Abstract
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.
Highlights
Consider these longstanding, unanswered questions in human biology
Uncovering the lex naturalis revealed that malignant transformation represents a fundamental force opposing vertebrate speciation, and that species-specific mechanisms of tumor suppression evolved as countermeasures to suppress such opposition when speciation involved adaptive increases in body size and lifespan (Nyce 2018, 2019)
The ‘kill switch’ tumor suppression mechanism that we reported is based on the extraordinarily high levels of circulating dehydroepiandrosterone sulfate (DHEAS) that distinguish the primate lineage (Supplementary Fig. 1, see section on supplementary materials given at the end of this article), the very highest of which levels occur in humans, the only primate species to harness fire as a tool
Summary
Consider these longstanding, unanswered questions in human biology. Why the extraordinary levels of circulating dehydroepiandrosterone sulfate (DHEAS) in humans – ten thousand times higher than in mice and rats – when its proximate metabolite (DHEA) is a potentially irreversible inhibitor of so crucial an enzyme as glucose6-phosphate dehydrogenase (G6PD), the major source of the NADPH required to detoxify reactive oxygen species (ROS)?
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