How do elephants keep cancer at bay?

The majestic elephant is unusually resistant to cancer, a phenomenon that has puzzled scientists for decades. The answer may lie in its genes.

Logically, elephants should be developing cancers at 100 times the rate humans do because elephants have 100 times more cells. © Paul Souders/Corbis

Elephants are magnificent beasts, fabled for their cognitive abilities, which are thought to be on par with primates, dolphins and whales. What you might not know is that elephants are unusually resistant to cancer, and scientists have been trying to figure out why for decades.

A study conducted by researchers at the University of Utah, Arizona State University and the Huntsman Cancer Institute may have just figured it out. Their paper was published online this week in the Journal of the American Medical Association.

The reason that elephants may be able to fight cancer more effectively is that they have 38 additional gene variants, or alleles, that contain a protein called p53, well known for tumour suppression. Humans, in comparison, only have two alleles that contain p53.

Elephants also seem to have a more efficient mechanism for killing damaged cells that could become cancerous. An elephant cell has twice the damaged-cell-destroying activity that is found in a healthy human cell, and five times more than is found in humans with Li-Fraumeni Syndrome, which is indicated by only one healthy copy of p53 and a lifetime cancer risk of over 90 percent.

"Nature has already figured out how to prevent cancer. It's up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people," said co-senior author Joshua Schiffman, pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children's Hospital.

The study was conducted over several years, in collaboration with Utah's Hogle Zoo and Ringling Bros Center for Elephant Conservation. The team examined a large database of elephant deaths, and determined that elephants have a cancer mortality rate of less than five percent. Humans, by comparison, have a cancer mortality rate of 11 percent to 25 percent.

This is even more curious than it sounds. For years, scientists have thought elephants ought to be more likely to get cancer than humans. This is because elephants have 100 times more cells than humans do; which, logically, meant that they should be 100 times more likely to develop a cancerous cell over the course of their lifespan.

To figure out why, the research team carefully pored over the elephant genome. There, they found 40 genes that contained p53. Of these 40 genes, 38 were found to be retrogenes, or modified copies of genes that have evolved over time.

Elephants have a long lifespan in the wild, typically living up to 60-70 years. © DLILLC/Corbis

"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," Schiffman said. "We think that making more p53 is nature's way of keeping this species alive."

To test whether the p53 in these genes is keeping the cancer at bay, the team subjected white blood cells extracted from the elephants during wellness checks to cancer-triggering treatments that damage the DNA. These cells reacted with a response that is characteristic of p53 mediation; that is, they died. The comparative results when healthy and Li-Fraumeni human cells were subjected to the same treatment seemed to indicate that p53 helps protect elephants from cancer.

"It's as if the elephants said, 'It's so important that we don't get cancer, we're going to kill this cell and start over fresh,'" Schiffman said. "If you kill the damaged cell, it's gone, and it can't turn into cancer. This may be more effective of an approach to cancer prevention than trying to stop a mutated cell from dividing and not being able to completely repair itself."

While this study strongly indicates that p53 is directly involved in elephant cancer prevention, further research is required for confirmation.