﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  557 
  

  

  making 
  a 
  study 
  of 
  staphylococci. 
  Culture 
  dishes 
  of 
  the 
  bacteria 
  were 
  

   kept 
  in 
  the 
  laboratory 
  for 
  periodic 
  inspection, 
  during 
  which 
  they 
  

   were 
  exposed 
  to 
  the 
  air. 
  Fleming 
  noticed 
  that 
  in 
  one 
  dish, 
  which 
  had 
  

   become 
  contaminated 
  with 
  a 
  mold 
  (similar 
  to 
  the 
  common 
  blue 
  mil- 
  

   dew 
  on 
  jam 
  or 
  citrus 
  fruits), 
  the 
  surrounding 
  Staphylococcus 
  colonies 
  

   became 
  transparent 
  and 
  were 
  dissolved. 
  This 
  is 
  the 
  type 
  of 
  observa- 
  

   tion 
  of 
  a 
  chance 
  occurrence 
  which 
  is 
  frequently 
  made 
  by 
  scientific 
  in- 
  

   vestigators. 
  But 
  it 
  is 
  only 
  by 
  the 
  alert, 
  inquisitive, 
  and 
  trained 
  worker 
  

   that 
  further 
  exploitation 
  is 
  made. 
  In 
  the 
  words 
  of 
  Pasteur: 
  "Chance 
  

   favors 
  the 
  mind 
  that 
  is 
  prepared." 
  Fleming 
  transferred 
  the 
  mold 
  to 
  

   a 
  liquid 
  nutrient 
  solution 
  and 
  found 
  that 
  there 
  appeared 
  in 
  the 
  fluid 
  

   a 
  substance 
  that 
  was 
  markedly 
  inhibitory 
  toward 
  many 
  of 
  the 
  more 
  

   common 
  disease-producing 
  bacteria. 
  The 
  mold 
  was 
  later 
  identified 
  

   as 
  Penicillvwm 
  notatum 
  and 
  its 
  bactericidal 
  culture 
  filtrate 
  was 
  des- 
  

   ignated 
  "penicillin." 
  Recently 
  a 
  preparation 
  with 
  very 
  similar 
  

   antibacterial 
  properties 
  has 
  been 
  obtained 
  also 
  from 
  Penicillium 
  

   chrysogenum. 
  

  

  Fleming 
  clearly 
  realized 
  the 
  potential 
  utility 
  of 
  the 
  active 
  material 
  

   as 
  a 
  chemotherapeutic 
  agent, 
  which 
  must 
  have 
  two 
  essential 
  character- 
  

   istics: 
  ability 
  to 
  inhibit 
  pathogenic 
  organisms 
  and 
  low 
  toxicity 
  toward 
  

   living 
  tissues. 
  Penicillin 
  was 
  found 
  to 
  combine 
  these 
  properties 
  to 
  an 
  

   unusual 
  extent. 
  It 
  was 
  not 
  at 
  all 
  toxic 
  to 
  animals 
  but 
  was 
  at 
  least 
  

   twice 
  as 
  powerful 
  an 
  inhibitor 
  as 
  carbolic 
  acid 
  toward 
  sensitive 
  organ- 
  

   isms, 
  such 
  as 
  the 
  various 
  pus-producing 
  cocci. 
  

  

  Local 
  application 
  of 
  penicillin 
  to 
  septic 
  wounds 
  was 
  tried 
  in 
  a 
  

   limited 
  number 
  of 
  cases 
  with 
  generally 
  favorable, 
  although 
  not 
  

   miraculous, 
  results. 
  The 
  further 
  investigation 
  of 
  the 
  substance 
  as 
  a 
  

   therapeutic 
  agent 
  suffered 
  from 
  a 
  serious 
  handicap 
  — 
  it 
  was 
  very 
  diffi- 
  

   cult 
  to 
  prepare 
  in 
  sufficiently 
  large 
  quantity 
  and 
  in 
  purified 
  condition, 
  

   owing 
  chiefly 
  to 
  its 
  chemical 
  instability 
  which 
  resulted 
  in 
  loss 
  of 
  anti- 
  

   bacterial 
  activity. 
  In 
  the 
  decade 
  following 
  its 
  discovery, 
  no 
  further 
  

   progress 
  along 
  this 
  line 
  was 
  made, 
  although 
  it 
  was 
  employed 
  for 
  the 
  

   purpose 
  of 
  isolating 
  certain 
  types 
  of 
  bacteria 
  which, 
  on 
  the 
  ordinary 
  

   culture 
  media, 
  were 
  overgrown 
  by 
  accompanying 
  species. 
  By 
  this 
  

   means 
  it 
  was 
  shown 
  that 
  the 
  so-called 
  influenza 
  bacillus 
  was 
  present 
  in 
  

   the 
  mouths 
  of 
  all 
  normal 
  persons 
  examined 
  and 
  hence 
  was 
  probably 
  

   not 
  the 
  causal 
  organism 
  of 
  epidemic 
  influenza, 
  as 
  had 
  theretofore 
  been 
  

   widely 
  assumed. 
  More 
  recently, 
  penicillin 
  has 
  been 
  used 
  to 
  isolate 
  

   the 
  acne 
  bacillus 
  from 
  acne 
  pustules 
  and 
  so 
  to 
  make 
  possible 
  a 
  simple 
  

   method 
  for 
  the 
  preparation 
  of 
  autogenous 
  vaccines 
  of 
  the 
  organism. 
  

  

  The 
  discovery 
  and 
  rapid 
  development 
  of 
  the 
  sulfonamide 
  drugs 
  

   since 
  1935 
  had 
  stimulated 
  renewed 
  interest 
  in 
  chemotherapy, 
  and 
  the 
  

   success 
  of 
  gramicidin 
  had 
  directed 
  attention 
  to 
  the 
  antibiotic 
  agents 
  

   of 
  microbial 
  origin. 
  In 
  1940 
  a 
  research 
  team 
  at 
  Oxford 
  University 
  

  

  