February 28, 2025, 9:12 am | Read time: 4 minutes
Elephants do not get cancer more often than mice. Yet large animals have many more cells that can change and mutate as they grow and regenerate. This discrepancy was first described in 1977 and was given the name Peto’s paradox. However, a study refuted this long-held assumption and found a different explanation.
Peto’s paradox is one of the most exciting puzzles in biology. While larger individuals within a species — such as humans — tend to have a higher risk of cancer, this correlation has not yet been proven between various other species. It was, therefore, long assumed that large animals get less cancer than small ones. However, a study shows that this is not true and that some animals have actually developed effective mechanisms to deal with their higher cancer risk.
Large Animals Develop Tumors More Frequently
Why don’t elephants get cancer more often than mice? This apparent discrepancy is known as Peto’s paradox. It states that larger animals do not have a higher cancer rate than smaller animals despite having a much higher cell count. However, a study has now completely challenged this concept.
Researchers have discovered that larger terrestrial vertebrates, in particular, actually develop cancer more frequently. However, the study also shows that birds and mammals have developed mechanisms over the course of evolution to reduce the cancer risk associated with their body size.
The study, published in the Proceedings of the National Academy of Sciences (PNAS), analyzed data from 263 species from four major vertebrate classes. The researchers made a clear distinction between mammals and birds, as well as amphibians and scaly animals such as snakes and lizards. This is because these animals do not have a fixed end to their growth and must, therefore, be considered separately.
The study used a phylogenetic analysis of cancer prevalence data from 31 amphibians, 79 birds, 90 mammals, and 63 reptiles. As no reliable body weight data was available for many reptiles and amphibians, the snout-cloaca length was used as a measure. Not only benign tumors (neoplasms) were considered, but also explicitly malignant cancers (malignomas).
Why Large Animals Get Cancer More Frequently
A decisive methodological difference to previous studies was that the number of cancers observed per species was directly incorporated into a regression model. Previously, only relative cancer rates were often calculated, which led to distortions. The model also took into account differences in the evolutionary development of body size over time. In this way, possible protective mechanisms of larger species can be better captured.
Despite these differences in growth patterns, both groups showed the same overall trend: larger species had higher cancer rates. So, there was a clear correlation between body size and cancer prevalence. Larger species also had higher cancer rates in all classes of terrestrial vertebrates studied:
- In amphibians and reptiles, the prevalence of benign tumors increased significantly with increasing snout-cloaca length.
- In birds and mammals, cancer prevalence was positively associated with body mass.
- The incidence of malignant tumors also increased with body size in all animal groups.
The study thus contradicts the previous understanding of Peto’s paradox. At the same time, the researchers found evidence that improved mechanisms for cell control have developed in the evolution of mammals and birds, which reduce the risk of cancer.
It was previously known that whales, among others, are capable of gigantic growth. However, these gigantism genes also have the property of suppressing the emergence of cancer cells. However, this new study now shows that this mainly affects species that have developed into large animals in a short period of time. This is because they have developed better mechanisms to control cell growth and prevent tumors. Thus, an elephant actually has about the same cancer risk as a tiger — a creature that is only a tenth its size.
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Dr. Joanna Baker, co-author from the University of Reading, added in a press release: “When species have had to grow larger, they have also developed remarkable defenses against cancer. Elephants shouldn’t be afraid of their size — they have evolved sophisticated biological tools to keep cancer at bay. This is a great example of how evolution finds solutions to complex challenges.
What exactly these mechanisms look like in the different animals now needs to be further researched through genetic analysis. Dr. George Butler, lead author of the research at University College London and Johns Hopkins, said: “Finding out which animals are naturally better at fighting cancer opens up exciting new avenues for research. By studying these successful species, we can better understand how cancer develops and potentially discover new ways to fight the disease. This could lead to breakthrough treatments in the future.
In fact, the researchers’ work shows that this does not only affect large animals. Naked mole rats, which were also previously thought to be resistant to cancer, demonstrated this correlation as well. In reality, however, they are simply an example of a species that has developed particularly effective protective mechanisms. These findings could also be relevant for cancer research in humans.1