Elephants’ Unusual Disease Resistance Could Help Humans

elephant facts

Story at-a-glance -

  • Researchers are looking to elephants and other cancer-resistant species for clues to how and why human cancers develop and how to suppress it
  • Fewer than 5 percent of elephants die from cancer, compared to up to 40 percent of humans
  • Elephants have 40 copies of TP53, a tumor suppressor gene, while humans have only two
  • TP53 also helps activate the so-called “zombie gene” in elephants, which causes cells to die when they have DNA damage

By Dr. Karen Shaw Becker

Elephants, with their large bodies and long lives, have more cells than humans by 100-fold. This large number of cells should theoretically correlate with an increased risk of cancer relative to smaller creatures, simply because the more cells there are, the greater the chances that mutations will develop.

However, there is no such correlation between body size and cancer risk, a phenomenon known as “Peto’s paradox,” where different species are concerned. Elephants are actually one of the species that’s least likely to develop cancer.

They’re so cancer-resistant that fewer than 5 percent of elephants die from cancer, compared to up to 40 percent or more of humans.1,2 Researchers are now looking to elephants and other cancer-resistant species for clues to how and why human cancers develop and, along those lines, how to suppress it.

What Makes Elephants so Resistant to Cancer?

Theoretically speaking, "Because of their body size and how many cells they have and how long they live, they [elephants] should all be developing cancer," Dr. Joshua Schiffman, professor of pediatrics at University of Utah, told CNN.3 They’re not, though, which is why Schiffman and other researchers are looking for their secrets.

One may be the TP53 gene, which acts as a tumor suppressor, activating genes to fix DNA damage or instructing irreparably damaged cells to undergo apoptosis, or cell death.4 Elephants have 40 copies of TP53 while humans have only two.

“Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53,” Schiffman and his team wrote in JAMA.5 “Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage.”

TP53 also helps activate the so-called “zombie gene,” which causes cells to die when they have DNA damage. Writing in the journal Cell Reports,6 researchers found that elephants contain numerous LIF pseudogenes, which duplicate the original but in a mutated way. One of the LIF pseudogenes is the “zombie” version, triggering the on-off switch that tells cells to die in response to DNA damage.

“These results suggest that the origin of a zombie LIF gene (a reanimated pseudogene that kills cells when expressed) may have contributed to the evolution of enhanced cancer resistance in the elephant lineage and thus the evolution [of] large body sizes and long life spans,” they explained.7

Elephants’ Cancer Resistance May Help Humans With Cancer

Beyond the zombie gene and TP53, other genes have also been associated with DNA repair in elephants that helps protect against cancerous mutations, including the FANCL, VRK2 and BCL11A genes.

Christopher Gregg, Ph.D., assistant professor in neurobiology and anatomy at the University of Utah Health, and colleagues, including Schiffman, have been looking into the noncoding regions of the genome, which were long considered to be “junk DNA” but which actually contain important switches that control genetic expression.

“We identified candidate mechanisms beyond p53 [TP53] in the elephant genome for evading cancer … The elephant results revealed noncoding sequences in the human genome that we predict may control gene activity and reduce the formation of mutations and cancer,” Gregg said in a news release.8

“This is where the field is moving as a whole," Schiffman told CNN. "If we can understand how these genomic changes are contributing to ... cancer resistance, then we'll be able to start thinking about how do we translate this to our patients?"9

Dogs Also Help Advance Human Cancer Treatment

Animals with surprisingly low rates of cancer, like elephants, may one day help researchers crack the code to tumor suppression in humans. In the meantime, dogs, which have more than 80 percent genetic similarity with humans, are also helping in the war against cancer, in large part because a dog’s tumor is indistinguishable from a human’s.10 By studying cancer in dogs, researchers can:11

  1. Understand environmental risk factors for cancer
  2. Examine genetic/familial determinants for cancer predispositions seen in some dog breeds
  3. Develop and optimize novel cancer and gene imaging systems
  4. Evaluate novel therapeutic strategies for a variety of cancers
  5. Add biological relevance to genomics data generated from microarray and other molecular techniques

The field of comparative oncology, which describes the study of naturally occurring cancers in pets as models for human cancer, is advancing in large part because tumors in dogs act similarly to those in humans. Plus, pets are exposed to many of the same environmental risk factors as their owners, and the prevalence of the disease in pets, unfortunately, means there are plenty of study opportunities.12

In the best-case scenarios, experimental treatments that prove to be successful in dogs prove to be successful in people as well, adding one more way that “man’s best friend” may end up helping their human owners. This is exactly what Ketopet Sanctuary discovered using a profound nutritional strategy to address some of the most aggressive cancers found in both dogs and humans. We documented this amazing research in our Dog Cancer Series Documentary we completed last year.

Getting back to elephants, their cancer resistance is actually not unique in the animal world. “Nature has already figured out how to prevent cancer,” Schiffman said,13 as many other species, including the naked mole rat, gray squirrels, horses, whales and certain bat species, are also remarkably cancer resistant.14

He continued, “It’s up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people.”15

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