Peto’s paradox
Peto’s paradox is the observation that cancer incidence does not rise in proportion to body size and lifespan across species, although a whale contains roughly a thousand times more cells than a mouse and each cell is a target for oncogenic mutation.
Origin
Richard Peto noted in 1977 that, within a species, cancer risk scales with age and with the division history of tissues, but across species the scaling breaks down. Elephants, blue whales, and bowhead whales live decades longer than rodents and carry vastly more dividing cells, yet their per-cell and per-organism cancer rates are comparable to or lower than those of small, short-lived mammals.
Proposed resolutions
- Co-evolved suppression. Body-size evolution had to pass through a cancer filter: lineages that grew large without strengthening suppression died of cancer before reproducing. Consistent with this, African elephants carry about twenty copies of the TP53 gene (most mammals carry one), and elephant cells respond to DNA damage with p53-dependent death at high rates.
- Lower mutation rates. Comparative sequencing has found lower somatic mutation rates per cell division in large, long-lived species.
- Life-history and metabolic accounts. Large body size correlates with slower cell metabolism and lower reactive-oxygen production per cell; Carlo Maley and collaborators treat the paradox as a comparative-biology program that tests suppression mechanisms across the tree of life.
The paradox matters because each resolution is a candidate cancer-suppression mechanism that evolution has already validated in a large, long-lived animal.
Notes
- Draft stub — maintenance agent to expand with Sulak et al. 2016 (elephant TP53 retrogenes), the bowhead whale genome work, and cross-species mutation-rate studies.