^""'Marcii  im™' }  Biological  Standardization  of  Drugs.  103 
As  a  further  objection  it  may  be  suggested  also  that  a  general 
toxic  method  would  not  show  adulteration  or  accidental  contamina- 
tion of  a  digitalis  preparation  since  a  lethal  effect  could  easily  be 
secured  from  an  action  of  any  of  a  number  of  poisons  or  possibly 
also  from  substances  formed  in  the  deterioration  which  digitalis 
preparations  are  known  to  undergo.  To  be  certain  of  a  heart 
tonic,  a  digitalis  action,  such  a  method  would  need  to  be  controlled 
by  tests  upon  the  heart  itself. 
The  other  type  methods  are  based  on  a  general  principle  which 
it  would  seem  worth  while  emphasizing — namely,  that  any  biological 
assay  method  for  any  drug  should  take  into  account  that  action 
of  the  drug  upon  zvhich  its  chief  therapeutic  usefulness  rests  and 
that  in  so  far  as  practical  difficulties  did  not  interfere  this  action 
should  he  made  the  basis  of  the  biological  method  used  in  its  assay. 
In  the  case  of  the  digitalis  group  it  would  seem  of  considerable 
importance,  if  this  be  true,  that  the  end  reaction  should  be  one 
involving  the  characteristic  effect  of  the  group  upon  the  circulation 
apparatus  and  this  can  be  done  on  mammals  only  by  making  use 
of  recording  devices  and  maintaining  artificial  respiration. 
The  type  method  of  determining  the  comparative  value  by 
noting  their  effects  upon  the  heart,  especially  of  the  frog,  is  per- 
haps the  oldest  and  at  the  present  time  the  most  widely  used  of 
all  methods  as  it  is  used  by  at  least  three  manufacturers  in  this 
country  and  exclusively  in  Germany. 
Three  sub-methods  may  be  described  although  others  are  occa- 
sionally used ;  in  one  the  drug  is  given  to  the  intact  animal  which 
is  subsequently  operated  on  to  note  the  condition  of  the  heart,  in 
another  the  drug  is  given  to  the  animal  subsequent  to  the  operative 
procedure  in  which  the  heart  is  exposed.  In  the  third  the  heart 
is  removed  from  the  body  and  perfused ;  however,  the  last  named 
methods  are  not  used  in  this  country  and  will  not  be  discussed 
on  that  account  in  this  paper. 
The  first  sub-method,  that  of  examining  the  heart  at  some 
time  subsequent  to  the  injection  of  the  drug,  the  chief  points  of 
differences  in  the  manner  of  experimicntation  has  been  in  the  time 
at  the  end  of  which  the  heart  of  the  frog  should  be  found  in  com- 
plete systole.  Time  limits  varying  from  thirty  minutes  to  two 
hours  have  been  used. 
This  method  has  been  provisionally  adopted  at  this  Laboratory 
for  testing  digitalis  and  allied  preparations.    The  general  method 
