The old-established hereditary equilibrium of the germ-plasm must be most easily disturbed when the species is in some way brought into new conditions of existence, as, for instance, when plants or animals are domesticated, and when in consequence, as we have already assumed, the nutritive currents within the id gradually alter, quantitatively and qualitatively; and on this account alone certain kinds of determinants are favoured, while others are at a disadvantage. In this way there arises the intensified general variability of domesticated animals and cultivated plants which has been known since the time of Darwin. Something analogous to this must occur in natural conditions, though more slowly, when a species is subjected to a change of climatic conditions, but we shall discuss this later on in more detail. We have thus arrived at the idea that the slight variations of the determinants may be counteracted whether they be directed upwards or downwards, and that in the case of so-called constant species they do frequently equalize themselves; but that more marked variations, produced by more pronounced nutritive fluctuations, may in a sense go on without limit, and then can only be restricted and controlled by personal selection, that is, by the removal of the ids concerned from the genealogical lineage of the species. In one direction variation can be proved to go on without limit, and that is downwards, as is proved by the fact of the disappearance of _disused organs_, for here we have a variation-direction, which has been followed to its utmost limit, and which is completely independent of personal selection; it proceeds quite _uninterfered with_ by personal selection, and is left entirely to itself. It is a significant fact that the disappearance of the individual parts of a larger organ, according to all the data that are as yet available, proceeds at a very _unequal rate_, so that it evidently depends to a great extent on chance whether a disused part begins to degenerate sooner or later. Thus in one of the Crustaceans living in the darkness of the caves of North America the optic lobes and optic nerves have disappeared, while the retina of the eye, the lens, and the pigment have been retained, and in others the reverse has taken place, and the nerve-centres have persisted while the parts of the eye have been lost (Packard). Variations of the relevant determinants towards the minus direction may thus occur, sometimes sooner, sometimes later; but when once they have started they proceed irresistibly, though with exceeding slowness.