Scientists have recently shed some light on exactly why elephants, one of the biggest animals on the planet, paradoxically experience unusually low rates of cancer. The research found these remarkable mammals carry unique genetic variants that reduce their risk of tumors, and the findings could help develop new cancer therapies for humans.
Editor's note: Readers often ask us for follow-ups on memorable stories. What has happened to this story over the years? This article was originally published in 2022 but has been re-edited and updated with new information current as of May, 2025. Enjoy!
As an organism grows older, and its cells continue to replicate, the chances of cancerous mutations increase. And the bigger the organism, the more cells it has, so the more chances for mutations, and the higher risk for cancer as it ages. Right?
Within individual species this observation has generally held true. From taller humans to bigger dogs, cancer risk has been found to positively correlate with body size. So in theory big animals that live long lives should experience higher rates of cancer than smaller, short-lived organisms.
But this hasn’t been found to be the case, and the discordancy has long been known as “Peto’s Paradox”, named after epidemiologist Richard Peto, who discovered per-cell carcinogenesis rates were not consistent between species. In fact, in some larger species such as whales and elephants there seemed to be very little evidence of cancer at all, despite them being massive and living long lives.
In early 2025 a team of researchers challenged the basic idea of Peto's paradox, offering the first large-scale dataset of cancer prevalence in around 260 organisms. They found larger species do tend to have a slightly higher prevalence of cancer compared to smaller species. However, things got really interesting when they homed in on how certain large organisms evolved techniques to protect themselves from cancer.
While it is generally understood that each species evolved its own unique abilities for suppressing cancer, elephants have always been of particular interest to researchers. These animals have similar lifespans to humans yet, despite their size, show little signs of cancer, even in very old age. It has been estimated as little as 5% of elephants ultimately succumb to cancer, compared to 25% of humans.
A landmark study a few years ago homed in on one of the key ways these massive mammals may be avoiding cancer. Elephants seem to have 20 different copies of a tumor-suppressing gene known as p53.
This gene encodes a protein, also known as p53, which serves as a crucial cell protector. This protein acts a bit like a guard whose job is to stop a cell dividing when it detects any DNA damage or mutation.
When the p53 gene is not working properly damaged cells can multiply and cancerous tissue accumulates. Dysregulation of the gene is thought to play a role in more than half of all human cancers, but unlike elephants, we only have one copy of the gene.
A 2022 study set out to investigate exactly how the variety of p53 genes in elephants suppress cancer.
“This intricate and intriguing study demonstrates how much more there is to elephants than impressive size and how important it is that we not only conserve but also study these signature animals in minute detail,” explained study co-author Fritz Vollarth at the time. “After all, their genetics and physiology are all driven by evolutionary history as well as today’s ecology, diet and behavior.”
The activity of p53 in a cell is regulated by another gene known as MDM2 that encodes a protein that essentially inactivates the p53 protein.
This p53–MDM2 pathway is fundamental to the workings of healthy cells – p53 stepping in to check the health of a cell, and MDM2 stopping p53 from triggering cell death by sending a signal to say everything is working fine. The new research found elephants have an incredible array of different p53 proteins that can increase the ways around MDM2 inactivation.
In humans, because we only have one copy of the p53 gene, it doesn’t take much for MDM2 to take over and allow cancerous cells to replicate. But in elephants the p53 protein takes on dozens of different molecular shapes, avoiding inactivation by MDM2, and stopping the replication of so many more cancerous cells.
“This is an exciting development for our understanding of how p53 contributes to preventing cancer development,” said study co-author Robin Fåhraeus. “The existence of several p53 isoforms in elephants with different capacities to interact with MDM2 offers an exciting new approach to shed new light on p53’s tumor suppressor activity.”
The 2022 study presented impressive new insights into the mechanisms evolved by elephants to avoid cancer. As well as demonstrating how these massive mammals deployed different p53 molecules to suppress the growth of cancerous cells, the study also pointed to potential human clinical outcomes. By highlighting dozens of novel ways p53 molecules can be activated researchers are now presented with a number of new pathways for targeted cancer therapies in humans.
The next year, in 2023, a different team of researchers presented a bold new hypothesis to explain why elephants may have evolved so many iterations of the p53 gene. The question they asked was what could have prompted so many variations in the p53 gene when cancer primarily develops during old age, long after an animal has reproduced. If elephants were dying of cancer after they produced most of their offspring then there wouldn't be a great deal of selection pressure to minimize cancer.
Here, they suggested the answer lay in the animal's testicles.
In most sperm-producing mammals, the testicles drop from the body into the scrotum. This is crucial because healthy sperm needs to be kept at a temperature slightly cooler than mammalian body temps. But elephants are somewhat unique in lacking the evolutionary tactic of housing its testicles outside of the body. This means elephant sperm is frequently exposed to high body temperatures that can damage DNA.
So this novel hypothesis claimed the proliferation of p53 genes in elephants was not to protect the animals from cancer but instead to protect the animals' sperm. These genes have a general job of stopping a cell dividing when DNA damage is detected so they likely are important in maintaining the health of elephant sperm. The cancer protections are possibly a secondary benefit helping the animals further live long healthy lives.
A version of this article was originally published in 2022.
