526 



NA TURE 



[March 29, 1900 



birds was examined again. I scarcely expected any result so 

 complete and decisive. Every one of the five birds was now 

 found to contain parasites — and not merely to contain them, but 

 to possess such immense numbers of them as I had never before 

 seen in any bird (with H. relicta) in India. While wild sparrows 

 in Calcutta seldom contain more than one parasite in every field 

 of the microscope, those which I had just succeeded in infecting 

 contained ten, fifteen, twenty and even more in each field — a 

 fact "due probably to the infecting gnats having been previously 

 fed over and over again on infected birds, a thing which can 

 rarely happen in nature. 



The experiment was repeated many times — generally on 

 two or three healthy birds put together. But I now improved 

 on the original experiment by also employing controls in the 

 following manner. A stock of wild sparrows would be ex- 

 amined, and the infected birds eliminated. The remainder would 

 then be kept apart, and at night would be carefully secluded 

 from the bites of gnats by being placed within mosquito nets. 

 These constituted my stock of healthy birds. From time to 

 time two or three of these would be separated, examined again 

 to ensure their being absolutely free from parasites, and then 

 subjected to the bites of "old infected mosquitoes," and, of 

 course, kept apart afterwards for daily study. Thus my stock 

 of healthy birds was also my stock of control birds. Until they 

 were bitten by gnats, I found that they never became infected 

 (except in a single case in which I think I had overlooked the 

 parasites on the first occasion), although large numbers of 

 healthy birds were kept in this manner. The result in the case 

 of the sparrows which were subjected to the bites of the infected 

 gnats was different indeed. Out of 28 of these, dealt with from 

 time to time, no less than 22, or 79 per cent., became infected 

 in from five to eight days. And, as in the first experi- 

 ment, all the infected birds finally contained very numerous 

 parasites. 



It was most interesting to watch the gradual development of 

 the parasitic invasion in these birds ; and this development 

 presented such constant characters that, apart from other reasons, 

 it was quite impossible to doubt that the infection was really 

 caused by the mosquitoes. The course of events was always as 

 follows. The blood would remain entirely free from parasites 

 for four, five, six or even seven days. Next day one or 

 perhaps two parasites would be found in a whole specimen. 

 The following day it was invariably observed that the number 

 of the organisms had largely increased ; and this increase con- 

 tinued until in a few days immense numbers were present — so 

 that, finally, I often observed as many as seven distinct parasites 

 contained within a single corpuscle ! Later on, many of the 

 birds died ; and their organs were then found to be loaded with 

 the characteristic melanin of malarial fever. 



I also succeeded in infecting on a second trial one of the six 

 sparrows which had escaped the first experiment ; and also a 

 crow and four weaver-birds ; and, lastly, gave a new and 

 more copious infection to four sparrows which had previously 

 contained only a few parasites. 



These experiments completed the original and fundamental 

 observations on the life-history of the Haemamrebidae in mos- 

 quitoes. The parasites had been carried from the vertebrate host 

 into the gnat ; had been followed in their development in the 

 gnat ; and had finally been carried back from the gnat to the 

 vertebrate host. The theories of King, Laveran, Koch and 

 Bignami, and the great induction of Manson, were justified by 

 the event : and I have given a detailed historical and critical 

 account of these theories, and of my own difficulties and ex- 

 periences, in the hope of bringing conviction to those who 

 might, perhaps, otherwise think the story to be too wonderful 

 for credence. 



But work of great importance remained to be done. I had 

 intended, immediately after making this study of one of the 

 parasites of birds, to extend the investigation more fully to those 

 of man — a work which now presented no difficulty, since both 

 the kind of mosquito hospitable to them {^Anopheles) and the 

 form of the parasites in the mosquito were well known to me. 

 Unfortunately I was obliged to attend to other and less 

 important duties, which kept me fully occupied for several 

 months — an interruption which practically put an end to my 

 own study of the mosquito-theory at a very interesting point. 

 No time, however, was really lost. In December 1898, Dr. 

 Daniels, of the Malaria Commission of the Royal Society and 

 the Colonial Office, arrived in Calcutta to examine and report 

 upon my results. After carefully repeating the various experi- 



ments, he fully confirmed the statements made by me.^ At the 

 same moment, the work was taken up with great brilliance and 

 success hy Dr. Koch and by Prof. Grassi and Drs. Bignami and 

 Bastianelli, in Italy. I must now describe the investigations of 

 these observers — though I have scarcely space to do so at the 

 length they deserve. 



Ever since the discoveries of Laveran and Golgi, the Italian 

 observers of the Roman school had done much important work 

 on malaria, facilitated by the well-known prevalence of the 

 disease near Rome — work, if not of much originality, yet full of 

 careful detail. More recently, however, this work had been 

 practically arrested by their theory— wholly gratuitous,' but 

 which they accepted as a dogma — that the motile filaments are 

 forms of disintegration in vitro. When Manson propounded his 

 theory, Bignami, for instance, rejected it on this ground. But 

 at the same time he evolved a gnat-theory of his own— a theory 

 that malarial fever is inoculated by gnats which carry the 

 parasite from marshy areas. The arguments he used were the 

 epidemiological ones already advanced by King, and which can 

 scarcely be said to amount to more than a plausible hypothesis : 

 the only solid basis for the theory— that of Manson— was op- 

 posed by him. Later, however, the work of Simond, Schaudinn, 

 Siedlecki, MacCallum and myself, explained by Manson, ren- 

 dered the Italian position concerning the motile filaments quite 

 untenable ; and Bastianelli, Bignami and Grassi now undertook 

 a study of the mosquito-theory on sound principles. My own 

 results, with descriptions of the technique employed and with 

 illustrations of the zygotes, had been published from time to 

 time ; a summary of them had been given by Manson in June 

 1898, and ahother, including the infection of healthy birds, 

 before the British Medical Association, early in August ; and 

 there could therefore be no difficulty in following up the obser- 

 vations therein recorded. In September, Grassi published a 

 paper in which he described certain investigations made in Italy 

 with a view to ascertaining the species of gnats which are 

 associated with the prevalence of malaria in that country. Such 

 investigations are not, I think, trustworthy ; and as a matter of 

 Tact two out of the three species of gnat then selected by Grassi 

 as b|ing malaria-bearing ones have now been rejected by him. 

 Thelhird species was an Anopheles, namely A. claviger, Fabr. 



At the same lime Bignami resumed his study of the subject. 

 Some years previously, following his theory, he had endeavoured 

 to infect healthy persons by the bites of gnats brought from 

 malarious places. He had failed, and abandoned his efforts — 

 and I believe that his method would of itself never have led to 

 a solution of the problem. In the autumn of 1898, however, he 

 renewed his efforts ; but was again unsuccessful until he used a 

 number of Anopheles clavtger, brought from a house containing 

 infected persons. The result was successful, the subject of the 

 experiment becoming infected after some time. This important 

 experiment gave the first confirmation with human malaria of 

 my previous inoculation experiments with the malaria of birds ; 

 but since other species of gnats as well as A. clavtger had been 

 employed, it failed to fix suspicion entirely on the latter. In 

 order to obtain this result, these observers were finally obliged 

 to resort to the correct method of Manson and myself — namely 

 that of direct cultivation of the parasites in the gnat. Success 

 was now immediate. The zygotes and blasts of the parasites 

 were found, -exactly as previously described by me, in the 

 tissues of A. claznger ; and, lastly, healthy persons were infected 

 by the bites of these insects. Pushing forward with admirable 

 rapidity, the Italian observers next found that all three species 

 of the human HremamoebidEe are cultivable in A. clavtger ; and 

 not only in this, but in other Italian species of Anopheles ; 

 while, like me, they failed in cultivating the parasites in Culex. 

 Almost simultaneously Koch repeated and confirmed with the 

 weight of his authority most of the results which had been 

 obtained as regards both the human and avian parasites. In 

 August 1899, the malaria expedition sent to Sierra Leone by 

 the Liverpool School of Tropical Medicine (of which expedition 

 I was a member) found the human parasites in two species of 

 Anopheles in that colony, namely A. costalis, Loew, and A. 

 funestus, Giles. I hear also that the same result has been ob- 

 tained with Anopheles in two other parts of the world ; so that 

 it would appear that something like nine species of Anopheles 

 have now been inculpated — while as yet every species of Culex 

 which has been tried has failed to give positive results. 



From this point it becomes impossible to follow in detail the 

 researches carried out in connection with the mosquito-theory 

 1 Naturf, August 3, 1899. 



NO. T587, VOL. 61] 



