Being an elephant is risky business. I'm not talking about poaching, habitat loss, or fighting with males in musth—I'm talking about the simple fact of living. Every time an elephant cell divides, it runs the risk of going haywire and developing into an out-of-control tumor. Since elephants have 100 times the number of cells that human beings do, they should have 100 times the risk of getting cancer. That's a lot of mistakes waiting to happen.
In reality, given their size and prodigious lifespans, elephants have one of the lowest cancer mortality rates in the animal kingdom: 4.8 percent, compared to a range of 11 to 25 percent for humans. How can this be?
Scientists at the Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children’s Hospital helped figure out the answer, published Thursday in the Journal of the American Medical Association. Another team, made up of University of Chicago researchers and their colleagues, posted a related paper this week. As it turns out, elephants have developed some ingenious safeguards against developing cancer. Understanding their cellular protections might help us learn more about how to suppress cancer in humans.
There are countless ways that cell division can go wrong. That’s why—as we learned from the winners of this week’s Chemistry Nobel Prize—your cells come equipped with a host of repair enzymes whose sole purpose is to prevent or repair genetic mistakes. These cellular copy editors proofread each strand of newly divided DNA, identifying errors and repairing the faulty bits to ensure that your DNA stays fresh and clean and functional. In humans, just one of those enzymes can fix a thousand different kinds of errors. Not too shabby!
But elephants have one-upped us. For the JAMA study, researchers first compared cancer rates across the animal kingdom to find out that elephants were remarkably cancer-free given their size. (Other animals fared well, too. For comparison, rock hyraxes have a 1 percent cancer mortality rate, African wild dogs have an 8 percent rate, and lions have a 2 percent rate.) Then, they scoured the elephant genome to find out why.
The answer resided in a key tumor-suppressing protein called p53, known as the "guardian of the genome." Compared to humans, elephants had far more genes for this protein: 38 versions versus just two. The result was a superior genetic safety net for correcting errors and ensuring that damaged, tumor-prone cells get nipped in the bud. "The enormous mass, extended life-span, and reproductive advantage of older elephants would have selected for an efficient and fail-safe method for cancer suppression," the authors write.
To see how the genes suppressed tumors, researchers teamed up with Utah’s Hogle Zoo and Ringling Bros. Center for Elephant Conservation to isolate elephant cells and subject them to cancer triggers. (No elephants were harmed; this was all during routine wellness checks.) When they compared elephant cells to human cells, they found something amazing: The damaged cells in elephants were far more likely to resort to cell suicide—known as apoptosis—to avoid propagating errors in their descendants. It was a brutally efficient, even ruthless, system for protecting the organism at all costs.
To behold an elephant in the wild is to be humbled before majesty. Yet perhaps it isn't just their tremendous size that contributes to this sense of smallness. It's also all the things we can't see: from their advanced memories, to their long lifespans, to their individual cells, so altruistic that they are willing to die for the benefit of the many. From these cancer-resistant Methuselahs, we humans have much to learn.