On bowhead whales, longevity and DNA repair
Some professions seem inherently more glamorous than others. Amongst the top ones, in the usual perception, there would be rocket scientists, movie actors, fashion designers, and architects. Less prestigious positions would include electricians and plumbers. However, glamour does not equate to or reflect usefulness. A city that had no rocket scientists or movie stars but did have electricians and plumbers would be far better off than one with the reverse make-up.
Perhaps we similarly and unconsciously construct an analogous prestige hierarchy of biological functions. For most molecular biologists, for instance, DNA replication and gene expression seem sexier than subjects like intermediary metabolism or urine production. As with human jobs, however, perceived rank does not map to usefulness. If your intermediary metabolism or ability to produce urine were to suddenly shut down, you would soon be dead.
The biological function I am going to discuss here is one that might sound rather humdrum: DNA repair. Many people have probably never even heard of DNA repair. Like plumbing, it sounds like a good thing but perhaps not very exciting. Compared to biological subjects frequently in the news -- infectious diseases, ecological disasters, biodiversity issues, agricultural advances, cancer cures – DNA repair has a fairly low public profile.
Yet every now and then, a news story comes along in which DNA repair is central. Such was the case recently with a story about bowhead whales. All whales are fascinating, charismatic creatures. Their size, intelligence, communication skills, long distance travel, make them so. Some are of special interest, however. Bowhead whales, for instance, are exceptional in their size – they are the second largest mammal on earth, at up to 88 tons per individual – and their ability to live all year round in frigid Arctic waters is unique. For that trait, there must be special aspects of their physiology that give them great resistance to cold.
A third special feature is their longevity. Bowhead whales can live to great ages. This was revealed in the late 20th century when a few were caught and killed and found to have more than a century old harpoon heads embedded in them from hunts in the 19th century that they had survived. The Inuit in the Arctic, however, had long known about bowhead longevity. They could recognize individual bowhead whales from their markings and knew that certain bowhead whales had lived for as much as two human lifetimes. Today, we know that bowhead whales can live up to 268 years, far longer than any terrestrial mammal or reptile.1
Before explaining how DNA repair links up with the story of bowhead whales, we should state exactly what it is. Every DNA molecule, as found in a specific kind of chromosome (one of our 23 pairs of chromosomes for instance), or segment of such a molecule (for example, a particular gene) consists of a highly specific sequence of nucleotides, with a particular base pair (A-T, T-A, C-G, or G-C) at every specific position in the double-helical molecule. (For discussion of this point, see Reflections. 2. How do new scientific ideas arise?) For all members of the species to which that chromosome or segment belongs, the sequence is basically the same (except for a relatively small number of positions where there will be differences from the standard. It is the sum total of those relatively few differences that make for the genetic differences between individuals.) DNA repair consists of the set of processes that help ensure that any changes in the normal sequence are found and eliminated and the normal sequence restored.
DNA replicates with remarkable accuracy, with each molecule giving rise to two essentially identical double helices, so called “daughter DNA molecules”. That accuracy is essential for the reproduction of living things, which, in turn, makes the continuity of life on Earth possible. Yet, no biological process operates perfectly and there is a low error rate in DNA replication. It varies amongst species but is generally between 10-9 and 10-10 per base pair per round of replication. That comes out to a low number of mistakes per molecule per replication. For the human genome, with 3 x 109 base pairs, and an error rate of 10-10 per base pair per replication and two copies of each genome per body (somatic) cell, that would come out to about 0.6 errors per round of replication. Given that the great majority of single base pair changes are relatively harmless (see Should genes be seen as controllers or nudgers of biological development?), and this low rate of errors, one might well conclude that there is no problem.
However, consider that there are about 40 trillion cells in the adult human body and that each had arisen from a long sequence of cell replications; the picture alters. Even a small error rate – say 1 in 3 billion -- over trillions of cell replications can add up to something significant. Remember also that changes in DNA sequence can occur not just by rare errors in replication but from various kinds of damage to the DNA structure after replication, often from chemicals or radiation. Taking this into account, one realizes that keeping the changes in DNA sequence to the absolut minimum must be of great benefit.
How do DNA errors harm the organism? Most obviously, they can do so in reducing the degree of functional activity of genes. Such deleterious changes might occur in the gene itself or in one of the regulatory sequences near the gene that determine whether it is turned on or off or to what degree. Hence, naively but realistically, one might expect that as an individual animal ages, it will accumulate progressively more defective genes which do their jobs less well. However, something even more serious happens. Many kinds of genetic damage can potentiate cancer and the more DNA damage there is, the more likely cancer initiation becomes..
Preventing errors and limiting DNA damage is exactly where DNA repair comes in. Efficient, high quality DNA repair is crucial not just to slow the rate of ageing but to reduce the chances of cancer. Seen in this light, DNA repair is not just a helpful add on to keep the organism in good shape but is vital. Also remember that DNA repair almost certainly goes back to the beginnings of cellular life on Earth, roughly 3.7 billion years ago. Something retained that long must be of great value.
There are many different kinds of DNA repair – from correcting a mis-pairing of bases (such as an A with a C or a G with a T), to replacing a whole set of missing bases on one strand to fixing double-stranded breaks, without loss of any DNA sequence and more. That variety of kinds of repair, each the product of its own evolutionary sequence, further testifies to the essentiality of DNA repair for the organism.
Let us return to bowhead whales. One might well think that such large animals face a special biological challenge. After all, the bigger the animal the more cells they have, the more cell replications they will have undergone and the more DNA they contain that might be subject to damage. One might think therefore that larger animals are especially prone to ageing and cancer. In fact, it is just the reverse: larger animals can be exceptionally long-lived and very cancer resistant. This realization is named Peto’s Paradox after Richard Peto, a British epidemiologist who first described it in 1977.
One living embodiment of Peto’s Paradox is the elephant, long known to rarely experience cancer. The explanation began to emerge in a paper that appeared in 2015 and concerns one of the genes known to protect against cancer called “tumor suppressor genes”. The particular gene is named the p53 gene, which has been extensively studied in humans and mice. Most mammals have just one such gene (though, of course, two copies). Elephants, it was shown, have 20 copies of a modified p53 gene. P53 works by detecting cells that have DNA damage and which may be on the route to becoming cancerous. Cells detected in this way by this protein are then triggered to undergo programmed cell death (“apoptosis”) and are eliminated. It seems virtually certain that it is the increased p53 gene activity in elephant cells that give elephants their special resistance to cancer; when the elephant p53 gene is transferred to mammalian cells, they acquire extra resistance to becoming cancerous.2
While eliminating DNA-damaged cells is one way to increase protection against cancer, improved DNA repair should also do that. This brings us back to bowhead whales. Connecting them to the story of DNA repair, however, came about accidentally from a research group exploring these whales’ great ability to tolerate cold oceanic waters year round. Previous work had shown that a protein induced by cold temperatures, CIRBP, helps confer cold resistance in bowhead whales. Other work had indicated that the protein was also present around chromosomal DNA in unexpected amounts and this led to the discovery that bowhead CIRBP functions in DNA repair, specifically the ability to repair double-strand breaks efficiently and with fewer errors. This might not be the only factor contributing to the bowhead’s great longevity but it is probably a crucial one.
If the bowhead whale were the fruit fly or the mouse, two of the premier genetic model systems, one could do what is called a “knock out” experiment. In these, one inactivates a specific gene and looks at the consequences. Would bowhead whales without CIRBP activity suffer a big decrease in longevity (allowing somehow for their decreased cold resistance) or suffer more cancers? That kind of experiment is completely unfeasible in whales. Instead, the bowhead whale CIRBP gene has been inserted into the genome of the fruit fly and into human cells in culture. Both the fruit fly and human cells showed an increased capacity for DNA repair. Even more importantly, the fruit flies also showed increased longevity. Such gene addition experiments are now being carried out in mice.3
There is further relevant evidence. One mammalian species of special interest is the naked mole rat. In contrast to mice for instance, which live only one or two years, naked mole rats can live up to 30 years. They have greatly increased activity of a DNA repair gene named cGAS and this is very likely to be a big part of the answer to their longevity. Second, there is evidence from humans in the form of natural loss-of-function mutations in two genes. These mutations lead to greatly accelerated aging in the individuals that have them. Those mutations lead to conditions known as Cockayne’s syndrome and Werner’s syndrome, named for the physicians who first described them. Both of these genes happen to be important DNA repair genes. Reduce DNA repair substantially and human aging greatly speeds up; the individuals when in their teens look like people in their 80s.
Altogether, the picture is developing with increased detail and clarity: efficient DNA repair is a major defense against both cancer and ageing. One last thing to consider: it may be that the capacity for DNA repair was essential for the evolution of heredity based on DNA itself. It now seems that life on Earth began with RNA, probably single-stranded RNA, as the genetic material. However, a double stranded polynucleotide molecule with complementary base pairing has the potential to repair itself in a way that a single strand polynucleotide cannot. If for instance, a base has been wrongly inserted or damage has occurred, DNA repair mechanisms can remove the error or damage and then, by the rules of base pairing, the correct base pairs are restored. A single-stranded molecule cannot do this. The argument is made in more detail in a paper published in 2018.4 If correct, it may mean that the vast panoply of DNA-based life on Earth today was made possible by the advent of DNA repair.
Hence, far from being an unglamorous, rather routine set of maintenance processes, DNA repair has been central to complex life, as it initially evolved, as we know it today, and all through the intervening 3.7 billion years. Elucidating the importance of DNA repair in the history of life on Earth may be the great Cinderalla story of modern biological science.
With ancient and big trees, one can determine their age by counting their rings. Whales do not have the equivalent of tree rings, hence another method for determining their age had to be found. Amino acids, which are the building blocks of proteins, come in two different forms, which in solution bend light in two different directions. These are called the L- and D-forms. All living things on Earth use the L-forms. It was discovered that, over time and unaffected by temperature, one of them, L-aspartic acid transforms to the D form at a steady rate. Given the relative amounts of D- and L-aspartic acid, if one has a stable biological structure in which the D-form can accumulate, one can estimate the age of the animal from which the structure came. Using bowhead whale teeth, this was how it was deduced that they can live up to 268 years.
For a short review, see Callier, V. (2019). Solving Peto’s Paradox to better understand cancer. Proc. Natl. Acad. Sci. USA 116: 1825-1828. Doi.org/10.1073/pnas.1821517116.
For a popular account, see Zimmer.C.. Scientists find clue to whales’ long lives. International New York Times, 3 November, 2025, p. 2. The detailed research report is Firsanov, D. et al. (2025). Evidence for improved DNA repair in long-lived bowhead whale. Nature doi: 10.1038.s41586-025-09694-5
See Strauss, B. (2018). Why is DNA double-stranded? The discovery of DNA excision repair. GENETICS 209 (2): 357-366. Doi/10.1534/genetics 118.300958