Too Big for Cancer? The Mystery of Peto’s Paradox.

How the world’s largest mammals challenge what we know about cancer

It is possible for the bowhead whale to live for over 200 years and to weigh more than 80,000 kilograms. The majority of people would expect such a large size and long life span to be associated with a serious problem; cancer. Since a whale’s body contains a very large number of cells and mutations can occur each time cells divide, there should be more opportunities for things to go wrong with more cells over a longer period of time. Interestingly, however, large and long-lived animals do not seem to suffer from cancer to the extent that we might anticipate (Vincze et al. 2022). 

The observation in question is called Peto’s paradox. Cancer arises when mutations build up in cells and interfere with the normal regulation of cell growth and division. It follows that an animal with a greater number of cells and a longer lifespan should have more opportunities to accumulate such harmful mutations. However, a large study involving more than 110,000 mammals from 191 species showed that cancer mortality was mostly unrelated to both body mass and adult life expectancy (Vincze et al. 2022). 

Then what does a huge whale do to achieve this? A possible explanation involves the bowhead whale and its highly effective DNA repair mechanism. It has recently been discovered that the cells of the bowhead whale repair certain types of DNA damage more efficiently and accurately than do the cells of other mammals. Moreover, researchers have found unusually high levels of a protein known as CIRBP, which seems to play a role in repairing double-strand breaks in DNA. By keeping the integrity of their DNA, bowhead whales might stop some potentially harmful mutations from building up initially (Firsanov et al. 2025). 

There is most likely no single universal method of avoiding cancer. Various large and long-lived mammals seem to have evolved distinct protective measures (Perillo et al. 2024). This is precisely what makes Peto’s paradox so interesting. Evolutionary biology can explain why such protections have developed, whereas genetics and cell biology show us how they function at the level of individual cells. When animals evolved to become larger and live longer, natural selection also favoured mechanisms that enable those bodies to remain functional without uncontrolled cell growth. 

The importance of understanding these mechanisms might one day extend beyond whales. Comparative Oncology, which is the study of cancer in different species, includes researchers examining the biological solutions that evolution has been testing over millions of years. Scientists are currently looking into whether the mechanisms linked to bowhead whale DNA repair could give us further insights into maintaining genome stability in other mammals (for example, in human cells), although turning these discoveries into therapies is still a possibility for the future and not something that is currently available as a treatment (Firsanov et al. 2025). 

What is most interesting about Peto’s paradox is that whales do not merely ignore the rules of cancer biology; their biology might show that our understanding of those rules is still incomplete. 

References

Firsanov, Denis, Max Zacher, Xiao Tian, et al. 2025. “Evidence for Improved DNA Repair in the Long-Lived Bowhead Whale.” Nature 648: 717–725. https://doi.org/10.1038/s41586-025-09694-5.

Perillo, Matteo, Alessia Silla, Angela Punzo, et al. 2024. “Peto’s Paradox: Nature Has Used Multiple Strategies to Keep Cancer at Bay While Evolving Long Lifespans and Large Body Masses. A Systematic Review.” Biomedical Journal 47 (2): 100654. https://doi.org/10.1016/j.bj.2023.100654. 

Vincze, Orsolya, Fernando Colchero, Jean-François Lemaître, et al. 2022. “Cancer Risk across Mammals.” Nature601: 263–267. https://doi.org/10.1038/s41586-021-04224-5.