Body size, longevity, and cancer resistance in animals

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Every time a cell divides there is the risk that, either through chance or chemical damage to DNA, the cell will sustain a mutation. When enough specific mutations occur in a cell's DNA, cancer develops. Based on this, one would expect that large sized animals and/or animals with a long lifespan would be at high risk of developing cancer, since they have more cells dividing and more cell divisions over their lifetime - however, this is not always the case. The largest animals that have ever lived, the bowhead, blue and other whales, have lifespans that exceed 100 years, yet have 1000-fold more cells than a human and only rarely develop cancer. Likewise, African elephants, which are 100 times heavier than humans, have less than half the incidence of cancer. This lack of association between body size, longevity, and cancer incidence is often referred to as Peto's paradox. Elephants and some whales have multiple functional copies of tumour suppressor genes, as do some long-lived bats. The proteins produced by these genes counteract the factors that promote cancer development. The goal of my research program is to explore the mechanisms underlying the lower than expected cancer incidence in large and/or long-lived animals. We have assembled a unique and diverse collection of tumours that arose in large and/or long-lived animals ranging from whales to parrots to bats, and in this research program we will compare tumour suppressor gene copy numbers in these animals to those that do not have a long lifespan for their size, such as dogs and mice. We will measure expression of the genes, assess their function in cell culture by removing specific genes, test each species' cells response to DNA damaging agents, and measure how readily the cells are transformed. The research laid out in this program is designed to yield fundamental new knowledge of how organisms with large body size and/or long lifespan resist development of cancer. My long-term goals are to apply evolutionary comparative methods to test potential relationships between longevity and tumour suppressor gene copy number and expression. This will help us to understand the importance of patterns in gene copies that repeat during evolutionary history.