Vol. 60, 1909 - University of North Carolina at Chapel Hill

ORIGINAL COMMUNICATIONS. 91
as we have said, but they did not offer a strated, what is now well known, the fatal
satisfactory explanation. Asearly as 1S39, result of a second injection of horse serum
Magendie found that rabbits which had into guinea pigs. He showed that the phetolerated
two intravenous injections of egg nomenon was not due to the presence of
albumin without any ill effects, after a diphtheria toxin in the circulating blood
lapse of a certain number of days, died im- but that the presence of these toxins renmediately
after a further injection. Later ders the animals more susceptible than the
workers with precipitins have frequently injection of horse serum alone. He demonnoted
the same thing. Knorr, in lS9.=i, strated that immunity to the reaction might
found that guinea pigs develop an in- be obtained by repeated injections of large
creasing sensitiveness to tetanus toxin, amounts of serum at short intervals. He
Hericourt and Richet, in 1S9S, found that also demonstrated that specific precipitins
they were not able to immunize dogs played no part in the reaction,
against eel serum, but that, on the contrary, The most complete and brilliant work on
the dogs developed an increasing sensibili- anaphylaxis has been done by Rosenau
ty and finally died. Behring and Kitash- and Anderson of the Hygienic Laboratory
ima, in 1901, found an increasing sensi- of the U. S. Public Health aad Marine IIostiveness
to tetanus toxin on the part of pital Service. They have shown that,
guinea pigs. Portier and Richet, in 19ii2, although a single injection of horse serum
found that dogs given a very small dose of is usually harmless to a normal guinea pig,
a glycerin extract of the tentaclesof actinia, a second injection after a definite interval
after a lapse of fifteen or twenty davs, is usually fatal. The length of time necesquickly
succumbed to a subsequent inject- sary between the first and second injections
ion. Athus, 190.1 found that repeated in- they termed the "incubation period," and
jections of horse serum in ral)bits at some this was found to be about ten days. They
days interval, even in small doses, were demonstrated, as Otto had done, that the
followed by results which were local or poisonous property of the serum bore no regeneral
and benign or grave according to lation to the specific toxins or antitoxins in
the number and methods of the previous the serum. They found that the poisonous
injections. Richet, in 1904-19O.S, again principle was specific and that the reaction
experimenting with actinia, found that if would occur only after a second injection
congestin and thalassin (two poisons ex- of an homologous serum. They demontracted
from actinia) were injected into strated that a guinea pig may be sensitized
dogs in doses so small as to cause no symp- to several different proteids at the same
toms, that, after a lapse of twenty-two days, time and react to a second injection of each,
they became very sick or quickly died after provided of course the first reactions were
a subsequent injection. not fatal. Haemolysis was excluded as a
Von Pirquet and Schick (vide supra) in factor and also precipitin formation, which
19(1.5, however, were the first to reach origi- Otto also demonstrated. They advanced
nal and far reaching conclusions in regard the theory that the substance which sensitothe
phenomenon which they occasionally tizes the guinea pig is the same which later
observed in man after injection of horse poisonsit and that perhaps profound chemiserum
and which they termed the "Serum- cal changes in the central nerve cells take
krankheit." 'J'hey showed the relation of place after the first injection. They have
the phenomenon to the hypersusceptibility not been able to isolate the sensitizing subobserved
in animals and indicated the im- stance but they have shown that it is unportance
of these facts in general patholo- affected by the various chemical preservagy.
They cited the well known tuberculin lives: by drying; by precipitation with
reaction as analogous. amonium sulphate or magnesium sulphate.
Portier and Richet, in 1902, were the It is not affected by heating to 60 degrees
first to suggest the name Anaphylaxis to Centigrade for thirty minutes. Thyroidindicate
hypersensitiveness to a poison, ectomy and splenectomy have no effect on
This term is now employed to indicate the the reaction. The blood serum of sensi-.
state of hypersensitization of man and ani- tized animals contains the poisonous sub-
mals to proteid substances either poisonous stance ( "anaphylactin" j as is demon-
or non-poisonous. Anaphylaxis, then, strated by the fact that normal guinea pigs
is a condition of exaggerated suscepti- may be rendered anaphylactic to horse sebility
of the organism to a foreign sub- rum by the injection of the serum of sensistance
of proteid nature, which may or may tized pigs into their circulations.
not be poisonous. Rosenau and Anderson have shown fur-
Otto's work on the essential features of ther that the toxic principle is destroyed by
anaphylaxis was the first to appear. Otto heating at 100 degrees Centigrade for twendesignated
the phenomenon as the "Theo- ty-five minutes. It is not affected by vabald
Smith" phenomenon. He demon- rious chemicals nor alkaloids and similar