"As is evident, these two species, closely related normally, show too a marked similarity in their behavior toward quinin. The small, crescent forming parasites can be studied better in stained than in unstained preparations.
"Baccelli observed that the ameboid organisms showed at first an increased liveliness of movement, but after twenty four hours the majority had usually disappeared.
" In cases of quotidian of a mild character, I have found, three hours after a dose of 0.5 quinin, that the nucleoli of some of the ameboid organisms either did not stain or stained very poorly. On continuing the therapy for a further twelve hours I found only isolated parasites with a nucleolus, and many of the remainder were in process of breaking up; some, in fact, showing only a few amorphous fragments.
"The failure of the nuclear chromatin to take the stain indicates naturally beginning necrosis. This is quickly followed by complete destruction, and, after forty eight hours, nothing more can be seen of the parasite.
"The action of quinin on the tertian parasites is very similar. I found that a few hours after the first administration of quinin the majority of the small and medium sized forms no longer showed stainable nucleoli, while the clear vesicle, representing the nucleus, was seen as before. The further fate of these necrotic parasites consisted likewise in destruction.
" I found, further, that some sporulation forms manifested peculiar changes when the quinin had been administered several hours before the paroxysm; namely, a segmentation, which appeared complete in unstained preparations, but which, when stained, showed spores capable of life-that is, with well developed structure-in only a small portion of the segment, while the remaining showed no nucleoli and were, therefore, incapable of life.
" From this I concluded that, under the action of quinin, segmentation may be abortive, and I, therefore, named these segments without nuclei dead born spores.
"Yet it is possible that Golgi's opinion, after a like observation, is the correct one, namely, that the spores died only after they had been formed capable of life. Between these two possibilities there is no important difference.
"According to Romanowsky, the adult large parasites manifest a most decided effect in that they often show no nucleoli and only diffusely stained nuclei. I mentioned before that I consider the diffuse staining of the nucleus and the disappearance of the nucleolus in the large forms not necessarily as necrosis, but sometimes as a preparatory stage to sporulation. I believe, therefore, the young forms without nuclei are decidedly more characteristic for the action of quinin than those described by Romanowsky. In accordance with my observation, Romanowsky perceived in the sporulation forms a defective staining of the nucleoli (according to him, nuclei).
"From the studies of stained preparations, therefore, we find that quinin produces a necrosis in the malarial parasites of different species and ages, which satisfactorily explains the specific effect of the drug. It need scarcely be mentioned that not all the parasites die at once after the first dose.
"One form of malarial parasite is totally resistant to quinin, namely, the crescent.
"It is the unanimous statement of all observers that crescents remain unchanged after the most persistent administration of quinin, and that the therapy is incapable of playing even a prophylactic role, in that relapses occur whether or not quinin is exhibited in the apyretic interval.
"From his observations of unstained preparations Golgi gives the following scale of susceptibility to quinin for the developmental phases of the quartan parasites:
"1. Spores. 2. Mature forms before the beginning of segmentation. 3. Endoglobular young forms.
"The spores are the most sensitive; then come the large organisms that have completely replaced the blood corpuscles, and, finally, the endoglobular young forms, for which, according to Golgi, the blood corpuscle acts as a protecting mantle. Golgi, as well as myself, has found the endoglobular young forms of the tertian parasite very sensitive, and he concludes that the hypertrophy of the blood corpuscle produces a relaxation of structure which permits the quinin to pass through it. . .
"It was previously mentioned that the appearances presented by the malarial parasites after the administration of quinin were very similar to those observed by Binz in infusoria. This resemblance is strengthened by his work in 1869, in which he found that the large infusoria were, in the beginning, irritated to increased activity when the quinin solution was very dilute. We have already described the same in the malarial parasites."
On the grounds of these observations Binz, as far back as 1869, drew the conclusion that the inexplicable effects of quinin on malaria must be due to the fact that malaria is caused by organisms possessing a susceptibility to quinin similar to that manifested by infusoria. This assumption was brilliantly confirmed by Laveran's discovery.
The effect of quinin on malaria depends, therefore, on its power of destroying the parasites in the circulation. All the other actions of quinin on the physiologic and pathologic organism-for instance, its action on the innervation of vessels, on the heart, on oxidation, on diapedesis, the white blood corpuscles-are of secondary or of no importance. If the paralysis of the leukocytes by solutions of quinin, discovered by Binz, signifies anything in the therapy of malaria is doubtful. The frequent occurrence of melaniferous leukocytes after the paroxysms tends rather to the conclusion that the activity of the white cells is not interfered with.