HORMONES, DRUGS, AND TOXINS 725 



with ' chemo-receptors ' for all of these numerous cases, one mystery is merely 

 changed into another. The existence of chemo-receptors for poisons is not to be 

 denied, but this is not a universal fact, and therefore no general theory can be 

 based upon it." There are also some definite experimental facts which show that 

 it does not apply to certain typical cases. Straub himself (1907) has shown that 

 the action of muscarine on the heart of Aplysia, and Neukirch (1912) that the 

 action of pilocarpine on the mammalian intestine, are absent after the drug has 

 entered the cells, and are only manifest when it is in the act of either entering or 

 leaving. Further, Neukirch (p. 166) shows that no perceptible diminution in the 

 strength of dilute solutions of pilocarpine is produced by the lying of the intestine 

 in them, a fact difficult to understand if it were taken up in chemical combination 

 in the cells. 



Additional interesting facts come out in the investigations of Straub (1910) 

 on strophanthin, a glucoside of the digitalis group. When injected into the 

 organism, its action is most marked on the ventricle of the heart, next on the 

 other heart cavities, and finally on the blood vessels. The active doses are 

 extraordinarily small. Straub had previously found that the action of alkaloids 

 is reversible, in that they can be regained from the organs which had stored 

 them up, by simple washing with water. But on testing the case of strophanthin, 

 he found that it could not be regained by washing out. It seemed possible that 

 it had entered into a definite chemical compound with the heart muscle, or 

 some constituent thereof, although it is difficult to see what kind of a compound, 

 undecomposed by boiling, such a chemically inert substance as a glucoside could 

 form with cell materials. On this account Straub thinks it always necessary to 

 test other possibilities before making the assumption of a chemical union. On 

 proceeding to investigate the question further, the unexpected result was obtained 

 that, contrary to the case of the alkaloids, the reason why no glucoside could be 

 extracted from the cells was because there was none there. The cells had not 

 taken it up at all. Thus, if 1 c.c. of a solution containing O'Ol mg. of the drug, 

 which is sufficient to produce a powerful action without killing the ventricle, 

 be perfused backwards and forwards, it is found, by applying it to a second heart, 

 that it is quantitatively as powerful as at first. The method of measurement 

 was carefully worked out, and will be found in the paper. It was also found 

 that the intensity of the action was always proportional to the concentration of 

 the solution, not to the total amount present. It is obvious that some slight loss 

 must take place in such a powerful action, and, by repeated perfusion of a solution 

 through six hearts, it was found that each heart had used 0'002 mg. This amount 

 could not possibly be detected, and hence the reason why it seemed impossible to 

 wash any out, since there was none in sufficient quantity to be detected if it were 

 washed out. It is to be remembered that this quantity taken up by the heart would 

 have no perceptible action if applied to another heart. Straub is inclined to think 

 that the results show that an adsorption at the cell membrane is responsible 

 for the activity, since these glucosides are allied to the saponines, which have 

 great power of lowering surface energy, as we have seen. It will be remembered 

 that, in adsorption, the amount taken up is in proportion to the concentration, 

 just as the action of strophanthin was found to be ; and that a certain minimum 

 concentration would be necessary in order that the quantity necessary for action 

 should be adsorbed. 



On the view that the cell behaves as a " giant molecule " in the chemical sense, 

 it might be held that one molecule of an active drug would be sufficient to enter 

 into chemical reaction with a cell. It is possible to calculate from Clark's data 

 (1912), together with some which he has kindly given me, what must be the 

 molecular weight of the compound with which strophanthin combines. This 

 glucoside is favourable for the purpose, since it acts directly on the muscle cell. 

 Clark had a more powerful preparation than Straub's, and found that 0*00008 mg. 

 was sufficient to act on 5 mg. of heart muscle (dry weight). The molecular weight 

 of strophanthin is 922, so that a simple proportion gives us the result : 



0-00008 : 5 = 922 : x, 



