Science Friday - An Animal’s Size And Its Cancer Risk | Bastetodon, A 30 Million-Year-Old Apex Predator

Episode Date: March 4, 2025

A study finds that Peto’s Paradox, which states that larger animals are no more likely to get cancer than smaller ones, may not hold up. Also, a nearly complete predator skull was found in the Egyptian desert. Its lineage indicates that it was a top carnivore of the age.What Does An Animal’s Size Have To Do With Its Cancer Risk?If you throw a huge party, there’s more of a chance of problems than if you host a quiet get-together for a couple of friends. The logic is simple: Having more people around means more opportunities for chaos. Similarly, it would seem to make sense that in animals, a bigger species with more cells might have a greater chance of something going wrong with one of those cells, including mutations leading to cancer.Back in 1977, a British epidemiologist named Richard Peto observed that that didn’t seem to be true. Bigger animals didn’t seem to have a greater risk of cancer than smaller ones. That became known as Peto’s Paradox, and has been a topic of debate among cancer biologists ever since.Research published this week in the Proceedings of the National Academy of Sciences takes a new look at Peto’s Paradox using an unusual set of data—death reports from zoos around the world. Dr. Sarah Amend of Johns Hopkins Medical School joins Host Flora Lichtman to explain why, in their findings, Peto’s Paradox doesn’t seem to hold up—and what studying animal cancer rates could teach scientists about improving human health.Meet Bastetodon, A 30 Million-Year-Old Apex PredatorOnce upon a time, some 30 million years ago, what is now Egypt’s Western Desert was a lush forest. Humans had not evolved yet, the nearest relatives being monkey-like creatures. And through those forests stalked Bastetodon syrtos, a newly described apex predator from an extinct lineage known as the Hyaenodonts—one of the top carnivores of the age.Researchers recently discovered a nearly complete skull of the creature. They reported on the find in the Journal of Vertebrate Paleontology. Host Flora Lichtman talks with Shorouq Al-Ashqar of the Mansoura University Vertebrate Paleontology Center about the discovery, and the picture it helps paint of ancient life.Transcripts for each segment will be available after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Flor Lichten. Today in the podcast, looking for clues to fighting cancer in creatures big and small. Chickens, for example, have high rates of cancer. On the other side of the coin, we know that dolphins, for example, have very low rates of cancer. If you throw a huge party, there's more of a chance of something going haywire than if you host a quiet little get-together with a couple of friends. And it makes sense, right? More people, more chance for chaos. So it also kind of makes sense that, in an organism, a bigger species with more cells might have more of a chance of something going wrong with one of those cells, like a mutation leading to cancer. Back in 1977, a British epidemiologist named Richard Pito observed that that didn't seem to be true.

Bigger animals didn't seem to have a greater risk of cancer than smaller ones. This became known as Pito's paradox and also the source of phrases like elephants, don't get cancer, which side note, elephants do, in fact, get cancer. Anyway, research published this week in the proceedings of the National Academy of Sciences takes a new look at Pito's Paradox using an unusual set of data, death reports from zoos around the world. Joining me now to explain is Dr. Sarah Amund. She's an associate professor of urology and oncology at Johns Hopkins University Medical

School and one of the authors of that paper. Sarah, welcome to Science Friday. Thanks so much for having me. Okay, is Pito's paradox like a hot topic in cancer circles? The cancer research community is a really big place. But there is certainly a growing interest in this idea of comparative oncology. So what can we learn about cancer rates and how cancer grows or doesn't grow in organisms in order to understand human disease?

So this isn't just one simple, small study. This isn't just us interested in this question. We're really building upon the work of a lot of scientists since Richard Pito, in 1977 and many of our colleagues today. And is it, is it debated still or is it sort of accepted as gospel? So that's a difficult question to answer because it was largely accepted, except for perhaps a few outlier species, largely because of a limitation in what samples we had. So you mentioned that really special data set that drew from veterinary autopsies from zoos. And we were only able to do the analysis that we did because that data set was published. It's the largest of its kind.

It was generated by other scientists and was published last year. So the only way we could even begin to answer these questions that were really posed by Pito's Paradox was because of this data. Okay. So does Pito's Paradox hold up? Do big animals not get as much cancer as smaller animals? This was one of the exciting things about this study is that our results show that Pito's Paradox is false. but larger species have an increased prevalence of cancer compared to smaller species. So it didn't hold up. There are, again, a handful of species that are those outliers. So you talked about at the top this myth that elephants don't get cancer.

They do get cancer, but they are more resistant to it. Well, what explains that? That's kind of interesting. So the elephant has been the poster child for this for a long time. And it has been well published that they get less cancers you would expect for their size because they have many, many copies of a particular, tumor suppressor gene, P53. So they have that higher protection level than other species do. Do we know why they have that higher protection level? Like, why do they have that tumor

suppressor gene in higher levels? This starts to get into some of the things we try to probe in our study and that others have tried to probe and understanding how these outliers come to be. So one thing in particular that we looked at was the evolution of a particular treat. So in this case, we're thinking a lot about body size, of course. But when we think about the evolution of a trait, it's different species to species. And so if we consider the relationship of cancer prevalence of body size, we can also look at the rate that that body size evolved. So how fast, how quickly did the species evolve to get to the size now, we find that the species that went through that rapid change in body size. So those who have much bigger or much smaller very quickly have a decreased prevalence of cancer than a species of the same size.

Wait, wait, wait. So if you evolved quickly in terms of body size, big or small, you have less of a chance of getting cancer? Correct. That's what our data say. And to bring it back around to the Asian elephant, that elephant had a very high rate of evolution for body size. They got big really fast. So in practical terms, that means that the Asian elephant has an expected cancer rate of a smaller animal, like the tiger. Do we understand the mechanism, though, linking those things? So this is really where we can now move to understand the specific mechanisms of that cancer resistance. I think that's something really exciting that we can learn from this data is looking at those outliers. So we highlighted the elephant, but other animals also don't get very much cancer. For example, the naked mole rat.

Love naked mole rats. They have very low rates of cancer. And it's through a number of different mechanisms. and something that I think is exciting as a cancer biologist is that there are different mechanisms, the elephant. There are species that have much higher rates of cancer than would be expected for body size. But for example, the common budgie, the bird,

it only weighs about an ounce, about 30 grams, and it has cancer rates about 40 times higher that would be expected for body size. We also know that chickens, for example, have high rates of cancer and hedgehogs. On the other side of the coin, we know that dolphins, for example, have very low rates of cancer. So you found big animals do get cancer more than smaller ones, with the exception of some of these outliers.

But, you know, to be clear, when we talk about humans, does that mean like a tall person is more cancer prone than a short person? So that's a great question. Our study is strictly at the species level. It's not at the individual level. So we compare between species, not within species. Humans in particular are difficult to understand in this setting because we have access to modern medicine. We have a longer life than perhaps we would expect of animals and zoos. But all that said, our models would predict that a human-sized species would have a cancer prevalence similar to the size of a bat. So you mentioned the elephant's protection. What are some of the other adaptations that might protect? against cancer? There are a few different mechanisms that would be protective against cancer. So I already mentioned an expansion of a tumor suppressor gene, P53, and that's been shown in the elephant.

There are other tumor suppressor roles, for example, in the naked mole rat, where they express both P-16 and P-27, which are also tumor suppressor genes. In other cases, there are reports of changing the tumor microenvironment, so what the cells are actually responding to in the body. For example, naked mole rats have very, they have extremely high molecular weight, hyloronin. How do you think these findings could be adapted to human health? So I think something that's really excited about understanding both the species that get cancer, as you would expect, with their body size, with each shell division, that tells us a lot about what cancer biology can look like in a patient. I think what's also really exciting is that

looking at these outliers, so those organisms that are getting cancer more or less frequently than you would expect, it gives us places to start so that we can understand human cancer better. So, for example, we can understand the role of P53, a tumor suppressor in human cancer, the role of P16 or ribosomes that make error-free proteins better in the cancer setting, in human patients with the disease. And that will mean that we can understand those mechanisms better and so that then we can intervene better. So by studying the successful species, we can understand how cancers develop in patients and discover new ways to fight the disease. It gives us another place to start asking

questions. How has your paper been received? Are people like up in arms and banging their desks about it? Yeah, I think that this is a really beautiful example of how science is supposed to work. you know, this work would not have been possible by this data set that was generated by other scientists. And we know these scientists. We talk with them at meetings. We have calls with them. We ask each other questions about our work, both related to this and sort of more broadly. And so when this community of scientists can come together, it's good to disagree. And so the response to this has been, I think, overwhelmingly positive, not just because people are agreeing with us, though some people are, but some people are challenging. Some people are saying, is this actually paradigm shifting? Some people are saying, are you using the appropriate statistical models? What nobody is saying is that this is bad science. What's exciting is that this is coming together and we are pushing. forward and asking new questions within the scientific community.

Thank you so much for taking the time to talk. Absolutely. Thanks for having me. Dr. Sarah Amund, Associate Professor of Urology and Oncology at Johns Hopkins University Medical School in Maryland. After the break, a 30 million-year-old fossil from the Egyptian desert. One of my colleagues shouted excitedly. It seemed like we had made a big discovery. Don't go away.

Archaeologists found a real. remarkably intact, 30 million-year-old skull in the Egyptian desert. The skull belongs to a previously unknown hyena d'at, a big cat-like apex predator that prowled what used to be a jungle. Here to tell us more is one of the study authors, Cheru al-Ashgar. She's a Ph.D. candidate at Mansour University Vertebrate paleontology center. And she teaches at the American University in Cairo. And she joins us today from Cairo.

Shruk, welcome to Science Friday. Oh, thank you. It's nice to be here with you. Okay, so your team found this fossil early in the pandemic. Yeah. Set the scene for me. Yeah. In the spring of 2020, Dr. Salam and the team decided to take a break from COVID and spend some of the quarantine in the desert, specifically in the Sayum depression in the western desert of Egypt.

There, one of my colleagues spotted teeth sticking out from the ground and shouting. excitedly to the rest of the team. It seemed like we had made a big discovery. Teeth sticking out of the ground. Did you all know right away you had something big? Not right away. In the beginning, we were impressed by the preservation. It's perfectly preserved. And it was a big deal. But after preparing the fossil for studying and started to realize the nature of the fossil. At the time, we have really made a big discovery. And what makes this fossil such a big deal?

Yeah. It's a big deal because it's complete and it has new traits. So we have a new genus to name. Wow, new genus. Yeah. And we performed several phylogenetic analysis to get the life tree. and to study the movement in migration of hyaenadont group throughout contents. So it provides us with very impactful and interesting information.

So it's a hyena dant. Should I be picturing a hyena? What does it look like? Hyena dund, it's a group of extinct meat-eating mammals that lived all over the world in North America, Europe, Arabia, and Asia. after the dinosaur extension and before the diversification of the modern-day carnivora like dogs, lions and cats. It's like a pre-cat. Yeah, yeah, I like this exorption.

How big was it? It weighed 27. 27 kilograms? Yeah, kilogram, yeah. Okay, so like, I'm just Googling. So, like, 60 pounds about? Okay. Yeah, take my word for it.

Yeah. So it's in the same weight of leopard or modern hyena. Like a modern day leopard. And was it the top of the food chain? What was it eating? What was its life like? Well, that's a very good question. I lived in a tropical forest, tropical rainforest,

and may have bred on the ancestor of elephants and hippos, as well as our monkey-like ancestor, Egyptopithecus. Really? Egyptopithecus. Yeah, yeah, yeah. All of these fossil were discovered at the same site. Wow. It sounds like the ecosystem was completely different back then, too. I mean, you're excavating in a desert, but it was a jungle rainforest.

Yeah, it's amazing. If you one time go to Fayum, you will see the logs of trees, the petrified forest, and you can, Imagine how this desert was like a tropical forest. It's like a fairy tale. And until now, we don't know the exact reason for the extinction of Hainadondah. Maybe climate change has played a big role in their extension. So it's like an analog for what's happening today.

We as Egyptian are fascinated by our ancient Egyptian history. So we need to connect our natural heritage to our ancient Egyptian history. You know, I think when Westerners think about ancient Egyptian heritage, they think about human civilizations. But I hear you broadening it beyond that. Yeah. Before our ancestors were here to put their foot on earth. There is this whole other world.

That's completely different. What name did you give this basil? Bastetodon. Basidudon, we named it after the cat-headed goddess Bastet in our ancient Egyptian history. It's like the symbol of the protection and the pleasure in ancient Egyptian. So I know that cats are depicted often in ancient Egyptian art. Do you think there's any chance that early human civilizations were encountering these bones of bestodon or other hyena dans that may have inspired any of these depictions? Oh, that's really a deep question.

We found a lot of stone tools near the size of the hyenadons. And we also found a lot of artifacts from the first time. additionally there is the oldest paved road in the world so yeah maybe people saw the the spoons before but they didn't realize what they are they may not have known that they were a cat-like creature yeah pre cats pre cats yeah i loved hearing about this thank you so much for joining us today okay thank you it was nice being with you Sharuk Al-Ashgar is a PhD candidate at Mansour University Vertebrate Paleontology Center and teaches at American University in Cairo.

And that is about all we have time for. Lots of folks helped make the show happen, including... Dee Petersmith. Flissomeres. Emma Gomez. Jackie Hirschfeld. I'm Flora Lichtman. Thanks for listening.