— = ey:mCU oA ’ a? 
: 1 
247 
unfortunately limited to the tissues. We have never been able with cer- 
tainty to detect either in the virus of smallpox or vaccinia, or in the blood 
of an infected animal or man, the forms which in the tissue we recognize 
as parasites. If the very minute bodies which we speak of as gemmules 
in the cytoplasmic cycle and as spores in the nuclear cycle were present 
in such fluids, we do not know how they could be recognized. The bodies 
can only be regarded as parasites or as products of cell degeneration. If 
degenerations, they are totally unlike any of the ordinary substances found 
in degenerating cells. Moreover, their presence inaugurates the cell 
changes which are found in the lesions. The cytoryctes occur in cells 
which but for their presence show no departure from the normal type. 
They are specific. No other disease shows the same changes in the cells. 
If degenerations, it would be necessary to assume that the virus of small- 
pox causes certain cells to produce substances within them which have a 
certain form and size and which grow and change their structure with 
growth. In other diseases such as molluscum contagiosum and in the 
epithelioma contagiosum of fowls we find substances in the cells which 
are regarded as degenerations and which in their mass and extent are 
specific. But the character of the degeneration is not specific, and the 
same changes are found in single cells in other processes. Along with the 
inclusions in cells, which are definite in size and form and which we 
recognize as parasites, there are others which are irregular and indefinite. 
We are inclined to regard these in part as imperfectly developed or degen- 
erated parasites. The immune substance produced in variola and vac- 
cinia has been shown to act as a germicide. It may be formed in the 
lesion or elsewhere, but it certainly is present and may exert its influence 
on the organisms which are present. We believe that the inclusions are 
living organisms for the reason given and that they are the cause of 
the disease because their relation to the lesions is that of other causal 
organisms. 
In our work on smallpox which is now nearing its temporary con- 
clusions, certain questions have presented themselves. These questions 
relate: First, to the parasite and its life history. Second, to the inter- 
relationship of vaccinia, variola inoculata, and variola vera. Third, the 
immunity and its mode of production. Fourth, to the mode of produc- 
tion of the exanthem. Fifth, to the mode of infection in variola vera. 
In our work both in Boston and Manila we feel that we have made some 
contributions to all these questions. None of them are completely an- 
swered. ‘Their answers involve long and arduous work by skilled inves- 
tigators, on both vaccinia, variola in man, and the experimental disease 
in monkeys. For the work a constant supply of virus and of animals 
for experiment is necessary, and we believe that the work can only be 
carried out in places where both these conditions can be fulfilled. The 
most important contribution which could at present be made would be 
the discovery of an animal in which variola vera can be experimentally 
produced. 
