Why don't elephants get cancer?

It follows that, the bigger you are, the more cells you have and therefore the higher the likelihood of one of those cells becoming cancerous.

But if you look at progressively larger animals you don't see an increased rate of cancer. This is called Peto's Paradox after Oxford University's Richard Peto who pointed out - on a cell-by-cell basis, humans have a lower cancer risk than a mouse. So why does it happen?

The University of Chicago's Vinny Lynch has been looking at elephants for inspiration...

Vinny - So we were curious in why elephants don't get cancer and we cared about elephants because their closest living relatives is actually very, very small. It's about the size of a groundhog or a small cat or something that's called a hyrax. So, within a few million years after these things diverged, elephants ancestrally went from being very small to being huge. So because these two things are closely related to each other, we can therefore compare their genomes to see what genetic case occurred in elephants that may be associated with an increased ability to kill cancer cells or maybe to stop cells from becoming cancerous to begin with. So we basically just looked in the elephant genomes for things that might be associated with cancerous events.

Chris - Did you just go to the database and get the DNA sequences of different elephants or did you get some real elephant DNA for yourself?

Vinny - So we have real elephant DNA and we have elephant cells but it was even easier. So for 10 years or more now, the NIH and lots of other foundations around the world have been sequencing animal genomes. So the elephant genome and the hyrax genome along with many others had already been sequenced. So we were basically able to just go to this website and type in a bunch of names of the genes that we're interested in and see them pop up on the screen. So we did that for a couple of elephant genes and found some things that we thought might be associated with enhanced resistance to cancer in elephants.

Chris - Did you literally do a letter by letter comparison or were you saying, "Well, we know that there are certain mechanisms that cells use to stop cancers in their tracks. There are certain genes that cause cancer so we're going to focus our attention on both of those and see if there's a difference."

Vinny - That's exactly what we did. So cancer has been very well studied for decades now so we know that they're basically - at least in cancer biology, there's two different kinds of genes. There are genes called the oncogenes and when they're mutated, they cause cancer and there are genes that are called tumour suppressors and their job is to supress the formation of tumours. They did very well characterize about a few hundred of each kind so we just wanted them to be elephant genome and counted up how many tumour suppressors they had and how many oncogenes they had. We found that for this one special kind of tumour suppressor, they had 20 copies whereas every other animal that we looked at had one.

Chris - Are those copies all functional because one of the things that we have learned from the human genome project is that there are sort of fossilised copies of certain genes lurking in the genome. When you read for them, you can find these genes there. It doesn't mean they work though. So do these 20 copies in the elephants actually do something?

Vinny - So it looks like about half of them. So maybe 10 have signatures that they do something and then the remainder have signatures of these non-functional genes. They're called pseudo-genes because they look like genes, but they're not really genes. So I think a subset of them are actually functional.

Chris - The oncogenes: did you see any evidence that they have fewer abilities for cells to become cancerous in the first place?

Vinny - So, we didn't find that elephants had fewer oncogenes.  So that couldn't be the strategy. If you have these genes, when they get mutated, they cause cancer. One way you can reduce your risk of developing cancer is to just get rid of these genes. But elephants had just as many as everybody else. That's not entirely unusual, because these oncogenes play essential roles in animal development. So it's probably the case that, if you got rid of them, your development would be weird. So, they're probably really conserved. You can't mess with them.

Chris - So it does look like the mechanism, at least in elephants, is a big expansion of your ability to supress cancer in cells; but what about other animals? Because elephants, just because you see it in them, it doesn't prove the rule, does it? What about other close relatives of elephants, things like mammoths, or other massive animals like whales? Have you looked in those examples for instance?

Vinny - So we've looked in mammoths. Mammoths are most closely related to Asian elephants. Both mammoths and Asian elephants, for which there's also a genome data have similar numbers to African elephants. So, there seems to be this increase in the copy number of the special gene called the p53, seems to be an elephant thing. but then we did obviously figure if it's expanded in elephants, what's going on with these other things that don't seem to get cancer at the rate that they should. At least for whales, we didn't find a change in the number of this gene in whales so whales have one copy just like everybody else. We did however see that there's one lineage of bats which are very small but live a very, very long time, they may have extra copies. We haven't checked it down entirely yet. We're working on that now, but it looks like at least initially that they have one extra copy.

Chris - And rhinos, hippos, they're also pretty big. Do they also show an expansion of these p53 genes?

Vinny - So, we've looked at everything that we could find including rhinos and hippos, and they don't seem to have an expansion of these p53 genes which is probably telling us something more fundamental about evolution and that, there's more than one way to solve a problem. So elephants found this particular way to solve the problem but the other lineages that get big or live a long time like bats live a long time, whales live a long time, and rhinos, and hippos. They just found other ways to do it.