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The origin of multicelled animal life required collagen-family molecules whose own formation depended on the availability of molecular oxygen. Cancers, by contrast, are characterized by their low use of oxygen. In discussing the relationship between the origin of multicelled life and the origin of cancer, it is useful to think in terms of tissues rather than individual cells or complete animals. When animal tissues are disturbed, their constituent cells may be partially released from the constraints of multicellularity. This permits or obliges cells to reactivate anaerobic metabolic ways used by their single-celled ancestors in the oxygen-deficient Precambrian seas. Inhibition or loss of cell respiration under such circumstances may cause reversion to glycolytic fermentation, a less efficient metabolic style that generates waste products that are retained, thereby producing excess cell-growth. Distortion of tissue architecture may ensue with impairment of cell-to-cell adhesion, thereby liberating individual cells. Cells freed from tissue constraints undergo Darwinian variation which leads to loss of differentiation and produces cell types that are incompatible with the normal functioning of tissues. These steps, which may manifest themselves as carcinogenesis, are not reversible by restoration of oxygen and in effect constitute a demergence from the metazoan state. The existence of cancer among diverse phyla and especially among domesticated animals, suggests that the risk of cancer may be an initial condition of complex multicellular life and that it remains preferentially associated with newly modified designs. If so, there would be therapeutic strategies that have not yet been adequately considered. □Cambrian explosion, cancer, cell differentiation, collagen, glycolysis, hard parts, metazoan origins.