'Zombie gene' protects elephants from cancer

Approximately 17 percent of people worldwide die of cancer. The figure for elephants is only five percent, although on average they live to about the same age as humans - just under 70 years.

This is all the more surprising because the number of cells that can potentially turn into cancer is much higher in elephants than in humans - about a hundred times as many.

A team led by an expert in human genetics, Vincent Lynch, who teaches at the University of Chicago and researchers from the University of Utah suspect it might have something to do with the tumour suppression gene p53.

This gene is present in humans and in almost all mammals in one copy. Its specialty is to recognise damaged DNA and drive it into death, also called autophagy (meaning: "self digestion"). It functions like the body's garbage disposal system. 

Read more: Medicine Nobel for Ohsumi: How cells digest themselves

Elephants have more of these genes than we do

To the amazement of the researchers, elephants have not only one, but 20 copies of the p53 gene in their genetic make-up. As a result, the cells react much more sensitively to damage in the genome and initiate cell death earlier. If cells with damaged DNA are not eaten by the immune system in time, they can develop into tumour cells.

The breakthrough for the researchers came with another gene, however. "Genes duplicate all the time," says Lynch. "Sometimes they make mistakes, producing non-functional versions known as pseudogenes."

While looking into p53, the researchers found a pseudogene, called leukemia inhibition factor 6 (LIF6). Incredibly, unlike in humans, this pseudogene had suddenly become functional again in the elephant. In other words, it had practically come back from the dead.

Awakened zombie gene destroys the energy supply of the sick cell

And it turned out that LIF6 played an important role in the removal of damaged cells: it perforated the mitochondria - the power stations of the cells - and led to the cells dying.

"Hence, zombie. This dead gene came back to life. When it gets turned on by damaged DNA, it kills that cell, quickly," Lynch explains. "This is beneficial, because it acts in response to genetic mistakes, errors made, when the DNA is being repaired. Getting rid of that cell can prevent a subsequent cancer." The researchers published their study inCell Reports on August 14, 2018.

The LIF6 gene has also been active in elephants for quite some time. It seems to have been present in the ancestors of today's elephants, the Hyrax, 25 to 30 million years ago, which at that time were barely larger than marmots. It is possible that the suppression of cancer is also partly responsible for the large size of elephants.

Will this gene revive in humans?

Large animals have many more cells and thus cell divisions than small animals. Therefore, the researchers assume that they also need a very effective mechanism to suppress or remove tumour cells.

Now Lynch and his colleagues want to try to use the elephant strategy in human cancer medicine. "Maybe we can find ways of developing drugs that mimic the behaviors of the elephant's LIF6 or of getting cancerous cells to turn on their existing zompbie copies of the LIF gene," the human geneticist said.