Elephants Stomp Cancer, But Humans Unlikely to Benefit

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elephant-1389977-640x480Some unfounded scientific beliefs tend to persist in popular culture for years, even decades, despite being sufficiently debunked by reputable sources.

If you were to watch CBS on Tuesday nights, you'd see a whole TV series (there's a movie, too) based on the thoroughly-debunked idea that humans only use 10 percent of their brain. Humans actually use all of their brain.

Another popular misconception is that sharks, or alligators, or some other animal, doesn't get cancer. However, the truth is that all animals get cancer, but according to a new study elephants may actually have an extra guardian against the disease that other animals do not.

A recent publication in JAMA reports that these giant animals get cancer at surprisingly low rates. The researchers analyzed necropsy results from 644 zoo elephants and found that only five percent of them died from cancer. In contrast, the estimates of human cancer mortality are between 11 and 25 percent.

Looking more closely, there are two conflicting ideas at play here.

One is the long-held belief that elephants and other large animals are more susceptible to cancer, because more cells means more opportunities for mutations that cause cancer to develop. On the other hand, some have argued that these larger animals should have evolved extra mechanisms for dealing with more cells. This is called the Peto paradox.

For elephants, the extra protection comes in the form of a gene called TP53 which codes for the tumor-suppressing protein p53. This protein is a very significant and historic protein.

We can trace its evolution back to sea anemone, and some scientists believe it predates cancer. In the cell cycle it is responsible (along with some other proteins) for making sure that a cell has not incurred too much DNA damage. If the cell has, p53 signals one of two events: either a stopping of the cell cycle to ensure the DNA can be repaired, or initiating programmed cell death.

A cell that has an inflective, or mutated, version of p53 will lose this important check on its genome and is prone to grow into a tumor. Some estimates say that more than half of human tumors have a defective TP53 gene, and for people who inherit just one defective copy (a condition called Li -Fraumeni syndrome) have a 90 percent chance of having cancer during their lifetime. For its role in normal cell behavior, the protein has been dubbed "The Guardian of The Genome."

Humans have one TP53 gene (2 alleles). Elephants? The researchers found they have 20 copies of the gene, or 40 alleles, in their genome. Furthermore, they found the proteins are active in the elephants. This means, that unlike humans, elephants have a substantial backup system if one of the alleles is mutated.

So what does this mean for cancer treatment in humans? Probably nothing.

We have known about the significance of p53 in humans for several decades. In fact, we are already close to treating patients with a gene therapy that would replace the mutated p53 with a functional one. Other therapies using small molecules are also being developed that target reactivation of a functional version of p53.

All this study really does is further validate our understanding of p53, while highlighting the importance of moving forward with therapies that target this mutation.