A bowhead whale’s DNA offers clues to fight cancer : NPR

Scientists searching for new ways to fight cancer believe they may have discovered a promising new leader hidden inside the cells of a bowhead whale.

Results published in magazine Natureare part of a growing field studying the ways in which long-lived animals such as bowheads manage to continue transporting cargo without being damaged by malignant cells.

There is a mystery in cancer biology known as Peto's Paradox: Large animals have many cells, which theoretically should mean a greater chance of getting cancer. And long-lived organisms have more time to acquire the mutations needed to turn healthy cells into cancerous ones.

And yet, “this doesn’t happen,” he says Vera Gorbunovabiologist from the University of Rochester. “This suggests that these large, long-lived animals have additional protection against the cancers that they develop.”

Gorbunova and her colleagues now say they have found such protection in the bowhead whale, a long-lived leviathan. These animals use a protein they produce in abundance that is excellent at repairing damaged DNA.

“Instead of destroying malignant cells,” says Gorbunova, “they do a better job of supporting their cells so they don’t accumulate as many mutations.”

Vincent LynchAn evolutionary biologist at the University at Buffalo, who was not involved in the study, says the findings may one day have wider applications. “Translation to human health and disease is really difficult,” he says, “but perhaps you can develop treatments that mimic what we learn from other species.”

Live two human lives

In other work, researchers found that elephants have their own way to reduce the risk of cancer. They have 20 copies of a tumor suppressor gene, sometimes called the “guardian genome.” It produces a protein called p53. People only have one copy.

This protein helps eliminate cells that become precancerous and begin to grow abnormally. “[The] The p53 protein can cause cell death,” says Gorbunova. “Cells commit suicide.” This protein can also initiate DNA repair and prevent cell division.

It is believed that by having more copies of this gene, elephants destroy more potentially problematic cells and reduce cancer rates.

Gorbunova and her colleagues wanted to take the research to the extreme. “We decided: what if we look at whales that are even larger than elephants?” she says.

They targeted bowhead whales. These are not the largest cetaceans, but Gorbunova says they are the longest-living: the animals can be up to 200 years old. This is something that the Alaskan Inuit have known for generations – according to one version, local whaling captains told biologists that these animals live two human lives.

Scientists confirmed this observation by examining the proteins in the whales' eye lenses and dating the harpoons embedded in the animals' flesh.

Gorbunova was particularly interested in the bowheads because “I can tell you there have been no reports of malignant tumors,” she says.

She contacted the Inupiaq community in Barrow, Alaska, who hunt bowheads for food. “They use their traditional methods, such as rowing boats, to harvest very small numbers of whales each year,” she says. “They very kindly agreed to share very small pieces with us so we could do the research. So none of this would have been possible without the generosity of Alaskan Inuit whalers.”

In fact, Gorbunova says that in the future, this research could benefit the Inuit, a community struggling with increase in cancer incidence.

A little protein goes a long way

With fresh bowhead tissue in hand, Gorbunova and her team began their experiments. She thought that since bowheads were larger than elephants, perhaps they were simply even more copies of the tumor suppressor gene that produces p53.

“But that’s not what we found,” she says with a laugh. “We can build some kind of hypothesis, but then nature proves us wrong.”

Researchers looked at what else whales can do to avoid cancer. “Perhaps they prevent cells from accumulating mutations at all,” says Gorbunova. “Just don’t let things deteriorate to the point where the cell has to be destroyed.”

According to Gorbunova, such a strategy could involve improving DNA repair, since breaks in DNA can be dangerous and lead to cancer. And so it turned out.

“People are pretty good at repairing DNA breaks,” says Gorbunova. “But the whales were even better than humans—almost two to three times better. They didn't lose pieces of DNA. They connected the ends correctly.”

Bowheads derive this ability, at least in part, from a protein called CIRBP (which stands for cold-inducible RNA-binding protein). Gorbunova says there is much more of it in Greenland pike cells than in other species, and it is produced by a gene that is activated when exposed to cold.

She explains the logic this way: “For the bowhead whale, which can live for more than two centuries, maintaining healthy cells by repairing damage may be more beneficial than destroying those cells, as the elephant does. The whale's strategy is to invest in maintenance rather than cleanup.”

When the researchers forced human cells to overproduce the protein, the cells were more efficient at repairing DNA breaks. And when they forced live fruit flies to produce a lot of protein, “they lived longer and also became more resistant to DNA damage,” Gorbunova says. “The most important takeaway for us as humans is that there is room for improvement.”

She says increasing levels of this protein in humans could one day help slow the rate at which mutations accumulate in our cells. “If we understand the mechanism of longevity in this exceptionally long-lived mammal,” she argues, “we may be able to find a way to clinically apply this mechanism to benefit human health.”

Ocean of possibilities

Amy BoddyAn evolutionary biologist at the University of California, Santa Barbara, who was not involved in the study, found the results impressive and useful for those in comparative oncology, a field focused on the formation, growth and suppression of cancers and tumors across species.

“We want to be able to better treat cancer in people,” she says. “And so it's really interesting to know that animals have evolved different pathways to long life and protection from cancer that have been tested by evolution.”

Additionally, linking possible advances in human health that long-lived animals could provide could send a powerful signal for conservation, says Boddy, who studies elephants, among other species. This is especially true for animals that are at risk of extinction, she adds. “We need to protect ourselves from poaching because these are amazing magical creatures that may one day help human health.”

However, Boddy notes that any strategy to combat cancer must be a compromise. “These whale cells repair damage,” she says. “But what's the trade-off in that? Because there must be a lot of energy and investment.”

Lynch, who was also not involved in the study, finds the results compelling and suggests this is just the beginning. He believes that animals such as bowhead whales and elephants (not to mention some anomalous smaller organisms such as bats And naked mole rats) may have developed additional ways to prevent cancer.

“We literally discovered several mechanisms that are responsible for their resistance to cancer,” he says. “There’s still a lot to be determined, which is great because it gives us something to do.”

Gorbunova says this is an opportunity to go beyond typical laboratory animals such as mice and fruit flies. “If we only study very short-lived organisms, we won't be able to find longevity mechanisms because they don't have them,” she says.

On the contrary, whales and elephants seem to have a lot to teach us during their many years on this planet.