Animals with more cells tend to have a higher risk of cancer, yet whales, with trillions of cells compared to humans, seem to be immune.
The Wellcome Sanger Institute (UK) and researchers from various centers, including the Zoological Society of London (ZSL), are investigating the mystery: Why do some species avoid cancer while others suffer from tumors that reduce their lifespan?
A comprehensive answer to this question is expected to help humanity avoid the disease that kills 10 million people each year.
Whales have an average lifespan of about 70 years. For the bowhead whale, the average lifespan can reach between 100 to 200 years. Compared to humans, all of them have thousands of times more cells, each cell carrying the risk of mutations leading to cancer, yet they remain unaffected by this disease – (Photo: AFP).
Researchers from the University of Rochester in New York found that whales excel at repairing damaged DNA. This means they can correct the “errors” that could potentially lead to cancer. Other animals, such as elephants, have also been discovered to use biological strategies to avoid cancer, but the approach of whales seems quite unique.
“By studying a mammal capable of maintaining health and avoiding death from cancer for over two centuries, we gain a unique insight behind the curtain of a global evolutionary experiment that has tested many mechanisms affecting cancer and aging beyond what humans could hope to explore,” the researchers wrote in their paper.
The Peto Paradox of Cancer
Cancer is the leading cause of death for dogs and cats, but it is rarely seen in whales. Foxes and leopards are susceptible to the disease, while sheep and antelopes are not. Bats are also relatively well protected against cancer, but house mice and brown rats are not.
Project leader Alex Cagan noted that cancer occurs when a cell in the body undergoes a series of mutations in its DNA and begins to divide uncontrollably, allowing the body’s defense system to be unable to prevent its growth. Thus, according to Cagan, the more cells an animal has, the higher its risk of cancer.
Simon Spiro, a wildlife veterinary pathologist at ZSL, likened cells to lottery tickets: the more tickets you have, the higher your chance of winning the jackpot, in this case, “the jackpot” being cancer.
Therefore, if an animal has thousands of times more cells than a human, it would inherently have a cancer risk thousands of times higher than normal.
From these perspectives, some species of whales should not be able to live to one year old without developing cancer due to their vast number of cells—trillions of cells compared to humans.
Giant whales are less likely to develop cancer relative to their body size.
In fact, many large creatures like whales and elephants often avoid cancer, despite their large number of cells, with each cell having the potential to cause tumors.
Recent independent studies have found that the elephant genome contains more copies of cancer-fighting protein-coding genes than the human genome. This leads to a cancer rate in elephants that is consistently below 4.8%, while in humans, the rate ranges from 11% to 25%.
Subsequent studies have further confirmed this observation. In other words, having more cells does not necessarily mean a higher likelihood of developing cancer, which is quite surprising. Particularly, whales have an astonishingly low cancer incidence rate, despite their large size.
The researchers conducted several laboratory experiments on bowhead whale cells. They discovered that whale cells have superior DNA repair capabilities compared to human, mouse, and cow cells. These organisms have developed a unique and highly effective mechanism to combat DNA damage. This allows them to endure and recover from the damage inflicted on their genomes.
Moreover, the study found that bowhead whale cells exhibit significantly higher levels of a crucial DNA repair protein known as CIRBP. Interestingly, when human cells cultured in the lab were genetically modified to produce increased levels of CIRBP, their DNA repair capabilities were also enhanced. This suggests that it may translate into a treatment method for humans at some point in the future, but further research is needed.
This phenomenon has been referred to as the Peto Paradox, named after British statistician Richard Peto, who first outlined it. This is also the focus of the investigation by the research team led by Cagan at the Wellcome Sanger Institute.
Can Preventing Aging Halt Cancer?
To gain a clearer understanding of this paradox, the Sanger team studied a variety of animals that died from natural causes at the London Zoo. All were mammals, including lions, tigers, giraffes, ferrets, and ring-tailed lemurs.
Hairless moles from another center were also included in the study. Cagan explained that although their size is comparable to a regular mouse, their lifespan can reach up to 30 years and they almost never develop cancer – (Photo: AFP).
The study results showed that the number of mutations accumulated each year varies significantly.
Essentially, long-lived species were found to accumulate mutations at a slower rate, while short-lived species accumulate mutations at a faster rate. For instance, humans have an average lifespan of 83.6 years and accumulate about 47 mutations per year, while mice only live four years but accumulate around 800 mutations each year.
Additionally, it was found that by the end of their life cycles, all the different animal species studied had accumulated around 3,200 mutations.
The exact reason why long-lived animals slow down their DNA mutation rate remains unclear. According to the study, the relationship between mutation rates and lifespan was established only for animals with low to medium lifespans.
The project will soon expand its research to include reptiles, plants, and insects.
Should Mice Be Used for Cancer Research? Cagan’s team’s research suggests that mice, commonly used in cancer experiments, may not be the best research model due to their short lifespan. “Currently, we might consider looking into studying longer-lived species to better fit and provide a useful model for understanding cancer resistance,” Cagan stated. |
