1^6 



NA TURE 



[December 6, 1900 



• ■ tropical malaria: ' The quartan has proved the mildest of the 

 three.' • ■ 



■ iThe process of sporulation might seem at first sight to explain 

 . the whole life-history of the parasites. For their , propagation 



within the human body that process does indeed make ample 

 provision. But the mystery remained— how did they gain 

 ' entrance into the human system ? Though present in abundance 

 in the blood of the malarial patient, they are absent from the 

 excreta.- Spontaneous generation having been long since 



• exploded, what could be their mode of origin in the external 

 ^ world ? This problem has of late been completely solved. 



" Among the forms of the parasite observed by Laveran was 



one which he termed '* flagellated," possessing filamentous 

 appendages which exhibited extremely active movements, by 

 virtue of which they were often seen to break off from the 

 parent microbe and swim away. These flagella were regarded 

 by many biologists as products of degeneration resulting from 

 the abnormal influences to which the parasites were exposed in 

 blood outside the body. This Laveran could not believe : 

 indeed, it was the remarkable activity of the flagella that finally 

 satisfied his own mind that what he had discovered were really 



• living parasites : he regarded the flagella as the highest form of 

 development of the microbe. There was another observer who 

 felt equally convinced that the flagella were living elements — 

 our Fellow, Dr. Manson. ■ He, however, went a step further. 



■ Seeing that the flagella were never met with in blood when first 

 drawn, but only made their appearance after some little time 



• had elapsed, he conceived that their function must be that of 

 spores for spreading the parasite in the external wOrld, and some 

 suctorial insect seemed to him the probable agency for their 

 diffusion. He had observed several years ago that another 



i parasite of the human blood, a microscopic nematode worm, 

 Filaria, is drawn with the blood into the stomach of a kind of 

 mosquito, and finds in the insect a secondary host, in the tissues 

 of which it passes through a new cycle of development. He 

 became deeply impressed with the idea that a similar series of 

 events might occur with malaria, and. he expounded his views 

 fully before the College of' Physicians. 'The notion that 



' mosquitoes might be in some way associated with malaria had 

 occurred to Laveran and to others, but' by no one had it been 

 brought home with such logical force as by Manson. 



Major Ronald Ross, of the Indian Medical Service, on a visit 

 to this country, became deeply impressed by Manson's argu- 

 ments, and determined to test his theory on returning to India. 

 Using mosquitoes bred in bottles from the larva, he caused them 

 to bite persons affected with the crescent form of malaria, and 

 afterwards sought in the bodies of the insects for evidence of the 

 development of the parasite within them. For two long years he 

 pursued this search, making about a thousand observations, but to 

 no purpose. So far he had employed two kinds of mosquito com- 

 mon in the district where he was stationed ; but in August 1897, 

 having been supplied with some larvte of a species rare in that 

 locality, and having bred the fully developed insects from them, 

 he induced eight of them, to bite a patient with crescents in his 

 blood, and examined their tissues at successive periods. Four of 

 them were killed at once for the investigation of the flagellated 

 bodies. Of the remainder, one examined four days after biting 

 showed, under a high magnifying power, several rounded bodies 

 imbedded in the wall of the stomach, differing from any natural 

 structure of the insect, and containing granules of pigment 

 "identical in appearance to that of the parasite of malaria" 

 {vide British Medical Journal, December 18, 1897). The 

 eighth mosquito was killed one day later, and exhibited bodies 

 precisely similar except that they were distinctly larger and more 

 substantial, implying that: they had grown in the interval. 

 Thinking that in all probability he had at length found that 

 which he had been so long in search of, and feeling uncertain 

 when he might again obtain the rare species for confirmatory 

 investigation, he at once sent a description of his observations to 

 •London, accompanied by his preparations and an independent 

 report upon them by a colleague. Dr. Manson, to whom, among 

 others, they were submitted, was so much struck with the 

 preparations that he had a drawing made of the pigmented 

 bodies in them for publication along with Ross's . paper. 

 Though, like Ross, expressing himself with caution, he inclined 

 to his interpretation of the appearances. The paper contained 

 a minute description of the rare mosquito, which seemed to 

 Ross to belong to a "family distinct from the ordinary" 

 kinds. 



In the following month he made a similar experiment with 



NO. 1623. VOL. 63] 



another species of mosquito which appeared closely allied to the 

 subject of his last observations. He succeeded, though with 

 some difficulty, in getting. two of them to bite a patient with 

 crescents. One of these insects, killed next day, was examined 

 with a negative result ; but in the second, killed forty-eight 

 hours after biting, the. peculiar pigmented- bodies were again 

 seen among the tissues of the stomach. Meanwhile, " some 

 scores" of the species, "unfed or fed on healthy blood, had 

 been examined without finding the pells." 



In the same month he observed precisely similar pigmented 

 bodies in a common mosquito which he had seeri feeding on a 

 patient affected with the parasite of mild tertian fever. ' Here he 

 had not the rigorous evidence supplied by insects bred from the 

 larva ;^ arid it was quite a new thing to find the 'pigmented 

 bodies in ordinary mosquitoes. But all the patients on whom 

 his previous observations on the common species had been made 

 had been affected with crescents ; and the parasite concerned 

 being in; this case a new species, it did not seem unlikely, that it 

 might be harboured by the common insects.'- These new facts re- 

 moved all doubt from his mind ; and he felt that he had the sub- 

 ject in his grasp, and. wrote to that effect to Manson. , But, to 

 his bitter disappointment, he was at this time despatched to 

 another part of India to study another disease ; and thus several 

 precious months were lost. 



In February 1898, however, he was told off" for, the special 

 investigation of malaria, and a laboratory in Calcutta was set 

 apart for his use.^ Few cases of human malaria being available 

 at that season of the year, he turned his attention to some closely 

 allied forms of disease common 'in birds. . He sooii found that 

 one of the ordinary kinds of mosquito, which had invariably 

 given negative results when fed ori patients with ; crescents, 

 developed pigmented bodies among the tissues of the stomach 

 if fed on birds, such as sparrows, containing in their blood the 

 form of bird parasite known as Proteosoma. The. birds pre- 

 sented a ready field for experiment ; and the kind of mosquito, 

 the grey mosquito as he termed it, was very abundant in Cal- 

 cutta, so that it was easy for him to hatch from the' larva any 

 number that he might require. Discoveries now followed 

 each other in quick succession. He soon announced that the 

 pigmented bodies grew rapidly from day to day, till after about 

 a week they assumed large proportions, projecting like buttons 

 from the outer surface of the stomach, and often showing a 

 curious appearance of radiating striae. Next we learned that 

 the striae had been indications of spore formation, and that when 

 the bodies had attained maturity they burst into the general 

 body-cavity, discharging enormous numbers of minute elongated 

 organisms which he termed " germinal rods." Then followed 

 the remarkable observation that the germinal rods soon leave 

 the general body-cavity, and accumulate in the cells of the 

 salivary or poison glands and in the duct leading from them to 

 the proboscis, with which the bites of the insect are inflicted. 

 And, lastly, he completed the cycle of evidence by ascertaining 

 that healthy sparrows could be infected with the Proteosoma 

 by causing mosquitoes to bite them at the appropriate period 

 after biting an infected bird. 



Thus was, in truth, established the mosquito theory of malaria. 

 For taking into account the close resemblance of the Proteo- 

 soma to the parasites of human malaria, together with the facts 

 ascertained by Ross regarding the infection of the rare mosquitoes 

 with human crescents, we could not doubt that the course of 

 events which he'had traced in the sparrow occurred also in man. 

 And the two sets of observations, taken together, clearly estab- 

 lished the fact that, as Manson had predicted, different species 

 of malarial parasite may require different kmds of mosquito as 

 their alternative hosts. 



At the same time, the presence or absence of the pigmented 

 bodies in the stomach wall afforded a sure means of distinguish- 

 ing those kinds of mosquitoes which convey malaria to man 

 from those which are incapable of doing so. And it may be 

 added that the multitude of negative results after feeding grey 

 mosquitoes with crescent blood, considering the great prevalence 



1 Vide British Medical Journal (February 26, 1898). In this second 

 paper Ross did not repeat the description of his method, given in the 

 former article, of using mosquitoes bred in bottles from the larva. But_ as 

 that had been his practice for more than two years, there can be no reason- 

 able doubt that he continued it with this new species. 1 have also his 

 personal assurance that such was the case. 



2 As the result of further knowledge, there is no doubt that this common 

 mosquito had derived its pigmented bodies, not from the man it was seen 

 biting, but from a bird affected with another species of malarial parasite. 



3 It has seemed necessary to refer to these points in detail, as consider- 

 able misapprehension has prevailed in som2 quarters regarding them. 



