654 



SCIENCE 



[N. S. Vol. XLI. No. 1061 



one was likely to cause changes in some struc- 

 ture not afFected by the antagonist, hence side 

 effects turned up to confuse the issue. This 

 trouble was due to the fact that more than one 

 function was affected and the criterion had 

 thus become complex. (2) A second difficulty 

 arose from differences in the point to which a 

 given action was referred. For example, Luch- 

 singer found that pilocarpine stimulated the 

 activity of the sweat gland of the cat to a point 

 above normal activity, while atropine brought 

 it helow the normal rate. In carefully adjusted 

 doses of physiological equivalents, the result- 

 ant action was a normal rate. Here the point 

 of reference was the normal rate of activity 

 and activities could be counted as plus or 

 minus. When, however, Einger tested the 

 action of atropine and muscarine on the beat 

 of the isolated frog's heart another type of 

 situation developed. When the heart was 

 treated with muscarine the beat sank to zero 

 or near it. When it was treated with atropine 

 depression also resulted, but only to such a 

 degree as to clearly slow the beat. Both were 

 thus depressants, although in unlike degree. 

 When a " muscarine " heart was treated with 

 atropine it was apparently stimulated, since 

 the beat rose to the rate characteristic of 

 atropine, but, with reference to the normal 

 beat, it still remained depressed. When an 

 " atropine " heart was treated with muscarine 

 no change of beat was seen, muscarine being 

 clearly not able to antagonize atropine. Here 

 two substances acting alike as depressants are 

 called antagonists not because one can raise 

 the action above normal or even to it after 

 depression by the other, but because one is able 

 to efface the other and bring up the action to 

 its own characteristic rate. Here the antag- 

 onists are both minus quantities with refer- 

 ence to normality and the result is the lesser 

 minus quantity. Einger called this a case of 

 antagonism; it was not, however, mutual an- 

 tagonism, since only one was able to replace 

 the other and no opposite physiological state 

 was produced. These two instances are clearly 

 different in important particulars. 



A little later, Einger, working with small 

 organisms placed in salt solutions, introduced 

 still another phase of the problem. The quan- 



titative plus and minus action, seen when the 

 effect exerted on the single function was taken 

 as the criterion, following successive applica- 

 tions of the chemical substances, was replaced 

 by the action produced by a mixture of ions 

 acting on the total organism. Here the effect 

 of substances in simple solutions on the sur- 

 vival time gave the pure effect of each sub- 

 stance. The antagonistic action could not be 

 tested as heretofore by successive exposures to 

 the substances concerned, since death was the 

 point sought in the experiment. Consequently 

 a change of method was introduced by testing 

 the organisms in mixtures of different pro- 

 portions. A new sort of result appeared also. 

 With a definite function as a criterion, antag- 

 onists merely offset each other more or less 

 completely, the range of results being above 

 or below the normal mark according to the 

 magnitude of the stimulating action of one 

 or both of the antagonists. No resultant ac- 

 tion seen was more favorable than that of the 

 more stimulating antagonist. A new feature, 

 therefore, appeared when Einger found that 

 organisms sometimes lived longer in mixtures 

 of salts than in the most favorable of the com- 

 ponents. The term antagonism was again ex- 

 tended by Einger to cover this third type of 

 situation. 



The introduction of life or death, the sur- 

 vival time, as the criterion, complicated the 

 problem in at least one important way. Since 

 in a more or less orderly manner, death means 

 that one or more functions break down or cease 

 to correlate. Hence a disturbing influence in- 

 troduced by a given ion may harm one func- 

 tion and bring about death, another ion may 

 affect an entirely different function and in a 

 quite different way bring about the same visi- 

 ble response. Hence several ions may all be 

 operating in a cell entirely independently of 

 each other as regards function, and bring about 

 an unvarying response. Death is the uniform 

 result following from a variety of types of in- 

 jury in the organism. Here, all idea of antag- 

 onism, as originally defined, may be absent, 

 owing to the possibility that ions may not meet 

 each other in physiological opposition in any 

 one function. With death as the criterion it 

 seems that one is hardly justified in asserting 



