Why Don’t Elephants Get Cancer?

This collared elephant, photographed in Botswana’s Chobe National Park, has a large breast mass – most likely mastitis, an inflammation or abscess of breast tissue often caused by blocked milk ducts. Although harmful bacteria may be present in her milk, nursing might relieve her mastitis symptoms. I don’t know the outcome for this mother, but it’s highly unlikely her breast mass was cancer related. Why? For elephants, the overall lifetime chance of dying from cancer is less than 5%. The mortality rate for humans is 20%.

Why should a mammal with 100 times more cells than we do have such a low cancer rate? Oddly enough, there is little relationship between cancer rates and body size of mammals – even though the cells of elephants will divide many more times throughout their lifetimes than ours will, simply because they have so many more of them. Elephants ought to have a greater quantity of random mutations predisposing them to cancer than we do.  But they don’t.

Studies using the autopsy reports of 36 mammals at the San Diego Zoo (ranging in size from mice to elephants) and the database of 644 captive Asian and African elephants confirmed that the relationship of cancer to body size did not matter. But those studies also found something highly unusual in the blood cells of elephants. African elephants have twenty TP53 genes (and therefore 40 alleles of that gene); Asian elephants have fifteen. TP53 is sometimes called the “guardian of the genome” for its ability to create a protein that suppresses tumors.

Humans have just one gene and two alleles of TP53. (An allele is basically a copy of a specific gene at the same position on a chromosome.   Chromosomes are located in the nucleus of cell and contain DNA, the genetic instructions that make mice mice and elephants elephants.) In humans, one allele is inherited from each parent – both crucial to prevent cancer. Having only one allele causes Li-Fraumeni syndrome, which is characterized by a more than 90% lifetime risk of cancer.

TP53 codes for the protein p53, a crucial tumor suppressor that stops cells with damaged DNA from dividing. TP53 goes into action when cells suffer DNA damage, churning out copies of its associated p53 protein and either repairing the damage or killing off the cell. But instead of repairing DNA damage, compromised elephant cells have evolved to always commit suicide rather than pass on potentially harmful mutations acquired in trying to repair itself. Once the damaged cell is dead and gone, it can’t turn into cancer.

Most of the elephant TP53 genes are retrogenes, which evolved into their genome at a later time than the original gene. Two factors explain why elephants developed more TP53 genes: a long gestation period (22 months) and a reproductive lifespan that lasts well into their 50s (elephants live 60+ years in the wild). Unlike mice, elephants don’t reproduce often – thus they pass along the extra copies of TP53 even in old age, and their progeny benefit.

In contrast, humans reproduce only into to middle age and most of our cancers are diseases of aging. We are the legacy of short-lived ancestors (compared to modern life expectations), who mostly didn’t get cancer throughout their years of reproduction and raising children. As modern humans age, our chances of contracting cancer become greater since we have less suppressing genes than elephants do. And any cancer-fighting mutations within our genes don’t get passed along in our older years.

Do elephant genes hold the secret of a cure for cancer? Researchers are investigating. Meanwhile, elephants are being slaughtered for their ivory, for short-term gains. What if elephants were our saviors, our partners in longer, healthier lives? What if elephants were worth much more alive than dead? #worthmorealive Spread the word.