim round the vessel, still on the side, 

 and then resume their position on the bottom. Shortly before death they 

 often turned belly upwards. 



Minimum Lethal Dose. — In order to determine the minimum lethal 

 dose, solutions of different strength were tried, and the results are given in 

 the next table (Table III). 



In these experiments the quantity of fluid used was small. Death 

 frequently occurred in the control when the experiment lasted over twelve 

 hours. But the results show that the fatal effects begin when the per- 

 centage is about 0-001, and are very definite at 0-004 per cent. This cor- 



