﻿558 
  ANNUAL 
  REPORT 
  SMITHSONIAN 
  INSTITUTION, 
  194 
  3 
  

  

  commenced 
  a 
  concerted 
  attack 
  on 
  the 
  penicillin 
  problem 
  from 
  several 
  

   directions; 
  the 
  promise 
  of 
  the 
  initial 
  results 
  inspired 
  a 
  large 
  number 
  

   of 
  investigators 
  on 
  both 
  sides 
  of 
  the 
  Atlantic 
  to 
  take 
  up 
  the 
  work. 
  In 
  

   the 
  United 
  States 
  a 
  number 
  of 
  governmental 
  laboratories 
  are 
  now 
  

   participating 
  in 
  this 
  research. 
  

  

  Obviously 
  the 
  widespread 
  utilization 
  of 
  any 
  rare 
  biological 
  product 
  

   would 
  be 
  greatly 
  facilitated 
  if 
  the 
  substance 
  could 
  be 
  prepared 
  artifi- 
  

   cially. 
  In 
  recent 
  years 
  we 
  have 
  seen 
  numerous 
  instances 
  of 
  the 
  rapid 
  

   extension 
  of 
  use 
  which 
  follows 
  the 
  success 
  of 
  the 
  chemist 
  in 
  synthesiz- 
  

   ing 
  natural 
  materials 
  ; 
  some 
  of 
  the 
  vitamins 
  are 
  outstanding 
  examples. 
  

   Further 
  than 
  this 
  there 
  always 
  exists 
  the 
  possibility 
  of 
  improving 
  na- 
  

   ture's 
  product 
  by 
  some 
  modification 
  of 
  the 
  chemical 
  structure 
  of 
  the 
  

   molecule. 
  As 
  a 
  matter 
  of 
  fact, 
  it 
  is 
  not 
  the 
  synthesis 
  but 
  the 
  deter- 
  

   mination 
  of 
  the 
  structure 
  of 
  the 
  natural 
  product 
  which 
  is 
  the 
  funda- 
  

   mental 
  and 
  difficult 
  problem, 
  for 
  once 
  the 
  chemical 
  pattern 
  is 
  known 
  

   the 
  synthetic 
  chemist 
  can 
  usually 
  devise 
  one 
  or 
  more 
  ways 
  to 
  duplicate 
  

   it 
  by 
  starting 
  with 
  much 
  less 
  rare 
  and 
  expensive 
  materials. 
  

  

  As 
  in 
  the 
  famous 
  recipe 
  for 
  rabbit 
  stew, 
  so 
  the 
  first 
  requirement 
  in 
  

   elucidating 
  the 
  structure 
  of 
  a 
  chemical 
  is 
  to 
  obtain 
  a 
  supply 
  of 
  the 
  pure 
  

   material. 
  This 
  was 
  the 
  problem 
  which 
  confronted 
  the 
  Oxford 
  work- 
  

   ers. 
  A 
  method 
  was 
  worked 
  out 
  for 
  growing 
  the 
  Penicillmm 
  on 
  shal- 
  

   low 
  layers 
  of 
  liquid 
  in 
  special 
  stoneware 
  bottles 
  for 
  a 
  period 
  of 
  10 
  days 
  

   after 
  which 
  the 
  fluid 
  was 
  removed 
  for 
  extraction 
  of 
  the 
  penicillin. 
  

   All 
  operations 
  must 
  be 
  performed 
  with 
  the 
  most 
  exacting 
  bacteriologi- 
  

   cal 
  cleanliness, 
  since 
  certain 
  bacteria, 
  if 
  they 
  gain 
  access 
  to 
  the 
  solu- 
  

   tions, 
  cause 
  a 
  marked 
  reduction 
  in 
  the 
  yield 
  of 
  active 
  material. 
  Nor- 
  

   mally 
  about 
  14 
  gallons 
  of 
  culture 
  solution 
  could 
  be 
  harvested 
  each 
  day, 
  

   an 
  amount 
  which 
  contains 
  about 
  one-half 
  gram 
  of 
  penicillin, 
  although 
  

   only 
  a 
  part 
  of 
  this 
  can 
  be 
  obtained 
  in 
  purified 
  form, 
  due 
  to 
  the 
  losses 
  

   which 
  occur 
  during 
  the 
  many 
  stages 
  of 
  the 
  purification 
  process. 
  

  

  Quite 
  recently 
  there 
  has 
  been 
  worked 
  out, 
  on 
  a 
  laboratory 
  scale, 
  a 
  

   continuous-flow 
  method 
  similar 
  to 
  that 
  used 
  for 
  the 
  production 
  of 
  

   vinegar. 
  The 
  mold 
  is 
  cultured 
  in 
  a 
  long 
  glass 
  column 
  packed 
  with 
  

   wood 
  shavings. 
  Fresh 
  culture 
  medium 
  is 
  slowly 
  dripped 
  in 
  at 
  the 
  top 
  

   and 
  the 
  fluid 
  containing 
  the 
  penicillin 
  is 
  constantly 
  drawn 
  off 
  at 
  the 
  

   bottom. 
  At 
  the 
  time 
  of 
  writing 
  (summer 
  of 
  1943), 
  a 
  large 
  number 
  

   of 
  pharmaceutical 
  concerns 
  are 
  engaged 
  in 
  production 
  of 
  penicillin; 
  

   some 
  of 
  these 
  have 
  already 
  progressed 
  to 
  the 
  pilot-plant 
  stage. 
  

  

  Penicillin 
  has 
  not 
  so 
  far 
  been 
  obtained 
  in 
  absolutely 
  pure 
  form, 
  so 
  

   that 
  its 
  chemical 
  constitution 
  cannot 
  as 
  yet 
  be 
  fully 
  determined. 
  For- 
  

   tunately 
  it 
  has 
  turned 
  out 
  that 
  certain 
  derivatives 
  may 
  be 
  prepared 
  

   from 
  penicillin 
  which, 
  while 
  retaining 
  its 
  full 
  antibacterial 
  activity, 
  

   are 
  also 
  permanently 
  stable 
  and 
  may 
  be 
  kept 
  indefinitely. 
  

  

  