694 
tion of artificial immunity. Recalling the 
researches of Jenner, and the quotation 
from Ehrlich relative to the work of 
Pasteur, at that time it appeared as 
though artificial immunity was brought 
about by specific micro-organisms. Op- 
posed to this view the investigations of 
Toussaint, Chauveau, Salmon and Smith, 
Roux, C. Frankel and others brought 
forward evidence to show that artificial 
immunity could be induced by the ‘ meta- 
bolic products’ freed from bacteria—accus- 
toming the organism to the specific poison 
seemed all-sufficient. Later it was shown 
by Hueppe, Gamaleia and Buchner that 
the specific toxins found in the culture fluid 
outside the bacterial cells were not identi- 
cal with the protective substances found in 
the germs and their metabolic products. 
At this point Hueppe says: It has been 
“established that: (1) undergoing the dis- 
ease; (2) inoculation with attenuated germs; 
(8) inoculation with disease germs which 
have become wholly impotent; (4) inocu- 
lation with saprophytes, and (5) inoculation 
with the metabolic products of the parasite, 
can all confer immunity ; while, (6) inocu- 
lation with the specific poisons effects no im- 
munization.”” Then followed the experi- 
mental proof that completely attenuated 
bacteria can no longer produce the specific 
poison. This effectually separates the pro- 
tective substance and the poison. 
The next important advance was the dis- 
covery of substances in the blood serum of 
animals immunized against diphtheria and 
tetanus that were able to specifically protect 
other animals against the toxines of these 
diseases. This discovery was made by 
Behring, and it at once opened an entirely 
new and promising field for investigation. 
December 3, 1890, in No. 49 of the Deut- 
sche med. Wochenschrift, Behring and Kitasato 
published an article: ‘ Ueber das Zustande- 
komen der Diphtherie-Immunitat und der 
Tetanus-Immunitat bei Thieren’ in which 
SCIENCE. 
(N.S. Vou. XIII. No. 331. 
the statement is made that: ‘‘ The blood of 
tetanus-immunized rabbits possesses the 
property of destroying tetanus toxin. This 
is possessed by the extravascular blood and 
is the cell-free serum.’”’ They showed that 
the blood serum of non-immunized animals 
did not possess this antagonizing action, 
and that the prepared serum was of thera- 
peutic value. Ogata and Jasuhara proved 
that blood serum from an animal naturally 
immune contained substances which, when 
injected into mice, conferred upon them the 
same type of immunity. Tizzoni and Cat- 
tani (1891) found that the quantitative 
protective value of the blood serum of an- 
imals naturally immune to tetanus (the 
dog, for instance) could be greatly increased 
by repeated injections of gradually increas- 
ing amounts of tetanus-toxin; and that 
such serum possessed decided therapeutic 
value when inoculated into animals suffer- 
ing from tetanus. This line of investiga- 
tion has been greatly extended and enriched 
by Behring, Roux, Koch, Yersin, Haffkine, 
Pfeiffer, Buchner, Sanarelli, Ehrlich and 
others, and, as a result, there is to be found 
in the open market to-day a variety of anti- 
toxin sera, such as antidiptheritic, antite- 
tanic, Marmoreck’s antimycotic, antipneu- 
mococcic, antibubonic, antirhabic, yellow- 
fever, ete. 
March 20, 1896, Professor Thomas R. 
Fraser, M.D., at the Royal Institution of 
Great Britain, presented a very important 
contribution on ‘Immunisation against Ser- 
pents’ Venom, and the Treatment of Snake- 
bite with Antivenene,’ in which, for the 
first time, the quantitative relation between 
the ‘toxic’ and the ‘anti’ substances is 
shown. The contribution is rich in splen- 
didly marshaled experimental evidence 
which leads the author to the logical con- 
clusion that, so far as snake venom is con- 
cerned, the antidotism of the ‘antivenene’ 
is not the result of physiological reaction, 
is not due to phagocytic action, nor to the 
