372 Drs. J. W. Pickering and J. A. Hewitt. 



produced by, venom. This conclusion falls into line with the recent observa- 

 tion of Pickering and Hewitt (22), that the slow addition, drop by drop, of 

 tissue extract (nucleo-protein), prepared from kidney, to unsalted bird's blood 

 in vitro, produces a " negative phase " in its coagulation, and is explicable by 

 the suggestion that the " negative phase " of blood coagulation is a physical 

 process involving an adsorptive union of the tissue extract, the substances 

 forming the alkali reserve and fibrinogen, and is in its essence closely akin to 

 the following in vitro reactions : the Dansyz reaction with the toxins and anti- 

 toxins of diphtheria and ricin (Dansyz, 23), the variations in the toxicity 

 incidental to the fractional neutralisation of arsenious acid by ferric hydroxide 

 (Hewlett, 24), the " negative phase," or temporary inhibition of the precipita- 

 tion of gelatin by the slow addition of either alcohol or ammonium sulphate, 

 and to the similar phenomena following the addition of electrolytes to certain 

 inorganic sols (Spring, 25, Hober and Gordon, 26, Paine, 27, Galecki, 28, 

 Burton, 29). 



Arthus concluded that in poisoning by proteotoxins, the liver is either not 

 the organ which produces anti-thrombin, or is not the only organ. Doyon (30) 

 immediately perceived the significance of Arthus' work, and, adopting his 

 methods, injected " peptone " into dogs in which the hepatic circulation had 

 been ligatured. Again, no attention was paid to the probable increase of 

 carbon dioxide in the blood during the experiments in which anaesthetics 

 were employed. Doyon states that, in the cases he observed, the speed of 

 clotting of shed blood was normal, but the clots were soft and completely 

 dissolved on standing, so that the blood again became fluid. This result 

 Doyon ascribed to the action of anti-thrombin formed in parts of the body 

 other than the liver, and reverted to Contjean's views (loc. cit.), which have 

 also been supported by Popielski (31). 



It is, it is thought, clear that Doyon's clots are not true fibrin clots, as such 

 do not re-dissolve in vitro. In a recent paper (Pickering and Hewitt (loc. cit.) ) 

 evidence has been brought forward that the first stage of coagulation of 

 mammalian and frog's blood, surrounded by oil, is the formation of a reversible 

 gel, which is soluble in excess of tap water. In the case of frog's blood this 

 stage may,, when undisturbed, persist for several hours, but if thromboplastic 

 material is added to it a typical clot is formed in a few minutes. It therefore 

 appears possible that " peptone," as administered by Doyon with the liver out 

 of circulation, retarded the coagulation of the blood so that it remained in the 

 first stage of the process. Only in one of the series of experiments now 

 recorded, in which " peptone " was injected into both intact eats and into cats 

 deprived of hepatic circulation, has any evidence been noted of the temporary 

 formation of a gel which dissolves on standing (No. 4). It has consequently 



