But, 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. 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 amoeba-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 [daily recurrent] intermittent fever, or a remittent of first invasion, may suffer a loss of 2,000,000 red blood corpuscles per cubic millimeter 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 millimeter, 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 continued hæmoglobin [the red substance in the blood], it may be thought that the etiological rôle 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. Marchiafava and Bignami, in their elaborate article upon "Malaria," published in the _Twentieth Century Practice of Medicine_, say: "The transmission of the disease occurs equally whether the blood is taken during the apyretic [aguish] period or during a febrile [feverish] paroxysm, whether it contains young parasites or those in process of development, or whether it contains sporulation [minute spore-like] forms. Only the crescent forms, when injected alone, do not transmit the infection, as has been demonstrated by Bastianelli, Bignami and Thayer, and as can be readily understood when we remember the biological significance of these forms.