It’s an elephant–sized mystery. Big animals like elephants live longer and their cells have to divide more, so you would expect them to be more susceptible to cancer. But that doesn’t seem to be the case – a phenomenon that has become known as Peto’s paradox.

Now there might be an explanation: elephants have extra copies of a gene that spots trouble in cells.

Joshua Schiffman, a paediatric oncologist at the University of Utah, and his team confirmed that Peto’s paradox is a real phenomenon in elephants by studying necropsy records from San Diego Zoo. Using more extensive data from an “Elephant Encyclopedia” that records the causes of death of captive elephants worldwide, Schiffman estimated that less than 5 per cent of elephants die of cancer, compared with 11 to 25 per cent of humans.

When they studied samples of elephant blood, they found that African elephants have at least 20 copies of the p53 gene from each parent.


P53 is an ancient gene found in all multicellular animals. It detects stress or damage in the cell, and stops the cell from dividing until the stress has passed or the DNA is repaired. Humans inherit one copy from each parent, and it has a crucial role in protecting us from cancer. People who have a defective version – a condition called Li-Fraumeni syndrome – usually get cancer in childhood, and their lifetime risk is close to 100 per cent.

Next, the team exposed elephant cells to radiation to see what happens when their DNA gets damaged. They expected elephant cells to be better at repairing DNA, but this wasn’t the case. Instead, the cells were twice as likely to die when they had faulty DNA.

Schiffman realised this made sense as an evolutionary adaptation. “If you just kill the cell, that’s the ultimate way of getting rid of the risk for cancer,” he says.

Cells from individuals with Li-Fraumeni syndrome were less likely to die when they were exposed to radiation, adding support to the idea that the number of working copies of p53 determines the response to DNA damage.

Another team led by Vincent Lynch at the University of Chicago reached the same conclusions and published the results this week on BioRxiv.

Genome studies in other large animals have uncovered different adaptations that could help keep cancer at bay. Earlier this year, researchers published the genome of the bowhead whale, which lives for more than 200 years and can weigh up to 100 tonnes. They found that it has mutations or duplications in several genes linked to DNA repair and ageing.

Naked mole rats are small but unusually long-lived and free of cancer. Research has shown they have unusual variants of molecules that regulate the cell cycle and how cells stick together.

“It wouldn’t be surprising if different long-lived or big animals came up with different solutions to the presumed extra risk of having more cells,” says Mel Greaves of the Institute of Cancer Research in London.

Schiffman says he hopes the findings will lead to new approaches to cancer prevention and early detection. “Evolution has had 55 million years to figure out how to avoid cancer,” he says. “Now I think it’s up to us to take a page out of nature’s playbook and learn how to take this information and apply it to those who need it most.”

His team plans to screen large numbers of compounds to look for molecules that might mimic the effect of extra copies of p53 in elephants, condemning damaged cells to death instead of trying to repair DNA. He also suggests that new technology such as nanoparticles might be able to deliver elephant p53 into human cells as a means for cancer prevention or treatment.

Greaves is more sceptical. “I think there are no obvious implications for treatment,” he says. “The interest for me in this is that it brings into focus the extraordinary risk that humans have in relation to other large, long-lived animals.”

Journal reference: Journal reference: Journal of the American Medical Association, DOI: 10.1001/jama.2015.13134

(Image: Michael Nichols/National Geographic Creative)