For many years, Dr. Joshua D. Schiffman, a researcher at the Huntsman Cancer Institute at the University of Utah, drove past Utah’s Hogle Zoo on his way to and from work every single day. But he had no idea that animals inside, elephants to be precise, might provide the answer to a question his research had been trying to answer: Who gets cancer and why?
In his new study, published Thursday in the journal JAMA, Schiffman and colleagues argue that their recently gained insight into why elephants so rarely die of cancer could pave the way to a better understanding of the disease in humans, and possibly even spur research into how to combat the disease in the future.
First, a little background. Humans have two copies of every gene. We inherit one from our mom and one from our dad, and each gene has a different job. One of these genes is called TP53. And TP53, as Schiffman and other scientists describe it, is the so-called “Guardian of the Genome.” That’s because the gene plays an important role in protecting us from cancer by encoding for the protein p53, which is a tumor suppressor.
If we get any mutations in our DNA, which can happen spontaneously, TP53 steps in and stops that mutated cell from dividing and then tries to fix it. If it can’t do that, then TP53 helps coordinate cell death, which also lowers cancer risk. Over half of all human cancers, according to Schiffman, have a dysfunctional TP53 which means mutated cells keep dividing.
So where do elephants come in?
Three years ago, Schiffman was listening to a talk by Carlo Maley, an associate professor at the School of Life Sciences, Arizona State University, who was explaining something called Peto’s Paradox. The paradox is this: Logical thinking would suggest that since every cell in the body has an equal chance of turning into cancer, the more cells you have, and they longer time they have to divide, the greater the risk for cancer. So it would make sense that elephants, which are much larger than humans and live 60 to 70 years, would die of cancer pretty regularly. But the opposite is true. Elephants hardly ever develop cancer. Why? Maley and his colleagues suggested elephants may have more copies of the TP53 gene.
After the meeting, Schiffman suggested to Maley that they study how elephant blood cells respond in a lab setting compared to human cells. But neither man knew how they would obtain it. Thankfully, only three weeks later, Schiffman visited Utah’s Hogle Zoo with his family, and while admiring the elephants, a zoo keeper happened to mention that once a week the zoo draws blood from its elephants to make sure they are healthy. Bingo.
Schiffman and the study co-authors (which include Maley) were able to obtain blood from African elephants at Utah’s Hogle Zoo as well as blood from Asian elephants with Ringling Bros and Barnum & Bailey circus (the head veterinarian heard about the study and offered to help). Ringling Bros also provided funding.