Can you think of an animal that’s larger than a human, lives about as long as we do, and doesn’t get cancer nearly as often? Yes, it’s elephants! Only 5 percent of elephants die of cancer, compared to about 25 percent of humans. We don’t know why.
Cancer is caused by mutations in the DNA, the blueprint of life in each of our cells. When the cells accumulate enough of these mutations, they can grow and spread out of control in the body, in other words: cancer. Every cell has sensors that examine the DNA, looking for mutations and correcting them. If the DNA cannot be repaired, the cells are sent off to die and be recycled via a process called apoptosis.
One of these DNA sensors is called TP53, and humans have two copies of it. African elephants have 40 copies! Asian elephants have 15 to 20 copies, suggesting that TP53 duplication occurred before the African and Asian elephant species separated about 8 million years ago. The hyrax, a relative of the elephant, has only two copies of TP53. The hyrax and elephant lineages split 54 to 65 million years ago, so elephants got the extra copies of TP53 sometime after that.
So how did elephants get all those extra copies of TP53? Most of them are copies that were made throughout evolution. TP53 is a vital tumor suppressor gene which is mutated in most human cancers. It’s called the “guardian of the genome,” because it identifies and eliminates cells with DNA damage so that they don’t cause cancer.
Scientists worked with the Hogle Zoo in Utah and the Ringling Bros. Center for Elephant Conservation to determine if the extra copies of TP53 protect elephants from cancer. During routine wellness visits, veterinarians collected white blood cells. These white blood cells were then exposed to treatments that damage DNA and cause cancer. As expected, the cells reacted to the damage by undergoing apoptosis.
People with a genetic disease called Li-Fraumeni syndrome have only one active copy of TP53, and they have a 90 percent chance of developing cancer. The researchers compared elephant cells with normal human cells and cells from patients with Li-Fraumeni Syndrome. Elephant cells were found to undergo apoptosis in response to DNA damage at twice the rate as normal human cells and at five times the rate of Li-Fraumeni cells. This suggests that the extra copies of TP53 drive elephants’ bodies to clear out cells with DNA damage more effectively, protecting them from cancer. Scientists then added elephant TP53 genes into human cells and they behaved exactly like elephant cells when exposed to DNA damage. Another study examined tissue from 60 other animals and so far, only elephants and wooly mammoths, an extinct ancestor, had extra copies of TP53.
Imagine the number of cell divisions that are required for an elephant to grow from a birth weight of 200 pounds to more than 6,000 pounds. That’s a lot of opportunities for mutations to cause cancer. You can see why elephants would have to evolve an effective way to eliminate defective cells.