Now the influence of functioning upon the form and structure of an organ is twofold. There is first the immediate change brought about by the very act of functioning--for example, the shortening and thickening of skeletal muscles when they act. This is a purely temporary change, for the organ at once returns to its normal quiescent state as soon as it ceases to function. Such temporary functional change, brought about in the moment of functioning, is usually dependent for its initiation upon some neuro-muscular mechanism, though it may be elicited also by a chemical stimulus. It is thus always a phenomenon of "behaviour." "From such temporary changes are sharply to be distinguished all permanent alterations which first appear in perceptible fashion through oft-repeated or long-continued, enhanced functional activity. These produce a new and lasting internal equilibrium of the organ, consisting in an insertion of new molecules or a rearrangement of old. For this reason they outlast the periods of functional form-change, or, if as in the case of the muscles they themselves alter during functional activity, they regain their state when the organ ceases to function" (p. 72, 1910). "Oft-repeated exercise or heightened exercise of the specific functions, or repeated action of the functional stimuli which determine them, produces, as we have said before, true form-changes as a by-product. These are of two kinds. In so far as these form-changes facilitate the repetition of the specific functions, I have called them _functional adaptations_.... Such as do not improve the functioning of the organ are indeed by-products of functioning, but without adaptive character; they do not belong to the class of functional adaptations at all" (p. 75, 1910). We may now enquire in what way functional adaptations can arise as by-products of functioning. It is clear that natural selection in the sense of individual or "personal" selection cannot adequately explain the origin of functional structure and the functional harmony of structure, for thousands of cells would have to vary together in a purposive way before any real advantage could be gained in the struggle for existence, and it is in the highest degree unlikely that this should come about by chance variation.[486] The development of purposive internal structure is only to be explained by the properties of the tissues concerned. In illustration and proof of the statement that functional adaptation is due to the properties of the tissues we may adduce the development and regulation of the blood-vascular system, which has been thoroughly studied from this point of view by Roux and Oppel (1910).