f^e^^i920^^^"'^  }    Active  Principle  of  Thyroid  Gland.  415 
peutics.  B.  C.  Kendall,  working  in  the  clinic  of  the  Brothers  Mayo, 
of  Rochester,  has  succeeded  in  isolating  in  a  crystalline  form  the 
iodised  active  principle  of  the  thyroid  gland,  that  mysterious  body 
which  seems  to  play  such  an  exceedingly  important  role  in  living 
processes.  In  the  Journal  of  Biological  Chemistry  (Vol.  xxxix.) 
lie  reviews  his  investigations  on  this  point,  which  began  as  far  back 
as  1 9 10.  At  first  he  used  barium  salts  to  separate  this  substance,  to 
which  the  name  of  "thyroxin"  has  been  given,  and  first  succeeded  in 
isolating  it  in  December,  19 14,  the  total  amount  obtained  being 
100  milligrams.  In  February,  191 6,  the  action  of  carbonic  acid  on 
the  process  of  isolating  this  body  was  discovered,  resulting  in  the 
production  of  7  grams  by  May,  191 7.  This  amount  was  used  to 
ascertain  the  chemical  structure  of  the  new  body,  and  based  on  these 
findings.  Osterberg  succeeded  in  preparing  a  small  quantity  of 
thyroxin  by  synthetic  methods.  At  the  time  of  publishing  his  paper, 
the  author  had  succeeded  in  preparing  about  35  grams  of  thyroxin 
from  3,275  kilograms  of  fresh  thyroid  glands,  obtained  almost  exclu- 
sively from  pigs.  The  yield  consequently  works  out  at  the  ratio 
of  I  gram  of  thyroxin  for  100  kilograms  of  thyroid  gland.  The  fol- 
lowing process  was  adopted:  The  fresh  thyroid  glands  are  hydro- 
lysed  in  a  5  per  cent,  soda  solution.  The  fats  are  removed  by  being 
transformed  into  insoluble  sodium  soap.  The  alkaline  filtrate  is 
acidified  after  cooling,  and  the  precipitate  thrown  down  contains 
practically  the  whole  of  the  thyroxin  present.  This  precipitate  is 
separated  and  dissolved  in  a  solution  of  soda,  and  again  precipitated 
by  the  addition  of  hydrochloric  acid.  The  precipitate,  after  drying 
at  ordinary  temperatures,  is  dissolved  in  alcohol  (95  per  cent.),  and 
to  neutralize  the  remaining  excess  of  hydrochloric  acid  present  in 
this  dried  precipitate,  solution  of  soda  is  added,  which  gives  rise  to  a 
compact,  black  and  sticky  precipitate,  which  is  separated  by  filtra- 
tion. To  the  alcoholic  filtrate  a  very  concentrated,  hot  aqueous 
solution  of  barium  hydroxide  is  added,  and  the  mixture  is  boiled 
under  a  reflux  condenser  to  remove  all  the  impurities  and  coloring 
matter  present.  A  trace  of  soda  is  added  to  the  filtrate,  through 
which  a  current  of  carbonic  acid  gas  is  passed,  whereupon  the  car- 
bonates which  have  formed  are  removed  by  filtration,  and  the 
alcohol  by  distillation.  Hydrochloric  acid  is  now  added  to  the 
aqueous  solution,  the  precipitate  thrown  down  is  dissolved  in  an 
alkaline  alcoholic  solution,  and  the  latter  saturated  with  carbonic 
acid  gas.    The  solution  is  filtered,  the  alcohol  removed  by  dis- 
