Ronald Ross

Ronald Ross, son of an Army Major, a brilliant and polyvalent mind, poet of romantic lyrics, part time novelist, playwright, painter, musician and mathematician, who never wanted to be a medical practitioner, became a researcher by accident, designed some of the most elegant experiments with sheer instincts and his own shrewd observations and ultimately won the second ever Nobel Prize in Medicine in the year 1902. Having faced a lot of hardship and administrative interference and apathy (what he called “administrative barbarism”) and spent from his own pocket to pay the assistants and ‘volunteers’ for his research, he converted adversity to advantage and overcame all odds with his single minded pursuit to carry out his well designed and elegant experiments. With his penchant for writing, he has left for posterity detailed and poetic accounts of his path-breaking research and work thereafter.

rossRoss was born on May 13, 1857 at Almora near the Himalayan Mountains, India only three days after the outbreak of the Indian Sepoy mutiny. Ross was the first of ten children of Sir Campbell Claye Grant Ross, a Scottish officer in the British Indian army, and Matilda Charlotte Elderton. Ross’ grandfather, Lieutenant Colonel Hugh Ross, had also been a fierce Indian border fighter. Young Ross was witness to his father falling seriously ill with malaria. At the age of eight, young Ronald was sent to England for his education. After completing his early education in two small schools at Ryde, he was sent to a boarding school at Springhill, near Southampton in 1869. When he was 14 years old, he won a prize for mathematics. The prize was a book titled Orbs of Heaven. It was later that this book inspired Ronald to study mathematics in depth. At the age of 16, Ronald was bracketed first in England in the Oxford and Cambridge local examination in drawing. He had made a pencil copy of Raphael’s painting titled Torchbearer, and that too in just a few minutes! At age 17, Ross declared his ambition to become a writer. But his father would have none of it. He was told in no uncertain terms what career to pursue. In Ross’s own words later: “I wished to be an artist, but my father was opposed to this. I wished also to enter the Army or Navy; but my father had set his heart upon my joining the medical profession and, finally, the Indian Medical Service, which was then well paid and possessed many good appointments; and, as I was a dreamy boy not too well inclined towards uninteresting mental exertion, I resigned myself to this scheme….” Forced by his father, he joined the St. Bartholomew’s Hospital in London in 1875. Most of his time in medical school was spent composing music or writing poems and plays. During the course of his medical school, Ross came across a woman from the Essex marshes who was complaining of headaches, pains in her muscles and feeling very hot and then very cold. Essex marshes who was complaining of headaches, pains in her muscles and feeling very hot and then very cold. Ross questioned her exhaustively and diagnosed her as suffering from malaria, which was unusual, as it was only found in hot tropical countries such as South America and India. His detailed diagnosis however, frightened the woman away and she never returned, so Ross was unable to prove his diagnosis. Not surprisingly, he completed his medical studies “without distinction” and flunked the qualifying examinations for the Indian Medical Service. When his father threatened to cancel his allowance, he took a job as ship’s surgeon on a vessel sailing between London and New York. In 1881 he repeated the qualifying examinations and this time ranked seventeenth of twenty-two successful candidates. After four months’ indoctrination at the Army Medical School, Ronald Ross finally fulfilled his father’s wish by entering the Indian Medical Service in 1881.

With his not-so-impressive result, Ross was commissioned for the Madras service, the least prestigious of the three Indian Presidencies (Bengal and Bombay were the more desirable appointments) and worked in many places like Mysore and Madras and also served in the Burma War and in the Andaman Islands. While in Madras, a large part of his work was treating soldiers ill with malaria. The treatment with quinine was successful, but many died because they failed to get treatment. He also studied mathematics which he applied to the study of malaria later on [See below].

From the early days of his work in India, mosquitoes engaged Ross one way or the other. In 1883, Ross obtained the post of Acting Garrison Surgeon at Bangalore. Although Ross found the bungalow that was provided for his accommodation pleasant to live in, he was irritated by the large number of mosquitoes which constantly buzzed around the rooms. He also noticed that there seemed to be more mosquitoes in his bungalow than in others and that there was a particularly large swarm around a barrel with water that was kept outside the window. When Ross looked in to the barrel he saw lots of “wriggling” grubs breeding in the water, which he identified as mosquito larvae. Ross tipped the barrel to empty the water and found that the number of mosquitoes reduced. This started him thinking that if the places where mosquito bred were removed it might be possible to eliminate them completely. But everyone did not approve of this solution. “When I told the adjutant of this miracle,” Ross wrote, “and pointed out that the mess house could be rid of mosquitoes in the same way (they were breeding in the garden tubs, in the tins under the dining table and even in the flower vases) much to my surprise he was very scornful and refused to allow men to deal with them, for he said it would be upsetting to the order of nature, and as mosquitoes were created for some purpose it was our duty to bear with them! I argued in vain that the same thesis would apply to bugs and fleas, and that according to him it was our duty to go about in a verminous condition.” Ross held these views on mosquito control till the very end and found the same apathy from governments!

But even with all this, he was not at all enthused. He spent his free time concocting equations he hoped would revolutionize mathematics and writing poetry, music, plays, and bad novels that he published at his own expense. However, he did develop some interest in tropical diseases, like all his peers would have during the period when these were rampant in most parts of India, particularly malaria that killed more than a million in India each year. His experience with malaria as a student also probably stirred Ross’s interest in malaria. True to his style, Ross composed this verse about his first impressions of malaria that killed millions:

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.

After working for 7 years in India from 1881, he got bored and returned to England on a furlough in 1888. But he was aware that his literary career was not promising, being unable to establish a readership beyond his family and friends. So he took a course of Diploma in public health in London and acquainted himself with microscopic skills and laboratory techniques. In between he found time to write another bad novel, invented a new shorthand system, devised a phonetic spelling for the writing of verse, and was elected secretary of a local golf club. During the same period, he courted and married Rosa Bessie Bloxam in April 1889 and returned to India with her. Their first daughter was born in 1891 and the second one in 1903.

Back in India, he was posted to a small military hospital in Bangalore. Here, Ross began to formulate theories of malaria. Ignorant of Laveran’s work, he hypothesized that malaria was probably due to some form of poisoning from the bowel and published his first paper with this claim. Even later, although he learned of Laveran’s discovery in 1892 from several papers published in Indian medical journals, he was not convinced. He pricked the fingers of anyone who came to him with fever and spent hours peering through his microscope at blood smears, yet was unable to see the crescents. Thoroughly exasperated, he strongly questioned the soundness of Laveran’s observations and concluded that the parasite had been some lucky microscopic finding without any value and turned this parasite into ridicule, even wondering if the Frenchman might have falsified his data. This inability to confirm Laveran’s work, a problem shared by many investigators, was apparently due to the crude microscopic techniques of the day and the inferior illustrations in the original articles.

When he took his second furlough to England in 1894, Ross believed he had accumulated overwhelming evidence that Laveran was incorrect. “Everything I had tried had failed,” he told his colleagues. But they informed him that the parasites did indeed exist and sent him to Dr. Patrick Manson, the foremost authority on tropical diseases in London.

Manson

Manson

On 9 April 1894, he called on Patrick Manson. But Manson was not at home, but with the help of the London post that had five or six deliveries a day, they got together the following day. “Within a few minutes,” Ross wrote, “he showed me the Laveran bodies which are technically called ‘crescents’ in a stained specimen of malaria blood, and I recognized at once that no such bodies could exist in healthy blood. My doubts were now removed….” Then Ross spent many hours following Manson on ward rounds at the Seamen’s Hospital and in Manson’s private laboratory. Manson was impressed with this eager, capable student and chose to expound upon his ideas to Ross. In 1894, one November afternoon at “half-past two”, as they were walking down Oxford street on the way to the hospital, Sir Patrick Manson told Ross: “Do you know, I have formed a theory that mosquitoes carry malaria just as they carry filaria.” This was to change Ross’s life forever. Ross saw himself as the man to prove it. Manson suggested that the filaments in the crescents were actually living bodies and the mosquito sucked the filamented crescents into its stomach while feeding on the blood of a malaria patient. The filaments proceeded to travel through the stomach into the insect’s tissues. After the mosquito died laying its eggs, the “flagellated spores” emerged into the water, ready to infect anyone who came to drink. These theories, which had earned for Manson the titles “pathological Jules Verne” and “Mosquito Manson,” sent the young Ross into raptures of ecstasy. Suddenly the fame that had eluded him despite years writing poems, music, plays, novels, and equations seemed within his grasp. He had but to prove what Manson had presented to sound like gospel truth. Ross returned to India in March 1895, determined to prove what he called Manson’s “grand induction” and went about it with an almost manic enthusiasm.

Manson guided Ross throughout his research, suggested new approaches, encouraged Ross when he became depressed and came to his aid whenever superiors thwarted him. There was a continuous exchange of ideas between the two men, first directly and then by letters. The 173 letters that the two men exchanged between 1895 and 1899 constitute one of the great scientific correspondences and offer a wonderful insight into the research that led Ross to his Nobel Prize. The two men were separated by thousands of miles and a 3-week transit time for a letter or a slide to reach the other; nevertheless, their intimacy grew apace. The avuncular Manson acted as Ross’s London agent and sounding board, offering advice, both good and bad, on the best way to nail down the mosquito hypothesis. Above all, he tried to cheer his young protégé in his frequent periods of discouragement and despair. He lost his temper only once, when Ross threatened to throw up his medical career, take early retirement from the Indian Medical Service, and devote himself to literature.

On the ship to India, Ross rushed among passengers and crew members, frantically pricking fingers and examining blood. At the ship’s ports of call, he besieged the local hospitals for blood specimens of malarious patients. He even tried to prepare himself for anatomical studies of Indian mosquitoes by dissecting the ship’s cockroaches.

Soon after returning to India, Ross continued looking for cases of malaria in his Military hospital. Patients ran from him for fear of getting their fingers repeatedly pricked and colleagues kept proven malaria cases from him. Spurned in his hospital, he haunted the municipal hospitals and the other regiment infirmaries looking for cases of malaria. He even offered a rupee a prick. Following Manson’s instructions, Ross captured the mosquitoes and tried to induce them to bite malaria patients. But they obdurately refused to bite any one, even Ross. He made the mosquitoes raised from the larvae bred in captivity to feed on persons carrying malaria crescents in their blood, by putting the patient under a mosquito net and releasing the insects into it. He then expressed their ingested blood on a glass slide, and examined it with his microscope. Just as Manson had prophesied, there were the parasites. To be certain of the results, Ross tried the same experiment with six more mosquitoes the next day. “Every point that you predicted seems to come true,” he wrote to Manson. “Certainly there is nothing contrary to the theory. The parasites are present in the blood of the mosquito, and what is even more, they appear to be there in greater numbers than in blood from the finger. Also, the development of the crescents, and the formation of the flagella, seem to be favored by conditions in the mosquito’s stomach. Yes, the crescent-sphere-flagella metamorphosis does go on inside the mosquito to a much greater degree than in control specimens of finger blood.”

Manson immediately wrote back with more instructions. “Let mosquitoes bite people sick with malaria,” he advised, “then put those mosquitoes in a bottle of water and let them lay eggs and hatch out grubs. Then give that mosquito-water to people to drink.” So Ross allowed four mosquitoes to feed on a patient named Abdul Kadir. These insects were then kept in a bottle full of water until they died. After the promise of a suitable emolument, Lutchman, Ross’s native servant, and two others were persuaded to drink the sample of water in which mosquitoes had died. Lutchman developed a fever, but recovered three days later, and Ross could not find any malaria parasites in his blood; the other men remained healthy.

Ross was thoroughly discouraged and he began writing poems again. But Manson desperately tried to re-energize hm: “Above everything, don’t give it up. Look upon it as a Holy Grail and yourself as Galahad and never give up the search, for be assured that you are on the right track. The malaria germ does not go into the mosquito for nothing, for fun, or for the confusion of the pathologist. It has no notion of a practical joke. It is there for a purpose and that purpose, depend upon it, is its own interests–germs are selfish brutes.” Manson was also worried that someone else who would give him no credit might appropriate his precious theory. “The Frenchies and Italians will pooh-pooh it, then adopt it, and then claim it as their own,” he warned Ross in one letter, “see if they don’t. But push on with it, and don’t let them forestall you. They won’t have this autumn, and they will not have a chance to work seriously at the matter until next June or so. You have got a year ahead of them.”

But his superiors had other ideas for Ross. He was transferred to Bangalore on the 9th September 1895 to combat a serious outbreak of cholera. During his eighteen months stay at Bangalore, he tried to continue his work on malaria finding time in between with great difficulty. Finding that he was unable to transmit malaria through the ‘mosquito water’, he wrote to Manson at the end of May 1896: “The belief is growing on me that the disease is communicated by the bite of the mosquito… She always injects a small quantity of fluid with her bite – what if the parasites get into the system in this manner.” To test this idea, Ross allowed mosquitoes that had fed on a malaria patient to bite a healthy man. Nothing happened. The experiment was repeated again and again but in vain. Unfortunately, as he was using Culex mosquitoes, which do not transmit malaria, experiments to test this theory came to nothing. Writing to his wife he said: “I have failed in finding parasites in mosquitoes fed on malaria patients, but perhaps am not using the proper kind of mosquitoes “. On the other, Manson, who believed that the mosquito bit only once during its life, was not convinced about that Ross’s idea. “Follow the flagella,” he wrote back, and forget this crazy idea. Ross obediently went back to dissecting mosquitoes and in February 1897 was able to observe the true fate of the flagella. Within a blood smear he saw two parasites near each other. The first was giving off flagella, while the second, which was spherical and unsegmented, had a single flagellum wiggling slowly inside. He surmised that the single wiggling flagellum was trying to escape the sphere rather than fertilize it. When McCallum in Baltimore correctly interpreted the process a few weeks later, Ross was deeply humiliated, and “always felt disgraced as a man of science” for incorrectly interpreting his own observation.

In 1897, he went to the Sigur Ghat near the hill station of Ooty. Three days later he went down with malaria, despite having slept under a mosquito net and behind closed windows. Feeling depressed with no success in sight, he wrote poetry:

What ails the solitude?
Is this the Judgment Day?
The sky is red as blood;
The very rocks decay
And crack and crumble, and
There is a flame of wind
Wherewith the burning sand
Is ever mass’d and thin’d
The world is white with heat;
The world is rent and riven;
The world and heavens meet;
The lost stars cry in heav’n

Then one day, his attention was drawn to a mosquito that was sitting on a wall in a peculiar posture and had what he called “dappled-wings”. He was inspired again and was reminded of the fact that only one species of mosquito among the four found in Amoy, Culex fatigans, was capable of carrying filariasis. Manson had also suggested that each form of the malarial plasmodia might require a particular mosquito species. Ross suddenly realized he had used the wrong species of mosquito.

He returned to Secunderabad in June 1897 but was down with cholera, only to recover with a cup of hot tea. Once up, he commenced work by making a careful survey of the various kinds of mosquitoes. He continued his study by examining the dissected mosquitoes under the microscope. After feeding on patients, the gorged insects were collected in small bottles containing a little water and were kept for several days before being dissected. Almost every cell was examined under the microscope, even the integument and legs were not neglected. With the facilities that he had in the hot Secunderabad weather, Ross really toiled hard. In his own words: “But the weather became very hot again in August. At first I toiled comfortably, but as failure followed failure, I became exasperated and worked till I could hardly see my way home late in the afternoons. Well do I remember that dark hot little office in the hospital at Begumpett, with the necessary gleam of light coming in from under the eaves of the veranda. I did not allow the punka to be used because it blew about my dissected mosquitoes, which were partly examined without a cover glass; and the result was that swarms of ‘ eye-flies ‘-minute little insects which try to get into one’s ears and eyelids-tormented me at their pleasure, while an occasional Stegomyia revenged herself on me for the death of her friends. The screws of my microscope were rusted with sweat from my forehead and hands, and its last remaining eye-piece was cracked”.

Page from notebook where Ronald Ross recorded his discovery of the mosquito transmission of malaria, 20 August 1897

Page from notebook where Ronald Ross recorded his discovery of the mosquito transmission of malaria, 20 August 1897

On the 15th August, 1897, one of his assistants brought a bottle of larvae, many of which hatched out next day and among them he found several “dappled-winged mosquitoes”. Delighted with this capture, on August 16th, he fed them on his malaria patient, Husein Khan,with crescents in his blood. (Husein Khan was paid 1 anna per mosquito he was bitten by; he came away with 10 annas.) That evening he wrote to his wife: “I have found another kind of mosquito with which I am now experimenting, and hope for more satisfactory results with it.” On the 17th he dissected two of these mosquitoes but found nothing unusual. On the 19th he killed another and found “some peculiar vacuolated cells in the stomach about 10 microns in diameter.” On August 20th, a dull, hot day, Ross went to the hospital at 7 a.m., examined his patients, dealt with his correspondence and had a hurried breakfast in the mess. One of his mosquitoes had died and this he dissected without noting anything significant. He had two mosquitoes left of the batch fed on Husein Khan on the 16th and at about 1 p.m. he began to sacrifice one. Dissecting it he scrutinized the tissues micron by micron, when suddenly, in the stomach wall he “saw a clear and almost perfectly circular outline.. of about 12 microns in diameter. The outline was much too sharp, the cell too small to be an ordinary stomach-cell of a mosquito..” On looking a little further, there “was another and another exactly similar cell “. He changed the focus of his microscope and there within each of these new cells was a cluster of black pigment. He made rough drawings in his notebook, sealed his specimen, went home to tea and slept for an hour.

The pigment puzzled him, for the flagella contained no pigment, but the thought struck him that if the cells were really parasites they should grow in size in the last remaining mosquito during the night. He spent the night in agony lest his last remaining mosquito should die and decompose before morning. Next day he killed and dissected this remaining specimen. There were the cells again, twenty-one of them, just as before, only now much larger… The cells were therefore parasites, and, as they contained the characteristic malarial pigment, were almost certainly the malaria parasites growing in the mosquito’s tissues. He wrote to Manson with his exciting news: “Now prick up your ears because the hunt is up again.” Next morning Ross wrote a poem which he sent to Manson on Aug. 22:

This day relenting God

Hath placed within my hand
A wondrous thing; and God
Be praised. At his command,

Seeking his secret deeds
With tears and toiling breath,
I find thy cunning seeds,
O million-murdering Death.

I know this little thing
A myriad men will save,
O Death, where is thy sting?
Thy victory, O Grave?

August 20th continues to be celebrated as Mosquito Day! On the 4 September he joined his family at Bangalore where he wrote a paper on his findings. This paper titled “On Some Peculiar Pigmented Cells Found in Two Mosquitoes Fed on Malarial Blood,” was published in the British Medical Journal on December 18, 1897.

Yet Ross still had his doubts. Perhaps, circular cells might not be related to the malarial parasites at all. “I really believe the problem is solved,” he wrote to Manson, “although I don’t like to say so. I look at them myself daily; those of the fifth day have grown bigger than those of the fourth day….Pigment-it is almost proof already! What else can the thing be? What are we to think: What do you think?”

Now eager to take his work to its logical conclusion, Ross wrote to Manson on September 22, 1897: “I shall be much disappointed if I don’t get a practical proof in a week’s time,” and continued his attempts to transmit malaria with the newly found mosquitoes. But two days later, he was asked to proceed to Bombay.

Then he was transferred to Kherwara, a distant village in the deserts of Rajasthan where malaria was very rare. But true his style, Ross did not quite languish. He knew of Danielewsky’s studies of bird malaria, and verified for himself that some types of pigeons carried the disease. At the time, many biologists believed that mosquitoes did not attack birds. After studies of pigeons, sparrows, and crows, Ross verified that birds were indeed bitten by mosquitoes, as well as by other insects.

In the meantime, after much lobbying by Manson and others he was transferred to Calcutta on January 29, 1898.

ross1

Ronald Ross, Mrs. Ross, Mohammed Bux and assistants at the laboratory in Calcutta

He managed to get a dilapidated laboratory of a recently retired physiologist. Now Ross advertised for assistants who would be paid from his own pocket. Of the twenty or so job applicants, Ross chose one Mohammed Bux, because “he looked the most rascally of the lot and was therefore likely to have considerable intelligence” and another named Purboona who disappeared after the first payday. But Mohammed Bux became quite devoted to Ross, so much so that he would even sleep on the laboratory floor at night to keep stray cats from killing the experimental animals.

Ross directed Mohammed Bux to capture mosquitoes, hoping again to find the circular, pigmented cells within the insects’ stomachs. Bux climbed through the sewers, the drains, the stinking tanks that abounded in Calcutta and brought back all kinds of mosquitoes. At this time, plague was raging and the people were scared of inoculations. Ross tried his best to get some human volunteers for his study. He sent his assistants into the bazaar (the market) to try to induce patients to come to him on payment. Although several beggars with fever were induced to come on large payment, they generally left their money, took up their crutches, and fled without a word when he proposed to prick their fingers to examine their blood! Left with no choice, Ross turned to the birds again. His laboratory soon became filled with a number of live crows, pigeons, weaver-birds, sparrows and larks that Mohammed Bux had snared. Into the cages covered with mosquito netting went the mosquitoes. Ross found that five out of nine mosquitoes fed on birds infected with Proteosoma contained the pigmented cells in the stomach and he brought in his mathematics to calculate the probability suggesting that the pigmented cells had been derived from the Proteosoma. He then commenced a long series of differential experiments in order to establish the fact thoroughly. It was also established that the common gray mosquito (Culex) was the carrier of bird malaria and that the brown, dapple-winged vector of human malaria could not be infected by the bird parasite.

These studies were carried on in desperate haste, haunted by the fear that hostile superiors would once again interrupt his work. He was forbidden to publish any of his results, though compelled to send detailed summaries to headquarters. The only outsider aware of the research was Manson, who often received whimsical accounts, like this one with Ross taking the role of the pigmented circular cell:

“I find that I exist constantly in three out of four mosquitoes fed on bird malaria parasites, and that I increase regularly in size from about a seven-thousandth of an inch after about thirty hours to about one seven-hundredth of an inch after about eighty-five hours… I find myself in large numbers in about one out of two mosquitoes fed on two crows with blood parasites…”

During this period, Ross tried to obtain some assistance for his work. But his superiors never obliged him for reasons he found inexplicable.

Unperturbed by all this, Ross continued his single-minded work. To test Manson’s hypothesis that the parasites were ingested with water in which the mosquitoes had died while laying eggs, Ross fed the infected mosquitoes to healthy sparrows but the birds remained free of malaria. Now convinced that malaria did not spread that way, he continued to study infected mosquitoes. On the 2nd July 1898, he found in the thorax of a mosquito a large cell which contained within it several of the thread-like bodies. On July 4, 1898, examining the insect’s head, he found the the part of the mosquito to which these bodies were destined – the gland lay in the neck and upper thorax and it was the salivary gland. By July 8th, he was very sure: Malaria was passed back to the birds in the mosquito’s saliva during the act of biting. The exact route of infection was thus revealed.

This remarkable finding, Ross later wrote, “brought him up standing.” As a final verification, he sent Mohammed Bux to capture a group of healthy sparrows. Mosquitoes that had fed on infected birds were allowed to bite these healthy ones. Within a few days the blood of the new birds was loaded with malarial parasites. At the same time he kept as controls a number of healthy birds in mosquito-nets, safe from the bites of mosquitoes, and found that none of them became infected.

Ross communicated his results to Manson in a state of intense excitement. “I think I may now say Q.E.D.,” he wrote, “and congratulate you on the mosquito theory indeed. The door is unlocked, and I am walking in and collecting the treasures. Well, I have become unbearable with conceit…. I brag openly about it!”

Manson received the news at a meeting of the new Tropical Diseases Section of the British Medical Association. When he read Ross’s report to the assembled delegates it was greeted with a standing ovation. “I am sure you will agree with me,” Manson said, “that the medical world, I might even say humanity, is extremely indebted to Surgeon Major Ross for what he has already done, and I am sure you will agree with me that every encouragement and assistance should be given to so hard-working, so intelligent, and so successful an investigator to continue his work.”

But the Indian Medical Service was again not on his side. Ross was ordered to abandon the malaria work and report to a new post in Assam to do research on kala azar. “Columbus having sighted America was ordered off to discover the North Pole,” he remarked bitterly. “No, the man who can do is not allowed to do, because the man who cannot do is put in authority over him.”

Unhappy with the administrative apathy and exhausted by work and heat, Ross decided to quit. He closed his small laboratory, set his feathered prisoners free from their cages, emptied the jars of mosquitoes. After sadly wishing Mohammed Bux good-bye, Ronald Ross left Calcutta on the 13th August, 1898. Before leaving, he urged upon Government the importance of taking active measures for the prevention of malaria in accordance with his observations. Besides advising the strict use of mosquito-nets for a personal prophylaxis, he urged especially a campaign against mosquitoes as the best measure for towns and cantonments, particularly against the dappled-winged mosquitoes, which breed principally in water on the ground.

Ronald Ross did not stop at identifying the vector for malaria and its habits. He was thrilled at the possibility of controlling this scourge for millions by controlling the breeding of the mosquito vector. Ross had proved that malaria was related more to the stagnant water in the pots, tubs, and tanks scattered around human dwellings where its vector bred in millions than to the marshes and pools as was believed until then. Ross’s discovery also explained the seasonal variations, the increase in cases during the rainy season, and how subsoil drainage that was practiced for centuries helped in controlling it. It was therefore enough to clear the breeding sites rather than drain a whole area, thus bringing down the expenses considerably. Ross did not stop at writing about malaria control either. He accepted the challenge to implement his ideas.

Major General Ronald Ross

Major General Ronald Ross

He stood at the vanguard of implementing his ideas till his end. Ross attempted to eradicate malaria from England by forming ‘mosquito brigades’ to eliminate mosquito larvae from stagnant pools and marshes. In August-September 1899, he was sent to Freetown, the capital of Sierra Leone where he organised a sanitation drive, clearing the streets of tyres, bottles and empty cans and levelling roads so that rain water would not gather into puddles. But the Freetown malaria control programme did not yield desired results, probably because Ross had underestimated the number of breeding pools as well as the sheer number of vectors that he was trying to control. Ross had very limited funding and the best available technology was to pour oil on the numerous breeding sites around Freetown. As soon as the oil treatment stopped, breeding would begin again. Ross redoubled his efforts with increased funding from private sources and ensured the removal of all potential breeding sites, including rubbish, broken bottles and other potential water containers. Despite these concerted efforts, the programme was remembered more for its impact on the Freetown’s rubbish than for malaria control. J.W.W. Stephens and S.R. Christophers, who had worked with Ronald Ross in Freetown, organised a similar drive in Mian Mir in Lahore, India in 1901, without much success either.

The sanitation drive suggested by Ronald Ross was successfully tried elsewhere. During the U.S. military occupation of Cuba, a campaign against yellow fever and malaria was commenced at Havana early in 1901. Under the leadership of the Assistant Surgeon General William Crawford Gorgas of the United States Army the anti mosquito measures produced very marked results. Pyrethrum, a natural insecticide derived from the chrysanthemum flower, was first used by William Gorgas in Cuba where it was burned inside sealed dwellings. Mosquitoes entirely disappeared from many parts of the city, and were decreased everywhere.

At the end of 1902, Prince Auguste d’Arenberg, President of the Suez Canal Company asked Ross to save Ismailia, the city that was built as a base for construction of the canal. It was gravely threatened by malaria for a long time. Ross led a sanitation drive so successful that by the following year, the city officials announced that they no longer needed mosquito nets and by 1904, a whole year had passed without a single reported case of malaria in Ismailia. Ross’s drastic sanitary measures were even dubbed as “sanitary Bolshevism”.

In the following years, Mosquito Ross, as he was called, lent his services to Greece, Mauritius, Spain and Panama and during World War I, at various places on the battle front, always preaching the gospel of war against the anopheline mosquitoes. His position within malaria research gave him special kudos, even if his stridency and concentration on mosquito control at the expense of social betterment or the systematic use of quinine sometimes marginalized him from the malaria community.

The experience of the US Army in Cuba was replicated during the construction of the Panama Canal between 1905-1910, where Ronald Ross and William Gorgas worked together. Yellow fever was eliminated and malaria incidence markedly reduced through an integrated program of insect and malaria control.

In 1910, Ross wrote his sanitary axiom: “Widespread diseases … cause much pain, poverty, sorrow, expense and loss of prosperity … and the rule is to grudge spending a hundred pounds for disease which costs thousands…[Therefore] “for economic reasons alone, governments are justified in spending for the prevention of [malaria] a sum of money equal to the loss which the diseases inflict on the people”. [Ross, R. The Prevention of Malaria. London, John Murray. 1910. pp. 295-296.]

During World War I (1914-1918) Ross was appointed a consultant physician on tropical diseases to Indian troops and was sent to Alexandria for four months to investigate an outbreak of dysentery which was hampering troops in the Dardanelles.

Ross also initiated organizations for the prevention of malaria within the planting industries of India and Ceylon.

Ross’s Prevention of Malaria ebook

Ross made many contributions to the epidemiology of malaria and to methods of its survey and assessment, greatest being the development of mathematical models for the study of its epidemiology. He worked on the mathematical theory of epidemics. Through the survey of the parasite index and the assessment of the spleen rate in children he founded the malariometry as a epidemiological tool, focused attention on the relation of malaria and the community and on the complexity of the transmission dynamics. It provided the basis for calculating the rate at which malaria spreads and the quantity of material and personnel required for checking the epidemic. By demonstrating how much malaria cost the governments of malarious countries, and how it was much more efficient to prevent it in the first place, Ross offered a sober reminder of the economics of prevention. He demonstrated mathematically how reducing the concentration of anopheline mosquitoes could have a real and potentially cumulative effect, but his mathematics went over the heads of his contemporaries. His pioneering contributions to malarial epidemiology were not appreciated until two decades after his death. Ross’s analysis of the economics of malaria control also went largely unheeded. The message is still relevant and is still too little-heeded by politicians and health planners.

Ross had lot of appreciation for Laveran, Koch and of course his mentor, Sir Patrick Manson. Koch’s suggestions on immunity in malaria also impressed Ross. Koch’s support for control efforts was also praised by Ross.

But Ross had a bitter feud with Italian physician Giovanni Battista Grassi, who in September 1898, reported that Anopheles claviger was the carrier of human malaria. Grassi, Amico Bignami and and Giuseppe Bastianelli made the mosquitoes bite a human volunteer and on the eleventh day, the patient developed a malarial chill. Examination of his blood revealed large numbers of plasmodia. But when he published, Grassi failed to give credit to Ross. Ross was furious. Thoroughly convinced that Grassi was trying to steal his discovery from him, Ross sent angry letters to the journals that had published Grassi’s papers, asserting that Grassi was a mountebank, a cheap crook, a parasite who survived on the ideas of others. Grassi replied in equally acrimonious terms. So vicious did the correspondence become that journal editors, fearful of libel, hesitated to publish the letters. But Ross and Grassi did not stop feuding. Both enlisted the aid of the authorities on tropical medicine. Ross was able to obtain letters from Dr. T. Edmundston Charles, an English observer of the Italian work in Rome. Using this evidence, Ross asserted that Grassi had been aware of the studies on bird malaria, though Grassi later denied such awareness. When Ross could not find a publisher for a book containing his case against his Italian adversary, he paid for the printing himself, carrying the work through two editions. This bitter conflict lasted for more than two decades. But the Nobel Committee had no difficulty in identifying the merits. Ross was awarded the Nobel Prize in 1902.

Awards and recognition came behind Ross. In 1901 Ross was elected a Fellow of the Royal College of Surgeons of England and also a Fellow of the Royal Society, of which he became Vice-President from 1911 to 1913. In 1902 he was appointed a Companion of the Most Honourable Order of Bath by His Majesty the King of Great Britain.

In 1902 he was awarded the Nobel Prize for Medicine “for his work on malaria, by which he has shown how it enters the organism and thereby has laid the foundation for successful research on this disease and methods of combating it”. (Nobel Prize in physiology and medicine has never been awarded for work in biostatistics or epidemiology. The “exception who proves the rule” is Ronald Ross, who won the second medical Nobel; but Ross himself considered the mathematics of epidemic theory as his most important scientific contribution).

That Sir Patrick Manson missed the Nobel Prize also did not go down well with those who knew of his contribution to Ross’s work. The 100 or so letters that they wrote to each other in the two decades afterward poignantly document the gradual cooling of a creative friendship and the difficulty of a teacher-pupil relationship evolving naturally into one of equals.

In 1911 he was Knighted. In Belgium, he was made an Officer in the Order of Leopold II. He was given Honorary Membership of learned societies of most countries of Europe, and of many other continents. He got an honorary M.D. degree in Stockholm in 1910 at the centenary celebration of the Karolinska Institute. Whilst his vivacity and single-minded search for truth caused friction with some people, he enjoyed a vast circle of friends in Europe, Asia and America who respected him for his personality as well as for his genius. He was the Editor of Science Progress from 1913 until his death in 1932. In 1926, Ross Institute and Hospital for Tropical Diseases was opened and the Prince of Wales came down to honour Ross, who was named its director in chief.

Sir Ronald Ross

Sir Ronald Ross

But these awards and recognitions brought him little contentment. Despite receiving many other awards and honours during his life, he felt embittered that he did not receive monetary reward for his discovery and petitioned the Government on this subject. He resented the fact that his medical practice (and income) had never thrived (like Manson’s), and that his life as a researcher seemed undervalued and underpaid. He had always longed to be in London, not Liverpool, although by the time he settled there in 1912, even London offered him no real peace. Above all, he was aggrieved that the growing band of malariologists did not support his ideas on the control of malaria and was not satisfied with the attitude of the administration towards malaria control efforts. Ronald Ross hoped that the difficulties that he faced during his research and work would open the eyes of the powers-that-be and hoped that the life would be easier for the future generation of scientists.

Ronald Ross’s literary works include the novel The Child of Ocean (1899 and 1932); The Emigrants; Edgar; The Judgement of Tithonus; Philosophies, Psychologies, and other Poems; novel, The Revels of Orsera; novel, The Spirit of Storm; selected Poems (1928); Fables and Satires (1930); collection of melancholy poems In Exile (1931); Lyra Modulatu (1931); five mathematical works (1929-1931). He also compiled an extensive account The Prevention of Malaria in 1910 and another Studies on Malaria in 1928. His autobiography, The Memoirs was published in 1923; it is a long (547 pages) and powerful account of his trials and tribulations. Its subtitle –“with a full Account of the Great Malaria Problem and its Solution”–speaks volumes about his assessment of his own worth. Ross saved virtually everything about himself: correspondence, telegrams, newspaper cuttings, drafts of published and unpublished material, and all manner of ephemera; he also retrieved a fair number of his own letters while preparing his memoirs. In 1928, Ross advertised his papers for sale in Science Progress, making it known that he needed the money for the provision of his wife and family. They were bought by Lady Houston for £2000, who offered them to the British Museum. They refused the collection, partly due to Ross’ stipulation that his arrangement of the papers had to be retained and also due to some canvassing from members of the Ross Institute who thought that the collection would be better placed with them. The majority of these papers are now held by the London School of Hygiene & Tropical Medicine (See http://www.lshtm.ac.uk/library/archives/rossproject.html). Altogether, there are some 30,000 catalogued items in the two major Ross repositories, at the London School of Hygiene and Tropical Medicine (LSHTM), and the University of Glasgow.

Ross and Rosa had two sons, Ronald and Charles, and two daughters, Dorothy and Sylvia. He lost his elder son in the British retreat from Mons and his own health deteriorated during the war. In 1925, his older daughter died. In 1927, Ross had a stroke. His wife died in 1931. Ross survived her until a year later and died at the Ross Institute, London, on September 16, 1932. The Nobel Prize winning scientist, mathematician, epidemiologist, sanitarian, editor, novelist, dramatist, poet, and an amateur musician, composer and artist was buried next to his wife at Putney Vale Cemetary.

Like many prophets before and since, he said things that we forget at our peril. Three things stand out. First, Ross quantified the economic costs of malaria. Both the figures and the percentages will have changed over time, but Ross’s approach should still command assent. He showed in hard figures that had the money spent in treating and burying soldiers and civilians been turned to prevention, the result would be a world with less malaria. His bitter contempt for penny-pinching governments who could respond only to the crisis at hand rather than legislate for the future earned him few friends. Second, Ross was an eloquent spokesman for what later would be called the vertical program. Even during Ross’s lifetime, malariologists were divided into those who believed that socioeconomic amelioration would in itself largely solve the malaria problem (as was happening in Europe) and those who held that holoendemic malaria was itself a block to economic improvement. Despite the fact that horizontal approaches are now in fashion, focused campaigns targeted at specific diseases can still pay off. Ross firmly believed that malaria was one disease ripe for deliberate control. Ross came to see that anopheline mosquitoes were not so delicate as he had once thought, and malaria would require longer and more sustained effort. But the scientific understanding was in place, he argued, and all that was really lacking was the political will. Finally, Ronald Ross passionately believed in the social value of biomedical research. Such research should be adequately rewarded, he insisted, and society should always hold its scientists in high regard, whose worth, he always thought, was socially undervalued. But he also worked tirelessly on behalf of the scientific community as a whole, campaigning for comrades who needed his help; and, through his long editorship of Science Progress, furthering the cause of what is now called the public understanding of science. His heart was almost certainly in the right place.

Even after more than a century of Ronald Ross’s painstaking efforts at control of malaria, the ‘administrative apathy’ towards malaria control programmes continues for “inexplicable” reasons as Ross put it. And unfortunately, the building of the Military Hospital at Secunderabad, where this discovery was made, now lies in ruins and little is done to remember the person who worked tirelessly to make a discovery that would benefit humanity. The super-sensitive, single-minded Ross went to his grave still holding the firm conviction that malaria could be eradicated if only weak-willed governments would commit themselves to exploit his discovery and attack the anopheline in their watery lairs.

Ross’s three part paper on the theory of epidemics is available on the web:

Sources:

  1. http://stevenlehrer.com/explorers/images/explor1.pdf
  2. http://www.cdc.gov/malaria/history/ross.htm
  3. Breslow NE. Are Statistical Contributions to Medicine Undervalued? Biometrics, Volume 59, Number 1, March 2003, pp. 1-8(8) Available at http://www.ingentaconnect.com/content/bpl/biom/2003/00000059/00000001/art00001
  4. http://www.lshtm.ac.uk/library/archives/rossproject.html
  5. http://www.libertyindia.org/pdfs/malaria_climatechange2002.pdf
  6. Bendiner E. Ronald Ross and the mystery of malaria. Hospital Practice. Oct 15, 1994:95-112
  7. Robert E Sinden. Malaria, mosquitoes and the legacy of Ronald Ross. At http://www.who.int/bulletin/volumes/85/11/04-020735/en/index.html
  8. http://www.litsios.com/socrates/page5.php
  9. http://www.zephyrus.co.uk/ronaldross.html
  10. http://www.tribuneindia.com/1999/99apr17/saturday/fact.htm
  11. http://www.aim25.ac.uk/cgi-bin/frames/fulldesc?inst_id=37&coll_id=4046
  12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9989333&dopt=Abstract
  13. http://banglapedia.search.com.bd/HT/R_0220.htm
  14. http://www.theotherpages.org/poems/gp1_14.html
  15. http://medicine.nobel.brainparad.com/ronald_ross.html
  16. http://www.aim25.ac.uk/cgi-bin/frames/fulldesc?inst_id=37&coll_id=4046&full=1&template=1
  17. http://www.lshtm.ac.uk/library/archives/rossbio.html
  18. http://www.geocities.com/~bblair/reflections_twp.htm
  19. http://www.bartleby.com/266/53.html
  20. http://www.answers.com/topic/ronald-ross
  21. http://www.sciencemag.org/cgi/content/full/295/5552/47
  22. http://www.cdc.gov/malaria/history/panama_canal.htm
  23. Ross R. Researches on malaria. Nobel Lecture, December, 12, 1902. (From Nobel Lectures, Physiology or Medicine 1901-1921, Elsevier Publishing Company, Amsterdam, 1967) Available at http://nobelprize.org/medicine/laureates/1902/ross-lecture.html
  24. http://nobelprize.org/medicine/laureates/1902/ross-bio.html
  25. Chidanand Rajghatta. India’s Nobel connections. Available At http://timesofindia.indiatimes.com/India/Indias_Nobel_connections/articleshow/2456211.cms

©malariasite.com ©BS Kakkilaya | Last Updated: Mar 9, 2015

4 Comments:

  1. Pingback: 10th DEC1902 SIR RONALD ROSS(13th MAY 1857-16th SEP 1932) | his1blog

  2. What a great piece of work. Example of life being unrewarding in monetary terms but still continuing his efforts for the sake of his interest, which at last lead to a ground breaking result. Hats off.

  3. Thank you for the wonderful help. I am a Greek-Cypriot working on my 4th Assignment on Life Writing: Creative writing Level 2.with the OCA, UK. I am permanently resident in the UK.since 1958. I am now 75yrs. Doing the work on Malaria eradication in Cyprus, and my early memories. I am also interested in obtaining some of Sir Roland’s writing of Literature, Poetry, Novels short stories, and Travel Writing. Thank you again. Nicholas Poulcherios. Retired senior Nurse. Have done a lecture course as an external student, a 6 month weekly Lectures in Tropical Diseases at the LSHTM in 1963-4-from Hammersmith POST Grad. Hospital (teaching) London. Nicholas309678 OCA.

  4. Pingback: 13 MAY 1857-16 SEP 1932 SIR RONALD ROSS | his1blog

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