Despite the ridiculous rumor, sharks do get cancer. Elephants, though, rarely do, and that’s a weird phenomenon that scientists have really struggled to explain. But they may have finally cracked it: According to a new study, it’s all in the genes. Well, one gene, and their 20 copies of it.
With a self-explanatory name, tumor suppressor, this helps get rid of damaged cells that could become cancerous. Humans only have one copy, so researchers think that owning extras could be behind the remarkable ability of these pachyderms to resist cancer. And later on down the line, these intriguing findings may help us in our own fight against cancer (but let's not turn them into supplements, please?).
But let’s rewind a little bit first. Why is it strange that elephants seem to have a reduced burden of cancer? Well, cancer, as you probably know, is a disease that results from cell division gone haywire. Elephants are obviously big animals, so you would logically assume that more cells equals a greater risk of something going wrong. Cell division isn’t error-proof, and mistakes that could lead to mutation are often made if not dealt with appropriately.
In steps the Peto paradox: We don’t actually see increased cancer incidence in larger species. So how are the big’uns staving off the disease? A study by the University of Utah and Arizona State University decided to find out.
They began by seeking to confirm the absence of a positive relationship between body size and cancer incidence, which involved scouring through 14 years of necropsy data in order to calculate tumor rates for 36 species of mammal, spanning six orders of magnitude in size. As expected, cancer mortality didn’t increase with body size, and elephants were estimated to only have a 4.8% cancer mortality rate; in humans it’s up to 25%.
Next, they scoured the elephant genome in search of clues, and they found something pretty remarkable. Unlike humans that only own the one, elephants have 20 copies, and therefore 40 forms, or alleles (remember chromosomes are in pairs), of a gene called TP53 which codes for a protein called p53. TP53 is what’s known as a tumor suppressor gene: these cellular safeguards function to prevent inappropriate cell division and kill off cells to keep things balanced.
When the researchers examined these alleles further, they found that 38 of them seemed to be modified duplicates of the original that have appeared throughout their evolutionary history. To find out if it’s this extra genetic baggage that’s helping the animals resist cancer, the team exposed cells isolated from humans and elephants to DNA-damaging radiation and observed the effects.
Compared to cells obtained from healthy humans, those from elephants committed suicide twice as frequently in response to the damage, which was found to be driven by p53. And when they compared them to cells isolated from patients with Li-Fraumeni syndrome, a disorder in which a missing working copy of TP53 results in a dramatically increased cancer risk, the suicide rate was found to be five times greater. The results are published in JAMA.
“By all logical reasoning, elephants should be developing a tremendous amount of cancer, and in fact, should be extinct by now due to such a high risk for cancer,” co-senior author Joshua Schiffman said in a statement. “We think that making more p53 is nature’s way of keeping this species alive.”
But before we start giving p53 all the praise, it’s likely that there are other factors at play. For example, an accompanying editorial points out that elephants’ sluggish metabolic rate is likely coupled with low rates of cell division, which could also contribute to the reduced risk. More research is needed, but it’s an interesting start nonetheless.