Why don’t whales get cancer? Unlocking one of medicine’s greatest mysteries is cancer

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Scientists are investigating one of medicine’s most perplexing mysteries: why some species avoid cancer while others suffer life-shortening tumors.

Whales tend to have lower rates of cancer but are the leading cause of death for dogs and cats. Foxes and tigers are susceptible, while sheep and antelopes are not. Bats are also relatively well protected against cancer but not mice or rats. Cancer is a major cause of death in humans and kills about 10 million people annually.

Even more puzzling is the fact that many massive creatures, including whales and elephants, generally avoid cancer, when instead they should be at particular risk because they possess large numbers of cells, each of which can give rise to a tumour.

This Peto’s paradox, named after the British statistician Richard Peto who first outlined it, is the focus of investigations by scientists at the Wellcome Sanger Institute in Cambridge, who work with researchers from a number of centres, including the Zoological Society. London (ZSL).

“Cancer is a disease that occurs when a cell in the body undergoes a series of mutations in its DNA and begins to divide uncontrollably, and the body’s defenses fail to stop this growth,” said project leader Alex Kagan. “The more cells an animal has, that indicates an increased risk of cancer.”

This point is supported by Simon Spiro, a wildlife veterinary pathologist at ZSL. “Think of cells as lottery tickets: the higher your chance, the greater your chance of hitting the jackpot which, in this case, is cancer. So if you have a thousand times more cells than a human, you should have a thousand times greater risk of developing cancer.” .

From this perspective, there are some species of whales that should not be able to reach one age without developing cancer because they have a large number of cells—several quadrillion compared to humans, who have only trillions, a thousandfold decrease in numbers. But this is not what is being observed. Bowhead whales have an average lifespan of 100 to 200 years, for example, while elephants have an average lifespan of about 70 years. However, compared to humans, they all have thousands of times more cells, each a potential starting point for a mutation that could lead to cancer.

In an effort to understand this paradox, Sanger’s team studied a group of animals that had died of natural causes at London Zoo. They were all mammals and included lions, tigers, giraffes, ferrets, and ring-tailed lemurs. In addition, naked mole rats from a different center were also included in the study.

“They look like cocktail sausages with teeth,” Kagan said. “They are the size of a mouse but they live for about 30 years and never get cancer.”

Think of cells as lottery tickets: the more you have, the higher your chance of hitting the jackpot which, in this case, is cancer.

The scientists then isolated cells known as intestinal crypt cells from each recently expired animal and studied their genomes.

These cells are constantly being replenished by stem cells and are a first-class method for comparing genomes. We used it to count how many mutations each species accumulated each year,” Kagan added.

“What we found was quite astounding. The number of mutations that accumulated each year varied greatly. Essentially, it was found that long-lived species accumulate mutations at a slower rate while short-lived species do so at a faster rate. For example, in humans, we get about 47 mutations per year while the mouse is present, which is about 800 mutations per year. The latter lives for 4 years. The average human lifespan is 83.6 years.”

In addition, it was found that at the end of life, all of the different animals studied had accumulated around 3,200 mutations. “The similar number of mutations at the end of life in these different animals is staggering, although it is not yet clear whether this is a cause of aging,” Kagan said.

But it’s not clear exactly how the long-lived animals slowed their rate of DNA mutations. In addition, the link between mutation rates and age was established only for animals with low to middle ages.

“We can only study creatures that died natural deaths, and those very long lifespans would be rare by definition,” Spiro said. “We’ll have to wait for that data.”

In addition, the first phase of the Sanger-Zoo project looked only at mammals. Now it extends to plants, insects and reptiles.

“Social insects like ants are particularly interesting,” Kagan said. “Worker ants and their queen have the same genome but the queen lives for 30 years while the workers last for a year or two. This suggests that perhaps the queen activates DNA repair better, although other explanations are possible.”

Kagan added that their research suggests that the mouse, which is used in cancer experiments, may not be the best model for research because of its extremely short lifespan.

“We can now consider looking at longer-lived species that may be more relevant and serve as useful models for understanding cancer resistance.”

A crucial point, scientists say, is that linking mutation rates, tumorigenesis, and aging provides new understanding of both processes and could lead to improved cancer screening and treatments that may mitigate the worst effects of aging.

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