If you want to be a good science communicator, you’ve gotta know how to hook people.

That includes crafting a  title that can entice people to learn about a subject that can be technical. But sometimes though, science does all the hard work for you.

Elephants’ giant hot testicles might be the reason they get less cancer?? Yes, that’s a real headline based on a real scientific idea called the “hot testicle hypothesis.” See, thanks to some super-protective genes, elephants are really good at not getting cancer. In fact, research suggests that elephants are up to five times less likely  to die of cancer than humans.

But this hypothesis posits that these genes didn’t originally evolve to fight cancer at all. Elephants may be special in  this way for another reason, and it has to do with their giant, hot testicles. [ INTRO JINGLE ] Our story begins in the elephant genome. Specifically, a gene called TP53, which controls the development of molecules called…p53 proteins.

Super original, I know. But these proteins are also called the “guardians of the genome”, because they protect against harmful mutations that pop up during a cell’s life cycle. In order to replicate, a cell also needs to duplicate the DNA inside of it.

But that duplication process  is never 100% perfect. You basically get a few typos in the new DNA. Or in other words, a few mutations.

So p53 proteins have the very important job to kick off the process of DNA repair. To edit as many of those mutations as possible. And if that process fails, the p53 proteins can also activate a cell’s self-destruct mechanism, stopping the mutation from spreading any further, and preventing the cell from harming the rest of your body.

This makes p53 proteins excellent at fighting cancers. But not just in elephants. Lots of other animals have these proteins, as well as the TP53 gene that codes for them.

Including you! In fact, humans with a mutated version of TP53… a condition called Li-Fraumeni syndrome… have a 70% chance of getting some kind of cancer over  the course of their lives! But here’s where we’re different from elephants: The human genome has a  single copy of the TP53 gene, like nearly every other species.

But elephants have 20 copies. And they’re all slightly different, which means they can make a bunch of different versions of p53 proteins with various different effects! It’s this suite of tumor-fighting proteins that gives elephants extraordinary defenses against cancer.

But exactly why elephants evolved to have such a suite isn’t totally clear. Part of the answer might be their size. Elephants are really big, and a bigger body has more cells.

More cells means more cell division. And every time a cell divides, it’s an opportunity for something to go cancerously wrong. Elephants are also long-lived, which means even more cell divisions during their lifetime.

This means they might naturally be at higher risk for developing cancer. So over time, evolution found a way to compensate by giving them extra copies  of a cancer-fighting gene. But whales are also gigantic and long-lived, and they don’t have multitudes of p53 proteins.

Instead, there is some evidence that they evolved their own unique adaptations for fending off cancer, which means they don’t have  to rely as much on p53 So maybe elephants evolved these cancer defenses simply because their size and  longevity put them at risk. But there’s another hypothesis: Maybe elephants originally evolved these proteins for a completely different purpose… to protect their extremely hot testicles. But before I explain that sentence, we’re gonna do an ad, so, real quick Thanks to Incogni for supporting this SciShow video!

Incogni’s mission is to help you avoid cybercrime and personal privacy breaches. Data brokers collect and sell personal information like Social Security numbers  and login credentials, putting you at higher risk of identity theft.   So Incogni reaches out to  data brokers on your behalf a nd requests that they remove your personal data. With their Family & Friends plan, you can let four additional members benefit from the exact same service you do.

You can try it for 30 days and get a full refund if you aren’t happy with the service. To take your personal data back and get 60% off an annual Incogni plan, use the code SciShow at http://incogni.com/scishow or click the link in the description. Testicles obviously, are where the body produces sperm cells, and this process requires  temperatures to be just right.

If things get too hot, the sperm end up with damaged DNA. And damaged DNA makes it really hard for sperm to do its job of… helping to create a fully-functional animal. Most mammals have an internal body temperature that’s too high for sperm production, and they get around that by dangling the testicles in a scrotum.

Down there, the testicles don’t  just get some cooling airflow. The scrotum also has a special  network of blood vessels where one half of them… the veins… can siphon away heat from the other. The arteries.

It’s a process known as countercurrent exchange. And it’s happening in some of you right now So all together, a typical human body has an internal temperature around 37 degrees Celsius. Meanwhile, if it’s also got some  scrotum-based sperm-factories, they’re hovering around a cool 34 degrees.

But elephants don’t have a scrotum. Their testicles are located deep inside their bodies, near their kidneys. So they can’t just hang them  out to cool like humans do.

But also, elephants can  run even hotter than we do. Their body temperature tends to hover around 36 to 37 degrees. But on a hot day… which is most days in their tropical homes… they can get into the 40s.

That means their testicles are constantly in danger of overheating. Now, elephants are not the only mammals with internal testicles, and therefore in need of  some special cooling system. For example, whales have a network of  heat-shedding blood vessels that operates similar to our  own scrotal cooling systems.

And hyraxes… which are close cousins to elephants, despite not looking like them at all… have simple physics on their side. It’s the inside of a mammal’s body that generates heat, and the skin that dumps all that heat into the outside world. A small animal like a hyrax has lots of skin area compared to their size, so they shed heat pretty quickly.

Meanwhile, an elephant is not small, it’s huge, with way more internal volume compared to its surface area. So they’re much better at  generating heat than shedding it. Which brings us back to the hot testicles problem.

What are they gonna do? Enter, the “guardians of the genome.” Those p53 proteins… which repair genetic mutations and destroy malfunctioning cells during cell division… might be excellent tools for safeguarding sperm production in an environment where the  temperature is too high. And with this in mind, back in 2023 one researcher proposed the “hot testicle hypothesis”: the elephants’ incredible array of TP53 genes originally evolved in response to their endangered sperm.

In which case, their decreased risk of getting cancer would just be a happy side-effect of increased protection for their hot testicles. Of course, the reason could ultimately be a mix of both these things. It doesn’t have to be just the fact that elephants have a lot of cells that divide over the course of a very long life, or just the fact that they need a way to keep their sperm in working order.

Research into elephant evolution suggests that the number of TP53 genes in their DNA expanded around the same time as other genetic changes that are associated with  having a larger body size. Bigger bodies present both a higher potential risk for cancer, and make it harder to shed excess heat. So, becoming elephant-sized might have created problems  in the cancer department and the sperm department at the same time.

And the evolution of a fleet  of tumor-suppressing proteins might have been a solution for both problems. Two birds, one stone. Or two birds, many copies of tp53 But what does this mean for me, for us? some research has already found that the elephant versions of p53 proteins are capable of combating cancerous cells in the tissues of other species, including dogs and humans!

So who knows? Someday, we might be a step closer to living cancer-free thanks to a protein cocktail cooked up in an elephant’s toasty testes. [ OUTRO ]