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Resolving Peto's Paradox: Why Aren't Whales Born With Cancer?

If we can understand how and why whales avoid cancer, maybe we'll be able to improve our own odds.

author

Dr. Katie Spalding

Freelance Writer

clockAug 15 2022, 14:40 UTC
A whale tail popping out of the sea to say hello
it's a wonderful, whaley life. Image credit: Sergey Uryadnikov/Shutterstock.com

In 1990, a team of doctors from the departments of urology and oncology at the Johns Hopkins University School of Medicine analyzed data on the rates of prostate cancer in elderly men. Prostate cancer is a very common type of cancer – the most common of all, in fact, for American men outside of skin cancers – but their findings were still surprising. 

In patients between the ages of 70 and 80, they found evidence of prostate cancer in the equivalent of every other man they examined.

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What was the reason for these astonishingly high rates? The key was their age. 

Cancer risk, explained Marc Tollis from the School of Informatics, Computing, and Cyber Systems at Northern Arizona University, is a function of the number of cell divisions occurring over the entire lifetime of an organism.

“[It’s] driven by somatic evolution – genetic changes that occur when body cells copy their genomes, divide and produce daughter cells,” he said. “The longer you live, the more cell divisions you have and the higher chance that a cancer-causing mutation will occur in the genome of the descendent cells.”

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Of course, there are many things that may influence your risk of developing cancer: smoking, alcohol use, obesity – the list goes on. But among those factors that aren’t down to lifestyle, there’s one that may seem surprising, at first glance: height.

“If you have more cells, you have a greater risk of cancer,” John O'Neill, a research group leader at the MRC Laboratory of Molecular Biology, told the BBC after a 2018 study found a link between height and cancer risk.

“Tall people have a greater surface area, and therefore more melanocytes, and so of course they're more likely to get melanoma.”

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But if cancer risk is increased by age and size, that raises an interesting question. After all, humans are hardly the largest or longest-living animal out there – so what happens with those creatures with even higher risk factors? What happens with, say, a whale?

Do whales get cancer?

“There’s a joke that whales should be born with cancer and not even able to exist,” Vincent Lynch, from the University at Buffalo, New York, told New Scientist. “They’re just too big.” 

And it’s true: Whales seem almost perfectly designed to get cancer. They’re absolutely massive – even the smallest baleen whale, the minke whale, can grow up to 10.5 meters (35 feet) long and weigh over 9,000 kilograms (20,000 pounds), which is almost certainly larger than you or me. On top of that, they live for ages: the bowhead whale in particular is thought to be one of the longest-living animals on the planet, with a maximum lifespan of more than two centuries.

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That’s a lot of opportunity for something to go wrong. And yet, paradoxically, it doesn’t.

“Large bodied and long-lived organisms should face a higher lifetime risk of cancer simply due to the fact that their bodies contain more cells and will undergo more cell divisions over the course of their lifespan,” explained a 2017 article on Peto’s Paradox, published in BMC Biology.

Peto’s Paradox, named after the epidemiologist Richard Peto, refers to the seemingly illogical fact that – to put it bluntly – that simple conclusion doesn’t hold. In fact, the authors pointed out, evidence suggests “a higher risk of cancer does not correlate with increased body mass or lifespan… larger long-lived mammals actually get less cancer.”

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If the lifetime risk of cancer was simply related to body mass, we would expect elephants, for example, to have a minimum of a 96 percent incidence rate of the disease. Instead, the figure is around five percent. Whales would fare even worse: their expected rate of cancer would be so high as to be essentially 100 percent. In fact, it seems to be pretty rare.

“The odds of developing cancer increase with longevity and body mass,” Daniela Tejada-Martinez, a postdoctoral researcher at Thomas Jefferson University in Philadelphia and lead author of a 2021 study on cancer resistance in whales, told CNN.

“However, the cetacean's mechanisms against cancer and aging remain a mystery.”

How to resolve Peto’s Paradox

According to Lynch, there’s a “super trivial” explanation for whales’ seemingly logic-defying cancer rates: “They just evolved better cancer protection mechanisms,” he told New Scientist.

But what are those mechanisms? In 2019, a team of researchers from Arizona State University took skin samples from a humpback whale named Salt to see what was happening in the genome of these cancer-beating beasts – they sequenced her DNA and RNA, and compared the results to other mammals to see where specific adaptations had arisen over the evolutionary tree.

What they found was that some parts of the whale genome – and in particular, areas which control cell growth and proliferation and DNA repair, which are often mutated by human cancers – have evolved much faster than in other mammals. 

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And equally, some parts of the genome – well, they really haven’t.

“Whales are unique among mammals, in that in order to evolve their gigantic sizes, these important ‘housekeeping’ genes, that are evolutionarily conserved and normally prevent cancer, had to keep up in order to maintain the species’ fitness,” explained Tollis, who led the study.

“We also found that despite these cancer-related parts of whale genomes evolving faster than [in] other mammals, on average, whales have accumulated far fewer DNA mutations in their genomes over time, compared to other mammals, which suggests they have slower mutation rates,” he added.

A mother humpback whale, seen from above, swimming with her calf on her back.
Whales are neat. Image credit: Mathias Sehnke/Shutterstock.com


So, far from being a death sentence, it seems the massive size of whales may be precisely what’s protected them all this time. But it’s not the only advantage scientists have found.

“We [found evidence] of positive selection in seven TSGs [tumor suppressor genes] and an accelerated gene turnover rate in comparison to other mammals,” wrote the authors of a 2021 paper on whales’ cancer-resistant genes. 

TSGs are thought to be one of the most important anti-cancer defenses in the body, and whales have so many that some are copies of each other: The team found duplications of more than 70 genes, and more than one in six are known to be linked to longevity and the ageing process. 

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What’s more, the genes which had been positively selected for “are implicated in multiple diseases, including bladder cancer, breast cancer, leukemia and immune system disorders,” the team found. “The turnover rate of TSGs was almost 2.4 times higher in cetaceans when compared with other mammals.”

In other words: Sure, whales may have far more cells than us, and that should theoretically make them more susceptible to cancer – but a lot more of those cells are directly involved in fighting and preventing those same diseases. Overall, whales have the advantage.

Why should we care whether whales get cancer?

Unless you’re a die-hard whale enthusiast, it might be hard to see a point to all this investigation – but it turns out the answer to “why don’t whales get cancer as much as we would expect?” has some very important consequences for us, too.  

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“Cancer is the original problem of multicellularity, and it is clear across numerous studies that nature has beat cancer in a myriad of ways in order to increase the fitness of organisms over the history of life,” Tollis told CNN.

"Since cancer is a body-size and age-related disease, the search for whale-specific changes in protein coding genes that are linked to human cancers can help target potential human cancer therapies," he explained.

Put simply: If whales – and elephants, and even some large dinosaurs – can beat the odds when it comes to cancer, maybe we can do it too.

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“It’s not like we’re gonna be taking whale genes and putting them into humans and making humans cancer resistant,” Lynch told New Scientist. “But if you can find the genes that play a role in tumor suppression in other animals, and if you could figure out what they’re doing, maybe you can make a drug that mimics that for human treatment.”

All “explainer” articles are confirmed by fact checkers to be correct at time of publishing. Text, images, and links may be edited, removed, or added to at a later date to keep information current.


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