12 
INTRODUCTION 
In  the  past  the  investigation  of  blackwater  fever  has  been 
essentially  clinical.  The  symptoms  and  course  of  the  disease  have 
been  studied  and,  as  regards  aetiology,  its  relation  to  the 
administration  of  quinine  has  been  established  ;  but  purely  clinical 
observation  has  failed  to  explain  the  significance  of  its  association 
with  malaria,  although  its  dependence  upon  malaria  has  been  assumed 
by  most  writers.  But  little  attention  has  been  given  to  the  mechanism 
of  production  of  blackwater  fever,  although  recent  advances  in 
experimental  physiology  and  pathology,  and  above  all  in  physical 
chemistry,  have  provided  numerous  methods  applicable  to  research  in 
this  direction.  In  the  investigation  which  we  have  made  upon 
blackwater  fever,  we  have  endeavoured  to  trace  out  some  of  the 
internal  processes,  whose  terminal  event  is  the  appearance  of  black¬ 
water,  believing  that  in  this  way  many  obscure  points  in  connection 
with  the  causation  and  treatment  of  this  condition  would  sooner  or 
later  be  cleared  up.  In  our  work  we  have  always  attempted  to  give 
our  observations  a  quantitative  character,  and  to  be  as  far  as  possible 
free  from  the  limitation  imposed  by  purely  qualitative  methods. 
Some  of  the  investigations  which  we  have  entered  upon  have 
necessarily  been  of  a  somewhat  tentative  character.  Thus  before  the 
direct  action  of  quinine  upon  the  red  blood  cells  in  blackwater  fever 
could  be  determined,  it  has  been  essential  first  of  all  to  determine  its 
action  upon  the  red  blood  cells  of  healthy  individuals.  The  next  step 
undertaken  was  that  of  determining  if  haemolysins,  present  in  the 
blood,  played  any  part  in  the  production  of  blackwater,  such  as  is 
known  to  be  the  case  in  paroxysmal  haemoglobinuria.  A  further 
point  has  been  the  investigation  of  the  relationship  of  haemoglobin- 
aemia  to  haemoglobinuria.  Again,  in  studying  the  condition  of  the 
urine  in  blackwater  fever,  it  has  been  found  desirable  to  estimate, 
whenever  possible,  the  amount  of  blood  cells  corresponding  to  the 
