May  I,  1896,] 
THE  TROPICAL  AGRICULTURIST. 
IMMJ.SIZATION  AGAINST  SNAKEBITE  J 
AN->  VENOM. 
^Abstract  of  lerlare  bi/  Professor  T.  11.  Fraser, 
F.E.S.,  before  the  llotjal  Inst'datlon,  Mai'cJo 
yiUth,  18Ub,  reported  for  “ Ce;ilon  Observer'' 
bi,  R.U.F.-] 
Snake-bites  have  become  so  common  in  tropical 
countries  whenever  snakes  have  either  received  an 
injury  or  have  been  expectiup;  one  that  the  “enmity” 
prophesied  in  Genesis  III,  1.5,  between  serpents  and 
the  human  race,  may  be  said  to  have  been  fulfilled. 
If  you  meet  with  a snake  and  manage  only  to 
bruise  his  head,  he  will  probably  turn  and  bruise 
thy  heel,  or  any  more  accessible  part  of  the  body. 
From  the  time  of  Pliny  onwards  we  find  remedies 
suggested  for  snake-bites.  But  after  studying  these 
I am  forced  to  the  conclusion  that  they  are  one 
and  all  of  no  effect  against  poison,  but  are  merely 
legendary  traditions  handed  down  through  the  ages. 
Nevertheless  from  a remote  period  of  time  the  be- 
lief has  existed  that  a power  may  be  acquired  by 
men  of  handling  venomous  serpents  and  then  of 
counteracting  their  poison ; and  in  more  modern 
times  the  same  belief  is  found  ih  the  writings  of 
natives,  especially  those  of  New  Guinea.  Among 
the  Hottentots  they  squeeze  out  the  poison  of  snakes, 
they  kill  and  drink  it  saying  it  is  a protection  there- 
after against  that  snake.  Dr.  Cumchbleiger  (?)  re- 
lates an  incident  in  this  connection.  A certain  fakir 
had  been  bitten  by  a serpent,  a very  poisonous  one. 
News  was  brought  to  the  Dr.  who  at  once  sent 
remedies.  On  visiting  the  bitten  man  afterwards  he 
was  surprised  to  find  him  alive  and  well,  (as  he  had 
doubted  his  remedies  would  have  been  in  time)  He 
attributed  the  cure  to  the  remedies  he  had  sent. 
But  he  found  them  untouched,  the  fakir  said  he 
did  not  believe  the  snake  could  harm  him.  Ho  al- 
lowed it  to  make  a second  bite;  no  harm  resulted. 
Then  the  snake  was  allowed  to  bite  a fowl ; the  Dr. 
took  the  fowl  home  and  it  died  in  3 hours. 
It  may  be  instructive  to  associate  with  this  belief 
the  fact  that  venomous  serpents  are  themselves  pr-o- 
tected  against  bites  from  their  own  and  other 
species.  Venom  must  somehow  have  been  intro- 
duced into  their  bodies  from  other  serpents.  We 
are  convinced  that  it  must  have  some  power  of 
protection  caused  by  the  direct  result  of  the  absorp- 
tion of  venom  into  the  system.  Experiments  there- 
fore would  be  able  to  prove  this. 
By  a succession  of  minute  doses,  animals  became 
able  to  receive  a portion  of  venom  without  any  in- 
jury. For  some  years  I had  to  relinquish  these  ex- 
periments-until  I received  further  consignments  of 
venom  from  friends  in  India  and  some  from  the  India 
Oftice.  From  America  I have  got  venom  of  a species 
of  a rattlesnake,  and  also  from  Australia  a consider- 
alde  number  of  venoms  of  different  serpents. 
The  result  of  the  inoculation  of  toxins  as  well  as 
protoxins  of  vegetable  substances  suggested  that  toxin 
of  venom  might  be  similarly  experimented  with. 
Sewell  and  Heuty  succeeded  in  proving  that  cer- 
tain animals  such  as  pigs  and  rabbits  thus  experi- 
mented on  might  safely  receive  more  than  the  lethal 
dose  is,  the  minimum  amoxmt  necessary  to  kill  a 
small  animal. 
In  1894  Calmet  published  evidence  containing  the 
results  of  earlier  investigations  showing  that  he  had 
succeeded  in  safely  administering  to  rabbits  about 
36  milligrammes  each,  after  8 or  9 months  working 
with  gradaully  increasing  doses. 
Here  I may  mention  that  hypochloride  of  cicum 
is  a good  antidote  to  poison. 
The  venoms  that  have  been  xxsed  are  four,  namely 
those  of, — (1)  the  cobra;  (2)  the  crutilus  horridus  (?) 
an  American  snake ; (3)  the  colubriue  serpent  from 
Australia.  (4)  the  Haemacetes  from  Africa.  These 
were  chosen  to  represent  the  difference  in  the  venoms 
of  the  serpents  of  the  four  countries. 
The  minimum  lethal  dose  for  a guinea-pig,  a rabbit, 
a white  rabbit  and  a frog,  showed  considerable  dif- 
ferences. For  a frog  the  dose  was  I milligrammes ; 
for  a cat  the  somewhat  large  dose  of  .6  milligrammes 
was  required,  a kitten  needed  about  b of  that  amount ; 
while  one  of  the  innocuous  grass  snakes  needed  the 
769 
relatively  large  dose  of  C times  that  amount.  The 
venoin  here  used  was  the  cobra  venom  which  takes 
a position  among  the  most  active  of  known  substances. 
ihese  facts  have  been  used  to  render  animals  nroof 
against  the  lethal  dose  or  even  5 or  (>  times  ‘that 
amount.  Notwithstanding  difficulties  rabbits  might  at 
last  receive  as  much  as  10,  20,  .30,  or  even  50  times 
the  lethal  dose,  without  manife.sting  any  symptoms  of 
injury.  But  these  results  were  obtained  only  by  the 
administration  of  very  gradually  increasing  doses 
each  succeeding  dose  rendering  the  animal  more  and 
more  capable  of  receiving  poison  with  safety  • 
eventually  the  increments  not  be  less  gradual  so 
that  as  much  as  50  times  the  lethal  dose  would  be 
reached  in  considerably  less  than  twice  the  time 
required  tor  24  times  the  lethal  dose.  That  is  to  say 
one  animal,  operated  on  thus  far,  might  receive 
enough  poison  to  kill  50  unprotected  animals  of  the 
same  kind  and  weight  in  2 hours;  and  the  hio-ffest 
amount  reached  in  the  case  of  any  one  animaf  was 
370  times  the  lethal  dose.  The  time  this  protection 
will  last  has  not  yet  been  generally  ascertained.  .V 
rabbit  received  4 times  the  lethal  dose,  and  20  days 
after  the  same  amount  failed  to  produce  any  toxic 
effects. 
A few  experiments  were  made  with  animals  which 
had  reached  a high  degree  of  protection.  It  was 
found  that  safety  could  be  secured  by  drying  the 
blood  serum  of  animals  thus  protected  using  it  as  an 
antidote  ; being  1-lOth  of  the  weight  of  the  liquid  and 
retaining  its  antidotal  properties  for  8 or  9 months 
it  was  very  convenient  for  storage  To  it  we  gave 
the  name  antivenine.  The  chief  interest  in  this 
substance  is  that  it  is  likely  to  be  used  in  a few 
years  in  the  treatment  of  snake-bites  for  man. 
In  dealing  with  ahorse  I proceeded  very  cautiously, 
giving  it  at  first  a great  many  doses  below  the 
lethal  dose  for  52  days,  and  after  169  days  I found 
it  extremely  difficult  to  go  beyond  20  times  the 
lethal  dose  ; but  by  the  use  of  antivenine  I was  able 
to  go  much  higher. 
In  using  the  antivenine  there  are  four  ways  of 
applying  the  poison  and  this  antidote  by  introducino- 
it  into  the  skin  : ” 
(1.)  When  mixed  outside  the  body  and  then 
introduced  into  the  skin.  “ 
(2.)  When  introduced  in  opposite  sides  of  the  body 
(3.)  When  introduced  into  the  same  place  one 
after  the  other. 
(4.)  When  introduced  into  the  same  place  one 
after  the  other  with  40  minutes’  interv.al  between  the 
poison  and  the  antivenine. 
In  the  first  method  with  the  minimum  lethal  doc  s 
it  required  part  of  a cubic  centimetre  of  anti- 
venine  t.e.  part  of  a drop,  to  counteract  the 
effects  of  the  poison  But  when  one  comes  higher 
the  amount  of  antivenine  has  to  be  more  than  pro- 
portionately increased.  Nevertheless  the  amount  still 
remains  wonderfully  small,  only  3 cc.  being  neces- 
sary to  prevent  injury  from  10  times  the  lethal  dose. 
By  the  second  and  third  methods  similar  results 
have  been  obtained.  These  results  are  in  marked 
contrast  to  those  obtained  when  an  antido'e  acts 
because  of  its  physiological  properties  suggesting 
that  the  change  in  the  system  produced  by  intro- 
ducing a poison  and  an  antidoto  is  of  a chemical 
rather  than  a physiological  nature.  By  the  fourth 
method  we  see  tlie  antidotal  power  of  antivenine 
•05  cc.  introduced  30  minutes  after  the  lethal  dose 
ot  venom  pievents  harm,  and  after  1^  hours  interval 
3'2  cc.  of  antivenine  will  stop  the ' lethal  dose  of 
poison  from  being  fatal  i.e.  h an  hour  before  reuiedv 
would  bo  too  late. 
Here  again  the  extraordinary  difference  in  the 
requited  quantities  of  the  antivenine  and  the  poison 
point  to  a chemical  change  in  the  system  as  the 
effect  of  the  combination. 
To  discover  the  stomachic  effects  of  the  poison  it 
was  mixed  with  milk  and  rats  were  given  it  to  drink. 
llesiilts:  (1.)  We  succeeded  in  discovering  that 
complete  immunization  .against  venom  could  be  pro- 
duced by  gradual  doses  in  this  way. 
(2.)  We  were  able  to  discover  the. amount  of  anti- 
venine to  counteract  tlio  minimum  lethal  dose  in 
similar  circumstam'o.s. 
