The bowhead whale lives two centuries without cancer, and not for the reason that was assumed

The bowhead whale exceeds two centuries of life and eighty tonnes. On that reckoning it ought to die of cancer long before. A team at the University of Rochester set out to find why it does not, and published its answer in Nature in 2025. The central result is the opposite of what everyone expected: its cells let themselves be turned into cancer cells more readily than ours do.

Peto’s paradox

Cancer begins in a cell whose DNA has accumulated the wrong mutations. An animal with more cells, living longer and so dividing them more often, ought therefore to develop far more of them. A bowhead whale carries thousands of times more cells than a mouse and lives a hundred times longer.

Nothing of the kind is observed: across species, size and longevity do not predict cancer risk. This contradiction has had a name since the 1970s, Peto’s paradox, and it has occupied the biology of ageing ever since.

The best-known answer comes from the elephant, which has about twenty copies of the tumour suppressor gene TP53 where we have one. Its strategy is summary: at the slightest damage to the DNA, the cell is eliminated. Effective against cancer, but costly, because destroying cells wholesale is no help in lasting.

A detail that matters in judging how solid the work is: the authors of the work on the elephant’s TP53, Lisa Abegglen and Joshua Schiffman, are co-authors of the whale paper. This is not one team setting its model against another, but a group finding that the solution differs from one lineage to the next. Also among them are Carlo Maley, a specialist in the paradox itself, and a French team, that of Mauro Modesti at the Cancer Research Centre of Marseille, responsible for the test-tube DNA ligation experiments.

The unexpected result

The researchers counted the genetic “hits” needed to turn a normal cell into a tumour cell. In the mouse, two are enough. In humans, five are required. More were therefore expected in an animal this large and this old.

The opposite is the case. Inactivating two genes, TP53 and RB1, and adding an activated HRAS oncogene was enough for bowhead whale fibroblasts to form colonies in soft agar and then tumours in mice. Fewer locks than in humans, not more.

The rest points the same way. The basal activity of p53 is lower than in humans, and whale cells do not die at any higher rate after genotoxic stress. The elephant’s strategy is therefore set aside: the bowhead whale does not protect itself by killing its damaged cells.

It repairs rather than eliminates

If the downstream defences are weaker, it is because the protection is played out upstream, and that is what follows shows: bowhead whale cells mutate much less.

Sequencing of the experimental tumours gives fewer point substitutions, fewer small insertions and deletions, and above all fewer large chromosomal rearrangements, the reduction being marked beyond 500 kilobases. After exposure to mutagens, the rise in mutation rate is the lowest of the species tested, the mouse being the most affected.

The cause lies in the repair of double-strand breaks, the most dangerous lesion for a genome. The two pathways that handle them, non-homologous end joining and homologous recombination, are more active in the whale than in humans, cattle or mice. Mismatch repair is more active too.

The most telling test is the fidelity assay. The authors induced a break at the same place in the PTEN gene in four species, then sequenced the outcome. In humans, cattle and mice, deletions dominate: the repair leaves a scar. In the bowhead whale, it is the proportion of intact alleles that is the highest. It does not merely repair more, it repairs better.

Strategy	Elephant	Bowhead whale
Tumour suppressor genes	about twenty copies of TP53	the ordinary number
p53 activity	enhanced	lower than in humans
Response to damage	eliminate the cell	repair the cell
Hits needed for transformation	more	fewer than in humans
Expected effect on ageing	none, possibly negative	favourable

A cold-induced protein

What makes this repair so effective remains to be established. Comparing repair proteins across species, the authors came upon a striking abundance of CIRBP, a cold-inducible RNA-binding protein.

It is highly abundant in bowhead whale cells and tissues, and almost undetectable in the other mammals tested, with the exception of the humpback whale, and with intermediate levels in dolphins.

The detail that gives the protein’s name its sense lies in the method. The whale cells were cultured at 33 °C, and not at 37 °C like the others, because field measurements give a core temperature of 33.8 °C in this animal. The authors tested the effect directly: human fibroblasts cultured at 33 °C rather than 37 °C produce more CIRBP and repair double-strand breaks better. A low body temperature could therefore be part of the mechanism.

Two causes combine to explain these levels. Five amino acids differ between the human protein and the whale’s, and substituting them is enough to change the abundance. But that does not explain everything: the whale’s coding sequence also uses more efficiently translated codons.

What CIRBP does, and what it does in other species

The gain-of-function and loss-of-function experiments answer one another. Introduced into human cells, whale CIRBP increases the frequency of both repair pathways, reduces micronuclei and chromosomal aberrations, and delays tumour transformation. Knocked down by RNA interference in whale cells, it causes repair to fall away.

In vitro, the protein protects the ends of cut DNA against degradation by an exonuclease, promotes the binding of the Ku70-Ku80 complex and stimulates ligation. The precise mechanism remains open; the authors put forward the hypothesis that it forms a protective condensate around the break.

The most striking test leaves the test tube. Expressed in Drosophila, CIRBP, human as well as whale, extends lifespan and markedly improves survival after irradiation. A cetacean gene that lengthens the life of an insect: the result is worth reporting, and invites caution in its interpretation.

The limits, set out by the authors themselves

They are written into the paper, twice over, and deserve to be reproduced as they stand.

Everything rests on fibroblasts, connective tissue cells, whereas the great majority of human cancers arise in epithelial cells. There is no guarantee that the same rules apply there. The mechanism of action of CIRBP is not established. And the link between properties measured on cultured cells and the cancer resistance of a whole animal remains an inference, not a demonstration: no one has followed a cohort of bowhead whales over two centuries.

An author correction was also published on 28 November 2025, a month after the online publication of 29 October. It is purely editorial: a missing article in the English title, the removal of a reviewer-only access link, and the specification of the repository where the proteomics data are deposited. No scientific conclusion is affected, and we mention it because a correction in Nature often causes alarm without cause.

Where the samples come from

This point deserves to be stated plainly, because it is rarely picked up. The tissues come from whales taken during the Iñupiat subsistence hunts of 2014 and 2018 at Utqiaġvik, Alaska, under a memorandum of understanding signed with the North Slope Borough Department of Wildlife Management and the Alaska Eskimo Whaling Commission, and under permit from the US National Oceanic and Atmospheric Administration. Sampling takes place only with the agreement of the whaling captain.

There is more than administrative formality in this. The paper opens by recalling that the Iñupiat have long held that these animals “live two human lifetimes”. Science confirmed it afterwards, by counting ovarian corpora lutea, dating the baleen and measuring aspartic acid racemisation in the eye lens.

What can be taken from this

The bowhead whale owes its longevity not to extra anti-cancer defences, but to a genome that is damaged less and repaired better. It is a conservative strategy: rather than sacrifice cells, restore them. Over two centuries, the economy makes sense.

The authors note that no approved therapy today aims to strengthen DNA repair, and that it has even been argued to be impossible. Their work provides a counter-example, without announcing a treatment. Our page on the sequenced genomes of cetaceans and the one on cetacean pathologies place this work in context, and the bowhead whale species page covers the animal itself, whose longevity record also appears among the records of cetaceans.

Sources

• Firsanov D., Zacher M., Tian X. et al., 2025. “Evidence for improved DNA repair in the long-lived bowhead whale”. Nature 648: 717-725. doi.org/10.1038/s41586-025-09694-5. Senior author: Vera Gorbunova, University of Rochester.
• Article published online on 29 October 2025. Author correction of 28 November 2025, Nature 648: E14, doi.org/10.1038/s41586-025-09952-6: editorial corrections to the title and to the data availability section, with no bearing on the results.
• Samples taken under National Marine Fisheries Service (NOAA) permit no. 21386, in collaboration with the North Slope Borough Department of Wildlife Management and the Alaska Eskimo Whaling Commission.