March 29, 1900] 



NA rURE 



523 



cause the three varieties of malarial fever — quartan, tertian, and 

 remittent or pernicious fever. For these three species I adopt 

 the names Haemamoeba malariae (quartan), Haemamoeba vivax 

 (tertian), and Haemotnenas praecox (remittent fever).^ Ac- 

 cording to Metchnikoff the group belongs, or is allied, to the 

 Coccidiidce. All the species have a close resemblance to each 

 other, and all contain the typical melanin of malarial fever. 

 The youngest parasites are found as minute amoebulae living 

 within the red corpuscle and generally containing granules of 

 this melanin (which, indeed, is derived by the parasite from the 

 haemoglobin of the corpuscle within which it makes its abode). 

 The amcebulte grow rapidly in size, until, after one or more 

 days (according to the species), they reach maturity. At this 

 point many of them become sporocytes — that is, give rise to 

 ordinary spores by vegetative reproduction. These spores pre- 

 sently attach themselves to fresh corpuscles, become fresh 

 amcebulie, and so continue the life of the parasites indefinitely 

 within the vertebrate host. Others of the amoebuloe, however, 

 instead of becoming sporocytes like the rest, h^como. !:;ainelocytes. 



Now it is to these gametocytes that an extreme interest 

 attaches, because it is to them, and to Manson's study of them, 

 that we owe the solution of the malaria problem. Numerous 

 observers had examined them before Manson's time, but all had 

 failed in arriving at a correct idea as to their function It had 

 been often observed that they circulate in the blood of the verte- 

 brate hosts without, apparently, performing any function at all. 

 As soon, however, as they are drawn from the circulation — as 

 when the blood containing them is made into a fresh specimen 

 for microscopic examination — they undergo the most remarkable 

 changes. They swell up and liberate themselves from the 

 L^-nclosing corpuscle ; and then some of them are suddenly seen 

 io emit a number of long viotile filaments. These filaments can 

 •asily be watched struggling violently, and may sometimes be 

 seen to break from the parent cell and to dart away among the 

 corpuscles, leaving the residue of the gametocyte, with its 

 melanin, an inert and apparently dead mass. 



Now it is not to be supposed that such an extraordinary 

 phenomenon as this — which was observed by Laveran during 

 his first investigations— could be witnessed without exciting the 

 liveliest curiosity. As a matter of fact a hot controversy rose 

 regarding it. Laveran, Danilewsky and Mannaberg maintained 

 that the phenomenon is a vital one — that the motile filaments 

 are living organisms, and constitute a stage in the history of the 

 parasite. Antolisei, Grassi, Bignami and others of the Italian 

 school fell back upon the old theory — which we always like to 

 employ when we cannot explain a phenomenon— that it is a 

 regressive phenomenon, a disintegration of the parasite due to 

 its death in vitro. Here, however, the controversy practically 

 stayed. While the Italians, in conformity with their views, 

 attached no signification to the motile filaments, Laveran, 

 Danilewsky and Mannaberg, who held an opposite opinion, did 

 not expressly or exactly state what their signification is. 

 Mannaberg, indeed, held that they are meant to lead a sapro- 

 phytic existence, but did not explain how they could escape 

 from the body in order to do so. 



It was reserved for Manson to detect the ultimate (though not 

 the immediate) function of these bodies. He asked why the 

 escape of the motile filaments occurs only after the blood is 

 abstracted from the host (a fact agreed upon by many observers). 

 From his study of these filaments, of their form and their 

 characteristic movements, he rejected the Italian view that they 

 are regressive forms ; he was convinced that they are living 

 elements. Hence he felt that the fact of their appearance only 

 ■iter abstraction of the blood (about fifteen minutes afterwards) 

 iiust have some definite purpose in the life-scheme of the para- 

 ites. What is that purpose ? It is evident that these parasites 

 ike all others must pass' from host to host ; all known parasites 

 ire capable not only of entering the host, but, either in them- 

 clves or their progeny, of leaving him. Manson himself had 

 1 1 ready pushed such methods of inductive reasoning to a 

 rilliantly successful issue in discovering by their means the 

 kvelopment of Filana nocturna in the gnat. He now applied 

 the same methods to the study of the para.sites of malaria. Why 

 -hould the motile filaments appear only after abstraction of the 

 lood ? There could be only one explanation. The phenomenon, 

 hough it is usually observed in a preparation for the microscope, 

 ^ really meant to occur within the stomach cavity of some 

 uctorial insect, atid constitutes the first step in the life-history 

 ' the parasite outside the vertebrate host. 



1 Nature, August 3, 1899. 



NO. 1587, VOL. 61] 



It is perhaps impossible for any one, except one who has 

 spent years in revolving this subjebt, to understand the full 

 value and force of this remarkable induction. To my mind the 

 reasoning is complete and exigent. It was from the first impos- 

 sible to consider the subject in the light in which Manson placed 

 It without feeling convinced that the parasite requires a suctorial 

 insect for its further development. And subsequent events have 

 proved Manson to have been right. 



The most evident reasoning — the connection between malarial 

 fever and low-lying water-logged areas in warm countries — sug- 

 eested at once that the suctorial insect must be the gnat (called 

 viosqtiito in the tropics) ; and this view was fortified by 

 numerous analogies which must occur at once to any one who 

 considers the subject at all, and which it is not necessary to 

 discuss in this place. 



Needless to say, since Manson's theory was proved to be right 

 it has been shown to be not entirely original. Nuttall, in his 

 admirable history of the mosquito theory, demonstrates its 

 antiquity. Eleven years before Manson wrote. King had already 

 accumulated much evidence, based on epidemiological data, in 

 favour of the theory. A year later (1884), Laveran himself 

 briefly enunciated the same views, on the analogy with Filaria 

 nocturna. Koch, and later, Bignami and Mendini, were also 

 advocates of the theory — partly on epidemiological grounds and 

 partly because of a possible analogy with the protozoal parasites 

 of Texas cattle-fever which Smith and Kilborne had shown to 

 be carried by a tick. Hence many observers had independently 

 arrived at the same theory by different routes. But I feel it most 

 necessary to point out here that there is a diff"erence between a 

 fortunate guess and a true scientific theory. Interesting and 

 suggestive as were many of the hypotheses to which I have just 

 referred, they were to my mind far from convincing. Filarta 

 nocturna, and even Apiosoma bigeminum, are not in close 

 enough relationship with the Hpemamoebidge to admit of very 

 forcible analogies in regard to the respective life-histories. 

 The epidemiological arguments of King and Bignami (some of 

 which were also used by Manson) were scarcely solid enough to 

 support by themselves a theory of any weight. All these were 

 hypotheses — little more : I can scarcely conceive a practical man 

 sitting down to laborious researches on the strength of arguments 

 like the.se. On the other hand, Man.son's theory was what I 

 have called it— an induction — a chain of reasoning from which 

 it was impossible to escape. 



I have wished to defend this work of Manson's because it has 

 been much misunderstood and much misrepresented, and even 

 (in a somewhat amusing manner) completely ignored by some 

 who, though they once strongly opposed his theory, now, as 

 soon as it has done its work, wish to forget it. It is true that 

 he endeavoured to predict the history of the parasites a little 

 too far, and that he was in error (as will presently appear) 

 regarding the immediate nature of the motile filaments ; but the 

 centre of his theory was invaluable. I have no hesitation in 

 saying that it was Manson's theory, and no other, which actually 

 solved the problem ; and, to be frank, I am equally certain that 

 but for Manson's theory the problem would have remained 

 unsolved at the present day. 



To leave these interesting theories and to return to actual 

 observations — I should begin by remarking that Manson thought 

 the motile filaments to be of the nature of zoospores — that is, 

 motile spores which escape from the gametocytes in the stomach 

 cavity of the gnat, and then occupy and infect the tissues of 

 the insect. In this he was proved, two years later, to have been 

 wrong. The motile filaments are not spores, but microgametes 

 — that is, bodies of the nature of spermatozoa. I have said that 

 some of the amojbulae in the blood-corpuscles of the host be- 

 come sporocytes, which produce asexual spores (nomospores) ; 

 while other amcebulce become gametocytes, which have no 

 function within the vertebrate host. As soon, however, as 

 these gametocytes are ingested by a suctorial insect they com- 

 mence their proper functions. As their name indicates, they 

 are sexual cells — male and female. About fifteen minutes after 

 ingestion (in some species) the male gametocyte emits a variable 

 number of microgametes — the motile filaments — which presently 

 escape and wander in search of the female gametocytes. These 

 contain a single macrogamete or ovum, which is now fertilised 

 by one of the microgametes, and becomes a zygote. We owe 

 this beautiful discovery to the direct observation of MacCallum 

 (1897), confirmed by Koch and Marchoux, and indirectly by 

 Bignami. Metchnikoff, Simond, Schaudinn and Siedlecki 

 have also demonstrated what are practically sexual elements 



