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“the immunity is germicidal in character for the serum of an immune 
animal renders vaccine virus inactive. We have not been able to make 
any tests with the serum of monkeys immunized by the variola virus. 
Experiments made to test the influence of unfavorable external conditions 
on the virus of vaccinia and variola showed that vaccinia was much more 
resistant. The variola virus seems to undergo an attenuation after 
passing through a series of monkeys, finally losing the power of producing 
an exanthem, although a typical local lesion followed inoculation. The 
same was true of variola virus which had been subjected to the influence 
of glycerin for various periods. 
It is generally believed that in man the primary variola infection takes 
place on some mucous surface, systemic infection following from the 
development of the organisms at the primary focus. ‘There is no anatom- 
ical evidence for this assumption. Such a protopustule has never been 
found. In the 52 autopsies made in Boston careful search was made 
for such a lesion, but in vain. The period of inoculation in smallpox runs 
its course without symptoms, but it would be possible for such a lesion to 
exist in the lungs without producing symptoms, as can a considerable 
tuberculous focus. We have rarely produced the evidence of systemic 
infection shown either by immunity or exanthem by inoculating on the 
mucous membrane of the nose, mouth, or palate, or on the cornea. In 
these places, owing to the absence of a dense, horny layer which would 
retain the products in the lesion, an open ulcer was formed and absorption 
was prevented. Systemic infection did result both from intratracheal 
inoculation and from blowing the dried virus into the lungs. In this case 
absorption would take place both from the lesion and from the mucous 
surface. The type of disease produced in the monkey was not affected by 
varying the place of inoculation. By insufflating the virus into the lungs 
a peculiar form of pneumonia was produced with proliferation of the 
alveolar epithelium and with the cytoplasmic forms of cytoryctes in the 
epithelial cells. The evidence shows that variola infection can take place 
in the lungs. 
The work in Manila has confirmed what was stated in the earlier publi- 
cations concerning the cytoryctes, but has added nothing. We feel sure 
from our work that the inclusions in the cells of the lesions are living 
organisms. It seems also sure that the organism described does not con- 
form to the type of the other known organisms. The evidence that the 
things described are living, comes in part from the analogy of structure 
with other things which are generally recognized as living organisms, and 
in part from the analogy with living things which they give by progres- 
sive growth and differentiation of structure. Certain forms are found at 
certain intervals of time and they occur in sequence. It has not been pos- 
sible to show in them nuclear material with the Romanowsky stain nor, 
so far as I know, has it been possible to stain with this the nuclei of 
malarial parasites in tissues. In the investigation of smallpox we are 
