Why do whales exist? Given their enormous size and longevity, and expected equivalent probabilities of cancer-associated gene mutation, whales should be disproportionately more prone to cancer than smaller mammals, succumbing to fatal metastasis at a relatively young age. Empirical evidence to date does not support this prediction, and this discrepancy between theory and observation is known as Peto’s paradox. In short; whales, and other large, long-lived mammals exist, and they must have evolved mechanisms to suppress and resist cancer in order to do so. What are those mechanisms?
This is where I come in! Using a combination of quantitative metabolic modelling, genomics and a series of in vitro experiments using transgenic mouse and whale cell lines, my DPhil is attempting to test two main hypotheses: i) the reduced cellular metabolic rate in larger mammals means mutations accumulate, and tumours grow, at a sufficiently protective low rate; and ii) the supernumerary, or otherwise altered copies, of cancer-associated genes found exclusively in the genomes of large mammals manifest themselves functionally in reducing cancer incidence, whether via more efficient DNA repair, higher rates of induced apoptosis or similar.