24
It is curious that the guinea pigs, though usually the more susceptible animals, had an incuba–
tion period double the length of that of the rabbits.
No. 2 consisted of portions of the optic thalamus and basal ganglia from the brain of a man
who had died of suspected hydrophobia in the General Hospital, Madras. Source of infection
unknown. Sections cut from five different pieces and stained by several methods failed to show
any Negri bodies or other indications of rabies.
One sub-passage was made from a piece preserved in glycerine.
Guinea pig 46.—Incubation 14 days, died same evening. Negri bodies from 1/µ-5µ, were
numerous in the hippocampus, cortex and cerebellum.
Case No. 1 is of considerable importance. It shows that typical Negri bodies are not always
to be found in human brains even when the tissue is obtained in a fresh condition and fixed and
stained. by methods which under ordinary circumstances never fail to give good results. It also
points to the possibility of the existence of varieties of the rabies organism which do not give rise
to the same microscopic appearances. Another notable feature is the reappearance of typical Negri
bodies in each of the sub-passage, though even then they were smaller than is usual in
s u b d u r a l p a s s a g e s f r o m s t r e e t v i r u s d o g s . I t i s m o r e t h a n p r o b a b l e t h a t t h i s m e t h o d . o f e x a m i n i n g t h e
brain of a sub-passage animal would set at rest the doubts that exist in some minds whether or
no a patient who has developed hydrophobia subsequent to treatment has succumbed to fixed virus
or street virus.
Case No. 2 shows nothing except that the basal ganglia of the human brain do not always
furnish material from which rabies can be diagnosed microscopically without fail, and that an
examination of the animal inoculated subdurally from this material will show typical Negri
bodies.
7. ON TOXINS IN RABIES.
BY
J. W. CORNWALL AND M. KESAVA PAL
The arguments in favour of the secretion in the system of a toxic product by the organism of
rabies are, as stated by Babes :-
(1) The premonitory fever.
(2) Leucocytosis.
(3) Cachexia, and death after injections of filtered virus.
(4) Occasional paralysis during the Pasteurian treatment.
(5) The possibility of obtaining an antirabic serum.
Without attempting to examine into the signification of these items seriatim one might
reasonably expect that the organism of rabies would. produce some excretion which would be
injurious to the tissues of its host, in addition to substances liberated in the disintegration of the
cells in which it is proliferating.
Expectation is nevertheless far removed from demonstration, and it is by no means easy to
devise a procedure which will indicate without a doubt that a definite toxin has any existence,
much less isolate it.
The most obvious lino of investigation is to endeavour to derive a toxin from the brains of
animals which have succumbed to rabies by making them into an emulsion and filtering it under
pressure through porcelain which will not allow the organism itself to pass. This has been
performed. by several. workers and the filtrate has been tested on animals subcutaneously and.
intraperitoneally with the result that some have died. in the course of time with cachexia and
marasmus. Occasionally definite paralytic symptoms have supervened. When recovery has
taken place it is claimed that immunity even to subdural inoculation with fixed virus has followed.
It cannot be said. that these experiments are satisfactory or that the conclusions drawn from
them carry great weight. The filtrate, besides containing any toxin there may be in the brain
substance, also contains the products of the disintegration of the brain both normal and
pathological, and any effects which have been attributed to the former may equally well have been
due to either of the latter. The filtrate is, moreover, owing to practical difficulties in filtration,
exceedingly dilute, so that the ridiculously large quantity of 500 cc has been introduced into a
rabbit subcutaneously to generate an effect (31).
Concentration of the filtrate over sulphuric acid iu vacuo does not seem to have produced a
more potent material. Marie (32) and others report that some immunity is conferred by the
filtrate of normal brains also.
Our own experiments with the filtrates of fixed virus brains add no conviction to the case for
toxin. No effect having been produced with the filtrates of fresh brains, other fixed virus brains