Schiffman specializes in treating children missing one of their TP53 gene's two alleles, which leads them to develop cancer. So after hearing Maley's talk, he wondered whether elephants held some biological insight that could help his patients. He teamed up with Maley, who had not yet published his work, and asked elephant keepers at Salt Lake City’s zoo whether they could spare some elephant blood so that he could test how the p53 protein works in the mammals' white blood cells.
At about the same time, in mid-2012, Vincent Lynch, an evolutionary geneticist at the University of Chicago in Illinois, was preparing for a lecture on Peto’s paradox, and wondered about mechanisms that could explain it. “Right before I gave the lecture, I searched the elephant genome for p53, and 20 hits came up,” says Lynch.
Schiffman and Lynch’s teams have now independently revealed their findings — Schiffman's in theJournal of the American Medical Association1, and Lynch's in a paper2 posted to the preprint site, but which is in review at the journal eLife.
Using zoo autopsy records for 36 mammals — from striped grass mice to elephants — Schiffman’s team recorded no relationship between body size and cancer rate. (Around 3% of elephants get cancer, according to the team’s analysis of hundreds of captive-elephant deaths).
The researchers found that elephants produce extra copies of the p53 protein, and that elephant blood cells seem exquisitely sensitive to DNA damage from ionizing radiation. The animals' cells carry out a controlled self-destruction called apoptosis in response to DNA damage at much higher rates than do human cells. Schiffman suggests that, instead of repairing the DNA damage, compromised elephant cells have evolved to kill themselves to nip nascent tumours in the bud. “This is a brilliant solution to Peto’s paradox,” he says.

Mammoth set

Lynch’s team — working with African and Asian elephant skin cells from the San Diego Zoo in California — found similar results. They also discovered more than a dozen TP53 copies in two extinct species of mammoth, but just one copy in elephants’ close living relatives, manatees and hyraxes (a small, furry mammal). Lynch thinks that the extra copies evolved as the lineage that led to elephants expanded in size. But he thinks that other biological mechanisms are involved too.
Mel Greaves, a cancer biologist at the Institute for Cancer Research in London, agrees that TP53cannot be the only explanation. “As large animals get bigger, they become more and more sluggish,” he notes, thereby slowing their metabolism and the pace at which their cells divide. And protective mechanisms can only do so much to stop cancer, he adds. “What would happen if elephants smoked and had a bad diet,” he says. “Would they really be protected from cancer? I doubt it.”