THE BLOOD. 537 



which of themselves do not clot, immediately coagulate if a little blood- 

 serum, or a clot of blood, be added to them. Now blood-serum by itself 

 does not clot; it is, in fact, formed by the clotting of blood. Thus the 

 union of two liquids,* either of which alone is not capable of forming a clot, 

 produces coagulation. Buchanan concluded from this, and correctly, 

 that two substances are necessary for the formation of blood-clot. He 

 assumed one of these to be fibrin, while the other, probably originating 

 from the white corpuscles, acted upon the fibrin and converted it into an 

 insoluble form. Denis 1 attempted to isolate this "soluble fibrin." He 

 first prevented coagulation by collecting the blood in one-sixth its volume 

 of a saturated sodium sulphate solution. He then allowed the heavier 

 blood-corpuscles to settle out, and precipitated, by the addition of common 

 salt, an albuminous substance from the plasma which he had siphoned off. 

 This substance dissolved in water, but coagulated after a short time; we 

 will give to it the name of fibrinogen. It may be considered as the ante- 

 cedent of fibrin. Buchanan recognized the fact that a second substance 

 was probably necessary to change fibrinogen into fibrin. Our thanks are 

 due to Alexander Schmidt, however, for showing that the coagulation 

 process is due to a fermentation. He succeeded in isolating a substance 

 from the blood-serum which was capable of causing the separation of a 

 large quantity of fibrin. The substance becomes inactive after it has been 

 heated to 100 C. Its optimum of activity lies at 37 C. This substance 

 Schmidt designated as fibrin ferment. By its action upon fibrinogen, 

 fibrin is formed. The circulating blood does not contain the fibrin fer- 

 ment. It is formed, according to the experiments of Schmidt, by the 

 disintegration of the white corpuscles. We must mention here that he 

 himself did not regard the formation of the fibrin ferment as such a simple 

 process. He did not assume the presence of an antecedent, but believed 

 that fibrin was formed from two entirely distinct substances, a fibrino- 

 genous substance and a fibrinoplastic one. Olof Hammarsten 2 dis- 

 puted this view, and attributed the fermentative action to a conversion of 

 fibrinogen into fibrin. Other investigation has shown that Hammarsten's 

 theory is correct. 



There is still another important point to mention. Alexander Schmidt 

 pointed out that the formation of blood-clot also required the presence of 

 neutral salts. According to his views, all soluble salts of the alkalies and 

 alkaline earths reacted similarly. Hammarsten noticed, on the other 



1 Nouvelles Etudes chimiques, physiologiques et me'decines sur les substances albu- 

 minoids (1856), and Me"moire sur le sang (1859). 



2 Nova acta Reg. Soc. Scient. Upsala, Ser. 3, 10, 1 (1875) ; Upsala lakareforenings 

 forhandlingar, 11, 1876; Pfliiger's Arch. 17, 413 (1878); 18, 38 (1878); 19, 563 (1879); 

 22, 443 (1880); 30, 437 (1883). See also Fr4d6ricq: Bull, de Tacad. roy. Belgique, 2 

 s<5rie, 44, 7 (1877). 



