﻿SULFONAMIDES— 
  FOX 
  571 
  

  

  well 
  as 
  in 
  the 
  body. 
  Since 
  this 
  sulfanilamide 
  part 
  had 
  first 
  been 
  made 
  

   in 
  1908 
  by 
  Gelmo 
  — 
  who, 
  by 
  the 
  way, 
  had 
  found 
  that 
  this 
  chemical 
  

   helped 
  dyes 
  stick 
  to 
  wool 
  — 
  there 
  were 
  no 
  patent 
  restrictions 
  and 
  every 
  

   chemical 
  company 
  began 
  making 
  sulfanilamide 
  so 
  that 
  doctors 
  every- 
  

   where 
  could 
  try 
  it 
  out. 
  

  

  In 
  the 
  meanwhile 
  research 
  was 
  conducted 
  in 
  many 
  laboratories, 
  

   including 
  this, 
  to 
  determine 
  how 
  sulfanilamide 
  worked. 
  

  

  It 
  was 
  soon 
  found 
  that 
  bacteria 
  were 
  not 
  killed 
  by 
  the 
  drug 
  but 
  

   that 
  their 
  rate 
  of 
  multiplication 
  was 
  temporarily 
  retarded. 
  This 
  

   was 
  called 
  bacteriostasis. 
  In 
  the 
  animal 
  organism, 
  this 
  retardation 
  

   aided 
  the 
  white 
  blood 
  cells 
  to 
  gain 
  the 
  upper 
  hand 
  and 
  effectively 
  

   dispose 
  of 
  the 
  inhibited 
  bacteria. 
  Furthermore, 
  this 
  bacteriostatic 
  

   effect 
  did 
  not 
  begin 
  immediately 
  but 
  only 
  after 
  a 
  lag 
  of 
  several 
  hours 
  

   during 
  which 
  time 
  the 
  bacteria 
  in 
  the 
  drug 
  environment 
  grew 
  just 
  as 
  

   well 
  as 
  the 
  control 
  bacteria. 
  It 
  is 
  possible 
  that 
  this 
  delay 
  in 
  action 
  

   represented 
  the 
  time 
  needed 
  for 
  conversion 
  of 
  the 
  drug 
  itself 
  by 
  oxida- 
  

   tion 
  to 
  an 
  active 
  principle. 
  

  

  A 
  recent 
  discovery, 
  however, 
  has 
  led 
  to 
  another 
  explanation. 
  That 
  

   is 
  Woods' 
  observation 
  that 
  para-aminobenzoic 
  acid 
  almost 
  specifically 
  

   nullifies 
  the 
  action 
  of 
  sulfanilamide, 
  and 
  that 
  there 
  is 
  a 
  definite 
  quanti- 
  

   tative 
  relationship; 
  i. 
  e., 
  one 
  part 
  of 
  PAB 
  can 
  "block" 
  or 
  nullify 
  

   5,000 
  parts 
  of 
  sulfanilamide. 
  This 
  ratio 
  obtains 
  regardless 
  of 
  which 
  

   bacterium 
  is 
  used 
  for 
  the 
  test. 
  Woods 
  suggested 
  that 
  PAB 
  is 
  an 
  

   essential 
  metabolite 
  for 
  the 
  bacteria 
  and 
  that 
  sulfanilamide 
  because 
  

   of 
  its 
  chemical 
  similarity 
  "blocks" 
  the 
  utilization 
  of 
  PAB 
  by 
  bacteria. 
  

   Although 
  PAB 
  has 
  been 
  shown 
  to 
  be 
  an 
  essential 
  growth 
  factor 
  for 
  

   two 
  nonpathogenic 
  bacteria, 
  it 
  has 
  not 
  yet 
  been 
  shown 
  to 
  participate 
  

   in 
  the 
  metabolism 
  of 
  pathogenic 
  bacteria 
  so 
  the 
  mechanism 
  of 
  the 
  

   definite 
  antisulfonamide 
  action 
  of 
  PAB 
  remains 
  to 
  be 
  discovered. 
  

  

  It 
  is 
  important 
  to 
  differentiate 
  PAB 
  from 
  the 
  other 
  so-called 
  "inhib- 
  

   itors" 
  of 
  sulfanilamide. 
  Pus, 
  peptone, 
  devitalized 
  tissue, 
  and 
  certain 
  

   bacterial 
  extracts 
  have 
  been 
  asserted 
  to 
  "inhibit" 
  the 
  action 
  of 
  sulfa- 
  

   nilamide. 
  Careful 
  study 
  has 
  shown, 
  however, 
  that 
  in 
  general 
  these 
  

   substances 
  improve 
  the 
  growth 
  of 
  bacteria 
  so 
  that 
  the 
  drug 
  has 
  to 
  

   grapple 
  with 
  more 
  vigorously 
  growing 
  organisms. 
  These 
  are 
  quite 
  

   different 
  from 
  PAB 
  which 
  does 
  not 
  appear 
  to 
  alter 
  the 
  growth 
  of 
  

   bacteria, 
  nevertheless 
  definitely 
  inhibits 
  sulfanilamide 
  bacteriostasis. 
  

   The 
  practical 
  importance 
  of 
  this 
  distinction 
  will 
  be 
  clarified 
  below. 
  

  

  During 
  this 
  time 
  chemists 
  were 
  attempting 
  to 
  synthesize 
  sulfanil- 
  

   amide 
  like 
  compounds 
  which 
  might 
  be 
  more 
  potent 
  and 
  more 
  effective 
  

   against 
  a 
  wider 
  variety 
  of 
  bacteria 
  than 
  sulfanilamide 
  itself. 
  Sulfa- 
  

   pyridine 
  was 
  the 
  first 
  important 
  improvement 
  and 
  established 
  its 
  

   merit 
  by 
  the 
  success 
  attained 
  in 
  the 
  treatment 
  of 
  pneumonia. 
  Soon 
  

   afterward, 
  sulfathiazole 
  was 
  synthesized. 
  This 
  substance 
  is 
  free 
  of 
  

  

  