A lex naturalis delineates components of a human-specific, adrenal androgen-dependent, p53-mediated ‘kill switch’ tumor suppression mechanism

摘要

We have recently described in this journal our detection of an anthropoid primate-specific, adrenal androgen-dependent, p53-mediated, ‘kill switch’ tumor suppression mechanism that reached its fullest expression only in humans, as a result of human-specific exposure to polycyclic aromatic hydrocarbons caused by the harnessing of fire – but which has components reaching all the way back to the origin of the primate lineage. We proposed that species-specific mechanisms of tumor suppression are a generalized requirement for vertebrate species to increase in body size or lifespan beyond those of species basal to their lineage or to exploit environmental niches which increase exposure to carcinogenic substances. Using empirical dynamic modeling, we have also reported our detection of a relationship between body size, lifespan, and species-specific mechanism of tumor suppression (and here add carcinogen exposure), such that a change in any one of these variables requires an equilibrating change in one or more of the others in order to maintain lifetime cancer risk at a value of about 4%, as observed in virtually all larger, longer-lived species under natural conditions. Here we show how this relationship, which we refer to as the lex naturalis of vertebrate speciation, elucidates the evolutionary steps underlying an adrenal androgen-dependent, human-specific ‘kill switch’ tumor suppression mechanism; and further, how it prescribes a solution to ‘normalize’ lifetime cancer risk in our species from its current aberrant 40% to the 4% that characterized primitive humans. We further argue that this prescription writ by the lex naturalis represents the only tenable strategy for meaningful suppression of the accelerating impact of cancer upon our species.