Am.  Jour.  Pharm. ) 
March,  1910.  / 
P 1 iys iological  S ta ndardiza tio n . 
105 
standpoint  of  biological  standardization  than  any  other  drug.  As 
long  ago  as  1866  Fagge  and  Stevenson  attempted  to  determine  the 
relative  activity  of  several  members  of  the  digitalis  group  by  their 
toxicity  to  frogs.  Their  studies,  however,  were  undertaken  chiefly 
with  the  idea  of  comparing  bodies  closely  allied  physiologically  to 
digitalis,  as  antiarin,  helleborein,  and  the  like,  rather  than  prepara- 
tions of  digitalis  itself.  Apparently  it  was  fifteen  years  later  that  the 
idea  of  using  a  similar  method  for  determining  the  quality  of 
preparations  of  digitalis  was  first  projected.  In  the  year  1881, 
two  papers  were  published  upon  this  subject,  one  by  Bennefield,  who 
used  a  method  based  upon  the  quantity  of  digitalis  required  to  kill 
a  rabbit,  and  the  other  by  Frankel  who  based  his  calculations  upon 
the  changes  caused  in  the  movements  of  the  dog's  heart.  It  is  not 
my  purpose  to  enter  into  the  vigorous  discussion  which  has  been 
waged  as  to  the  relative  value  of  different  methods  of  standardizing 
digitalis ;  I  wish  only  to  express  my  conviction  that  no  method  of 
biological  assay,  the  conclusions  of  which  are  expressed  in  units 
of  a  standard  preparation,  can  be  held  to  be  satisfactory.  The 
result  of  the  physiological  test  must  be  such  that  it  can  be  expressed 
in  absolute  language,  perhaps  like  that  which  is  used  to  express  the 
standard  for  diphtheria  toxin :  the  amount  required  to  kill  a  certain 
weight  of  a  certain  animal  in  a  given  period  of  time,  and  under 
conditions  which  are  accurately  described. 
The  first  result  of  the  physiological  assays  of  digitalis  was  to 
yield  scientific  proof  of  a  fact  that  was  already  shrewdly  guessed, 
namely,  that  different  samples  of  the  drug  varied  enormously  in  their 
potency.  It  has  been  shown  by  a  large  number  of  investigators  that 
the  ordinary  range  of  variation  of  different  specimens  of  digitalis 
is  anywhere  within  a  limit  of  400  per  cent.  That  is,  that  the  strong- 
est sample  will  be  about  four  times  as  active  as  the  weakest.  Farr 
and  Haynes  found  that  the  prejudice  in  favor  of  the  second  year 
leaves  of  the  Digitalis  purpurea  is  only  partially  justified;  for  while 
it  is  true  that  in  the  samples  they  examined  the  leaves  of  the  second 
year's  growth  were  slightly  more  active  than  those  of  the  first  year's 
growth,  the  difference  was  only  as  8  to  10.  Focke  has  shown  that 
the  leaves  of  the  wild  digitalis  are  more  potent  than  those  of  the 
cultivated  plant,  and  in  the  samples  he  examined  Ott  found  that 
those  which  came  from  Bohemia  were  more  potent  than  those  from 
other  parts  of  Europe.  Wolff  found  that  the  deterioration  of  the 
crude  digitalis  leaves  was  due  almost  solely  to  improper  methods 
