Singapore Med j 2011; 52(7) : 466

Singapore Med J 2011; 52(7) : 466

hen Ronald Ross won the Nobel Prize

in 1902, he completed a remarkable

turnaround in a career many friends

and  colleagues  assumed  would  go

nowhere. He had no initial interest in

medicine, and wished instead to be an artist. Born in 1857

in Almora, India, Ross was 17 when his father, General

Sir Campbell Ross, deposited him at St Bartholomew’s

Medical School in London. He was a poor student and

barely passed his qualifying exams, and so he began his

career as a Licentiate of the Society of Apothecaries, the

easiest medical license obtainable.

FroM poeT To ScienTiST

 

Ross  thought  incessantly  about

dropping  medicine  for  poetry,  but

his  verse,  described  as  “stiff  with

classical  allusion”,  never  gained  an

audience.  He  worked  as  a  reluctant

clinician in India from 1881 to 1889,

serving in the military branch of the

Indian  Medical  Service.  The  job

allowed him the free time he longed

for,  but  offered  him  little  access

to  leaders  in  medicine.  In  1889,

when  home  in  Britain  and  again

contemplating a change to a literary

career, he married Rosa Bloxam and returned to school

for a Diploma in Public Health. It was a turning point in

his life. For the first time, he developed an enthusiasm

for  medicine  and  became  an  ardent  contributor  to  the

Indian Medical Gazette. In 1894, he met Patrick Manson,

the  pre-eminent  Scottish  physician  who  was  to  be  his

tireless  mentor  and  advocate.  Manson  had  carried  out

important  studies  on  parasites  such  as  trichophyton,

filaria,  schistosoma  and  trypanosoma.  It  was  Manson

who, using filaria as his model, introduced the concept

of arthropods as vectors of disease. And it was Manson

who proposed that mosquitoes might play a similar role

in malaria.

 As late as 1893, Ross remained ignorant of malaria’s

pathogenesis,  subscribing  to  the  view  that  the  disease

was  caused  by  intestinal  bacteria.  This  was  despite

the  discovery  by  Charles  Laveran  of  the  Plasmodium 

protozoon on a blood smear more than ten years before.

Manson realised that Ross was employing an incorrect

technique with his microscope, and in their first meeting,

demonstrated  the  correct  preparation  of  the  smear.

Confronted with the ringed form of the parasite, Ross

underwent rapid conversion to Manson’s view.

THe perSiSTenT ScienTiST

 Ross’s  return

to  India  marked  the  beginning

of  the  most  productive  period  of

his  career.  Following  Manson’s

advice to look at the mosquito as a

vector,  he  began  by  collecting  the

insects  and  allowing  them  to  feed

on  human  “volunteers”  infected

with  malaria.  He  then  dissected

the  mosquito  specimens,  imitating

Manson’s  experiments  with  filaria.

Unfortunately,  the  dissections

revealed  none  of  the  ringed  forms

he had hoped to find. In retrospect,

Ross failed because the mosquitoes

he  used  were  likely  Culex  and

Aedes,  both  plentiful  in  India,  but  neither  capable  of

transmitting malaria.

 But  persistence  won  the  day.  Undaunted  by  the

initial  delays,  he  pressed  on  with  his  experiments.  In

August of 1897, one of his servants brought him a new

type  of  mosquito.    Ross  referred  to  them  as  “dapple-

wings”,  but  in  fact,  they  were  Anopheles.  He  allowed

the mosquitoes to feed on a malaria patient, and upon

subsequent  dissection,  discovered  the  parasite  in  the

stomachs of the biting insects. This was an exhilarating

breakthrough, and Ross published his findings in a letter

to the British Medical Journal. He was stalled in further

investigation by his inability to locate more anophelines,

Medicine in Stamps

ronald ross (1857–1932): 

discoverer of malaria’s life cycle

dworkin J, Md* and Tan S Y, Md, Jd**

* Research carried out during 3rd year internal medicine residency, University of Hawaii

** Former Professor of Medicine and Adjunct Professor of Law, University of Hawaii

W

Singapore Med J 2011; 52(7) : 467

and was soon transferred to a semi-desert region of India

where  malaria  cases  were  infrequent.  Expressing  his

frustration in characteristic verse, he lamented:

God makes us kings

Scornful answer rings

First be my scavenger

 At  this  desperate  moment,  when  Ross’s  research

was  on  the  precipice,  his  mentor  Manson  intervened

decisively. Pulling strings at the Colonial Office, he had

Ross  reassigned  to  Calcutta  to  pursue  his  experiments

through the final phase. The effort reached its summit in

June of 1898. Forced to develop an animal model due to

the lack of human volunteers, Ross dissected mosquitoes

at sequential points after they had fed on sparrows. By

observing the Plasmodium parasite at different times in

its maturation within the mosquito, he demonstrated the

importance of the vector in the normal development of

the parasite. His ultimate breakthrough came on July 4

when  he  discovered  sporozoites  in  the  salivary  glands

of  the  mosquito. This  was  final  proof  that  mosquitoes

infected through their bite. He informed both Manson

and  Laveran  of  his  discovery,  and  at  the  end  of  July,

Manson  presented  his  results  to  the  British  Medical

Association in Edinburgh.

aTTeMpTS aT eradicaTion

Ross now set as his

modest goal the destruction of all Anopheles mosquito

populations  in  the  tropics.  In August  1899,  he  landed

with  a  small  expedition  in  Freetown,  Sierra  Leone.

Accompanied by an entomologist, the team succeeded

in identifying the relevant local species of Anopheles,

as  well  as  the  moderate-sized  pools  of  stale  water  in

which they bred. The overconfident Ross wrote: “There 

are only about 100 of these (puddles) altogether, lying 

mostly in clusters.  All could be drained at little cost and 

most could be swept out with a broom”.

 Alas,  the  vector  control  effort  failed.  Ross  had

underestimated  the  number  and  variety  of  breeding

sites; the mosquito was quite adaptive about changing

its terrain when confronted by environmental pressure,

and  pouring  oil  over  stagnant  pools  was  at  best  a

temporary strategy. The colonial government ultimately

opted to abandon this effort and instead constructed a

segregated suburb in the hills above the city. Ross’s first

offensive against the mosquito had ended in the retreat

of the humans.

 Further  efforts  at  eradication  proved  equally

disappointing. A major push by the British in Mian Muir,

a barracks town in India plagued by malaria, ended in

a  spectacular  setback.  Despite  the  expenditure  by  the

British  Army  of  vast  money  and  manpower  in  larva

eradication between 1901 and 1909, malaria remained

rampant. It was only the larger campaigns launched later

in Europe that met with measurable success, although

they required the use of pesticides in addition to active

treatment of patients and drainage of swamplands.

 

legacY

 Ross  won  the  Nobel  Prize  for  Medicine/

Physiology  in  1902,  yet  the  award  betrayed  the  ego

that was his chief character flaw. Hearing a suggestion

that  he  should  share  his  award  with  Manson,  Ross

responded:  “The work was done by me alone, with 

Manson’s occasional advice, it is true, but not his 

instructions, as frequently pretended.” Surely this was

overly dismissive given the enormous correspondence

between  the  two,  Ross’s  imitation  of  Manson’s

experiments with filaria and Manson’s contribution of

the mosquito vector theory.

 The annual global research budget for malaria now

exceeds  four  hundred  million  dollars,  a  sum  that  is

considered by many experts to be too small for the task.

Contrast  this  with  the  few  hundred  pounds  that  Ross

budgeted for his eradication programme in Freetown in

1899. The Plasmodium parasite has proved remarkably

resistant  to  vaccine  development,  in  part  because  it

deploys sophisticated strategies of immune evasion. It is

also increasingly resistant to the drugs commonly used

in treatment. Ultimately, the secrets Ross unlocked have

led to even more vexing questions about malaria, which

Ross the poet called “million-murdering Death.”

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People, Research and Reality. New York-London: WW Norton

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most productive breeding sites for malaria mosquitoes in The

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Hostilities since 1880. New York: EP Dutton, 1978.

•  Talbott JH. A Biographical History of Medicine: Excerpts and

Essays of the Men and their Work. New York-London: Grune &

Stratton, 1970: 768-73.

•  Trager  L,  Spielman  A,  Simpson  L.  Malaria,  not  down  and

certainly not out. Am J Trop Med Hyg 2005; 73:824-5.

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