Whales, Elephants, and Bats

Gene Duplications in Peto's Paradox

One of the many observations we have made is frequently referred to as Peto’s Paradox, so named after Richard Peto, who showed in 1975 that, per cell, mice had a higher rate of cancer than humans, and mused about the relationship between body-size and cancer rates. The Paradox, in a nutshell, comes from the simple fact that every cell in an animal’s body has the potential to become a tumor given the right set of mutations; furthermore, cells will steadily accumulate mutations throughout their lifetime. Thus, if you compare two species - large or small, long-lived or short-lived - you would expect the one with more cells, and a longer lifespan, to have an astronomically larger incidence of cancer. However, the fact that whales, elephants, and other long-lived and/or enormous animals have cancer rates comparable or below our own as humans, means that there must be some other mechanisms at play which compensate for the increased cancer risk; somehow, these species are able to either lower their own per-cell cancer rates, or else detect and destroy tumors near their onset.

To explore this paradox, my research focuses on the genetic basis of cancer resistance in bats of various sizes and sizes. The diversity of size and lifespan in bats gives us the perfect comparison groups to see what genetic changes along each lineage is related to cancer resistance against increased size, lifespan, or both. To study them, I use a combination of comparative and functional genomic approaches using live cell culture and existing datasets. In addition to bats, we are also looking at the Bowheaded whale, which is the longest-lived mammal in our records, and whose size exceeds that of humans by several orders of magnitude. By studying the genetic basis that underlies how they stay healthy for most of their long lives, we can obtain valuable insight into how our own lifespans and health can be extended far beyond their current values.