“The deduction, therefore, which has been unduly based on Nussbaum’s experiments, that the testis of the frog contains an internal secretion, which, on being circulated in the blood, calls for the development of the secondary sexual characters, either with or without the mediation of the nervous system, is without experimental foundation.... The fact that the developmental cycle of the thumb depends for its normal course on the presence of normal living testicular tissue can be equally well explained on the theory that the testicular cells enter into a chain of metabolic processes in the body which do not pursue their normal course in the absence of the testicular cells. This disturbance of the normal metabolic processes of the body, resulting in the failure of the metabolic organs of the body to give rise to their normal products in normal quantities, may have the result of inhibiting the further development of the secondary sexual characters. The development of these latter characters may depend, therefore, not directly on the action of an internal secretion or hormone derived from the gonad, but on the elaboration of other products in other organs of the body in their due proportions. These substances may be tentatively called ‘sexual formative substances,’ but we have no reason for supposing that they are entirely devoted to sexual or reproductive purposes, and that they take no part in the ordinary metabolic processes of the body.”