202 
Use  of  Antitoxins  and  Vaccines. 
Am.  Jour.  Pharm. 
May,  1914. 
understand  in  the  theories  of  the  German  and  French  schools  of 
immunity.  This  theory  of  the  American  school  does' not  contradict 
the  fact  established  by  Metchnikoff,  and  further  elucidated  by 
Wright,  that  the  white  blood-corpuscles  play  an  active  part  in 
the  removal  of  foreign  proteins,  whether  they  be  cells  or  fluids; 
nor  is  it  out  of  harmony  with  the  theory  of  Ehrlich,  who 
gives  to  the  group  of  antibodies — collectively  called  "  the  ferment  " 
by  Vaughan — different  names  according  to  their  functions. 
The  guinea  pig,  then,  at  the  end  of  two  weeks  after  the  first 
injection  of,  let  us  say,  horse  serum  contains  in  his  tissues  no  trace 
of  horse  serum ;  but  he  does  have  within  his  body  a  large  quantity 
of  protein-splitting  ferment  which  may  remain  in  the  tissues  for  a 
long  time ;  and,  even  if  it  disappears,  the  power  to  generate  this 
ferment  upon  demand  may  remain  permanently.  If  we  now  inject 
into  this  guinea  pig  a  second  dose  of  horse  serum,  the  proteins 
contained  therein  are  at  once  attacked  by  the  specific  ferment ; 
digestion  occurs  almost  immediately,  resulting  in  the  liberation 
of  a  large  quantity  of  the  poisonous  part  of  the  protein  molecule ; 
the  animal  is  overwhelmed  by  it  and  dies  usually  in  less  than  five 
minutes.  A  dose  sufficiently  large  to  cause  death  depends  upon  the 
method  of  injection;  if  injected  into  the  circulation  or  into  the 
brain,  1/20  ex.  is  sufficient;  if  injected  subcutaneously,  however,  at 
least  5  c.c.  is  usually  necessary. 
Now  as  to  the  bearing  of  this"  phenomenon  upon  infectious 
disease — Vaughan  has  used  typhoid  fever  as  a  typical  illustration. 
Infection  results  from  the  entrance  of  a  few  typhoid  bacilli  into 
the  tissues  under  circumstances  which  permit  their  growth  and 
multiplication.  There  is  normally  present  in  the  body  a  small 
amount  of  a  non-specific  protein-splitting  ferment  which  attacks 
the  typhoid  bacilli,  liberating  the  non-poisonous  part,  which  in  turn 
begins  to  stimulate  the  tissues  to  the  production  of  a  specific  anti- 
typhoid ferment.  We  know  that  in  guinea  pigs  it  takes  from  eight 
to  fourteen  days  to  produce  enough  ferment  to  cause  serious 
symptoms  of  intoxication  upon  the  injection  of  a  second  dose  of  the 
protein.  Now  this  period  corresponds  exactly  to  the  incubation 
period  in  typhoid  fever.  It  is  during  this  time  that  the  typhoid 
protein-splitting  ferment  is  produced  in  increasing  quantities,  while 
the  typhoid  bacilli  are  rapidly  growing  in  numbers.  The  ferment 
sets  free  the  poisonous  part  in  gradually  increasing  quantities  with 
the  final  appearance  and  progressive  increase  of  fever  and  the  other 
