INTRODUCTION. 
The investigation of smallpox is attended with difficulties. The 
disease only appears at intervals. The cases are not treated in well- 
organized hospitals where there are facilities for and the habit of the 
investigation of diseases. As a rule the hospital in which the disease 
is treated are used only at intervals and are unprovided with laboratories. 
Clinical teaching, the great stimulus to research, has no place in them. 
The energies of the physician in charge are entirely taken up in con- 
trolling the exigencies of an unusual situation. This isolation of the 
disease is unfavorable in that the valuable aid given by constant com- 
parison with other diseases is lost. 
Difficulties also attend the experimental study of smallpox. Such 
study can not be carried out in ordinary laboratories, owing to the fear 
of infection extending from the laboratory.? The ordinary laboratory 
animals such as rabbits, guinea pigs, and all the domestic animals are 
immune to the disease; the only animal, so far as is known at present, 
which is susceptible is the monkey. These are expensive, difficult to 
acquire, and in this climate very susceptible to disease. The majority 
of monkeys obtained from animal dealers are infected with tuberculosis. 
During the epidemic of smallpox which prevailed in Boston in 1901 
and 1902, an investigation of the disease was undertaken by members 
of the pathological department of the Harvard Medieal School. The 
health authorities of the city gave every facility for investigation which 
was possible. Autopsies were held on 52 cases, embracing all forms of 
the disease and provision was made enabling certain of the investigators 
to live in the smallpox hospital and there to undertake some experimental 
work. 
In the course of this investigation it was found that certain cell 
inclusions, first described by Guarnieri, were constantly associated with 
the lesions of both vaccinia and variola. These bodies are not of invari- 
able form, but they show a series of forms corresponding to the develop- 
mental phases of a living organism. In the course of this development a 
body much larger and more complicated in structure follows the smallest 
and simplest forms, which body finally segments into a number of small, 
*It is remarkable how persistent is this fear of smallpox. That it so persists 
is an evidence of the horrors of the disease in the prevaccination period. There is 
no disease which is so feared by the community as is smallpox, and certainly none 
against which we have such perfect protection. 
241 
