286 
CHARLES H. HIGGINS. 
With the preparation of these sera as with the preparation of 
any new medicinal agent it was but natural that some means of 
standardization should be sought. The studies of Ehrlich and 
the elaboration of his side chain theory explained the chemical 
reactions involved in the process and he was first to take the 
necessary steps toward the standardization of antFdiphtheretic 
serum. Rosenau and Anderson in endeavoring to establish a 
unit on which they could always depend have given us an elab¬ 
orate process for accomplishing this end. They found that in 
the dry state serum would retain a certain strength for an almost 
indefinite period if kept in a vacuum and at a constant tempera¬ 
ture. It is their standard unit which is now used for the guid¬ 
ance of manufacturers in the United States and a suitable amount 
is supplied for the use of each at certain stated periods. Their 
method of testing requires accurately graduated glassware, a 
standard toxine which must be made by growing a suitable 
strain of the diphtheria organism on a special liquid medium, 
and an adequate supply of guinea pigs of 250 grammes in 
weight. 
I may here mention that the details which must be observed 
when manufacturing any of the biological products requiring 
the use of large cultures are very exacting. We must not only 
have a pure culture of the organism and a suitable medium, but 
we must have a strain capable of rapid growth on the surface 
of a liquid medium. All strains do not possess this feature. For 
some purposes solid media may be used, but for routine w'ork 
we must accustom any given organism with which we may be 
working to the artificial conditions necessary for our particular 
requirements. The strongest diphtheria toxine producer is not 
necessarily the most virulent culture, nor are we able to pro¬ 
duce a satisfactory mallein or tuberculin from the most virulent 
strains of their corresponding organisms. Detailed experiments, 
must be carried out with a large number of strains before we 
can hope to secure one suitable for the production of the large 
amounts of chemical by-products required in a limited amount 
of time. 
