In a study by scientists from the University of Utah and Arizona State University in conjunction with Utah’s Hogle Zoo and the Ringling Bros. Center for Elephant Conservation, published last week in the Journal of the American Medical Association, scientists said elephant genes may provide a crucial clue in the fight against human cancer.
The paradox that elephants are large animals that undergo innumerable cell divisions during their decades-long lives, yet less than 5% get cancer compared with 25% in humans, has long flummoxed scientists, but researchers now think they may have an explanation — one they say could lead to new ways to protect humans from cancer one day.
Dr. Joshua Schiffman, a paediatric cancer specialist at the University of Utah who led one of the teams, began his research after hearing a lecture a few years ago about Peto’s paradox. That refers to the fact that large animals including elephants and whales, have comparatively low cancer rates even though they have many more cells than smaller species. Cancer involves uncontrolled cell growth.
The lecture speaker mentioned that elephants seemed to have extra copies of the p53 gene. Schiffman’s patients include children with incomplete p53 genes because of a condition called Li-Fraumeni syndrome, which greatly increases their chances of developing cancer. So Schiffman sought to find clues from the blood of eight elephants, Ringling Bros. circus animals and local zoo animals.
As elephants have evolved over the years, they have found a way to not get cancer. Researchers in Florida are looking at Asian elephants in particular to see what humans can learn from their genetic material.
Two teams of scientists combed through elephant DNA and found a few deviations. Elephants have extra genes that stop tumours long before they form. They have “at least 40 copies of genes that code for p53, a protein well-known for its cancer-inhibiting properties” whereas humans have only two copies – one from each parent, to fight cancer by fixing a mutated cell, keeping it from multiplying, or triggering cellular death.
In other words, these animals have around 20 times the number of cancer-fighting genes as humans. The scientists exposed elephant cells to damaging elements like radiation, ultraviolet rays, and chemicals, and most simply killed themselves off to stop the progression.
The massive animals also detect damaged cells preemptively, which they then repair or kill. “Elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous,” the study said.
Schiffman and his colleagues compared how elephant cells reacted to radiation, compared with cells from 10 healthy humans and 10 patients with Li-Fraumeni syndrome. The elephant cells self-destructed at twice the rate of healthy human cells and more than five times the rate of cells from patients with the syndrome. Cells that don’t self-repair or self-destruct when exposed to carcinogens become prone to developing cancer.
What This Could Mean for Human Treatment
“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.”
While there are other contributing factors that make humans more at risk of getting cancer, experts said, the study provides insight on treatment.
“Nature has already figured out how to prevent cancer,” Schiffman said. “It’s up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people.”
“While the research won’t lead to any immediate treatment for humans, progress against cancer can come from unexpected directions,” said Dr. Ted Gansler of the American Cancer Society. He noted that studies of eyelid and tooth development in mice led to drugs used for colon cancer, throat cancer, and several other cancers.
More than half of all human cancers are missing functional p53, another clue to its importance in suppressing cancer.