io8  Biological  Standardization  of  Drugs.  {%S:mr"' 
show  the  therapeutic  activity  of  ergot.  Biological  tests,  however, 
have  been  used  for  many  years  and  to  Robert  and  Grunfeld  may 
be  given  the  honor  of  suggesting  a  method  of  biologically  deter- 
mining- the  activity  of  this  drug.  The  method  is  that  of  producing 
the  characteristic  bluing  or  gangrene  of  the  cock's  comb  and  in 
1898  Houghton  applied  such  a  method  commercially.  In  this 
method  the  drug  is  fed  or  injected  intramuscularly  into  roosters, 
in  such  a  dose  as  to  cause  bluing  of  the  comb  and  I  believe  in  all 
cases  comparing  the  intensity  of  this  action  with  some  standard 
preparation. 
A  second  method  is  that  of  estimating-  the  amount  of  rise  in 
blood  pressure  as  a  result  of  a  given  dose.  The  stronger  the 
preparation,  the  higher  the  blood  pressure  in  direct  proportion. 
A  third  method  is  that  of  using  the  uterus  itself  as  a  test  object, 
some  workers  carrying  on  the  experiments  on  the  intact  animal 
and  others  on  the  organ  isolated  from  the  body.  Usually  cats 
are  used,  but  dogs,  guinea  pigs,  and  rabbits  have  been  tried,  with 
less  satisfactory  results,  however.  The  drug  to  be  tested  must 
be  compared  with  a  standard  preparation  carrying  out  the  test 
upon  the  same  organ  since  different  uteri  react  very  differently. 
Recently  also  Dr.  Wood  has  suggested  a  chemical  method  based 
on  the  estimation  of  the  benzole  extractive,  probably  an  impure 
ergotoxin,  after  precipitating  the  ergot  with  water.  The  increase 
in  the  amount  of  extractive  was  found  by  him  to  increase  pro- 
portionally as  the  increase  in  blood  pressure  on  injection  of 
the  drug  in  dogs.  His  premise  is  that  blood  pressure  estimations 
are  a  true  index  of  the  activity  of  a  given  preparation  and  hence 
concludes  that  the  benzole  extractive  is  an  accurate  index  of  the 
drugs  therapeutic  properties. 
A  further  chemical  method  is  the  estimation  of  the  Cornutine 
content  of  ergot — cornutine  being  an  impure  mixture  of  ergotixine 
and  ergotinine. 
Dr.  Edmunds  of  the  University  of  Michigan  and  T  have  1)een- 
engaged  in  a  study  of  the  assay  processes  for  this  druo-.  Th^ 
investigation  is  not  yet  quite  completed  but  both  of  us  feel  that 
cert'^in  facts  are  fairly  well  established. 
The  chemical  methods  of  Dr.  Wood  and  Professor  Keller  were 
used.  In  all  cases  duplicate  and  in  certain  instances  quadruple 
estimations  were  made  of  both  the  cornutine  content  and  the 
benzole  extractive.     Rippetoe's  modification  of  Wood's  method, 
