The appearance of megaloblasts and megalocytes is therefore evidence that the regeneration of the blood in the bone-marrow is not proceeding in the normal manner, but in a way which approximates to the embryonic type. The extreme cases are naturally seldom, such as that of Rindfleisch, in which the whole bone-marrow was found full of megaloblasts. It is sufficiently conclusive for the pernicious nature of the case, "if only considerable portions but not the whole marrow, have lapsed into megaloblastic degeneration." We can now say that the megaloblastic metamorphosis is not a purposeful process, and for the following reasons: 1. Since the fresh formation of red blood corpuscles by means of the megaloblastic method is clearly much slower. This is especially borne out by the fact that the megaloblasts are present in the blood always in small numbers only, whilst the normoblasts, as above mentioned, are often found in much larger quantities. In agreement with this, "blood crises" are not to be observed in the megaloblastic anæmias. 2. Since the megalocytes which are formed from the megaloblasts possess in proportion to their volume a relatively smaller respiratory surface, and so constitute a type disadvantageous for anæmic conditions[10]. This is still more evident when we remember that the production of poikilocytes is on the contrary a serviceable process.
The megaloblastic degeneration of the bone-marrow is no doubt due to chemical influences, which alter the type of regeneration in a disadvantageous manner. We do not for the most part yet know the exciting causes of the toxic process; consequently we are unable to put a stop to it, and its termination is lethal. The Bothriocephalus anæmias, which in general as is well-known offer a good prognosis, by no means contradict this view. They hold their privileged position amongst the anæmias of the megaloblastic type, only for the reason that their cause is known to us, and can be removed. As in many infectious diseases, individuals react quite differently to the presence of the Bothriocephalus. Some remain well; others show the signs of simple anæmia, ultimately with normoblasts; whilst a third group presents the typical picture of pernicious anæmia. For many years, so long as its ætiology was unknown, Bothriocephalus anæmia was not separated on clinical grounds from pernicious anæmia. Severe Bothriocephalus anæmia may be described as a pernicious anæmia, with a known and removable cause. Good evidence for this point of view is afforded by a case of Askanazy, who describes a severe pernicious anæmia, with typical megaloblasts, in which after the complete expulsion of the Bothriocephalus, the megaloblastic character of the blood formation quickly vanished, was replaced by the normoblastic, and the patient rapidly recovered. This observation is so unequivocal, that it is a matter of surprise that Askanazy chooses to deduce from it, the ready transition from megaloblasts to normoblasts; whereas it is clear and definite evidence that =megaloblasts are only produced under the influence of a specific intoxication=. And in this way the presence of megaloblasts in the pernicious anæmias is to be explained. The megaloblastic degeneration of the bone-marrow depends on the presence of certain injurious influences, of which unfortunately we are as yet ignorant. Were it possible to remove them, it is quite certain _à priori_ that the bone-marrow--if the disease were not too advanced--would resume its normal normoblastic type of regeneration. Clinical observation supports this contention in many cases. In megaloblastic anæmias apparent cures are by no means rare, but sooner or later a relapse occurs, and finally leads with certainty to a lethal issue. These cases, familiar to every observer, prove with certainty that the megaloblastic degeneration as such may pass away, and that in isolated cases the conventional treatment by arsenic suffices to bring about this result. A definite cure however under these conditions is not yet attained, since we do not know the ætiological agent, still less can we remove it. =For this reason, the prognosis of megaloblastic anæmia, apart from the group of Bothriocephalus anæmia, is exceedingly bad.=