Researches on malaria Nobel Lecture, December, 12, 1902
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infected in this very district.
84 1 9 0 2 R.R OS S for months into a difficult pathological problem and a long pathological re- port. But the work was not without interest, and I may be pardoned for touch- ing upon it briefly. The disease had been first noticed by McNaught in 1882. A few years later Government sent Giles to investigate it; and Giles, who probably did not come much in contact with the real disease, seemed to have been considerably misled, and in a report (which was nevertheless a very able one) pronounced the malady to be ankylostomiasis 77 . Many of the practi- tioners in the locality were not satisfied, however, and in 1896 Government sent Rogers to make a further report. Rogers certainly saw the real disease and concluded that it was a virulent form of malaria 78 . As it was evidently com- municable, this implied that he held malarial fever to be communicable - a thing which no one would believe at that time; but he maintained his opinions with great courage and success. I was now sent in order, if possible, to decide the question; and as my researches had shown that contrary to accepted views malaria must be communicable from the sick to the healthy, Rogers’ position was justified. But the exact nature of kala-azar still required definition; and, as I was called upon to judge between opposite opinions, I was forced into a tedious enquiry - though it was my immediate personal impression that the disease is malaria. Mixed with the cases of kala-azar there were numerous cases of ordinary malaria; and I found that the local practitioners could not distinguish which was which until the cases became exceedingly severe, when they were declared to be kala-azar. This generally happened only in the later stages of the cases - so that in fact kala-azar seemed to be simply another name for a very severe and frequently fatal form of malarial cachexia. As, moreover, many of the pa- tients had ankylostomes, those who are familiar with the subject will under- stand that my task was indeed a complex one. The plague-scare not having penetrated here, I attacked the problem by examining the blood of all the cases, both of malaria and of kala-azar. My results showed that while the para- sites were easily found in the early cases, they became more and more scarce as the disease advanced; until, in the old typical cases of malarial cachexia and kala-azar neither parasites nor pigment were to be found, even in blood taken from the spleen. I inferred then that kala-azar is probably only malaria, though it was possible that some secondary infection might account for the gravity of the cases. I also inferred - what no one would accept before then - that the spontaneous disappearance of the parasites must be due to the gradual estab- lishment of immunity; and that the low fever present in these old cases was due, not to the parasites, but to some secondary intoxication from the greatly R E S E A R C H E S O N M A L A R I A 85 enlarged liver and spleen. And the same theories seemed to me to apply to kala-dukh.* This investigation required repeated examination of the blood of all the cases which I could procure in the town; and, being made at high pressure, involved another estreme strain on the eyesight. Nevertheless I examined several batches of dappled-winged mosquitoes fed on cases with parasites, but the insects selected for the work were like some of those abounding at Calcut- ta, namely Anopheles rossi. All proved negative. My disappointment was con- siderable, but I was not satisfied that the feedings, which were left to assistants, were properly done. Many of the same insects caught in the houses of patients were also negative. By the aid of my assistants, however, many fresh examples of the law that the dappled-winged mosquitoes breed in pools of water on the ground were obtained. During my stay at Nowgong I wrote a short report, dated the 11th Oc- tober, on the infection of birds by the bites of mosquitoes 46 . This was not published until some months later; but of course the principal facts had long previously been published by Manson 43 .
hausted, to Calcutta. 20. Calcutta (November, 1898-February, 1899). The work confirmed. Arriving at Calcutta on the 19th November I set to work to pick up the threads of my work on Proteosoma; to obtain cases of human malaria (the plague-scare hav- ing abated); and to write my report on kala-azar - this being a tedious business requiring a full discussion of many intricate details. But my health had now suffered greatly from the continuous exertion made under very trying cir- cumstances; and I felt scarcely able to complete even my report. The labour, the disappointments, even the successes, of the long and anxious investigations of a single subject had been too much for me. The cold and dry weather had now commenced in Calcutta; and the result was that the malaria parasites had become much more difficult to find, either in men or in birds. Added to this, as I had no room in my laboratory which could be warmed by a wood fire (a gas-stove injured the insects), the mos- quitoes could scarcely be persuaded to bite. And when they did so, it was ob- served that the parasites developed in them much more slowly than in hot weather. * It has just become highly probable that these diseases are due to a new parasite recently discovered by Leishman and Donovan.
86 1 9 0 2 R .R OS S Moreover, all this time I had failed to obtain any assistance in India, and saw no prospect of obtaining any. I had been told indeed by Manson that Dr. Da- niels was to arrive shortly; but he was being sent, not really to assist me, but to enquire into the correctness of my statements; and was to remain with me only for a month or two. The only persons who had hitherto taken sufficient interest in my proceedings even to look at my preparations (I mean from the beginning of my work in 1895) had been Drs. Smyth, Maynard, Dyson, and Cooke; and it was clear that no one really credited my results. Even the Di- rector General, who was then in Calcutta, would not visit my laboratory. It was the case of Galileo and the satellites of Jupiter over again! I was, however, much cheered by the arrival of Dr. Rivenburg of the Amer- ican Mission, who, hearing of my work, came all the way from a distant part of Assam with his wife and children at his own expense to assist me. He had been previously quite unknown to me; and I shall never forget his disinterest- ed action and the help he gave me. I had also been delighted to hear from Manson that the work was now being taken up by Koch and the Italians. My papers had been published as described; copies of my Proteosoma Report 42 had been sent to many persons interested in malaria. On the 8th November Manson wrote again informing me that he had just despatched some of my preparations to Rome, namely to Bignami and Charles. I did not become acquainted with the admirable work of Koch until later (section 23); but the efforts of Bignami and Grassi were now communicated to me in a series of interesting and well instructed letters by Dr. Edmonston Charles - a gentleman then staying in Rome, but whom I had never met, nor corresponded with before. From these and their own papers it was clear that the Italian writers had been inspired by my work and had been desperately endeavouring to follow it; that they had detected the genus (Anopheles) of my dappled-winged mosquitoes, and, after having seen my preparations, had succeeded at the end of November in finding my pigmented cells in an Italian species of this genus caught in infected houses. Bignami also claimed to have infected healthy persons by mosquitoes obtained in this manner; and, by a lucky stroke, one of the persons bitten by some A. claviger was found to have acquired the mild tertian parasite. I shall return to this subject when describing the confirmations of my work. The efforts of Bignami and Grassi were, however, obviously hasty and un- reliable; while their writings were historically most inaccurate. They there- fore did not impress me, and exercised no influence whatever in the comple- R E S E A R C H E S O N M A L A R I A 87 tion of my own labours. For several years afterwards, however, nearly all my work was credited to these writers. One interesting fact, however, I learnt from the Italians through Charles, namely that my grey mosquitoes belonged to the genus Culex and my dap- pled-winged mosquitoes to the genus Anopheles. Manson appears to have sent some of the former to Grassi, and, according to Charles’s letters of the 19th November, he thought they were Culex pipiens - as a matter of fact they were C. fatigans. Also from Charles’s letter of the 25th November and from their own publications 4 8 , 5 1 , it was clear that the Italians thought that my dap- pled-winged mosquitoes were Anopheles claviger; and in his letter of the 6th January it was stated that Grassi considered some dappled-winged mosquitoes which I sent him were A. pictus - they were really A. rossi, Giles. I satisfied myself more fully next year at the British Museum regarding the zoological names of the mosquitoes studied by me. The Italians had no difficulties in these respects as they had Ficalbi’s works on gnats to guide them. They received some more of my preparations, through Dr. Charles, early in January 1899. On the 22nd December Dr. Daniels, of the Medical Service of British Gui- ana, arrived. Though somewhat sceptical at first, he was soon convinced after seeing my preparations and repeating the experiments with care; and he fully confirmed my work in a paper, which however was not published by the Royal Society until much later 7 1 . I am much indebted to him for his assistance and advice in connection with my report on kala-azar - no one has a profound- er knowledge or a larger experience of malaria. In the time remaining to us we attempted several series of experiments on human malaria (cases now being more obtainable), mostly with the large brown dappled-winged mosquito of Calcutta with which I had made most of my few but negative experiments recently in Calcutta and Assam. These too proved to be negative. We ascribed our failure to some mistake; but the cause was ill-fortune. The mosquitoes were chiefly Anopheles rossi which in Bengal certainly do not easily take ma- laria.* * It was, of course, the cold weather in Calcutta, but Daniels and I used incubators. Ste- phens and Christophers later obtained positive results in Nagpur with A. rossi, but only by very careful artificial regulation of the temperature 71 .
were made under very unfavourable circumstances, and that I never considered my nega- tive results to be at all final. At this time I informed Daniels of some other details; and, in view of a controversy which arose later, he has kindly testified to this fact in the following letter: 88 1 9 0 2 R . R O S S Several distinguished visitors came to us at this time, F. Plehn, A. E. Wright and A. Ruffer. They all accepted our work, except the "black spores" men- tioned in section 17. Nevertheless Daniels and I did not think it right to abandon them without clear evidence; but when, later, I found closely similar bodies in large numbers in mosquitoes which had not been infected at all, my faith was shaken; and it was disturbed still more when I failed to find them in the infected mosquitoes of Sierra Leone. My doubts were mentioned in the concluding sentences of my report on kala-azar. That report was finished on the 30th January 79 , and contains eighty-one closely printed folio pages. My years’ special duty was now almost finished; but I could obtain no definite assurance from my chief that I was to be retained on the same duty for an extended period. Yet the matter was vital to me. Nearly all the money at my disposal had been spent in consequence of these researches, chiefly because of the expenses connected with the constant changes
Dear Ross, October 8th, 1900. I shall have great pleasure in testifying to the following facts : ( I
specimens of your "grey", "brindled", and "dappled-winged" mosquitoes. You pointed out to me the attitude assumed by the last, the position of its larvae in wa- ter, and the peculiarities of its eggs. Since then I have learnt that these are characteristics of the genus Anopheles. You contrasted these with the eggs and larvae of other mosquitoes, which I now know to belong to the genus Culex. (2) You showed me two species of "dappled-winged" mosquitoes, and I sent speci- mens of them to the British Museum where they now are. They have been described by Major Giles, I. M. S., as Anopheles. You also showed me a specimen of a stomach of a mosquito with what are now known as "zygotes". This you stated was the stomach of a "dappled-winged" mosquito, similar to those you had shown me, which had been fed on a patient with crescents in 1897. (3) I may add that the development of Proteosoma, as demonstrated to me by you in the "grey" mosquito, is essentially the same as the development of "crescents" in Anophe- les as observed by me in British Central Africa. I am, Yours very truly, C.W.Daniels. P.S. As regards breeding-places, you informed me that the "dappled-winged" mos- quitoes breed in puddles, the "brindled" mosquitoes generally in flower-pots, and the "grey" mosquitoes in tanks, ditches, etc. Major R. Ross. C.W.Daniels.
R E S E A R C H E S O N M A L A R I A 89 of station to which my family and myself had been subject; and if I were now compelled to return to Secunderabad, I should not be able later to pay for my passage to England. Moreover, both Daniels and Rivenburg were now leav- ing me, and it was evidently foolish to expect any further assistance in India- much more that of a trained entomologist, which I especially required for the completion of my work on human malaria. I therefore determined to leave India forthwith and to return to England, trusting to fortune to give me an opportunity for finishing the investigation in a manner which I thought suit- able. I mention these personal details as I have been blamed for leaving India at that moment. Before doing so, I urged upon Government the importance of taking active measures for the prevention of malaria in accordance with my observations. Besides advising the strict use of mosquito-nets for a personal prophylaxis, I urged especially a campaign against mosquitoes as the best measure for towns and cantonments, particularly against the dappled-winged mosquitoes, which I said breed principally in water on the ground. My letter was published later
55 , and I hope that the advice will soon begin to be taken. I had also written a brief abstract of my work dated the 31st December, 1898. This was presented by Laveran to the Académie de Médecine on the 24th January, 1899, and was published soon afterwards 55 . In this paper my obligations to Manson and Laveran were acknowledged, I hope, in the full manner which honourable science demands. I wrote : "Pour éviter tout commentaire erroné, qu’il me soit permis de déclarer ici que mes travaux ont été entiérement dirigés par Manson, et que j’ai eu l’as- sistance de ses conseils et de son influence à toute occasion; je dois aussi re- mercier le Dr. Laveran de m’avoir envoyé ses avis si autorisés. Quand, en mai dernier, je lui envoyai des spécimens de mes corps pigmentés du moustique, il reconnut immédiatement la vraie nature de ces éléments." And I added in conclusion, "Je considère comme probable que la malaria est communiquée á l’homme uniquement par les morsures des moustiques et peut-être d’autres insectes."
On the voyage to England (February 1899) I had full time to con- sider the present condition of our knowledge about malaria, especially in rela- tion to the all-important subject of prevention. It was almost certain that in- fection is caused solely by the bites of insects - but of what insects only? My long
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1 9 0 2 R .RO S S negative work had almost proved that the commonest Indian mosquitoes, the grey and brindled genera, do not carry aestivo-autumnal infection, at least. On the other hand, it was certain that two species of dappled-winged mosquitoes in Secunderabad, and one species in Rome, do carry it; while, if Bignami’s observation was to be trusted, the last species carries also the mild tertian infec- tion. But Secunderabad and Rome are not the whole world; even in Bengal, Daniels and I had not succeeded in infecting dappled-winged mosquitoes. The question as to which species do or do not carry malaria might prove to be a very complex one, not to be solved only by a few local experiences; there are probably hundreds of species of mosquitoes in the world, each of which would have to be tested unless we could find some good reason for limiting the enquiry. I therefore sought for some such reason, and found one. For cen- turies it had been known that malaria is connected with stagnant water on the ground - not with water in the pots, tubs, and tanks which abound close to all habitations, but with marshes and pools on the surface of the earth. Again malaria was known to increase every year at the rainy season, and subsoil- drainage was known to mitigate if not remove the disease. Hence it was ex-
For years we had assumed that the disease is caused by organisms which spring from marshes. We had been partially right, but not wholly right; it is not the infective but the infecting organism which springs from the marsh - not the germ but the carrier of the germ. Now, referring to mosquitoes alone, which varieties of these insects breed only or chiefly in terrestial waters? I re- membered my frequent observations on this point (sections 14, 15, and 19). The grey and brindled mosquitoes breed chiefly in tubs and pots in India; but the dappled-winged mosquitoes breed in pools on the ground. Now it was only these last which, hitherto, had certainly been connected experimentally with ma- laria.*
What a weapon for good was now placed in our hands! Hitherto when we wished to remove malaria we were obliged to drain a whole area, recognizing only that all terrestial waters seemed to be dangerous. Now we should be able to go to a place and to point out the actual pools which cause the disease, by showing that they contain the larvae of the culpable insects. The expense of dealing only with these would be much less. Shortly after my arrival in England in March I learnt something about the zoological classification of mosquitoes from Mr. E. E. Austen of the British * This reasoning was by no means obvious or even known until after our work at Sierra Leone. In temperate climates grey mosquitoes (Culex) also breed often in terrestial water. R E S E A R C H E S O N M A L A R I A 91 Museum. I found that, as I had already partially learnt through Charles, my dappled-winged mosquitoes were those of Meigen’s genus Anopheles and that both my grey and brindled mosquitoes belonged to the same genus, namely Culex. I was dissatisfied with this because it seemed to me certain that they were of different genera. Recently Theobald in his fine work on mosquitoes 75 has separated them, placing the brindled mosquitoes in the genus Stegomyia, and reserving the name Culex for the grey mosquitoes. Later, Giles deter- mined that the grey mosquitoes which carry Proteosoma are Culex fatigans, and called the large negative dappled-winged mosquitoes of Calcutta Anopheles
Meanwhile Manson had been urging his great scheme of creating special schools for the teaching of tropical medicine, and had now received the sup- port of Mr. Chamberlain. In Liverpool, Sir Alfred Jones, supported by Pro- fessor Boyce of University College, Mr. Adamson, Chairman of the Royal Southern Hospital, and many other gentlemen, had warmly taken up the scheme, and now appointed me the first lecturer of the Liverpool School of Tropical Medicine. I therefore found myself no longer an isolated worker, but a member of a company determined to advance the interests of life and health in the tropics. And it was an auspicious moment; for the great weapon which had just been forged for the prevention of the most important of tropical diseases needed strong hands to lift and wield it. Almost my first care on returning to England was to consult eminent zool- Yüklə 2,27 Mb. Dostları ilə paylaş:
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