Researches on malaria Nobel Lecture, December, 12, 1902
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ogists regarding the proper nomenclature for use in connection with the de- velopmental stages of the parasites in mosquitoes. With the aid of Professor Herdman I published a paper on the subject 59 , in which, abandoning the hasty provisional nomenclature hitherto used by me, I called the motile filaments, microgametes; the pigmented cells, zygotes; and the thread-like bodies, blasts. I also suggested a classification for the parasites of men and of birds. But there is still great divergence of opinion on these subjects. Evidently West Africa, a rich and enormous country hitherto paralysed by malaria, was destined to be the first objective. I lost no time in urging the ad- visability of sending me there in order to complete my studies of the disease and determine its agents on the spot. In July I delivered my inaugural lecture and demanded attention for my scheme for extirpating malaria by attacking the pool-breeding mosquitoes 5 8 . At the end of July 1899, accompanied by Mr. E. E. Austen of the British Museum and Dr. H. E. Annet, Demonstrator * Owing to an error he thought that it was this kind in which I had first found the pig- mented cells in 1897.
92 1 9 0 2 R.R OS S of the Liverpool School of Tropical Medicine, I left England for Freetown, Sierra Leone. 22. Sierra Leone (August-September, 1899). The investigation completed. We have now reached the last chapter of this history - which I fear has become tedious. If a literary simile may be allowed in a scientific narrative, I had at last come to my Ithaca, after many mischances sent by many opposing deities. Two years had elapsed since I had seen the pigmented cells of the human para- sites - two years of fruitless efforts, interruptions and bad fortune; and seven years had elapsed since I had commenced the special study of malaria; but now assisted by my able colleagues and myself, I needed but a week or two to dem- onstrate all the stages of the human parasites in dappled-winged mosquitoes, and also to ascertain the fundamental principles upon which State sanitation against tropical malaria should be based. I will be brief; the details are given in the publications 60,67 .
winged mosquitoes (Anopheles costalis, Loew, and Anopheles funestus, Giles) in abundance. On the 13th August, we detected a pigmented cell, evidently of the mild tertian parasite, in one of them. A few days later, in some barracks there was much malaria, we ascertained that a quarter of the mosquitoes (al- most exclusively A. costalis) were infected; and found in them pigmented cells evidently derived from all three varieties of parasites - quartan, tertian and aestivo-autumnal. We also made a few formal feeding experiments, and could have made as many more as we pleased. The material was unlimited; but our time was short, and the proof was already sufficient. We then investigated the conditions under which the Anopheles breed and propagate malaria. It was the rainy season and the place was full of stagnant pools. Everywhere the larvae of the dappled-winged mosquitoes were in these pools, while those of the grey and brindled mosquitoes occurred in tubs and pots. The great law of malaria - its connection with stagnant water on the ground - was explained. Moreover, simply by noting the presence of the lar- vae, we could tell at a glance which pools were dangerous to health and should be dealt with in the public interests. The habits of the insects were noted and found to be precisely similar to those of the Indian species. We studied particularly the characteristic attitude of the larvae and adults of the dappled-winged mosquitoes, as formerly ob- served in India - invaluable tests for the immediate and easy recognition of the agents of the disease; we noted the evidence demonstrating the short flight of R E S E A R C H E S O N M A L A R I A 93 the insects, and their connection with rank tropical vegetation; we disposed of the ideas that tidal swamps cause malaria, but showed how earth-works pro- duce outbreaks by the formation of pools of rainwater. In fact we were able to give a thorough explanation of the manner in which the old paludic and tel- luric theories of malaria originated. We were also able to establish for the first time the fundamental principles which the State must adopt in order to extirpate malaria in tropical cities. These are (1) scrupulous drainage of the soil; (2) pending this, the persistent treatment of Anopheles’ breeding-pools by culicicides; (3) the segregation of Europeans. We also recommended the protection of public buildings, such as barracks, gaols, hospitals, and rest-houses by wire gauze screens; the isola- tion of the sick; and the habitual employment of mosquito-nets and punkahs by individuals. Our results and recommendations were immediately communicated to Government and also published in the medical press 60 .
experiences 6 7
. In this book, written by myself and endorsed by my colleagues, I collected the principal results of all my researches on malaria made during seven years; and illustrated the life-history both of the human and avian para- sites in mosquitoes by numerous photo-micrographs made by myself. This work, therefore, which records the completion of these labours by the success- ful demonstration of the whole evolution of the human parasites in Anopheles, constitutes the summary and conclusion of all my previous papers. It has been said that the book was based on the writings of those who, as a matter of fact, learnt everything from me; but I can say with exact truth that if no one except MacCallum and Koch had touched the subject since 1895, scarcely a word in the Report would have been different. It should be added that in March 1900 I gave an abstract of the history of my work in a lecture at the Royal Institution 68 ; and particularly, that toward the end of the same year the President of the Royal Society, Lord Lister, for- mally accepted my results in his Address to the Society. From this time my own efforts have been devoted almost entirely to the practical campaign against malaria. Few people are aware of the fact that even the most solid discoveries of science may be allowed by the public to remain quite disused and inoperative unless strenuous efforts are made to urge them upon the popular attention. Even yet, in spite of the constant endeavours of many persons, very little has really been done towards the extirpation of mala- ria. This has been principally due to the fact that, for some inexplicable reason
94 1 9 0 2 R .R O S S which wholly escapes me, the chief prophylactic measure recommended by me, namely a campaign against mosquitoes by drainage and petrolage, has been generally held to be impossible; yet it is the only general prophylactic measure possible in tropical towns. The struggle over this matter has been al- most as severe as that over the original problem; but it is now drawing to a close. It is impossible to discuss the matter here. Suffice it to say that in the two principal towns, Havana and Ismailia, in which the measure has been ade- quately employed, the reduction of malaria has already been as much as eighty per cent. This then is the conclusion of the history. I fear that some of the personal details may have appeared out of place in the narrative; but they have been introduced - though unwillingly - for a special reason. No form of enterprise is of such transcendent importance to humanity in general as the investigation of disease - the principal enemy of every man. The interests of all nations, not only in the present but in the future, demand that every possible encourage- ment should be given to such investigations - particularly that medical men, who are in an excellent position to undertake them, shall receive the warmest assistance in their self-imposed task. The story, however, which I have felt it a duty to record in this lecture adds but one to the many instances of medical history which show that little attention is given to this point. My labours will be abundantly repaid if earnest students in this field of science receive, in the future, in consequence of this narrative, a little more assistance than was given to me.
It is impossible for me to describe here, even in detail, the vast amount of work which has been done in many parts of the world on the mosquito theory of malaria since 1899; but it is necessary just to touch upon some of the more immediate verifications of my observations. (1) Undoubtedly the first verification was due to Koch and his assist- ants 63,64
. Professor Koch was kind enough to communicate to me at my re- quest, in a letter dated the 15th May 1901, the origin and progress of his re- searches on the mosquito theory of malaria. He says: "The idea that mosquitoes may be the cause of malarial infection occurred to me on my first visit to the tropics in British India in the winter of 1883-1884, and since then I have always spoken in this sense in my lectures and to my as- sistants. I have not indeed myself published anything about these views; but you will find a notice in R. Pfeiffer’s work Beiträge Z ur Protozoen-Forschung, Berlin, 1892 (near the end). R E S E A R C H E S O N M A L A R I A 95 "The fact that malaria, when it occurs epidemically, is often confined al- most entirely to the children, the adults remaining free and therefore having become immune, I discovered first in villages in Java which lie in the valley of Ambarawa. That was at the beginning of November 1899. I reported on it on the 9th of December 1899, and my letter was published in the Deutsche Medi- zinische Wochenschrift, No. 5, 1900, beginning of February. I obtained my first, successful cultivation of Proteosoma in mosquitoes in company of Prof. R. Pfeiffer in Rome in September 1898. We continued the investigation in Ber- lin; and in the middle of November we followed the developmental stages of the parasite up to the sickle-shaped bodies in the poison glands of the mosqui- to - that is up to the end. We were able to determine the form of Würmchen (vermicule) in Proteosoma so easily because I, with Professor Kossel, had al- ready in June of the same year (1898), without knowledge of MacCallum’s investigation, detected the origin of the spermatozoa, the process of fertiliza- tion, and the formation of the Würmchen in Halteridium. "The publication of this investigation was very much delayed in conse- quence of the long time taken for the reproduction of the photographs in a way which satisfied me. "At all events I have not thought it necessary to attempt to assert my priority on this occasion as the matter concerned only the confirmation of already known things." Professor Koch has the honour of having been one of the first, not only in- dependently to conceive the mosquito theory of malaria, but also to attack it by experiment. He and Kossel independently observed the function of the motile filaments by the employment of correct methods of staining: this is practically admitted by Bignami (Lancet, 2 (1898), p. 1898) who was later able, probably through his instruction, to demonstrate the chromatin in the motile filaments 50 - a thing which he had refused to credit before. Koch also was the first to fill a gap in my own researches on Proteosoma by demonstrating the passage of the vermicule through the wall of the mosquito’s stomach - a sub- ject in which Grassi merely followed him later. That he succeeded in culti- vating Proteosoma in Rome and Berlin, in September to November, 1898, shows that he was the first to confirm my own observations. About that time Dr. Annett of the Liverpool School of Tropical Medicine saw some of his prep- arations of pigmented cells in Berlin. Koch’s discovery of the frequent infec- tion in native children in the tropics was one which I had entirely failed to make - although I should have made it; and is an addition to our knowledge of the very highest importance, being of far greater intrinsic value than much of 96
1 9 0 2 R.R OS S the trifling matter which has been put forward in other quarters with much réclame. It enables us to explain with ease the source of most malarial infections in the tropics, and, besides, gives a complete revelation regarding the possibil- ity of immunity in malaria, a thing in which no one would previously believe. Added to this Professor Koch has pressed still further onwards, and pushed with authority and ability the great subject of the practical prevention of the disease in the tropics - a matter the importance of which few writers on the subject have seemed able to comprehend. The methods recommended by me consist principally of the use of mosquito-nets and the extirpation of mosqui- toes; but Koch at once inaugurated a new conception which had not occurred to me and which consisted in the cinchonization of the people in malarious localities. Although this measure is not always possible in its full extent, still experience shows that in a modified form it is most useful; and I have come to the conclusion that it should always be enforced as much as practicable in addi- tion to the measures which I advocate. It was also Koch who was the first to call general attention to the important fact that a sudden and ill-advised dose of quinine is apt to precipitate attacks of blackwater fever in certain persons and localities.* (2). Many erroneous ideas have been formed about the Italian work (re- ferred to in section 20) by those who have no practical knowledge of malaria or full acquaintance with the literature. The facts are exactly as follows. The South of Italy affords unparalleled advantages for the study of malaria, because abundance of material is there combined with great facilities in connec- tion with laboratories, literature, and scientific communion; hence, though the principal discoveries have been made elsewhere, the writers of Southern Italy have been able to add to them much detail, which has proved more or less correct. It was hoped after Laveran’s discovery that they would be able to find the extracorporeal phase of the parasite; but, unfortunately, misled by fond- ness for hypotheses, they fell into fundamental errors. Most of them hastily concluded that the motile filaments are "agony-forms"; and, as described in sections 6 and 11, A. Bignami rejected Manson’s induction on this account; and another writer, G.B. Grassi, abandoned the whole mosquito theory (1) because mosquitoes do not bite birds, (2) because they abound in places where there is no malaria, and (3) because the malaria parasites die in the stomachs of mosquitoes. At the same time he maintained that the extracorporeal stage * I should like to add, in contradiction of many inaccurate statements which have been made, that his acknowledgment of my own observations has been the most complete possible. R E S E A R C H E S O N M A L A R I A 97 of the parasite is a free-living amoeba 10 . Bignami however, while rejecting Manson’s version of the theory, adopted King’s, and stated that he had even made some experiments on the subject in 1894; but these were only referred to as a past event 29 , and seemed to have been quickly abandoned. It is probable that these writers would have remained indefinitely in this position but for the researches of others. In 1895-1897, Sacharoff 23 , Simond
35 , MacCallum 36 , and myself 32 destroyed the Italian theory regarding the motile filaments; and then the publications of the 18th December, 1897 38 , the 26th February, 1898 39 , the 21st May 42 , the 18th June 4I , the 24th September 43 , and
11th October 46 , completely demonstrated the life-history of this group of para- sites in mosquitoes; clearly indicated the genus concerned in the propagation of aestivo-autumnal fever; and gave other details mentioned in section 17. As all these papers, except those of the 21st May and the 11th October (which were in fact covered by Manson’s papers of the 18th June and the 24th September), were published in such a prominent organ as the British Medical Journal, it is to be assumed that they were from the first known to the Italian writers, who have always shown a prompt knowledge of the labours of others. In his first publication 44 , Grassi refers to my work without mentioning my name or giving references - as if it were then perfectly well-known in Italy. The later publications of Bignami and Grassi 48 ,
show that they were quite intimate with it before they themselves attained any definite results. Such being the case, in order to follow my work in Italy and elsewhere, all that was now needed was to determine the genera of my grey and dappled- winged mosquitoes from such indications as I had been able to give. The for- mer had been described in two papers, and was most evidently closely allied to Culex pipiens; and the latter, in which the aestivo-autumnal parasites had been shown to develop, were described in 1897 38
as follows: "The latter are a large brown species biting well in the day-time, and in- cidentally found to be capable of harbouring the filaria sanguinis hominis. The back of the thorax and abdomen is a light fawn colour; the lower surface of the same, and the terminal segments of the body a dark chocolate brown. The wings are light brown to white, and have four dark spots on the anterior ner- vure. The haustellum and tarsi are brindled dark and light brown. The eggs - at least when not properly developed - are shaped curiously like ancient boats with raised stem and prow, and have lines radiating from the concave border like banks of oars - so far as I have seen, a unique shape for mosquito’s eggs. The species appears to belong to a family distinct from the ordinary brindled and grey insects; but there is an allied species here, only more slender, whiter, 98 1 9 0 2 R . R O S S and much less voracious." In the next paper 39 these small insects also are called "dappled-winged". At that time in Italy the Culicidae had been carefully studied by Ficalbi in several works 31
, and it was an easy task for anyone possessing these works, and also having fresh mosquitoes for dissection, to determine the genus of my dappled-winged mosquitoes from my description alone. Although I did not give the entomological criterion of the genus Anopheles (the long palpi of the female), I gave three other details which sufficed for the identification. First, the dappled-winged mosquitoes belonged to a group distinct from the grey mosquitoes (Culex pipiens type). Secondly, both species of this group had spotted wings ; and still more particularly, one of them (certainly) had exactly "our dark spots on the anterior nervure". Now it is well-known that very few Culices and Stegomyiae have spotted wings, while Anopheles almost always have them. The Anopheles, however, not only generally possess spotted wings, but the spots are generally four in number and arranged along or close to the anterior nervure. Lastly, if any doubt remained the observer would only have to catch the first spotted-winged female gnat and to examine the eggs within her, when they would be immediately seen to possess the characteristic boat-like shape, with the well-known clasping membrane simulating oars on either side. It is curious that some of those who have written on the subject have over- looked the fact that the very first Italian mosquito which from its name alone would be suggested by my description was Anopheles claviger. Two of the synonyms of this insect are Anopheles quadrimaculatus, Say, and Anopheles ma-
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There is, however, no doubt whatever that the Italians detected the genus of my dappled-winged mosquitoes, because they themselves say so in two of their articles of November 48,51
. Nuttall admits the fact 74 . But there is reason to suppose that they recognized the insects long before November. It was evidently Manson’s paper of the 18th June, 1898 which stimulated the Italians to renewed activity, because they set to work shortly afterwards. But their success was delayed by efforts towards originality. Grassi endeav- oured to find the guilty species of mosquito by its prevalence in malarious localities. His efforts were a close repetition of mine in the Sigur Ghat - even his servant was attacked by malaria as mine had been. He discovered three species of guilty mosquito, namely Culex penicillaris, C. malariae (so named by him - really C. vexans), and Anopheles claviger - principally (per lo meno) the Yüklə 2,27 Mb. Dostları ilə paylaş:
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