Larger whales have less cancer compared to their body size. It’s a natural contradiction known as Peto’s paradox, which explains how large, long-lived animals, even though they have billions of cells more than humans or smaller rodents, do not develop more cancers.
Cancer is a disease of cells that escape, where genetic changes drive cells to divide and divide, forming masses called tumors. So you would think that the bigger the animal, the more cells it has, and the greater the chance that those cells will accumulate errors that cause cancer, especially over a long period of time.
But in the late 1970s, the famous British scientist Richard Peto discovered that this was not the case by comparing mice with men. Subsequent studies have shown that in both large and small organisms, cancer is less common if more cells are involved. Elephants, like whales, don’t have tons of cancer.
It may sound like biologists are fixated on decades-old paradoxes that are only natural – but that’s important. Solving this puzzle could help develop new ways to prevent or suppress cancer in humans.
Now a team of researchers from the University of Rochester in New York has found a solution to the problem of bowhead whales, Balaena mysticetus, the second largest but longest animal in the world.
“By studying a mammal that can maintain good health and avoid dying from cancer for over 200 years,” wrote biologist Denis Firsanov and his colleagues. Denis Firsanov and his colleagues, in their press release, “offer a unique glimpse behind the scenes of the world’s most tried-and-true evolutionary experiment. processes that affect cancer and aging beyond what people might expect.”
In a series of lab experiments, the researchers found that whale cells can repair DNA damage better than human, mouse, and cow cells. Whales appear to repair DNA damage in the bud “more quickly and more accurately than other animals,” Firsanov and colleagues write.
In short, bowhead whales are able to withstand a blow to their species because they have a well-established, fast-acting system for repairing DNA damage. The researchers found that in the same region of DNA that whales, humans, mice, and cows all share, whale cells can repair DNA breaks (captured by CRISPR) without errors.
Bowhead whale cells also produced a DNA repair protein called CIRBP at higher levels than other species studied. And when lab-engineered human cells were engineered to produce more CIRBP, these genetic changes enhanced their ability to repair DNA without errors.
“This method that does not remove cells but repairs them may be important for the long and cancer-free life of the bowhead whale,” Firsanov and his colleagues conclude.
Yale University cancer biologist Jason Sheltzer, who was not involved in the work, he says the “impressive” publication – which has not yet been peer-reviewed – “provides a new example of how large animals prevent cancer”.
“Maybe they’re better at DNA processing than we are?” Sheltzer he wrote on Twitter. “As a next step,” he added, “I would like to see this confirmed in an animal model – if you run a large fish CIRBP [protein] in mice, do they have cancer?”
Of course, as previous research shows, translating findings like these into cancer treatments is not easy.
After scientists discovered in 2015 that elephants have extra copies of a tumor-suppressor gene called TP53, the next logical step was to test whether increasing TP53 activity in mice also reduced cancer. Tumor-suppressor genes ‘blow up’ any cells they find with severe DNA damage, and it appears that elephants have a very low threshold for fighting damaged cells.
However, overexpressing the TP53 protein in mice, while reducing cancer, also causes premature aging in the animals. Some research may find a way to work – and scientists are always looking for other possibilities.
“There are many ways to solve Peto’s Paradox in nature because body size has changed dramatically throughout life,” said Marc Tollis, a geneticist at Northern Arizona University, in a 2017 paper with two other researchers.
In other words, every long-lived or large animal, from naked rats to African elephants, has evolved its cancer-reducing mechanisms that scientists are trying to find.
Another explanation could be that tumors in larger animals grow more slowly and are less lethal or that larger animals have a stronger immune system. However, these solutions have not yet been observed in large animals and require more research.
“Every time we find a way to fight cancer at a genetic level, there is a chance that we can find new treatments and cancer prevention strategies to save lives,” write Tollis and colleagues. But there will undoubtedly be a need for “greater effort to translate recent discoveries into therapeutic strategies that benefit people.”
The University of Rochester study is available on the preprint server biorXiv for peer review.