August 6, 1915] 



SCIENCE 



173 



the metabolism of the body or with the 

 pathological changes induced by toxic doses 

 can not be taken up here. 



The discovery of the chemical structure 

 and pharmacological properties of epine- 

 phrin has greatly encouraged investigators 

 to take up the isolation of other active 

 principles. Thus Abelous^^ and his co- 

 workers showed that the intravenous injec- 

 tion of extracts from putrid meat caused a 

 rise of an animal's blood pressure. Barger 

 and Walpole^" then proved that this effect 

 was due to the presence of isoamylamine, 

 phenyl-ethylamine and para-hydroxyphe- 

 nylethylamine. 



These amines are produced by putrefac- 

 tive bacteria from proteids, and they ex- 

 hibit pressor or blood-pressure-raising ef- 

 fects that in general are very similar to 

 those produced by epinephrin. A close 

 similarity in chemical structure of two of 

 these amines, phenyl-ethyl-amine and para- 

 hydroxyphenylethylamine, to epinephrin 

 is shown in the graphic chemical formulae 

 which will presently be given. The last- 

 named base is of special interest to us, since 

 Barger has discovered that it is also pres- 

 ent in ergot and is in some degree respon- 

 sible for the characteristic activities of this 

 drug. It is also present to a small extent 

 in Emmenthaler cheese. More remarkable 

 still is the discovery of Henze that this 

 amine is the effective principle of a highly 

 active poison produced by the posterior, so- 

 called salivary glands of a certain cepha- 

 lapod found in the Bay of Naples. It has 

 long been known that this mollusc renders 

 its prey, as the crab, quickly helpless by 

 means of this poison and until Henze 's dis- 

 covery it was believed to be a toxalbumin. 



We find, therefore, that p-hydroxyethyl- 

 amine is produced by putrefactive bac- 



35 Compt. rend. Soc. de Biol., Vol. 58, I., pp. 

 463 and 530 (1906), Vol. 64, p. 907, 1908. 



36 Jour, of Physiol, Vol. 38, p. 343, 1909. 



teria, that it is present in ergot (the perma- 

 nent mycelium of the fungus, Claviceps 

 ■purpurea) , and that it is the product of the 

 metabolism of a glandular tissue. In each 

 case it may be assumed that it is obtained 

 by chemical reactions from the protein 

 molecule, its immediate precursor being 

 the innocuous tyrosin. 



By merely splitting off a molecule of CO, 

 from tyrosin, as was demonstrated by 

 Barger, we at once secure this amine, as 

 shown by the accompanying formula. As 

 a recent writer has remarked, "Our poi- 

 sons and our drugs are in many instances 

 the close relatives of harmful compounds 

 that represent the intermediary steps in the 

 daily routine of metabolism. "^^ 



The fact that putrefactive microorgan- 

 isms can produce poisonous amines by de- 

 earboxylating the harmless amino-acids 

 has become of the highest importance to 

 medicine. It would appear that we have at 

 last got onto the right road for the chemical 

 investigation of alimentary toxemia and 

 its alleged consequences, such as arterio- 

 sclerosis and chronic renal disease. Phenyl- 

 alanine, tyrosine, tryptophane and histi- 

 dine, the harmless precursors of toxic 

 amines, are always present in the intestine, 

 and when they are acted upon by an exces- 

 sive number of certain microorganisms the 

 resulting toxic bases will surely be formed 

 in excess. If they are then taken up into 

 the blood in quantities too large for trans- 

 formation by the liver, or other defensive 

 organs, into less harmful derivatives they 

 must inevitably manifest their pharmaco- 

 logical and toxicological properties. Let 

 me give but one further example of recent 

 advances in this field. It has been shown 

 by Barger and Dale^* that the highly poi- 



37 Jour. Amer. Med. Assoc, editorial comment, 

 Vol. 62, January 3, 1914. 



ssjour. of Physiol., Vol. 40, p. 1,910; Vol. 41, 

 p. 499, 1910-11. Consult also the work of Acker- 

 mann, who first demonstrated that when pure his- 



