28 
Knud Faber,® in 1890, first succeeded in demonstrating by physio- 
logical tests upon animals the poison in the filtrate of mixed cultures; 
but exact work upon the toxine dates from Kitasato’s anaerobic 
method, in 1889 and 1891, of growing the tetanus bacillus in pure 
culture upon solid and fluid media. 
Brieger’s experiments were repeated b^y Kitasato and Weyl ^ in 
1890 with pure cultures of tetanus. From their studies they con- 
cluded that Brieger’s tetanin, etc., did not produce the character- 
istic symptoms of tetanus in experimental animals. 
Brieger and Frankel,'' in 1890, in further experiments believed the 
tetanus toxine, as well as the poisons produced by the whole order of 
important pathogenic micro-organisms, to be ^ ' toxalbumins.” Brieger 
and Frankehs toxalbumin consisted practically of an alcoholic pre- 
cipitate from filtered broth cultures and was undoubtedly toxic. 
Hayashi'^ concludes, from his work upon the subject, that the 
toxine isolated according to the Brieger-Boers method, as well as by 
his own modification, shows a definite albumin reaction. However, 
this is not proof that the toxine is a proteid. 
The powerful action of tetanus poison in minute amounts, its ther- 
molability, and the period of incubation lend countenance to the view 
that the toxine may be a ferment. But ferments continue to act 
when the products of fermentation are removed. This has not been 
■shovm to be the case with tetanus toxine. Many of the higher albumi- 
nous substances are also readily destroyed by heat lower than 65° C., 
which is fatal for the tetanus toxine. The period of incubation is 
now explained by the time necessary for the poison to travel up the 
motor nerves to the centers. There is, therefore, nothing but analogy 
of an indefinite nature to class tetanus toxine with the ferments. 
Ehrlich,^ in a parallel work to his researches upon the constituents 
of the diphtheria toxine, showed that the tetanus toxine contains both 
a toxophore and a haptophore group, and that the antitoxic immunity 
is explained by the presence of free receptors in the blood of immu- 
nized animals. The receptors combine directly vdth the haptophore 
group, thus neutralizing the toxine. 
“ Feber, Knud: Die Patliogenese dfes Tetanus. Berl. klin. AVoch., vol. 27, 1890, 
pp. 717-720. 
^ Kitasato, S., and AA'eyl, Th.: Zu Kenntniss der Anaeroben. Zeit. f. Hyg., vol. 8, 
1890, pp. 41, 404. 
c Brieger, L., and Frankel, Carl: Untersucliungen iiber Bakteriengifte. ' Berl. 
klin. AVocli., vol. 27, 1890, p. 268. 
Hayaslii, H.: Weitere Forschungen iiber die chemische Xatiir des Tetanustoxins. 
Arch, exper. Path. u. Pharni., vol. 47, 1901-1902, pp. 9-18. 
« Ehrlich, P.: Die AVerthbestimmung des Diphtherieheilserums. Klin. Jahrb., 
1897. 
: Ueber die Constitution des Diphtheriegiftes. Deut. med. AA’och., vol. 24, 
1898. 
