movement. After a period of amoeboid activity of greater or less duration, the body again assumed an oval or spherical form and remained quiescent for a time. While in this form it was easily recognised, as the spherical shape caused the light passing through it to be refracted, and gave the impression of a body having a dark contour and a central vacuole, but when it was flattened out and undergoing amoeboid changes in form it was necessary to focus very carefully and to have a good illumination in order to see it. The objective used was a Zeiss's one-twelfth inch homogeneous oil immersion.

Very properly, skepticism with reference to the causal relation of these bodies to the disease with which they are associated was not removed by the demonstration that they are in fact blood parasites, that they are present in considerable numbers during the febrile paroxysms, and that they disappear during the interval between these paroxysms. These facts, however, give strong support to the inference that they are indeed the cause of the disease. This inference is further supported by the evident destruction of red blood corpuscles by the parasite, as shown by the presence of grains of black pigment in the amœba-like micro-organisms observed in these corpuscles and the accumulation of this insoluble blood pigment in the liver and spleen of those who

have suffered repeated attacks of intermittent fever. The enormous loss of red blood corpuscles as a result of such attacks is shown by the anæmic condition of the patient and also by actual enumeration. According to Kelsch, a patient of vigorous constitution in the first four days of a quotidian intermittent fever, or a remittent of first invasion, may suffer a loss of 2,000,000 of red blood corpuscles per cubic millimetre of blood, and in certain cases a loss of 1,000,000 has been verified at the end of twenty-four hours. In cases of intermittent fever having a duration of twenty to thirty days the number of red blood cells may be reduced from the normal, which is about 5,000,000 per cubic millimetre, to 1,000,000 or even less.

In view of this destruction of the red blood cells and the demonstrated fact that a certain number at least are destroyed during the febrile paroxysms by a blood parasite which invades the cells and grows at the expense of the contained hæmoglobin, it may be thought that the causal relation of the parasite should be conceded. But scientific conservatism demands more than this and the final proof has been afforded by the experiments of Gerhardt and of Marchiafava and Celli- since confirmed by many others. This proof consists in the experimental inoculation of healthy individuals

with blood containing the parasite and the development of a typical attack of periodic fever as a result of such inoculation. After such an inoculation a period varying from four to twenty-one days elapses before the occurrence of a febrile paroxysm. This is the so-called period of incubation, during which, no doubt, the parasite is undergoing multiplication in the blood of the inoculated individual. The duration of this period depends to some extent upon the quantity of blood used for the inoculation and its richness in parasites. It also depends upon the particular variety of the parasite present, for it has been ascertained that there are at least three distinct varieties of the malarial parasite one which produces the quartan type of fever, in which there is a paroxysm every third day and in which, in experimental inoculations made, the period of incubation has varied from eleven to eighteen days; one in which the paroxysm occurs every second day (tertian), in which the period of incubation is from nine to twelve days; and one, denominated the æstivo-autumnal type, in which the period of incubation rarely exceeds five days.

The parasite associated with each of these types may be recognised by an expert, and there is no longer any doubt that the difference in type is due to the fact that different varieties or "species"

of the malarial parasite exist, each having a different period of development. Blood drawn during a febrile paroxysm shows the parasite in its different stages of intra-corpuscular development. The final result of this development is a segmenting body, having pigment granules at its centre, which occupies the greater part of the interior of the red blood corpuscle. The number of segments into which this body divides differs in the different types of fever, and there are other points of difference by which the several varieties may be distinguished one from the other, but which it is not necessary to mention at the present time. The important point is that the result of the segmentation. of the adult parasites contained in the red corpuscles is the formation of a large number of spore-like bodies, which are set free by the disintegration of the remains of the blood corpuscles and which constitute a new brood of reproductive elements, which in their turn invade healthy blood corpuscles and effect their destruction. This cycle of development, without doubt, accounts for the periodicity of the characteristic febrile paroxysms; and, as stated, the different varieties complete their cycle of development in different periods of time, thus accounting for the recurrence of the paroxysms at intervals of forty-eight hours in one type of fever and of three

days in another type.

When a daily paroxysm oc

curs, this is believed to be due to the alternate development of two groups of parasites of the tertian variety, as it has not been possible to distinguish the parasite found in the blood of persons suffering from a quotidian form of intermittent fever from that of the tertian form. Very often, also, the daily paroxysm occurs on succeeding days at a different hour, while the paroxysm every alternate day is at the same hour, a fact which sustains the view that we have to deal, in such cases, with two broods of the tertian parasite which mature on alternate days. In other cases there may be two distinct paroxysms on the same day and none on the following day, indicating the presence of two broods of tertian parasites maturing at different hours every second day.

The hypothesis that malarial infection results from the bites of mosquitoes was advanced and ably supported by Dr. A. F. A. King, of Washington, D. C., in a paper read before the Philosophical Society on February 10, 1883, and published in the Popular Science Monthly in September of the same year. In 1894 Manson supported the same hypothesis in a paper published in the British Medical Journal (December 8th), and the following year (1895) Ross made the important discovery that when blood containing the crescentic bodies was ingested by the mosquito