Amju(i?,r'i9>o5ariri"}      Serum  Treatment  of  Hay  Fever.  331 
most  of  the  cases  which  were  under  observation  the  average  effect- 
ive dose  was  from  3  iQ  Q  to  2~oVo  °^  a  mimgram- 
Sensitiveness  to  the  toxin,  as  proven  by  our  tests,  is  almost  uni- 
formly constant  for  the  same  individual. 
Two  cases  may  be  cited  which  bear  upon  this  point,  one  of  them 
has  received  more  than  a  thousand  applications  of  the  toxin  to  his 
eyes  and  his  nasal  mucous  membrane  during  the  last  fifteen  months, 
and  the  other  several  hundred  during  the  same  period. 
The  reaction  in  these  two  cases  is  as  prompt  and  almost  as  intense 
as  it  was  at  first,  the  dosage  remaining  constantly  the  same.  This 
point  is  emphasized  in  order  to  show  that  there  is  no  noteworthy 
active  immunity  to  the  toxin,  notwithstanding  the  fact  that  this 
might  have  been  anticipated  in  accordance  with  Romer's  experi- 
ments in  producing  immunity  in  rabbits  by  the  instillation  of  Abrin 
into  the  conjunctival  sac.  These  investigations  have  shown  that 
the  victims  of  hay  fever  have  a  particular  sensitiveness  to  the  pollen 
of  certain  plants,  and  especially  to  that  of  the  graminaceae.  The  de- 
termination of  the  etiology  of  this  disease  may,  therefore,  be  regarded 
as  accomplished,  particularly  since  Liefman  has  demonstrated,  in  addi- 
tion to  the  facts  previously  established,  that  the  appearance  of  the 
pollen  of  the  graminaceae  is  parallel  with  that  of  the  appearance 
and  severity  of  the  hay  fever.  In  the  meantime  the  extensive  inves- 
tigations relating  to  the  preparation  of  an  antitoxin,  which  had  been 
undertaken  as  soon  as  the  origin  of  the  disease  had  been  definitely 
determined,  had  reached  a  preliminary  conclusion. 
By  the  inoculation  of  rabbits,  goats  and  horses,  serum  was  ob- 
tained which  neutralized  the  pollen  toxin  in  vitro,  and,  in  practice, 
protected  those  who  were  susceptible  to  hay  fever  from  its  attacks. 
The  manufacture  of  the  serum,  which  was  undertaken  by  Schim- 
mel  &  Co.,  of  Militz,  in  the  Spring  of  1904,  consists  in  injecting  the 
poison  subcutaneously  in  gradually  increased  doses  into  horses  which 
had  proven  sensitive  to  a  preliminary  inoculation.  As  a  rule  the 
formation  of  the  antitoxin  begins  after  two  or  three  months  of  treat- 
ment and  increases  from  week  to  week.  At  first  the  increase  is 
rapid;  it  then  gradually  becomes  less  rapid,  until  finally  the  maxi- 
mum appears  to  have  been  reached.  With  regularly  withdrawn 
samples  of  blood  a  systematic  titration  of  the  antitoxin  upon  the 
hay-fever  patient  is  accomplished  in  the  following  manner: 
First. — The  weakest  concentration,  for  example  of  a  solution  of 
