Josh Schiffman, University of Utah
Kat - So we’ve heard about the importance of studying cancer from an evolutionary perspective, and looking across different species - but that still leaves our original question unanswered: why don’t elephants get cancer? Josh Schiffman, a children’s cancer doctor working at the University of Utah, has found out - publishing his findings last month in the Journal of the American Medical Association - and it all boils down to an important protector gene called p53.
Josh - Elephants, when you look at their genome, seem to have evolved extra copies of a gene called p53. P53 is known as the guardian of the genome. It’s one of the most important genes in our body. It’s a superhero of the genome. It actually works hard to prevent cancer. It has two main functions: one is to stop our cells from dividing so they can be fixed and all of the mutations repaired. If the cell is not able to be fixed then p53 helps coordinate the death and destruction of the cell. In fact, some of the families that we care for back in Utah have something called Li-Fraumeni syndrome actually, a hereditary risk for cancer based on p53 mutation. If they don’t have p53, they go on to develop cancer at very high rates, 80 to 90 per cent lifetime risk of cancer, many cancers at a young age, multiple cancers over the course of their lifetime. Wouldn’t it be wonderful if we could try to figure out if the extra copies of p53 in elephants are what's protecting them from cancer? What if we could somehow get some elephant blood and compare the elephant blood to the Li-Fraumeni blood and look to see if we can understand why don’t elephants get cancer.
Kat - How on earth do you go about getting hold of elephant blood?
Josh - Several weeks later, I was back home visiting Utah’s Hogle Zoo where they have three African elephants. I was watching the elephant show with my children when they explained during the course of this elephant display that elephants have large ears. They have large ears because they have large veins in the back of their ears to circulate their blood and to keep them cool in the African heat. They also went on to explain that once a week at the zoo, they draw blood from these veins in the African elephant ears and they draw the blood to make sure that the elephants are healthy and their hormones are in balance. When I heard that, I said, “I've got to talk to this elephant keeper.”
So immediately, after the elephant show, I went right up. I introduced myself. I explained that I'm a paediatric oncologist. I explained about Li-Fraumeni syndrome. I explained about Peto’s Paradox and I asked a question. At which point, the elephant keeper said, “Go ahead. We love questions. Please ask a question. What's your question?” I said, “My question is, how can I get me some of that elephant blood?” Fortunately, the elephant keeper didn’t call security but rather explained that there was an ethical review process and a scientific review board at the zoo. And if I filled out all the paper work, it was possible to get some elephant blood at the same time they were drawing it for their own reasons at the zoo.
It took about two and a half months of paper work, but since that time, once a week, my clinical study coordinators, instead of drawing blood from our patients with Li-Fraumeni syndrome, actually go down to the zoo which is located only 15 minutes away from our laboratory, get the blood, rush it back to the laboratory where we’ve done the experiments and we think we figured out why elephants don’t get cancer.
Kat - So, what is the answer? What have you found when you compare the cells in the elephant’s blood to the cells in your patients or to normal human cells?
Josh - We take that elephant blood, we take the blood from the patients, and from healthy humans, and we bombard them with radiation to cause DNA damage. We look and we see how did the elephant cells respond to that DNA damage - which obviously, in normal situations would lead to cancer - and how do human cells respond to that? What we found surprised us. What we found was that the elephant cells didn’t actually stop the cells from dividing or repaired the DNA damage any faster than the human cells like we were expecting. But instead, what we saw is that they had increased cell death. The majority of all of the elephant cells underwent cell death suicide. They underwent apoptosis. It’s as if the elephant has said over evolutionary time, “Listen. It’s so important that we don’t develop cancer. We can't take any chances. If we stop the cell from dividing and we try to repair it, we might make a mistake and we might let a few of these mutations go on by and turn into cancer. But if we just kill the cell and get it over with then there's no way that cell can go on and cause cancer. We’re elephants - we have plenty more cells where that came from. We’ll just start over.” And now, we’re trying to figure out a way to use that information to help the children and families who develop cancer to make sure that they could live a long and healthy life.
Kat - So that’s elephants. What do some of the other animals in the zoo maybe have inside that could help us understand human cancers?
Josh - Absolutely. That’s an excellent question. One of the things that we’re most excited about in the lab and also, when we’re talking with patients is the field of comparative oncology. We’re learning that all animals develop cancer. Some more than others - some are resistant like the elephants, whales also turns out are resistant. But there are other animals that are more likely to get cancer. So for instance, dogs develop cancer at 11 times the rate of people. Now, we never give cancer to dogs in the laboratory, but once they develop their cancer, we’re able to look and see what is it about the dog cancer that's similar to human cancer or paediatric cancer so we can see what's in common and then target those genes.
Kat - Josh Schiffman, from the University of Utah.