﻿546 
  ANNUAL 
  REPORT 
  SMITHSONIAN 
  INSTITUTION, 
  1943 
  

  

  successful 
  chemotherapy 
  by 
  a 
  synthetic 
  compound 
  could 
  be 
  regarded 
  

   as 
  accomplished. 
  Hopes 
  were 
  again 
  raised 
  that, 
  having 
  reached 
  this 
  

   milestone, 
  further 
  progress 
  would 
  be 
  rapid, 
  but 
  once 
  again 
  the 
  expecta- 
  

   tion 
  proved 
  futile. 
  In 
  the 
  ensuing 
  quarter 
  of 
  a 
  century 
  only 
  a 
  hand- 
  

   ful 
  of 
  useful 
  chemotherapeutic 
  agents 
  were 
  developed 
  and 
  all 
  these, 
  

   like 
  quinine 
  and 
  salvarsan, 
  were 
  limited 
  to 
  the 
  treatment 
  of 
  protozoal 
  

   diseases. 
  All 
  experience 
  indicated 
  that 
  the 
  ordinary 
  pathogenic 
  

   bacteria 
  could 
  not 
  be 
  attacked 
  by 
  chemotherapy. 
  

  

  Then 
  in 
  1935 
  announcement 
  was 
  made 
  of 
  the 
  curative 
  effects 
  on 
  

   bacterial 
  infections 
  in 
  mice 
  by 
  the 
  dye 
  prontosil. 
  It 
  was 
  soon 
  shown 
  

   that 
  the 
  action 
  of 
  this 
  compound 
  is 
  due 
  entirely 
  to 
  a 
  small 
  portion 
  

   of 
  the 
  molecule, 
  sulfanilamide. 
  From 
  this 
  parent 
  substance 
  have 
  

   been 
  derived 
  all 
  the 
  sulfonamide 
  compounds 
  so 
  widely 
  used 
  in 
  recent 
  

   years. 
  In 
  a 
  period 
  of 
  half 
  a 
  dozen 
  years 
  approximately 
  three 
  

   thousand 
  derivatives 
  and 
  related 
  compounds 
  have 
  been 
  tested; 
  four 
  

   of 
  these 
  — 
  sulfapyridine, 
  sulfaguanidine, 
  sulfathiazole, 
  and 
  sulfadia- 
  

   zine— 
  have 
  been 
  outstanding. 
  The 
  introduction 
  of 
  these 
  drugs 
  has 
  rev- 
  

   olutionized 
  many 
  phases 
  of 
  medicine. 
  Dozens 
  of 
  infectious 
  diseases 
  

   have 
  responded 
  to 
  sulfonamide 
  therapy, 
  and 
  the 
  prospects 
  for 
  cases 
  

   of 
  septicemia, 
  pneumonia, 
  scarlet 
  fever, 
  and 
  meningitis, 
  to 
  mention 
  

   only 
  a 
  few, 
  have 
  been 
  dramatically 
  improved. 
  Without 
  doubt 
  

   hundreds 
  of 
  thousands 
  of 
  lives 
  have 
  already 
  been 
  saved 
  by 
  the 
  sul- 
  

   fonamides. 
  

  

  These 
  drugs 
  are 
  not, 
  however, 
  without 
  their 
  disadvantages. 
  In 
  

   many 
  patients 
  they 
  produce 
  symptoms 
  of 
  great 
  discomfort 
  and 
  may 
  

   even 
  cause 
  severe 
  toxic 
  effects 
  and 
  tissue 
  damage. 
  Further, 
  it 
  has 
  

   been 
  discovered 
  that 
  some 
  strains 
  of 
  pneumococci 
  and 
  other 
  bacteria 
  

   are 
  resistant 
  to 
  the 
  action 
  of 
  the 
  sulfonamides, 
  so 
  that 
  a 
  considerable 
  

   percentage 
  of 
  infections 
  by 
  these 
  bacteria 
  is 
  not 
  amenable 
  to 
  the 
  

   treatment. 
  Even 
  in 
  the 
  case 
  of 
  susceptible 
  organisms, 
  there 
  are 
  other 
  

   limitations 
  on 
  the 
  usefulness 
  of 
  the 
  sulfonamide 
  compounds. 
  Their 
  

   antibacterial 
  activity 
  is 
  greatly 
  diminished 
  in 
  the 
  presence 
  of 
  large 
  

   numbers 
  of 
  bacterial 
  cells, 
  even 
  of 
  dead 
  bacteria, 
  and 
  also 
  by 
  the 
  

   presence 
  of 
  pus, 
  blood 
  serum, 
  and 
  various 
  products 
  of 
  tissue 
  destruc- 
  

   tion, 
  all 
  of 
  which 
  are 
  very 
  likely 
  to 
  be 
  found 
  in 
  infected 
  wounds. 
  

  

  While 
  progress 
  in 
  the 
  sulfonamide 
  field 
  still 
  continues 
  and 
  further 
  

   valuable 
  discoveries 
  may 
  well 
  be 
  anticipated, 
  the 
  successes 
  here 
  have 
  

   served 
  to 
  stimulate 
  rather 
  than 
  to 
  deter 
  investigation 
  of 
  other, 
  un- 
  

   related, 
  chemotherapeutic 
  agents. 
  A 
  powerful 
  impetus 
  to 
  these 
  

   studies 
  has 
  been 
  furnished 
  by 
  the 
  present 
  war 
  with 
  its 
  greatly 
  

   increased 
  demand 
  for 
  better 
  antiseptics. 
  

  

  Within 
  the 
  past 
  few 
  years, 
  considerable 
  attention 
  has 
  been 
  given 
  

   to 
  a 
  number 
  of 
  substances 
  which 
  are 
  the 
  metabolic 
  products 
  of 
  various 
  

  

  