Scientists believe they may be able to explain elephants’ mysteriously low cancer rates, in findings that could provide some intriguing clues for preventing cancer in humans.
Elephants should have high rates of cancer, because they have huge numbers of cells and live a long time – so it has long puzzled researchers that their rates of the disease are so low.
A new study published in the Journal of the American Medical Association reveals that elephants have at least 20 copies of p53, a gene known as the ‘guardian of the genome’ because of its cancer-preventing properties.
Humans only have a single copy of p53, and mutations in the gene, either inherited or occurring spontaneously in the body’s cells, are a major cause of cancer.
The research was led by US scientists at the Arizona State University and the University of Utah, one of whom also has an appointment at The Institute of Cancer Research, London.
In an accompanying commentary, scientists at the ICR said the research provided a plausible explanation for the famous Peto’s Paradox – that bigger animals with more cells don’t necessarily have higher cancer rates.
Elephants have many more cells than humans, which should provide extra opportunities for mutations to arise – but the extra copies of p53 may continue to protect cells from the effects of potentially cancer-causing mutations even if the original copy has become mutated.
The study began through a chance visit to a US circus – where one researcher learned how elephants’ blood was taken as part of their routine care.
The researchers took blood samples from African and Asian elephants and decoded their DNA sequence, revealing that over the course of evolution elephants have acquired lots of extra copies of p53.
Although present in both African and Asian elephants, the extra copies were not present in DNA from their closest living species, the hyrax – suggesting they evolved 6–60 million years ago when the species diverged from a common ancestor.
In painstaking laboratory experiments on elephant cells the researchers proved that damaging DNA initiated cell death at a higher rate than in human cells – indicating that elephants are more effective than humans at preventing cells with potentially cancerous mutations from dividing.
Scientists also analysed cause-of-death data from 36 different species of mammal, from the striped grass mouse to the elephant, to investigate whether large, long-lived mammals, like humans, are more susceptible to cancer.
They found no link between risk of death from cancer and body mass – adding more evidence that larger, long-lived species have evolved effective ways to avoid cancer.
Less than 5% of elephants appeared to develop cancer – compared with 11–25% of humans.
Study co-leader Dr Carlo Maley, Associate Professor at Arizona State University and Associate Director of the Centre for Evolution and Cancer at the ICR, said: “Elephants have between a hundred and a thousand times more cells than humans – and yet they have a much lower cancer rate.
“Our research found that one of the reasons for this resistance to cancer may be that at some point in their evolutionary history, elephants have made extra copies of a gene that prevents tumours from forming. The findings give us some interesting routes to explore in bolstering our own defences against cancer. This is also the first study to conclusively provide that Peto’s Paradox is true – that larger animals with longer lifespans often get much less cancer than you would expect.”
Professor Mel Greaves, Director of the Centre for Evolution and Cancer at the ICR – and lead author of the accompanying commentary – said: “The new research provides a plausible answer to one of the most celebrated riddles in evolutionary biology – why some big animals with lots of cells still manage to have quite low rates of cancer.
“It is not immediately clear what lessons there are from this elephant tale for risk of cancer in humans. The main impact of this remarkable story is to bring into focus the question of why we are so uniquely predisposed to cancer for our size and lifespan – and what we can do to change this.”
Image credit: 'photo from Unsplash (2198)' by Du Truong, Flickr, CC BY 2.0. Home page image credit: 'Mother elephant with twins in Amboseli National Park, Kenya, East Africa' by Diana Robinson, Flickr, CC BY-ND 2.0.