For decades, scientists have mused over a curious observation: why don’t large and long-lived animals like elephants and whales, with their trillions of cells, get cancer more often than tiny mice? This mystery, known as Peto’s paradox after the epidemiologist Richard Peto who first made the observation, has been a cornerstone of cancer biology since 1977.

It’s always been an odd observation. After all, more cells mean more opportunities for mutations to arise and unleash the chaos of malignancy. But, according to a new study, the anomaly may be explained by the fact that it is not accurate.

Scientists from the University of Reading, University College London, and Johns Hopkins University have turned Peto’s paradox on its head, revealing that larger animals like elephants, giraffes, and pythons actually do have higher cancer rates than smaller species.

The Size-Cancer Connection

The study analyzed cancer data from 263 species, spanning amphibians, birds, mammals, and reptiles. It is the largest dataset of its kind ever assembled. The researchers examined veterinary autopsy records, looking for both benign and malignant tumors. What they found was unexpected considering the dogma around Peto’s paradox: larger species consistently showed higher cancer rates.

“Everyone knows the myth that elephants are afraid of mice,” said Professor Chris Venditti, senior author of the study. “But when it comes to cancer risk, mice are the ones who have less to fear. We’ve shown that larger species like elephants do face higher cancer rates — exactly what you’d expect given they have so many more cells that could go wrong.”

These findings put things back into basic logic: the more cells an animal has, the more opportunities for cancer. But this is far from a linear relationship. Species that ballooned in size over short evolutionary bursts — like elephants — have forged remarkable defenses against the disease. Although elephants tower over tigers, weighing ten times as much, their cancer risk rivals that of the big cat. This is likely due to elephants having evolved additional copies of a gene called TP53, which helps suppress tumor growth. 

 “When species needed to grow larger, they also evolved remarkable defenses against cancer,” said Dr. Joanna Baker, a co-author of the study. “Elephants shouldn’t fear their size — they developed sophisticated biological tools to keep cancer in check. It’s a beautiful example of how evolution finds solutions to complex challenges.”

The study also revealed outliers. Some species, like the common budgerigar (budgie), have cancer rates more than 40 times higher than expected for their size. On the other hand, the naked mole rat, a small underground rodent, has almost no recorded cases of cancer. These exceptions are truly fascinating and could provide lessons for scientists to identify new ways to prevent or treat the deadly disease.

An Avenue for Future Study

“Finding which animals are naturally better at fighting off cancer opens exciting new paths for research,” said Dr. George Butler, the study’s lead author. “By studying these successful species, we can better understand how cancers develop and potentially discover new ways to fight the disease. This could lead to breakthrough treatments in the future.”

But what about us? Cancer rates among humans are quite complicated to study. Modern medicine — chemotherapy, surgery, screening — muddies our place in this size-cancer trend. Humans also live much longer than they would “in the wild” due to our enhanced living standards that enable most to survive to their 60s and 70s. So, are we outliers, or do we fit the pattern? The study can’t say for sure. It does, however, hint at a broader truth: as species grow larger, cancer creeps in, but evolution sometimes crafts a shield.

Size matters after all. Yet in that truth lies hope. Evolution, relentless and creative, has armed some of Earth’s largest creatures with tools to tame cancer. The question lingers: can we borrow those tools for ourselves?

The findings appeared in the Proceedings of the National Academy of Sciences.