Elephants have long intrigued scientists for the fact they rarely get cancer – and a new study suggests this may be linked to their testicles.
Unlike humans and most other land mammals, elephants’ testicles don’t descend outside the body. Instead, they remain high up inside, close to the kidneys.
Keeping the testicles cool is essential for good fertility – high temperatures can damage the sperm – suggesting significant adaptation in elephants given their core temperature has been recorded at upwards of 40C in the African savannah.
In addition to being very hot, elephants are also very big, which should increase their risk of cancer.
Body cells are constantly dividing, and with every division, there’s a risk of mutation that could lead to cancer. The more cells, as in larger animals, the greater the risk.
To combat mutations, the body has a specific gene, TP53, which produces the protein p53. The main role of p53 is to identify and ‘neutralise’ damaged DNA during cell division, helping combat the spread of mutations and earning it the nickname ‘Guardian of the Genome’.
Humans only have one copy of the gene. Elephants have 20.
Scientists now believe they may have developed this super-charged defence against cancer as a byproduct of their ‘hot testicles’.
The risk of DNA mutation in the sperm at higher temperatures is vastly increased, meaning to help protect their reproductive capabilities and ensure survival of their own genes – and the species – elephants have evolved with extra genes to help keep on top of any potential mutations.
‘Elephants provide us with a unique system to study the evolution of a robust defence mechanism against DNA damage and explore the intricate details of the p53 complex in our own battle against cancer and ailments like ageing,’ said author Professor Fritz Vollrath.
In humans, the risk of cancer increases with age as cells become less efficient at replicating.
Peto’s paradox
Named after renowned Oxford epidemiologist Richard Peto, the phenomenon questions why larger, longer-living animals that should be more prone to cancer, such as elephants and whales, appear resistant to it.
Writing in the journal Trends In Ecology & Evolution, he said: ‘All things considered, it appears that the elephant’s testes may experience temperatures dangerously high for mammalian sperm production, even under normal body temperatures.
‘High temperature metabolism tends to be coupled with cellular oxidative stress, which increases the probability of mutations.
‘[The hypothesis] proposes that elephants initially evolved multiple copies of TP53 not to fight cancer but to protect sperm production in testicles that were increasingly temperature challenged as the animals grew in size during their evolutionary history.’
Professor Vollrath concluded: ‘For cancer researchers, probably the most important question would focus on the mechanism by which the elephant’s various TP53 retrogenes and p53 protein isoforms are able to guard, or not, the soma [body cells]. Such studies would probably rely on genetic profiling of tissue samples and cell lines.
‘Elephants are not as easily studied as mice.’
