Larger animals really are more prone to cancer, debunking ‘Peto’s paradox’

Despite the finding, scientists say bigger species also develop stronger defenses against the disease

LONDON — For decades, scientists believed something strange was happening in the animal kingdom: despite having many more cells that could potentially turn cancerous, elephants didn’t seem to get more cancer than mice. As it turns out, this puzzling observation, called “Peto’s paradox,” has been overturned by surprising new research.

Researchers from the University College London, the University of Reading and Johns Hopkins School of Medicine in Baltimore discovered that larger animals do, in fact, develop cancer more frequently than smaller ones. This finding follows the basic logic we might expect: more cells mean more opportunities for cancer-causing mutations.

“Everyone knows the myth that elephants are afraid of mice, but when it comes to cancer risk, mice are the ones who have less to fear,” said Professor Chris Venditti, senior author of the research at the University of Reading, in a statement. “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.”

The study analyzed cancer data across amphibians, birds, mammals, and reptiles, revealing a predictable pattern: as body size increases, so does cancer prevalence. However, species that evolved larger body sizes more rapidly also developed enhanced cancer-fighting mechanisms that helped mitigate their cancer risk.

“These results represent empirical evidence showing that larger body size is related to higher cancer prevalence, thus rejecting Peto’s paradox and demonstrating the importance of heterogeneous routes of body size evolution in shaping anticancer defenses,” the researchers write in their paper.

Why size matters in animal cancer

Cancer occurs when cells accumulate mutations during division, a normal process needed for growth and repair. With more cells and more divisions, there should logically be more chances for cancer-causing mutations. This relationship is already known within species—taller humans and larger dogs have higher cancer rates than their smaller counterparts—but until now, the pattern was thought to break down when comparing different species.

The research team examined autopsy data from 263 species: 31 amphibians, 79 birds, 90 mammals, and 63 reptiles. This dataset was much larger than those used in previous studies, allowing for better statistical analysis. Rather than calculating the percentage of cancer cases relative to the number of autopsies performed, the researchers directly counted the observed number of cancer cases, reducing statistical errors and improving accuracy.

The study found that larger animals consistently showed higher cancer rates than smaller ones. Despite adaptations that evolved to counteract cancer risks, an elephant still experiences more cancer than a mouse, following the biological prediction that more cells equal more cancer risk. However, species that underwent rapid increases in body size evolved specialized cellular controls that partially counterbalanced this effect.

“When species needed to grow larger, they also evolved remarkable defenses against cancer. 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,” explained Dr. Joanna Baker, co-author from the University of Reading.

Which animals buck the trend?

The study highlights the Asian elephant, which has about the same cancer risk as a tiger—an animal only one-tenth its size. This suggests that as elephants evolved to become larger, they developed stronger molecular safeguards against cancer, including multiple copies of the tumor suppressor gene TP53. These adaptations do not eliminate the connection between size and cancer, but they substantially reduce it.

The research also identified species that significantly deviated from expected cancer rates. The common budgerigar exhibited cancer rates 40 times higher than expected for its size, while the naked mole rat showed extraordinary resistance to cancer.

“Finding which animals are naturally better at fighting off cancer opens exciting new paths for research. 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,” explained Dr. George Butler, lead author of the research at University College London and Johns Hopkins.

Implications for Human Cancer Research

These findings reshape our understanding of how body size relates to cancer across species. Rather than a paradox, the relationship between body size and cancer follows expected biological principles, while evolutionary innovations modify these risks.

For decades, scientists pointed to elephants as the prime example of Peto’s paradox—large animals that seemingly escaped the cancer burden their size should bring. This research shows that elephants aren’t immune to the biological rules governing cancer risk; they’ve just evolved highly effective countermeasures that make them appear less cancer-prone than their size would predict.

Modern medicine makes it difficult to determine how humans fit into this pattern. While the research confirms that larger species generally have higher cancer rates, it also suggests that some have evolved advanced cellular defenses. This opens the door to new insights into cancer evolution and potential breakthroughs in human medicine.

Ultimately, the study demonstrates how evolution works not by breaking biological rules but by developing innovative solutions within them. Larger animals couldn’t escape the reality that more cells create more cancer opportunities, but they evolved molecular adaptations to reduce the impact of this relationship.

In the end, Peto’s paradox wasn’t a paradox at all – just an incomplete picture of the evolutionary relationship between body size, cellular controls, and cancer risk. The resolution of this long-standing biological mystery shows that nature’s patterns often become clearer when we examine them with better data and analytical methods.