Apbil 2, 1909] 



SCIENCE 



523 



right track, but our progress seems imnieas- 

 urably slow. 



Not only logic but experiment tell us that 

 fatigue has a twofold cause — diminution 

 of substances essential to protoplasmic ac- 

 tivity—and here oxygen and carbohydrate 

 loom large — and accumulation of toxic 

 products of katabolism, among which we 

 reckon carbonic dioxide, paralactic acid and 

 monopotassium phosphate. 



That lack of oxygen is a potent factor 

 seems probable from Hill's recent results, 

 which seem to demonstrate the efficacy of 

 pure oxygen taken into the lungs in quickly 

 restoring one who is suffering extreme fa- 

 tigue. 



That lack of carbohydrate is in part re- 

 sponsible for fatigue seems evident from 

 the abundant testimony, coming not only 

 from daily human experience, but from 

 many laboratory experiments, conducted 

 by a great variety of methods, to the effect 

 that sugar restores the working power of 

 the fatigued neuro-museular mechanism. 

 In view of the complexity of the chemical 

 changes involved in protoplasmic activity, 

 it seems hardly possible that fatigue sub- 

 stances are limited to two end products of 

 metabolism, carbonic dioxide and a phos- 

 phate of potassium, and one intermediate 

 product, paralactic acid. Indeed, Weich- 

 ardt has gone beyond this and claims to 

 have found among the products of extreme 

 muscular activity a specific toxin, which is 

 analogous to bacterial toxins and capable 

 of producing the symptoms of fatigue when 

 injected into animals. And he further 

 claims to have produced, by methods analo- 

 gous to those employed with bacterial tox- 

 ins, a specific antitoxin possessed of striking 

 recuperative powers. These claims he sup- 

 ports by a large amount of experimental 

 evidence. Without a repetition of his pro- 

 cedures — and I am unaware that any one 

 has yet done this — it is difficult to express 

 an opinion of value concerning the exist- 



ence of his toxin and antitoxin. That he 

 obtained from the tissues of his fatigued 

 animals a poison of a high degree of tox- 

 icity seems undoubted ; that this is capable 

 of ready neutralization is less clear; and a 

 sceptic may be inclined to be dubious of 

 the specificity of Weiehardt's products. 

 The preparation of his antitoxin in this 

 country is now protected by patents issued 

 from Washington, and it is gratifying to 

 feel that if it prove to be the long-sought 

 antidote to fatigue, now commercialized it 

 will come within the provisions of our pure 

 food law. 



Whether future research justifies Weieh- 

 ardt's claims or not, our conception of 

 fatigue substances is bound, I think, to 

 become extended. My study of the physi- 

 ological actions of the three now recog- 

 nized, and the similarity of these actions to 

 those of ;8-oxybutyric acid, indol and skatol, 

 have brought me to the conviction that we 

 shall in the future probably find many 

 intermediate products of metabolism which 

 have the power of depressing protoplasm 

 and putting it into the condition wherein 

 it manifests the physical characteristics of 

 fatigue. If this conviction proves to be 

 well founded, we shall in the future recog- 

 nize many fatigue substances. It may be 

 convenient to regard some of these as nor- 

 mal and some as pathological, although I 

 am inclined to interpret the difference be- 

 tween these two hypothetical groups as one 

 of quantity rather than of kind. 



We are stiU in the dark as to the respect- 

 ive parts played in the production of fa- 

 tigue by its two so-called causes. Ver- 

 worn's limitation of the term fatigue to the 

 result of poisoning by toxic substances, and 

 of the term exhaustion to the effects of the 

 lack of substances essential to activity, is a 

 convenient usage, but it should be borne in 

 mind that both processes go hand in hand 

 throughout the activity of the tissue, and 

 even in what is popularly understood by 



