Elephants: Large, Long-Living and Less Prone to Cancer

Carl Zimmer in The New York Times:

In 1977, a University of Oxford statistician named Richard Peto pointed out a simple yet puzzling biological fact: We humans should have a lot more cancer than mice, but we don’t. Dr. Peto’s argument was beguilingly simple. Every time a cell divides, there’s a small chance it will gain a mutation that speeds its growth. Cells that accumulate several of these mutations may become cancerous. The bigger an animal is, the more cells it has, and the longer an animal lives, the more times its cells divide. We humans undergo about 10,000 times as many cell divisions as mice — and thus should be far more likely to get cancer. Yet humans and mice have roughly the same lifetime risk of cancer, a circumstance that has come to be known as Peto’s paradox.

…“Every baby elephant should be dropping dead of colon cancer at age 3,” said Dr. Joshua D. Schiffman, a pediatric oncologist at the Huntsman Cancer Institute at the University of Utah.

…Dr. Schiffman and his colleagues found that elephants had evolved new copies of the p53 gene. While humans have only one pair of p53 genes, the scientists identified 20 pairs in elephants. Dr. Lynch and his colleagues also found these extra genes. To trace their evolution, the researchers made a large-scale comparison of elephants to other mammal species — including extinct relatives like woolly mammoths and mastodons whose DNA remains in their fossils. The small ancestors of elephants, Dr. Lynch and his colleagues found, had only one pair of functional p53, like other mammals. But as they evolved to bigger sizes, they steadily evolved extra copies of p53. “Whatever’s going on is special to the elephant lineage,” Dr. Lynch said. To see whether these extra copies of p53 made a difference in fighting cancer, both teams ran experiments on elephant cells. Dr. Schiffman and his colleagues bombarded elephant cells with radiation and DNA-damaging chemicals, while Dr. Lynch’s team used chemicals and ultraviolet rays. In all these cases, the elephant cells responded in the same way: Instead of trying to repair the damage, they simply committed suicide.

More here. (Note: Ga, between elephants and p53, we have a chance to collaborate)