For all its widespread occurrence and extensive study, cancer remains a bit of an enigma. Why do certain animals experience it more frequently than others? This query lies at the core of Peto’s paradox. This paradox notes that larger animals, due to having more cells, should statistically be more prone to develop genetic mutations that contribute to cancer compared to their smaller counterparts. Yet, surprisingly, they do not. Specifically, some large animals like whales and elephants show significantly lower cancer rates than what would be anticipated for their size and cell quantity.
Despite its widespread nature and the considerable research invested, cancer continues to be somewhat mysterious. Why are certain animals more susceptible to it? This question is central to Peto’s paradox—the idea that larger animals, owing to their greater number of cells, should have a higher statistical likelihood of experiencing cancer-causing genetic mutations, yet they often don’t. In fact, species like whales and elephants experience cancer at much lower rates than expected based on their body size and cell count.
Amy Boddy, an anthropologist from UC Santa Barbara, alongside her team, is striving to shed light on this and other cancer-related enigmas. After a decade of research, they have compiled data on cancer prevalence in 292 vertebrate species, spanning amphibians, reptiles, birds, and mammals.
This extensive study, the most comprehensive of its kind, will enable researchers to explore the cancer resistance mechanisms in species that rarely develop tumors. Notable among the species least likely to suffer from cancer are the common porpoise and black-footed penguin, while ferrets and opossums rank among those with the highest cancer rates. These are just a few examples of the extremes observed.
“One key takeaway from our data gathering is that every species experiences cancer,” stated Boddy, a biologist and evolutionary theorist, and a co-author of the recent paper published in the journal Cancer Discovery. “It’s simply part of being a multicellular organism. No organism is entirely immune.”
The research indicates that cancer is intrinsically linked to multicellularity itself. The transition to multicellular life introduced complex interactions among various cell types, but this complexity also brought the risk of genetic mutations, which can collectively lead to the erratic growth of tissues characteristic of cancer.
With a wide-ranging dataset, the researchers were able to consider various factors across species. In one instance, a minor deviation from Peto’s paradox appeared: when accounting for gestation periods, they found a correlation between adult size and cancer rates—something not seen in earlier smaller studies. However, Boddy emphasized that this correlation is quite minimal and doesn’t disprove the paradox.
Supporting Peto’s paradox, animals with longer gestation periods—which are generally associated with larger body sizes—tend to experience fewer cases of cancer. The researchers suggest that vertebrates with extended gestation periods invest more in mechanisms that prevent mutations.
“Larger, more long-lived species devote more resources to maintaining their cellular integrity,” Boddy commented. “I would anticipate they possess better defenses against cancer since they need to in order to grow and survive for a longer time. From an evolutionary standpoint, it’s not truly a paradox.”
The methods by which species avoid cancer likely stem from the adaptive strategies they have developed through evolution.
“Cancer has been a longstanding evolutionary challenge, influencing natural selection constantly,” Boddy noted. Animals and cancers have co-evolved over extensive timescales. As animal species have differentiated, they’ve faced distinct genetic trade-offs and devised various survival strategies. One notable approach is seen in elephants, which possess 20 copies of the tumor-suppressing gene P53. Other methods could involve slower somatic mutation rates, allowing these mutations to accumulate and progress into cancer at a less rapid pace.
“This variability is why we don’t observe a uniform pattern across all vertebrates; each species has its own unique narrative about cancer defense,” Boddy remarked.
The wealth of data gathered also presents new opportunities for cancer research, she added. Typically, research concentrates on rodent models, yet species with more spontaneous cancer development or differing cancer types can yield valuable insights for scientists studying cancer and rare ailments.
The next phase for Boddy’s lab will involve investigating particular cancer types across various species. “Cancer is not a singular disease,” she explained. “It’s akin to 300 distinct diseases.” They plan to explore whether other primate relatives experience the same cancers as humans. Additionally, they are keen to understand the mechanisms behind cancer development in species with higher prevalence rates.
