For almost half of us, cancer will become an unfortunate reality in our lifetime. But elephants have one of the lowest rates of cancer in any mammal.
Now, a new study from the University of Chicago published in Cell Reports reveals the elephant’s genetic secret and it could inspire new anti-cancer strategies in humans.
Cancer is ultimately a disease of one of two things: old age or having lots of cells. Any cell in the body can become cancerous with the right set of bad mutations to the DNA.
That should mean that elephants — the world’s largest living land animal — would be among the highest risk for cancer with over 100 times more cells than a human. Instead, it’s estimated less than five per cent of elephants die from cancer.
“We see in both dogs and humans and various other species that taller individuals have a higher risk of cancer than shorter individuals within that same species,” said Manny Vazquez, the lead author on this study from the department of human genetics at the University of Chicago.
“If this is a basic mechanism of cancer and having more cells leads to higher risk of cancer and living longer leads to a higher risk of cancer, then this should hold across species. In other words, an elephant should have a higher risk of cancer than the hyrax,” said Vazquez.
Yet elephants don’t have more cancer than a hyrax (basically, an oversized guinea pig and the closest living relative to the elephant).
For most mammals, the frequency of cancer ranges from 1 to 10 per cent of the population (way lower than humans because other mammals die of predation or other diseases) and elephants are on the low end of that number.
Elephants have an active cancer-killing gene
The researchers from the University of Chicago looked at the genes present in elephants and compared them to other living relatives and found one surprising gene called LIF6.
This gene is especially good at causing cells that have DNA damage to kill themselves in a process called apoptosis.
LIF6 has a very unusual history because all animals have these genes and sometimes even have multiple copies of these genes. But in most other species they don’t work. They are part of the unusable portion of the DNA—effectively dead genes.
But the researchers found that the elephants have a working copy of this otherwise dead gene that makes any pre-cancerous cells kill themselves before they have a chance to become a tumour.
A freak accident of evolution
The researchers postulate that somewhere in a manatee ancestor lineage there was an accident in the DNA where the switch that usually turns on one gene all of a sudden moved to the section of the genome with the otherwise unusable LIF6.
It was an incredibly fortuitous genomic accident that this little switch, called a p53 element, all of a sudden found itself sitting right beside and controlling LIF6.
These kinds of events where DNA moves around the genome are surprisingly common, usually with no consequence. In this case, the result was that the elephant cells were much more sensitive to the presence of DNA damage.
So now, with a working LIF6 under a p53 switch, the elephant cells can avoid cancer that much better than most mammals.
What does this mean for cancer in humans?
In the end, cancer is a disease of damaged DNA. If animals have figured out a way to avoid damage or avoid the consequences of damage, those strategies could work for humans.
The LIF-like genes that reduce the risk of elephants getting cancer are present in humans, but they aren’t functional in our genome. This opens the door to potential new gene therapies or other methods to treat and prevent cancer.
Unfortunately, we can’t merely add the active LIF6 gene from elephants, even though it may work in human cells, since it’s tough to introduce new DNA into human cells.
But whether it’s whales or elephants or any of the other species on the planet that have almost no instances of cancer, we know that we must share some of that DNA and there may be a way to eventually tap into that for us too.