What can elephants teach us about cancer?

They’re bigger, stronger and somehow still cuter than us, but elephants aren’t show-offs. You have to look closely to understand just how amazing they are.  

Start doing that and you might just learn something about yourself. 

Zoom all the way in and you’ll see that elephants and people are made of the same tiny building blocks, or cells. The numbers are just a bit different. A single African elephant has about as many cells as 100 adult humans. 

With all those extra cells, elephants should be more prone to cancer, which begins when the DNA in cells mutates, causing them to grow and divide uncontrollably. Cancer science tells us that more cells means more chances for mutations, especially as living things get older. Elephants and humans have similar lifespans, but 70-year-old elephants are actually less likely to get cancer than 70-year-old people.  

Much less likely, in fact. Cancer is extremely rare in elephants.  

A quarter of all human deaths in the UK are caused by cancer. Our stats on animals aren’t as exact, but one study suggests that for elephants, the number is more like one in 20. 

So, what’s going on? Why don’t more elephants get cancer?  

Can elephants get cancer?

To be clear, elephants can get cancer. The surprising thing is that they aren’t any more likely to get it than other animals.

In general, the bigger an animal gets, the more its cancer risk increases. Dogs are a useful example. Large dog breeds have many more cells than small ones, and they are also more likely to develop cancer. But when you compare different species, size doesn’t seem to matter. According to a study carried out at the San Diego Zoo, elephants have about the same cancer risk as striped grass mice, which are 100,000 times smaller.

The fact a species’ cancer risk doesn’t increase with its size is called Peto’s paradox, after Professor Sir Richard Peto, one of our researchers, who first laid it out in the 1970s. 

If we can solve the paradox – and learn how the world’s biggest animals avoid cancer – we‘ll have a much better idea of how the disease works. We might even be able to use some of nature’s techniques to improve how we treat cancer in humans. 

So far, scientists have found some important clues.  

An anti-cancer defence mechanism

Not long after Peto started pondering his paradox, two other Cancer Research UK-funded scientists, Dr Lionel Crawford and Professor Sir David Lane, went fishing for molecules with a monkey virus. They hooked a tiny protein we now call p53.  

It wasn’t clear straight away, but that was the first time anyone had found a protein our body uses to prevent cancer.

p53 is a tumour suppressor. It stops damaged cells from copying themselves so they can be repaired, and, if they can’t, it causes them to die, meaning DNA damage can’t build up into cancer.  

Lane nicknamed it the ‘guardian of the genome’.

Elephants’ extra anti-cancer genes

Problems with p53 are linked to most adult cancers.  

The gene responsible for making p53 is called TP53. Humans have one copy of it (containing two versions) in every cell.  

It’s so important for protecting us from cancer that people born with only one functioning version of TP53 (a condition called Li-Fraumeni Syndrome) have been reported to have a lifetime cancer risk of more than 70%. 

Every cell in an African elephant contains 20 copies (or 40 versions) of TP53.  

They don’t all work the same way. But with 38 extra versions of the gene on the job, elephant cells are much more vigilant about DNA damage. They will self-destruct to prevent mutations that our cells won’t even respond to.  

It’s not that all, or even most, of those changes would lead to cancer. With so many chances for things to go wrong, though, elephant cells shoot first and ask questions later. 

Elephant TP53 seems to act that way wherever you put it. Lab studies have shown that it presses the self-destruct button when introduced to human cancer cells, too.  

A study last year by a team of researchers from across Europe (including the Chairman of Save the Elephants, Professor Fritz Vollrath) helped explain how. There are important differences between each copy of elephant TP53. They all have their own ways of interacting with other proteins in the cell, making it harder for cancers to disable enough of them to escape detection. 

By comparing exactly how these different copies of TP53 work, the researchers hope to learn more about how our own bodies fight cancer. They’ve also suggested that supporting the TP53 in our cells – mimicking elephants’ different copies of the gene – could be a new model for cancer medicine. 

A trunk full of tricks

And then there’s the zombie gene. 

Elephants evolved from much smaller ancestors and acquired extra copies (or retrogenes) of TP53 as they grew. Some scientists think these may have helped elephants reach the size they are today. 

Somewhere in their evolutionary history, elephants also gained extra copies of another tumour suppressor gene: LIF, which works in concert with TP53. Scientists have also found extra LIF genes in elephants’ closest cousins: slow-swimming manatees (also known as sea cows) and short, stout balls of fur called hyraxes, which live on mountains and in trees.  

Most of these extra copies of LIF don’t seem to work. In manatees and hyraxes, only the original version of LIF comes with an ‘on’ switch. But, as they grew bigger, elephants managed to hotwire a second one.  

Now, when DNA in a cell is damaged, p53 is able to bring the ‘zombie’ copy of LIF back to life. It gives elephant cells an extra trigger to self-destruct (a process known as apoptosis, or programmed cell death) – another failsafe for responding to damage that could turn into cancer. 

The elephant in the classroom

We only found out about elephants’ extra copies of TP53 in 2015. Since then, scientists have been chasing down answers across millions of years of evolution. We weren’t there when these cancer-fighting changes happened, so we’re working with theories about how and why they came about. There’s a lot more to learn, but we’re learning fast. 

In June 2023, a study carried out at the University of Oxford – and led by Vollrath – suggested there could be another reason elephants have so many copies of TP53: their testicles. 

In mammals like us, hot sperm is at risk of mutating. That’s why most mammals’ testicles are outside their bodies: it’s cooler there. Elephants, with their testicles on the inside, are an exception. The extra copies of TP53 could be a way of making up for this, there to remove heat-damaged sperm cells so elephants have healthy offspring. 

And just last month, in July 2023, another research team found even more extra genes and proteins in elephants that could help them fight cancer. Interestingly, elephants seem to share some of these with very different cancer-resistant animals, like naked mole rats and horseshoe bats.  

If they play a role in protecting such diverse animals from cancer, there’s more of a chance they’re relevant to us, as well.

In fact, though elephants have variations and extra copies, many of these genes are in us too. We have much more in common with other living things than we might realise.

Time and again, that’s what scientific research shows us. Focusing on the smallest things can help us understand the biggest ones. And, sometimes, the further away we look, the better we can see ourselves.

Tim