loo  Biological  Standardization  of  Drugs,  {^^t^uj^n"^' 
no  less  than  15  or  20  methods  have  been  proposed  for  their  assay. 
So  much  discussion  of  these  metliods  has  been  indulged  in  and 
so  many  statements  more  or  less  supported  and  often  unsupported 
by  experimental  evidence  have  been  offered  by  the  exponents  of 
a  particular  method  that  it  seems  worth  while  to  take  up  the 
various  phases  of  the  problem  at  this  time,  and  this  especially 
because  of  the  possible,  and  I  hope  probable,  adoption  of  some 
method  by  the  committee  of  revision  of  the  next  Pharmacopoeia. 
If  accurate  and  reliable  are  the  modifying  phrases  in  the  recom- 
mendation of  the  Pharmacopoeial  Convention  regarding  biological 
standards.  How  accurate;  How  reliable — Digitalis  preparations, 
tinctures,  fluidextracts,  tablet  triturates,  and  hypodermic  tablets,  as 
purchased  direct  from  the  manufacturers,  vary  about  400  per  cent, 
in  activity.  Is  the  revision  committee  willing  to  adopt  any  method 
which  will  reduce  this  enormous  variation  to  50  per  cent?  I  am 
absolutely  certain  it  will  mean  that  lives  will  be  saved  every  year. 
If  any  biological  method  will  reduce  the  variation  of  the  prepara- 
tions on  the  market  to  25  per  cent,  instead  of  400  will  it  be  worth 
while?  Will  it  be  accurate  enough?  I  would  much  prefer  that 
I  myself  should  be  assured  by  the  Pharmacopoeia  of  a  drug  with 
no  more  than  25  per  cent,  variation  rather  than  to  tbke  my 
chances  with  a  drug  now  of  one  strength  and  on  a  refilled  pre- 
scription one  or  four  times  the  strength. 
In  this  country  four  methods  have  been  proposed,  namely, 
Houghton's  twelve  hour  frog  method,  Reed  and  Vanderkleed's 
method  using  the  guinea  pig,  a  method  proposed  by  Hatcher 
using  the  cat ;  all  of  these  methods  depending  on  the  determination 
of  the  least  fatal  dose  for  the  animal  in  question,  and  finally  the 
method  proposed  by  Famulener  and  Lyons,  that  of  determining 
the  least  amount  of  the  drug  to  stop  the  heart  of  a  frog  in  o-ne 
hour. 
Houghton's  method  is  to  choose  frogs  of  about  the  same  weight 
and  inject  them  with  a  given  amount  of  the  drug.  If,  at  the 
end  of  12  hours,  the  animal  is  dead  the  dose  is  reduced,  if  alive 
the  dose  is  increased.  By  use  of  a  series  of  frogs  with  varying 
doses  the  assay  may  be  hastened.  An  experiment  published  in  the 
American  Journal  of  Pharmacy  indicates  that  3  days  were 
required  to  make  the  assay,  and  the  assay  required  the  use  of 
14  frogs,  the  cost  of  which  in  any  section  of  the  United  States 
including  express  charges  would  be  under  one  dollar.    In  Washing- 
I 
