Peto’s paradox: What makes whales nearly immune to cancer

Why don’t giant animals get more cancer? Despite having vastly more cells, whales and elephants rarely develop cancer. This phenomenon, known as Peto’s paradox, reveals how evolution has equipped large, long-lived animals with powerful DNA repair, tumour suppression, and immune mechanisms, offering surprising insights for human cancer research.

Why don’t giant animals get more cancer? 

When cancer comes to mind, it is usually a human disease. While it might seem that every multicellular organism, including massive animals like whales, would be much more likely to develop cancer simply because they have so many more cells where something could go wrong, recent research shows that some large mammals have evolved special mechanisms to reduce their cancer risk. For example, elephants have lessened their risk by duplicating a key gene called TP53.

Surprisingly, this is not what is seen. Very large, long‑lived animals such as whales and elephants do not appear to get cancer nearly as often as simple ​“more cells = more cancer” reasoning would predict. This puzzling mismatch between expectation and reality is known as Peto’s paradox, and it has pushed scientists to ask a deep evolutionary question: How do giant animals stay cancer‑resistant for so long? 

Peto’s paradox in plain language 

Across species, cancer risk does not scale up straightforwardly with body size or lifespan. A blue whale has orders of magnitude more cells than a mouse and lives far longer, yet whales are not wiped out by cancer early in life. If each cell carries the same chance of turning malignant, whales should be in constant danger.

The fact that whale and elephant populations persist tells us something important: these species must have evolved extra layers of protection that keep cancer in check. Instead of being victims of their own size, they are products of intense natural selection for better tumour suppression, DNA repair, and immune surveillance.

The bowhead whales DNA shield 

One striking example is the bowhead whale, which can live for more than 200 years while showing surprisingly low cancer incidence. Research suggests that bowhead cells maintain their DNA with exceptional accuracy, especially when dealing with dangerous double‑strand breaks events where both strands of the DNA helix are cut at once. If these breaks are not fixed correctly, they can trigger mutations or outright cell death. 

Cells usually repair such breaks using a process called non‑homologous end joining (NHEJ), which rejoins the broken ends quickly but can introduce errors. In whales, this process seems to work with much higher fidelity. A key player is a protein called CIRBP (cold‑inducible RNA‑binding protein). Humans also have CIRBP, but the whale version appears to stabilize broken DNA ends more effectively and guide them into cleaner repair. When scientists introduced whale CIRBP into human cells, those cells repaired DNA damage more accurately and picked up fewer harmful mutations over time. 

Experiments in other organisms support this idea of a broad protective role. In fruit flies engineered to produce more CIRBP, researchers observed longer lifespans and better resistance to DNA‑damaging stress, such as radiation. Together, these findings suggest that bowhead whales are not just relying on extra tumour‑suppressor genes. Instead, they have evolved ultra‑precise DNA maintenance systems that reduce mutation accumulation across their unusually long lives, helping to explain both their longevity and their apparently low cancer rates. 

Genomes of giants: Humpback whales and beyond 

Whales defense does not stop at a single protein. When scientists assembled and analysed the humpback whale genome, the full set of its genetic instructions, they found extensive signs of adaptation in genes involved in body structure, immunity, and the control of cell growth and death. Many of these genes sit at key checkpoints where a cell either repairs damage, pauses division, or self‑destructs if things look too risky. 

Notably, humpback whales carry extra, active copies of several genes that help identify and remove damaged or unhealthy cells. These additional copies may allow whale tissues to cull potentially cancerous cells more aggressively before they can form tumours. Genomic and cellular data also indicate that whales, as a group, accumulate genetic errors more slowly than would be expected for animals of their size and lifespan. Fewer mutations over a lifetime mean fewer chances for a cell to become malignant, neatly fitting the broader pattern described by Peto’s paradox. 

What this could mean for human cancer 

All of this raises an exciting possibility: instead of fighting cancer only with drugs designed from scratch, medicine might borrow strategies that evolution has already tested at a massive scale in whales and other large animals. The goal would not be to use whale cells directly, but to understand and adapt their defenses. 

There are several promising avenues. Whale‑like versions of DNA repair factors such as CIRBP, or small molecules that boost their activity, might one day help human cells fix dangerous DNA damage more accurately. Extra copies or enhanced forms of certain tumour‑suppressor genes could inspire gene‑therapy or gene‑editing strategies that make high‑risk tissues more resilient. Insights from whale immune surveillance and cell‑death pathways might guide new immunotherapies that recognise and clear precancerous cells earlier and more reliably. 

Peto’s paradox shows that huge body size and long life do not have to come with a crushing cancer burden. 

Whales, elephants, and other giants demonstrate that biology can evolve powerful internal systems to keep cancer in check, even under extreme conditions. By decoding those systems in detail, biotechnology may eventually turn the same evolutionary tricks that protect whales into new tools for preventing and treating cancer in humans.