﻿134 
  

  

  Dr. 
  H. 
  H. 
  Dale. 
  

  

  with 
  a 
  proteolytic 
  ferment 
  in 
  the 
  blood, 
  and 
  initiated 
  its 
  rapid 
  digestion.* 
  

   In 
  a 
  more 
  recent 
  form 
  of 
  the 
  theory 
  it 
  is 
  supposed 
  that 
  the 
  formation 
  

   of 
  this 
  complex 
  removes 
  the 
  antitryptic 
  factor 
  present 
  in 
  normal 
  blood, 
  

   releases 
  the 
  action 
  of 
  the 
  tryptic 
  ferment, 
  and 
  thereby 
  initiates 
  an 
  autolytic 
  

   cleavage 
  of 
  the 
  blood 
  proteins.f 
  Another 
  type 
  of 
  theory 
  regards 
  the 
  forma- 
  

   tion 
  of 
  the 
  complex 
  of 
  antigen 
  and 
  antibody 
  as 
  disturbing 
  the 
  delicate 
  

   equilibrium 
  of 
  the 
  plasma 
  colloids 
  like 
  contact 
  with 
  a 
  foreign 
  surface, 
  thereby 
  

   initiating 
  changes 
  analogous 
  to 
  those 
  which 
  precede 
  clotting, 
  and 
  imparting 
  

   to 
  the 
  blood 
  a 
  toxicity 
  similar 
  to 
  that 
  which 
  appears 
  during 
  that 
  process, 
  

   or 
  in 
  some 
  vaguer 
  way 
  rendering 
  it 
  toxic 
  by 
  disturbance 
  of 
  the 
  state 
  of 
  

   colloidal 
  solution.} 
  

  

  If 
  we 
  consider 
  the 
  large 
  mass 
  of 
  evidence 
  put 
  forward 
  in 
  support 
  of 
  

   these 
  plausible 
  and 
  attractive 
  hypotheses, 
  we 
  find 
  that 
  it 
  almost 
  all 
  depends 
  

   on 
  the 
  possibility 
  of 
  artificially 
  enhancing 
  the 
  toxicity 
  of 
  blood 
  serum 
  

   in 
  vitro. 
  Serum 
  freshly 
  separated 
  from 
  clotted 
  blood 
  retains 
  some 
  of 
  the 
  

   toxicity 
  which 
  is 
  developed 
  during 
  clotting, 
  but 
  much 
  of 
  this 
  toxicity 
  

   seems 
  to 
  have 
  disappeared. 
  This 
  natural 
  slight 
  toxicity 
  of 
  a 
  fresh 
  serum 
  

   can 
  be 
  enhanced, 
  or 
  revived, 
  by 
  treating 
  it 
  in 
  various 
  ways. 
  Some 
  of 
  these 
  

   have 
  an 
  apparent 
  relation 
  to 
  the 
  anaphylactic 
  phenomena, 
  as 
  when 
  serum 
  

   is 
  incubated 
  with 
  the 
  specific 
  precipitate 
  formed 
  by 
  an 
  antigen 
  with 
  a 
  

   precipitating 
  serum. 
  In 
  some 
  the 
  connection 
  is 
  remote, 
  as 
  when 
  the 
  serum 
  

   is 
  incubated 
  with 
  an 
  emulsion 
  of 
  dead 
  or 
  living 
  bacteria. 
  Serum 
  has 
  been 
  

   rendered 
  toxic 
  by 
  shaking 
  it 
  with 
  chloroform, 
  by 
  acidulating 
  it 
  and 
  filtering 
  

   through 
  kieselguhr, 
  by 
  contact 
  with 
  kaolin, 
  and 
  with 
  sols 
  of 
  silica, 
  agar-agar, 
  

   starch, 
  inulin, 
  or 
  with 
  heat-coagulated 
  protein. 
  § 
  In 
  some 
  cases 
  the 
  

   appearance 
  of 
  the 
  toxicity 
  is 
  accompanied 
  by 
  autolytic 
  cleavage 
  of 
  the 
  

   serum 
  proteins, 
  in 
  others, 
  none 
  can 
  be 
  detected. 
  In 
  some 
  experiments 
  

   with 
  Walpole|| 
  I 
  found 
  that 
  autolysis 
  of 
  serum 
  or 
  plasma, 
  brought 
  about 
  

   by 
  removing 
  the 
  natural 
  antitryptic 
  factor, 
  was 
  accompanied 
  by 
  liberation 
  

   of 
  a 
  thrombokinetic 
  substance. 
  Injection 
  of 
  such 
  serum 
  into 
  a 
  guinea-pig 
  

   caused 
  rapid 
  death, 
  with 
  symptoms 
  having 
  a 
  superficial 
  resemblance 
  to 
  the 
  

   anaphylactic 
  shock 
  ; 
  but 
  the 
  cause 
  of 
  death 
  was 
  a 
  massive 
  coagulation 
  of 
  

   blood 
  in 
  all 
  the 
  vessels. 
  Serum 
  rendered 
  toxic 
  by 
  incubation 
  with 
  agar, 
  

   on 
  the 
  other 
  hand, 
  which 
  produces 
  no 
  perceptible 
  autolysis, 
  kills 
  the 
  

  

  * 
  Friedberger, 
  ' 
  Zeitschr. 
  f. 
  Immun.,' 
  vol. 
  4 
  (1909). 
  

  

  t 
  Jobling 
  and 
  Petersen, 
  ' 
  Journ. 
  Exp. 
  Med.,' 
  vol. 
  20, 
  p. 
  37 
  (1914); 
  Bronfenbrenner, 
  

   ' 
  Journ. 
  Exp. 
  Med.,' 
  vol. 
  21, 
  p. 
  480 
  (1915). 
  

  

  } 
  Doerr, 
  'Kolle 
  und 
  Wassermann's 
  Handbuch,' 
  1913, 
  Art. 
  " 
  Anaphylaxie 
  " 
  ; 
  Novy 
  and 
  

   De 
  Kruif, 
  'Journ. 
  Infect. 
  Dis.,' 
  vol. 
  20, 
  Nos. 
  5 
  and 
  6 
  (1917). 
  

  

  § 
  A 
  review 
  of 
  experiments 
  of 
  this 
  type 
  is 
  given 
  by 
  Sachs, 
  1 
  Kolloid 
  Zeitschr.,' 
  1919. 
  

  

  || 
  ' 
  Bioehem. 
  Journ.,' 
  vol. 
  10, 
  p. 
  331 
  (1916). 
  

  

  