It will serve no useful purpose here to follow the acute controversies as to priority which have arisen, not only as to the discovery of the malarial parasite, but also within the last few years as to the mosquito cycle. We shall give merely the principal dates and facts in the matter. On November 0. 1SS0, Laveran discovered the malaria parasite in Algeria and communicated his discovery to the Academy of Medicine on November 23 and December 28, 1880. King, in 1S83. advanced his theory that the malarial '"poison" is conveyed from marshes and human beings by mosquitos. Laveran, in 1884, believed that mosquitos were the agents concerned in producing malarial infection. Koch, in 1883-18S4, suspected the mosquito. Manson's article, in 1804. was. however, the true starting point of mosquito malarial work. It was based on his previous discovery that mosquitos are the intermediate hosts of Filaria bancrofti. The "flagellating bodies" which had so long puzzled observers he considered to be the forms of the parasite by which it is able to survive in water, from which, subsequently, man was infected by drinking the water containing these resisting forms, or, on drying up of the water, by inhaling them in the air. Ross was stimulated by Manson to pursue this line of investigation. In 1805 he began to investigate the fate of these flagellating bodies seen under the cover glass, and fed patients on drinking water in which mosquitos previously fed on malarial patients had died. In 3 out of 22 cases "a slight but noticeable reaction" occurred, and they were thought to be "in favor of the truth of Manson's theory."
Experiments were next undertaken to see if the mosquito could convey the germs from the blood of a malarial patient to a healthy one immediately after feeding,-in fact, mechanically,-but the results were negative. In 1897 Ross investigated more closely the different kinds of mosquitos in malarious regions and found three kinds: (1) Brindled (= Stegomyia); (2) gray (= Culex) and (3) dapple winged (= Anophclimv). These mosquitos, then, of all kinds, were fed on malarial patients and a search was made in the stomach and tissues for a possible developmental form of these motile filaments of the flagellating bodies-at first with no success, but later dapple winged mosquitos were used; eight only of these were procured. They were fed on malarial patients on August 16 and the stomachs examined, and on August 20, 1897, in one of the surviving mosquitos delicate circular cells in which were a few granules of pigment were found in the stomach. The last survivor of the original batch was dissected on the following morning, five days after feeding, and again these bodies were found, and they were larger. Though the pigment was difficult to explain, as some developmental form of the motile filament was being searched for, yet they gave the clue as to what the unknown developmental form was like, and in what kind of mosquito it was to be found. In September further experiments were made, and of two dappled winged examples reared from larvae that had fed on crescent cases, one that was killed two days later contained a large number of these pigmented cells.
Now, in 1897, MacCallum, observing the flagellating bodies and flagella in Halteridium in birds, had seen the motile filament break off and penetrate the other form of cell in the blood, which, as in malaria , did not flagellate, but when the filament had penetrated it, became elongated and capable of movement. Manson was able to connect this observation with the previous one of Ross. These pigmented bodies in the stomach of the mosquito were " vermicules," or fertilized female cells. The function of the "flagella" was at last explained. In this connection Simond's views that similar flagella seen in the Coccidiidce were male elements was of great importance. Ross at the time was so situated as to be unable to continue his work on human malaria, so he pursued the same line of investigation with the Proteosoma of birds. On March 20, 1898, out of nine mosquitos fed on Proteosoma of birds, five contained pigmented cells; the control mosquitos that had not fed were negative. The experiments were extended, and altogether, out of 245 gray mosquitos fed on birds with Proteosoma, 178, or 72 per cent., contained pigmented cells, while out of 249 fed on birds without Proteosoma none contained parasites. In July, 1898, the development of these bodies was followed. It was found that the cysts increased in size and that the thread like bodies inside of them, which had been noticed in similar experiments, apparently traveled to the thorax. They were eventually found in a glandular organ, the salivary gland, and it appeared certain that they passed out with the poison secretion. This idea was put to the test, and five birds free from parasites were exposed to the bites of mosquitos that had previously fed on birds containing Proteosoma, and which contained the thread like bodies in their salivary glands. Fourteen days later all these five birds contained parasites in their blood. Thus was completed the demonstration of the development of the malarial parasites in mosquitos and the mode by which they were transmitted. Though it was in birds that the complete cycle was first followed, yet it was in man that the pigmented cells had first been seen which gave the clue to the discovery. The complete cycle in man was then established by the work of the Italians. We may now briefly consider their results. Ross had "shown that not every species of mosquito can give lodgment to a given hematozoon. In fact, Ross found the developmental stages of his Proteosoma coccidia only in the gray mosquito" (Mar chiafava and Bignami). So that it seemed likely that only a particular species of mosquito can transmit the infection to man. Grassi consequently took up the study with a view to determining the distribution of particular species of mosquitos in malarial regions, and came to the conclusion that in malarial regions there are species present which are not present elsewhere. (This, we now know, was a premature conclusion, and there are exceptions to the statement, but it had a considerable element of truth in it.) In 1898 Grassi and Bignami succeeded in producing malaria in man by the bite of mosquitos collected from malarious regions (fortunately for the success of their experiments there were a few specimens of Anopheles maculi pennis among those used, though the majority were Culex), and they even attributed the result to the culices. Further, on November 28, 1898, Bastianelli, Bignami, and Grassi had succeeded in tracing out the complete development of malignant tertian parasites in Anopheles maculipennis. The problem was completely solved.