"^Sbiuatx^m^^^^        Preparation  of  Thyroid  Extract.  63 
whatsoever  from  the  injections.  They  were  scarcely  to  be  deter- 
mined from  the  control  pigs  that  received  no  injections  whatsoever. 
The  pigs  receiving  the  alcohol-soluble  portion  of  the  filtrate  from 
pepsin  digestion  lost  weight,  and  all  three  died  during  the  first 
month  with  a  large  loss  of  weight.  The  pigs  receiving  the  alcohol- 
soluble  portion  of  the  pepsin  digestion  residue,  corresponding  to 
iodothyrine,  increased  in  weight  like  the  normal  animals  and  were 
not  to  be  distinguished  from  the  animals  receiving  the  proteid  injec- 
tions. Those  animals  receiving  the  alcohol-soluble  portion  of  the 
extract  from  the  sheep  glands  from  which  all  coagulable  proteid  had 
been  removed  gained  somewhat  in  weight,  but  one  died  in  convul- 
sions before  the  experimental  period  was  over,  while  the  other  two 
were  not  to  be  compared  with  the  control  pigs.  From  these  results 
we  must  conclude  that  the  second  and  fourth  fractions  were  toxic. 
Their  precise  nature  we  do  not  know,  but  the  behavior  is  that  of  a 
simple  peptone.  Somewhat  similar  results  have  been  obtained  from 
other  of  the  cleavage  products,  and  further  experiments  have  given 
us  conclusive  evidence  that  these  substances  are,  in  proportion  to 
their  iodine  content,  not  to  be  compared  with  the  thyreoglobulin  in 
protecting  mice  from  acetonitril  poisoning.  The  extensive  experi- 
ments of  Cunningham  ^  give  facts  which  coincide  with  the  results 
obtained  in  this  laboratory :  z'/,c'.,  the  autolyzed  thyroid  gland  con- 
tains toxic  substances. 
Since  the  discovery  of  iodothyrine,  it  has  been  generally  con- 
sidered that  this  substance  is  the  physiologically  active  principle  of 
the  thyroid  gland,  and  that  all  the  effects  upon  metabolism  peculiar 
to  thyroid  activity  could  be  duplicated  by  the  administration  of  this 
substance  by  mouth.  It  is  the  writer's  opinion  that  such  a  conclusion 
is  not  justified  by  the  facts. 
The  physiologically  active  substance  in  the  thyroid  is  elaborated 
by  the  active  cells  lining  the  alveoli,  and  it  seems  probable  that  under 
normal  conditions  a  considerable  amount  of  this  substance  is  secreted 
into  the  alveoli  and  retained  there  as  reserve  material.  It  may, 
however,  pass  from  the  gland  cell  directly  into  the  blood  and  in  some 
pathological  conditions  we  find  practically  no  colloid,  but  an  un- 
usually well  vascularized,  actively  proliferating  parenchyma,  asso- 
ciated with  symptoms  of  over-activity  of  this  gland.  As  we  find  the 
secretion  in  normal  glands  it  is  not  in  the  form  of  iodothyrine,  but 
in  the  form  of  an  iodized  proteid,  and  a  drastic  chemical  process  is 
required  to  li1)crate  the  iodotliyrine.    Furtliermorc,  the  secretion 
