DNA Repair may be the Cancer-Defying Superpower of Bowhead Whales

Near the northern tip of Alaska, on the outskirts of the Arctic Ocean, bowhead whales have given scientists a glimpse into longevity.

The gigantic marine mammals can live more than 200 years — and tissue samples collected from the animals reveal a fix-it superpower that might explain how. Bowhead whales’ cells are whizzes at repairing damaged DNA, scientists report May 8 at bioRxiv.org.

That ability means the animals might mend damage that could otherwise lead to cancer-causing genetic glitches, says Orsolya Vincze, an evolutionary ecologist at the French National Center for Scientific Research in Paris, who was not involved with the research. Scientists have previously reported other animals’ biological strategies for avoiding cancer. But the new work, Vincze says, “shows that the whales approach cancer resistance from a very new perspective.”

The bowhead whale, Balaena mysticetus, can grow to roughly 18 meters long and is among the heaviest mammals on Earth. At more than 80,000 kilograms, it’s about the weight of six fully loaded school buses. All that body mass adds up to a vast number of cells. And every time a cell divides, there’s a chance that a dangerous mutation can arise.

But somehow, large-bodied animals are especially cancer resistant — a puzzle known as Peto’s paradox. That suggests the animals must “have much stronger cancer defenses,” says Lisa Abegglen, a cell biologist at the University of Utah Health in Salt Lake City who was not part of the new work.

Her team discovered that elephants, which can live nearly as long as humans and rarely die from cancer, have extra copies of a tumor-blocking gene called TP53 (SN: 10/13/15). This gene and another may help elephants deal with DNA damage by clearing out afflicted cells, other scientists have reported (SN: 8/14/18).

That’s one way to ward off trouble from damaged DNA, says Marc Tollis, an evolutionary biologist at Northern Arizona University in Flagstaff who did not participate in the new study. Another strategy is to “take the hit,” he says, “and then try to fix it.”

Hints from the bowhead whale genome published nearly a decade ago predicted that the mammals may use this alternate strategy (SN: 1/6/15). “But you need actual experiments to actually validate those predictions,” Tollis says.

In the lab, study coauthor Vera Gorbunova at the University of Rochester in New York and her colleagues ran an assortment of experiments on cells harvested from bowhead whale tissue, as well as on cells from humans, cows and mice.

The whale cells were both efficient and accurate at repairing double-strand breaks in DNA, damage that severs both strands of the DNA double helix. Whale repair restored broken DNA to like-new condition more often than cells from other mammals, the team found. In those animals, mends to the genome tended to be sloppier, like a poorly patched pair of jeans. The team also identified two proteins in bowhead whale cells, CIRBP and RPA2, that are part of the DNA repair crew.

Discovering how animals fend off cancer is “incredibly exciting,” Abegglen says, “because all of these strategies have potential to be translated into effective treatments for people with cancer.” Though that day may be far off, the new findings underscore the importance of studying animals with low cancer rates, she says. Abegglen wants to test whether the team’s results hold up in humpback whale and dolphin cells — or if those animals have different defenses.

There’s so much to learn from these and other animals with large bodies and long life spans, Vincze says.  “We probably have the solution to cancer medicine out there in nature already,” she says. “We just have to find it.”