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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