I usually focus this blog on research in humans, but this month I was particularly intrigued by an article published online October 8 in the Journal of the American Medical Association on elephants!
Cancer occurs when a normal cell develops many genetic mutations. These mutations are either acquired as a result of mistakes that occur during cell division or over time with exposures to carcinogens. Given this, one would hypothesize that the larger the mammal and the longer it lives, the higher its risk of developing cancer. To explore this, the researchers at the City of Hope in Salt Lake City, Utah, looked at 14 years of autopsy data from animals at the San Diego Zoo, and calculated the cancers for 36 species of mammals, ranging from the striped grass mouse to the elephant.
Since the risk of cancer depends on both the number of cells in the body and the number of years over which the cells are at risk for mutations, the researchers had to take into account both the size of the animal and how long it had lived. Surprisingly, the elephants had the lowest number of tumors; the Tasmanian devil had the highest. The researchers also checked the Elephant Encyclopedia database for cancer incidence. This showed that among 644 elephant deaths the cancer incidence was only 3.11%. Even if a few cancers were missed, this is far less than the expected risk based on the number of cells they have because of their size, which is 100 times greater than humans.
Why would this be? One hypothesis is that elephants might be better able to repair the mutations their cells acquire over their lifetime. To explore this, the investigators looked at TP53, a tumor suppressor gene mutated in many different types of cancer. Humans have one copy (two alleles) of TP53, and both need to be functioning properly to keep cancer at bay. People with LiFraumeni syndrome have only one copy that works properly, which is why they have a 90% risk of getting cancer.
The analysis showed that African elephants have one copy of TP53 that is comparable to that found in other species. But the African elephants also have an additional 19 copies of what the researchers called retrogene copies of TP53. The Asian elephant DNA was also found to contain 15-20 copies of TP53 variants.
The investigators then explored whether this was relevant, asking the question: Do elephants repair DNA better than humans? They tested this by using radiation to cause damage to white blood cells (lymphocytes). Low and behold, the African elephants were twice at good at killing (apoptosis) damaged cells than humans. The data also suggested the TP53 gene acted more quickly to remove damaged cells in elephants than it did in humans. In other words, we keep our slightly damaged cells while the elephants get rid of theirs! And, in humans, it is these damaged cells that have the potential to become cancers. In an analogy, we could say that the elephants have the death penalty for any misbehaving or damaged cells, while we pardon ours and allow them to maintain their normal place in our bodies. While this would probably not be good public policy, it does seem to work for the elephants!
While this is great news for elephants, how does it help us? Clues like these are what ultimately lead us to new ways of thinking about, treating, and preventing cancers. How can we get human cells to detect and repair these mutations at the same rate? That would certainly be one way to prevent cancer. You never know what you can learn from elephants!