Am.  Jour.  Pharm. 
Nov.,  1918. 
Diph  th  eria  A n titoxin. 
765 
THE  CHEMISTRY  OF  DIPHTHERIA  ANTITOXIN— A 
REVIEW.1 
By  Albert  C.  Crawford  and  Marjorie  G.  Foster. 
The  indications  at  present  are  that  rational  therapeutics  will  ad- 
vance mainly  by  using  chemotherapeutic  methods,  or  by  adopting 
those  used  by  nature,  that  is,  by  the  use  of  the  products  of  various 
glands  and  of  antitoxins,  etc.  With  this  latter, idea  in  view,  we  have 
endeavored  to  present  the  results  of  investigations  on  the  chemical 
nature  of  the  diphtheria  antitoxin,  and  hope  to  follow  this  summary 
with  a  report  of  our  own  experiments. 
Up  to  the  present  time,  very  little  has  been  ascertained  as  to  the 
chemical  nature  of  the  antitoxins.  Weichardt  says  that  in  spite  of 
hundred-fold  attempts  to  isolate  the  diphtheria  antitoxin,  as  yet 
these  have  been  futile.2 
Reports  differ  as  to  the  response  of  diphtheria  antitoxin  to  re- 
agents. Since  the  antitoxin  has  never  been  isolated,  the  colloids  of 
the  serum  presumably  may  modify  the  reaction  in  various  ways,  and 
protect  the  antitoxin  from  their  action.  Normally  the  degree  of 
concentration  of  colloids  in  the  serum  offers  an  obstacle  to  the  ac- 
tivity of  proteolytic  ferments.3  It  may  be  that  in  a  pure  form 
diphtheria  antitoxin  might  thus  react  differently  than  when  in 
serum,  in  milk,  or  if  combined  with  its  toxin.  Another  explanation 
may  be  that  the  antitoxin  is  a  colloid,  at  least  under  ordinary  condi- 
tions, with  a  large  molecule,  and  may  contain  numerous  reactive, 
groups.  In  colloids  the  properties  due  to  chemical  nature  may  be 
OA^er-shadowed  by  their  physico-chemical  condition. 
During  immunization,  lowering  of  the  freezing  point  and  of  the 
osmotic  pressure  of  the  serum  occurs.  The  electrical  conductivity 
decreases  in  proportion  to  the  antitoxic  activity.4 
According  to  Mellanby,  a  constant  current  (100  volts),  if  passed 
through  a  slightly  acidified  antitoxic  serum  by  means  of  zinc  elec- 
1  From  the  Division  of  Pharmacology,  Stanford  University  Medical 
School,  San  Francisco,  Cal.  This  report  was  supported  by  a  grant  from  the 
Therapeutic  Research  Committee  of  the  Council  on  Pharmacy  and  Chemistry 
of  the  American  Medical  Association. 
2  Abderhalden,  E.,  Biochem.  Handlexikon,  Vol.  5,  p.  518. 
3  Bronfenbrenner,  J.,  Proc.  Soc.  Exper.  Biol.,  Vol.  13,  p.  19,  1915. 
4  v.  Szontagh,  F.,  and  Wellmann,  O.,  Deutsch.  med.  Woch.,  Vol.  24,  p. 
421;  Butjagin,  P.  W.,  Hyg.  Rund.,  Vol.  12,  p.  1209,  1902. 
