E. A.
WATSON
255
Recovery from a specific virus infection leaves
more or less immunity against reinfection with
the same virus. But where the virus is re-
presented by a plurality of strains, high pro-
tection or solid immunity prevails against only
one strain. Protection will be slight or, at
best, only partial against other strains of the
same group. A solid immunity against the
homologous strain may therefore prove in-
effective against heterologous strains. The
coming into existence and development of im-
munologically distinct strains of a virus may
well be conceived as being brought about by
changed environment, animal host species and
mode of adaptation. Knowledge of- the multi-
plicity of virus strains is growing and it is pro-
bable, as investigations continue, that a much
greater number than at present recognized,
will be uncovered.
One of the greatest handicaps in the study
of viruses has been the difficulty in transmit-
ting them and propagating them in laboratory
experimental animals. But this is being over-
come with increasing knowledge of the suscep-
tibility of the guinea pig, rabbit, white mouse
and ferret to certain virus infections and of the
behaviour of such viruses in these animals and
in the developing chick embryo. Even now
there may be more or less difficulty in making
the initial transfer from the natural to the ex-
perimental host and in obtaining the first
'take.' which may cause little health disturb-
ance or escape observation. But after a few
serial passages the virus adapts itself to the
new host and environment with, as a rule, in-
creasing pathogenicity. With some viruses
and experimental animals only a few passages
or generations are required, and with others
many, for the attainment of fixed virulence
and type. With certain viruses, such as those
of South African horse-sickness, and yellow
fever of man, the phenomenon of changing a
typical viscerotropic into a fixed neurotropic
virus occurs as a result of intercranial inocula-
tions in serial passage, particularly in white
mice. Moreover, it would appear that the
type of virus which has been developed by
adaptation and fixation in the experimental
host is maintained and is not reversed when
re-introduced to the original host. Further
modification is indicated by the observation
that a virus, which has attained its highest
possible virulence in the passage animal and
kills it in a given period of time, is generally
less infective and pathogenic for its original
host than before its change of type and en-
vironment.
In our own distemper studies, virus strains
originating from the fox, mink and dog have
been maintained for a number of years by con-
tinuous serial passage in ferrets. Some minor
differences in their infectivity and pathogeni-
city were apparent at the time they were first
obtained, but none could be observed after
serial passage in ferrets.
And, while the
strains are evidently fixed at their highest
virulence for ferrets, these animals invariably
succumbing to inoculation between the 10th
and the 14th day following, usually between
the 11th and the 13th day, it is rarely possible
to produce clinical distemper with them in
either dogs or foxes which were raised under
strictly controlled conditions and which, theo-
retically, should be uniformly and highly sus-
ceptible to the disease. Thus, viruses that
change in type and reach highest virulence in
the passage animals may, at the same time
and in the same process, become greatly at-
tenuated for the original host species. Much
practical use is being made of this in the pre-
paration of living, attenuated viruses for pro-
phylatic and immunization purposes from the
brain tissues of white mice and the embryonic
tissues of the developing chick.
Experimenting with the virus of equine
encephalomyelitis, we succeeded after several
failures in establishing it in guinea pigs by
intracranial inoculations of naturally infected
horse brain. After a few passages it attained
high virulence and appeared fixed as a neuro-
tropic virus for guinea pigs. By similar proce-
dure the guinea pig strain was established and
fixed in white mice and, in turn, the mouse
strain in the chick embryo. The comparative
infectivity and. virulence of the three strains so
developed in the guinea pig, mouse and chick
embryo, respectively, are of significance. Tit-
rating the virus-containing tissues of these
animals in dilutions carried to 1: 100,000,000
using 0.1 c.c. of each dilution as the volumetric
dose for inoculation, the minimal infective
dose of the guinea pig virus is represented as
1: 1000, the mouse virus as 1: 100,000 and the
chick virus as 1: 100,000,000. That is to say:
the guinea pig virus has 50—100 times great-
er concentration and infectivity than the horse
virus, the mouse virus 100 times that of the
guinea pig virus, and the chick virus 1000
times that of the mouse virus. However, such
striking differences are probably due to quali-
tative as well as quantitative factors; and the
former, more difficult to put in evidence and
to recognize, may be of no less importance in
virus investigations, especially in their rela-