Why is it that some large, long-lived animals get cancer and some don’t? If all cells can become cancerous through chance mutations, animals with many more cells should have more chance of getting cancer.
This puzzle is known as ‘Peto’s Paradox’, after Oxford Professor Sir Richard Peto who observed some decades ago that whales can live for more than 200 years and yet very rarely develop cancer.
A new study published in the Journal of the American Medical Association analysed cause of death data from 36 different species of mammal, ranging from the striped grass mouse to the elephant, and found no link between risk of death from cancer and body mass. Elephants for instance had a surprisingly low rate of cancer – less than 5%, compared to 11–25% of humans – adding more evidence that larger, long-lived species must have evolved effective ways to avoid the disease.
But how can this information help humans? Scientists have also been trying to come up with explanations for Peto’s Paradox – to understand the machinery that large animals have evolved to resist cancer, with the aim of improving cancer prevention in humans in future.
How the elephant got its cancer resistance
In the same study, US scientists Dr Joshua Schiffman and Professor Carlo Maley – who is also an Associate Director of our Centre for Evolution and Cancer here at The Institute of Cancer Research – took a trip to the circus and the zoo.
The researchers, based at the University of Utah and Arizona State University, used blood samples taken from African and Asian elephants as part of their routine care to decipher their DNA code.
Their research revealed that elephants have at least 20 copies of p53, a gene known as the ‘guardian of the genome’ because of its cancer-preventing properties.
Humans only have a single copy of p53, and mutations in the gene, either inherited or occurring spontaneously in the body’s cells, are a major cause of cancer. The additional ‘back-up’ copies in elephants mean that if one copy of TP53 is mutated, the extra copies can still fulfil the tumour-suppressing role.
How the whale resists cancer
This elephant tale complements work published earlier in this year, where researchers wanted to find out how bowhead whales are able to live more than 200 years, apparently cancer free.
Through painstaking experiments, scientists found alterations in several genes associated with DNA repair, cell-cycle regulation, cancer, and ageing that would help protect bowhead whales against cancer.
For example, bow head whales appear to have two copies of a gene called proliferating cell nuclear antigen (PCNA). PCNA has a critical role in repairing damaged DNA and, like p53, mutations in this gene have been linked to several cancers in humans.
The moral of the stories?
The scientists involved in this research hope that understanding how large mammals have evolved to avoid cancer could provide us with important clues about how to prevent the disease in humans.
Professor Mel Greaves, Director for the Centre for Evolution and Cancer at the ICR, is more sceptical. In a commentary published in the Journal of the American Medical Association, Professor Greaves said: “It is not immediately clear what lessons there are from this elephant tale for risk of cancer in humans. The main impact of this remarkable story is to bring into focus the question of why we are so uniquely predisposed to cancer for our size and lifespan – and what we can do to change this.”
Professor Greaves argues that our lifestyles have changed so drastically over the past few decades that our DNA has not had time to adapt. We also partake in ‘risky’ behaviours that have long been known to increase our chances of developing cancer, but which are much less common in the animal kingdom.
“Have you ever seen an elephant smoking?” – asks Professor Greaves.
Just so.
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