How Elephants May Help Treat Cancer

By Jane Farrell

Researchers may have found the answer to a chronically puzzling question: why do elephants rarely get cancer?

The scientists were led by researchers at Huntsman Cancer Institute (HCI) at the University of Utah and Arizona State University, and included researchers from the Ringling Bros. Center for Elephant Conservation.

According to the results, published in the Journal of the American Medical Association (JAMA), elephants have 38 additional modified copies (alleles) of a gene that encodes p53, a well-defined tumor suppressor, as compared to humans, who have only two. Further, elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous.

In isolated elephant cells, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime cancer risk in children and adults. The results suggest extra p53 could explain elephants’ enhanced resistance to cancer.

“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,” says co-senior author Joshua Schiffman, M.D., pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children’s Hospital.

According to Schiffman, elephants have long been considered a puzzle. Because they have 100 times as many cells as people, they should be 100 times more likely to have a cell slip into a cancerous state and trigger the disease over their long life span of 50 to 70 years. And yet it’s believed that elephants get cancer less often, a theory confirmed in this study. Analysis of a large database of elephant deaths estimates a cancer mortality rate of less than 5 percent compared to 11 to 25 percent in people.

In search of an explanation, the scientists combed through the African elephant genome and found at least 40 copies of genes that code for p53, a protein well known for its cancer-inhibiting properties. DNA analysis provides clues as to why elephants have so many copies, a substantial increase over the two found in humans. A substantial majority, 38 of them, are so-called retrogenes, modified duplicates that have been churned out over evolutionary time.

Schiffman’s team collaborated with Utah’s Hogle Zoo and Ringling Bros. Center for Elephant Conservation to test whether the extra gene copies may protect elephants from cancer. They extracted white blood cells from blood drawn from the animals during routine wellness checks and subjected the cells to treatments that damage DNA, a cancer trigger. In response, the cells reacted to damage with a characteristic p53-mediated response: they committed suicide.

“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,’” says Schiffman. “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.”

“Participating in the research is not only amazing but a win-win for humans and elephants,” said Eric Peterson, of Utah’s Hogle Zoo. “If elephants can hold the key to unlocking some of the mysteries of cancer, then we will see an increased awareness of the plight of elephants worldwide. What a fantastic benefit: elephants and humans living longer, better lives.”