8o TOXIN AND ANTITOXIN. 



If an emulsion of brain tissue and a fatal dose of tetanus toxin are mixed and the mixture 

 injected into mice, the latter remain unaffected. According to Doenitz only the gray 

 matter and not the white substance of the brain possesses this absorption power. If the 

 brain emulsion is boiled, however, it loses this affinity for the toxin. 



Concerning the way by which the toxin reaches the central nervous sys- 

 tem, opinions vary. Most writers, especially Meyer and Ransom, consider 

 that the journey is made along the nerve paths. Zupnik on the other hand 

 believes that it is distributed through the blood stream and is taken up not 

 only by the nervous system, but also to a great extent by the muscles. 



That tetanus toxin is very labile is well known. According to Kitasato, 

 five minutes at 65 C. or twenty minutes at 60 is sufficient to weaken the 

 toxicity to a great extent, in fact even almost to destroy it. Light has a 

 similar effect upon it. Careful as its preservation may be, the soluble tetanus 

 toxin soon becomes attenuated. Hence the best way of keeping it in stock is 

 in a dry form. For estimating the strength of the toxin white mice are em- 

 ployed and are subcutaneously injected with fresh soluble toxin, the lethal 

 dose being the amount which kills the animals in four to five days. Animals 

 more susceptible than mice are horses, they being twelve times as sensitive 

 and guinea-pigs six times as much. Hens possess greater power of resist- 

 ance, being 30,000 times less susceptible to the toxin than mice. 



Tetanolysin acts upon the red blood cells and disintegrates them. The 

 erythrocytes of goats, sheep and horses, are best suited for experiments to 

 demonstrate this action. Ehrlich showed that the tetanolysin and the 

 tetanospasmin are really two identically different toxins and not one toxin 

 with a twofold function. When tetanus poison is mixed with red blood 

 cells the tetanolysin is absorbed and the tetanospasmin remains free. Even 

 the antitoxins of these two are different. 



As far as the standardization of the tetanus serum is concerned, it is 

 affected on the same lines as the diphtheria serum, i.e., the L + dose of toxin 

 being the one employed. 



"In America the method of standardization was regulated by a law passed 

 in July, 1908, based upon the work of Rosenau and Anderson at the United 

 States Hygienic Laboratories at Washington. Their unit of antitoxin is ten 

 times the smallest amount of serum necessary to save the life of a guinea-pig 

 for ninety-six hours, against the official unit of standard toxin. This toxin 

 unit consists of 100 minimal lethal doses of a precipitated toxin preserved at 

 the hygienic laboratory of the Public Health and Marine Hospital Service. 

 At the hygienic laboratory at Washington a standard toxin and antitoxin 

 are preserved under special conditions, and standard toxin and antitoxin, 

 arbitrary in their first establishment, are kept constant by being meas- 

 ured against each other from time to time. For details of this standardi- 

 zation the original article in the United States Hygienic Laboratory Bulletin 

 43, 1903, should be consulted." 



