242 
simple forms corresponding to the ones which are the first to appear in 
the lesions. In variola, in addition to the forms common to both vac- 
cinia and variola which are found in the cytoplasm of the epithelial cells, 
a new body appears in the nuclei of the epithelial cells, which undergoes 
a development dissimilar to that of the cytoplasmic forms, and which 
finally results in the formation of a sporoblast with spores. 
It was believed by the investigators that these inclusions were living 
parasites and that in both vaccinia and variola there was a simple develop- 
ment taking place in the cytoplasm of the epithelial cells. In smallpox 
there was a further development which took place within the nucleus and 
which terminated in the formation of spores, which spores constituted 
the contagium of smallpox. The material was further worked over by 
Prof. G@. N. Calkins, of Columbia University, who described a life history 
embracing both the cytoplasmic and intranuclear forms. It was further 
established that when vaccine virus was inoculated in a susceptible animal 
(and most animals are susceptible) a typical lesion was produced in which 
only the cytoplasmic forms of the organism were found. ‘The same was 
true when variola virus was inoculated in animals not susceptible to 
variola. No exanthem develops on such animals after inoculation with 
variola virus. When variola virus was inoculated on the monkey an exan- 
them analogous to that of variola in man was produced and in both the 
primary lesion and in the exanthem the cytoplasmic and the intranuclear 
forms of the parasite were present. 
The investigation in Boston was brought to a close by the lack of cases 
and the difficulties of experimental work. It had been carried to a point 
where further experimental work was necessary to secure all phases of the 
disease variola, to study further the interrelation between variola and 
vaccinia and the immunity problems involved. For these purposes the 
extensive use of monkeys as experimental animals was indispensable. 
To secure experimental material, the best conditions for laboratory 
work, with access to variola in man to obtain fresh virus, the Biological 
Laboratory in Manila seemed to offer the best facilities. The proposition 
was favored by the United States Philippine Commission, who gave us 
every facility for the prosecution of the work, and Drs. W. R. Brinckerhoff 
and E. BE. Tyzzer, who had taken a prominent part in the investigation of 
smallpox and vaccinia in Boston, were sent to Manila. ‘To the Hon. Dean 
C. Worcester, Secretary of the Interior of the Philippine Islands, we wish 
to express our appreciation and thanks for his numerous efforts in our 
behalf. Dr. Paul C. Freer, Director of the Bureau of Science,* took much 
interest in our work and essentially furthered it. Dr. Richard P. Strong, 
Director of the Biological Laboratory, Bureau of Science, in which we 
worked, was a constant support to us in our work and did much to make 
*Since the completion of the experimental work detailed in this paper, the 
Bureau of Government Laboratories of the Philippine Islands has been increased 
in its scope and its name has been altered to The Bureau of Science.—Eprror. 
