VIROLOGY—LILLY RESEARCH LABORATORIES 529 
because normally they are duplicated only once or a minimal number 
of times during each cell division and may never leave the cell during 
many generations. Such a viral nucleic acid might temporarily ap- 
pear to be a part of, or associated with, the genetic apparatus of the 
cell, but be subject to chemical or physical stimulation or shock which 
could cause it to mature, increase greatly its rate of replication, per- 
haps mutate, but in any case to separate and act as an independent 
functional unit.” 
DIAGNOSIS 
At one time a diagnosis of virus disease was made by “exclusion” 
(i.e., no bacteria as cause), but it is now possible to apply a new 
method—tissue culture. This technic has been a major stimulus to 
the recent growth of virology. 
A tiny piece of living tissue is placed in a bottle or tube together 
with a nutrient medium and antibiotics. It is the advent of antibi- 
otics, which inhibit the growth of contaminating bacteria without 
affecting tissue cells, that has permitted the rapid growth of this 
technic in many laboratories. Tissue cells are now grown in test tubes, 
either newly obtained from tissues or from long-maintained strains. 
A particular virus will grow better in some types of cells than in 
others; for example, adenoviruses are more readily isolated in HeLa 
cells (originally obtained from a case of human cervical carcinoma) 
than in cells from a monkey’s kidney. This is akin to the phenomena 
of specific differential media used commonly in bacteriology. 
In addition, the changes produced by different viruses vary. For 
instance, poliomyelitis virus invades individual cells widely; measles 
produces more localized lesions, and large masses may result from the 
apparent fusion of cells. Indeed, a plaquelike area of destruction 
can be obtained by a technic recently described (15). This, too, aids 
in diagnosis, 
Another technic of identification makes use of tissue culture. If 
serum containing antibodies against a specific virus is added to a 
tissue-culture broth, growth of the virus is neutralized. By use of 
this tissue-culture virus-neutralization test, a serum can be tested 
for its antibody content; and, through the use of known serum, un- 
known viruses may be identified. 
A striking and colorful advance in this field has resulted from 
the technic of labeling antibodies with a fluorescing substance which 
can be seen under the fluorescence microscope. This method permits 
the localization of antibodies (and hence antigens) in tissues. The 
work of Coons and Kaplan (16) has led to methods which enable 
investigators to localize antigens (e.g., virus material) to the indi- 
vidual cells. In fact, one can determine whether virus is in the nucleus 
or cytoplasm or both. By virtue of the specificity of the antigen- 
