SCIENCE
Malaria: The Indian Connection
By Dr. Rizwana Rahim
Chicago, IL
"...With
tears and toiling breath,
I find thy cunning seeds,
O million-murdering Death."
This is a fragment of what Sir Ronald Ross had composed
in August 1897 after he discovered that an Anophelese
mosquito that feeds on a malaria-infected patient
will also suck in malarial parasites (Plasmodium
sp. ), and transmit them to another person it bites.
The notebook in which Ross described the discovery,
with sketches, can be seen in the London School
of Hygiene & Tropical Medicine.
You probably didn’t know he was a poet (and
has written lot more), besides being a medical doctor,
mathematician, epidemiologist, sanitarian, editor,
novelist, dramatist, poet, amateur musician, composer,
and an artist. And, you may have forgotten that
there is a sub-continent connection to malaria research,
particularly the twin-cities of Hyderabad-Secunderabad
(India).
For finding crucial steps in the mosquito-borne
transmission of malaria, Ross received the Nobel
Prize for Medicine in 1902. It was over 100 years
ago but malaria is still very much with us (endemic
in parts of Asia, Africa, and central and south
America), taking its merciless toll, in spite of
many scientific and medical advances by a growing
number of international, governmental and regional
initiatives.
Ross was born in Almora, India in 1857 (three days
after the First War of Indian Independence, or what
used to be called ‘Indian Mutiny’);
his father was a General in the India Army. When
he was 8, he was sent to England, as was the practice
among the British residents in India then for the
education of their young children. He had early
interests in music, literature and math, but not
in medicine.
At his father’s insistence, he did complete
his medical studies (“without distinction”)
at St. Bartholomew’s, and entered the Indian
Medical service in 1881. He went back to get his
Public Health diploma, got married and returned
to India as staff surgeon. He worked in Madras,
Bangalore, Calcutta, Burma, and the Andaman Islands,
besides Hyderabad, Secunderabad.
In 1892 he got interested in malaria, even though
he had doubted the parasite theory of causation
by Alphonse Laveran. He was persuaded by Sir Patrick
Manson, the father of tropical medicine, who had
demonstrated four years earlier the mosquito-filarial
worm-elephantiasis connection. Ross started his
own research on malaria in 1895, and kept Manson
informed of his progress.
Like any research, his also had its ups and down,
and had false leads: he learned that the mosquito
species that transmits human malaria is only Anopheles
(and its female only) and not Culex sp., not all
infected mosquitoes can yield detectable parasites,
and parasites take different shapes at different
stages, and not remain the same, and experimentation
on human subjects (even under pre-WWI standards
and in the colonial population of an empire) is
not easy (not many volunteers for a ‘needle
prick’ even if you pay “an anna”
or two per jab, which he did pay, and no one likes
to drink for your research the water in which mosquitoes
had laid eggs, except in this case his servant “Lutchman”).
And when research itself has to receive approvals
from unsympathetic and unsupportive superiors, you
have some real problems.
After many bouts of depression, he did finally achieve
his goal: One report said: “On 20 August 1897,
in Secunderabad, Ross made his landmark discovery.
While dissecting the stomach tissue of an anopheline
mosquito fed four days previously on a malarious
patient, he found the malaria parasite and went
on to prove the role of Anopheles mosquitoes in
the transmission of malaria parasites in humans.”
He then demonstrated that another species of mosquitoes
(Culex sp) plays a similar transmission role for
malaria in birds.
In 1899 Ross left the Indian Medical Service, returned
to England. Sadly, the building of the military
hospital in Secunderabad where he made his landmark
discovery lies in ruins. Upon his return, Ross worked
first at Liverpool School of Tropical Medicine,
and then in 1926, in recognition of his work, a
new institute was established (‘Ross Institute
and Hospital for Trpoical Diseases’) in London.
He was made its first Director in Chief, a post
he held till his death in 1932. Two years later,
the Ross Institute was incorporated into the famed
London School of Hygiene & Tropical Medicine.
In this verse Ross recalls his first thoughts on
malaria:
In this, O Nature,
yield I pray to me.
I pace and pace, and think and think, and take
The fever'd hands, and note down all I see,
That some dim distant light may haply break.
The painful faces ask, can we not cure?
We answer, No, not yet; we seek the laws.
O God, reveal thro' all this thing obscure
The unseen, small, but million-murdering cause.
In addition
to collections of his poetry (1928, 1931), Ross
wrote an extensive book on ‘The Prevention
of Malaria’ (1910/11), five mathematical works
(1929-31), his huge autobiography ‘The Memoirs’
(1923), and a number of novels including The Child
of the Ocean, The Revels of Orsera, Spirit of the
Storm , The Emigrants, Lyra Modulatu, etc. Most
of his papers (more than 30,000 items) are held
in two Ross Depositeries one at the London School
of Hygiene & Tropical Medicine (http://www.lshtm.ac.uk/library/archives/rossproject.html)
and the University of Glasgow.
I recalled this a couple of weeks ago when I saw
a scientific report that proposed recruiting genetically-modified
(GM) mosquitoes in the anti-malarial fight. The
idea is not new, and not entirely without controversy:
just that this GM or transgenic mosquito have been
found to compete and outlive a normal one. GM variety
carries two newly-added genes, one codes for Green
Fluorescent Protein (GFP) which makes their eyes
glow green (easy to count), and the other expresses
a new peptide (SMI) that midgut, and which in turn
stops the parasite transmission to the next person
an infected mosquito bites.
If you think the idea is to release a huge number
of laboratory–bred GM mosquitoes into the
environment to compete and overpower the mosquito
population already out there, it IS --- but relax!
Authors admit that it could 10-20 years to release
GM mosquitoes in the field, but before that they’ll
have to demonstrate not only the effectiveness of
this approach but also satisfy many environmental,
ecological and ethical concerns over release of
GM organisms in the environment in the first place.
These findings would first need to be replicated
using human malaria parasites in their natural mosquito
vectors.
There is no question that we need different kinds
of weapons in the arsenal, along with different
strategies, to fight such a huge, persistent public
health problem. Considering all that is being done
today, as well as the progress made so far, malaria
still kills more that 1 million people a year, only
HIV/AIDS kills more (300 million infected or taken
ill), and 90% of cases occur in Africa, children
can die within 48 hours, and 90% of deaths in sub-Saharan
African young children (over 70% deaths in children
under-5; about 3,000 deaths per day). Symptoms include
neck stiffness, convulsions, abnormal breathing
and fever of up to 40C (104F)
Out of the four Plasmodium parasite species that
cause the disease, the most severe is P. facilparum,
spread by Anopheles gambiae mosquitoes
(particularly in Africa). According to some estimates,
malaria costs Africa over $12 billion in lost GDP
and eats up 40% of public health spending.
But the fight must go on ...
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