22
the retina they were plentiful and large, but could not be detected in the cerebellum though
Purkinje's cells were almost completely disorganised.
Hen 2 was inoculated subdurally with fixed virus from another rabbit. Incubation 14 days,
death five days later. In its brain Negri bodies were numerous but mostly small. In the Pons
Varolii some cells were normal ' others quite disorganised. Some cells were crowded with bodies,
the largest 3µ to 4µ in diameter, reminding one of spinal ganglion cells. There was much
leucocytic exudation round the vessels. The retina contained bodies of fair size but not numerous.
A guinea pig inoculated subdurally from hen 2 had an incubation of 11 days. In its cortex
tiny Negri bodies were mimerous and some cells contained the dark blue dots already mentioned
as occurring in the ganglion cells of the retina of a street virus guinea pig. The hippocampus was
unfortunately lost and no bodies were to be seen in the cerebellum, though Purkinje's cells were
much degenerated and there was a large amount of exudation round the vessels. No Negri
bodies were seen in the retina.
lien 3, inoculated subdurally from lien 1, had an incubation of 28 days. In its brain Negri
bodies were numerous in parts, varying in size from. 2µ in the cortex to 10µ in some of Purkinje's
cells. These large forms were not plentiful but they were indi stinguishable from the large forms
commonly found in street virus infections. The, most striking feature visible in the brains of all
three hens was the enormous amount of round cell infiltration in the neighbourhood of many of the
blood vessels corresponding to the " Wutknotchen of Babes, which are usually found in street
virus but not in. fixed virus infections. The retina also showed small bodies.
It would appear that hens are sufficiently resistant to infection with a fixed virus having an
incubation period of 6-7 days in rabbits to prolong its incubation to 1.4 days in the first passage
and to 30 days in the second.
The microscopic pictures of their brains are not like those seen either in 'fixed. or street virus
in mammals ; the Negri bodies are larger and more numerous than in mammalian :fixed virus and.
smaller than in street virus. There is in addition a far greater amount of round cell infiltration
than we have ever seen in either fixed or street virus mammalian brains.
Although the microscopic characters of street virus were not completely attained to in these
hens or in the sub-inoculated guinea pigs, there was enough alteration to give ground for the
belief that in time it will be possible to reconvert fixed into street virus, at any rate as far as
microscopical appearances go. This might be performed by subcutaneous inoculatioas of the
.salivary glands in preference to brain matter.
The difficulty of conveying rabies by subcutaneous inoculations with fixed virus leads us to
enquire why this should be so, and why a very much larger percentage of subcutaneous inocula-
tions with street virus should be successful.
As a working hypothesis it may be assumed that the causative agent in nature is always
introduced into the body of a non-immune animal by means of the saliva, of a biting rabid animal,
for no facts are on record. which support any other supposition. A base of infection may be estab-
lished at the site of the wound, since some authors have found the cicatrix infective some weeks
after the infliction of the injury. From this base the organism slowly spreads, apparently by way
of the nerve trunks, until it reaches the central nervous system where it rapidly multiplies till
practically the whole is invaded. Whether this is a, purely vegetative phase iu the history of the
organism or whether a sexual phase is also consummated in the brain no evidence is forthcoming.
From the brain it would. appear that the organism spreads further afield, involving many
of the larger nerve trunks and reaching internal organs such as the pancreas and. also the salivary
glands. No one with the exception of Stephanescu (28), already quoted, has seen a trace of any
orgranism outside the brain and. spinal cord., not even in the saliva, yet filtration experiments
show it to be present in both the brain and the saliva when it cant of be seen. If Negri bodies
in the brain represent one form of the parasite, the saliva must contain another form which
is perhaps another phase in its life history.
It is evident that the Negri bodies as we see them in the brain are not the immediate infecting
agents since they are far too large to pass through a filter which allows the rabic virus to pass, but
they may contain something analogous to sporozoites, which find their way to the salivary glands
and so to the outside of the body.. The rabic organism can be propagated. indefinitely by using
the contents of the crania of. living mammalia as the nutritive medium, but this just as artificial
as growing bacilli for years on agar in a, series of test tubes, and in both cases alterations occur.
The bacillus loses virulence or its power of producing 'pigment or some such property which
it may or may not be possible to restore ; the rabic organism loses its original appearance and its
power of infecting subcutaneously to a considerable degree, and whether these properties can be
restored remains to be discovered. It is justifiable, therefore, to regard fixed virus not as a more
highly virulent form of rabic virus, which is the accepted view, but merely as the artificial exhi-
bition of the purely vegetative phase of the organism's life history. It is more virulent than
street virus in that it kills rabbits with a shorter incubation period., but that is solely because it has
become accustomed to the medium in which it is forced to live and in which it eventually grows
more easily and rapidly than it did at first, just as a bacillus will often grow much more freels
on agar after a few subcultures than it did when first transferred. from its natural habitat.