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

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.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  WNYC is supported by Bayer. Science is about asking questions, testing, trying again. It's not easy, but it's relentless. It evolves, and that's why science delivers. Learn more at sciencedelivers.com.

• 0:18Flora Lichtman?

  This is Science Friday. I'm Flora Lichtman. Today on 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.

• 0:38Flora Lichtman?

  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 Pedo 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 Peto's Paradox, and also the source of phrases like elephants

• 1:21Flora Lichtman?

  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 Peto'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.

• 1:48Speaker 02

  Thanks so much for having me.

• 1:50Flora Lichtman?

  Okay, is Peto's Paradox like a hot topic in cancer circles?

• 1:54Speaker 02

  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 is just us interested in this question. We're really building upon the work of a lot of scientists since Richard Pedo in 1977 and many of our colleagues today.

• 2:23Flora Lichtman?

  And is it debated still, or is it sort of accepted as gospel?

• 2:28Speaker 02

  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 Peters paradox was because of this data.

• 3:03Flora Lichtman?

  Okay, so does Peters paradox hold up? Do big animals not get as much cancer as smaller animals?

• 3:10Speaker 02

  This was one of the exciting things about this study is that our results show that Peters paradox is false, that 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.

• 3:32Flora Lichtman?

  Well, what explains that? That's kind of interesting.

• 3:35Speaker 02

  So the elephant has been the poster child for this for a long time. And it has been well published that they get less cancer as 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.

• 3:53Flora Lichtman?

  Do we know why they have that higher protection level? Like, why do they have that tumor suppressor gene in higher levels?

• 4:02Speaker 02

  This starts to get into some of the things we tried 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 trait. 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 and 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 that have much bigger or much smaller very quickly, have a decreased prevalence of cancer than a species of the same size.

• 4:46Flora Lichtman?

  Wait, wait, wait. So if, if you evolved quickly in terms of body size, big or small, you have less of a chance of getting cancer?

• 4:55Speaker 02

  Correct. That's, 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.

• 5:12Flora Lichtman?

  Do we understand the mechanism though, linking those things?

• 5:15Speaker 02

  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, we highlighted the elephant, but other animals also don't get very much cancer. For example, the naked mole rat.

• 5:37Flora Lichtman?

  Love naked mole rats. Yeah.

• 5:38Speaker 02

  They, 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 than 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 than 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.

• 6:16Flora Lichtman?

  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?

• 6:33Speaker 02

  So that's a great question. Our study is strictly at the species level. It's not 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, you know, animals in 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.

• 7:05Flora Lichtman?

  So you mentioned the elephant's protection. What are some of the other adaptations that might protect against cancer?

• 7:11Speaker 02

  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 P16 and P27, 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 hyaluronin.

• 7:53Flora Lichtman?

  Hmm. How do you think these findings could be adapted to human health?

• 7:59Speaker 02

  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 cell 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,

• 8:38Speaker 02

  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.

• 9:09Flora Lichtman?

  How has your paper been received? Are people like up in arms and banging, banging their desks about it?

• 9:17Speaker 02

  Yeah, I, 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, 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

• 10:00Speaker 02

  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're, we are pushing forward and asking new questions within the scientific community.

• 10:24Flora Lichtman?

  Thank you so much for taking the time to talk.

• 10:26Speaker 02

  Absolutely. Thanks for having me.

• 10:28Flora Lichtman?

  Dr. Sarah Amund, Associate Professor of Urology and Oncology at Johns Hopkins University Medical School in Maryland.

• 10:37Flora Lichtman?

  After the break, a 30 million year old fossil from the Egyptian desert.

• 10:42Speaker 03

  One of my colleagues shouted excitedly. It seemed like we had made a big discovery.

• 10:48Flora Lichtman?

  Don't go away.

• 10:55Speaker 00

  Science Friday is supported by PBS, presenting Going Wild. If you love learning about the natural world and meeting the scientists who help us understand it, be sure to check out the new season of Going Wild with Dr. Ray Wynn Grant. It's the chart-topping and Webby award-winning podcast from the folks at Nature on PBS, now with a video companion series. In this season of Going Wild, host acclaimed wildlife ecologist Dr. Ray Wynn Grant heads out into the field to explore the animals, people, and stories that make nature worth saving. Stops include a hibernating black bear den in Arkansas and an underwater shipwreck site off the Florida coast. If you're looking for a place to start. Check out the season's debut episode, where Ray joins beloved biologist and influencer Jordan King in the Florida Everglades

• 11:39Speaker 00

  to learn about his unlikely journey into science and how to study a wetland when it's not very, well, wet. So don't miss out. Follow Going Wild with Dr. Ray Wengrant on Apple Podcasts, Spotify, YouTube, or wherever you get your podcasts.

• 11:52Speaker 04

  And from the Alfred P. Sloan Foundation, working to enhance public understanding of science, technology, and economics in the modern world.

• 12:05Flora Lichtman?

  Archaeologists found a remarkably intact 30-million-year-old skull in the Egyptian desert. The skull belongs to a previously unknown hyaenodont, 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, Shahrul Al Ashgar. She's a PhD candidate at Mansour University Vertebrate Paleontology Center, and she teaches at the American University in Cairo. And she joins us today from Cairo. Shahrul, welcome to Science Friday.

• 12:36Speaker 03

  Thank you. It's nice to be here with you.

• 12:38Flora Lichtman?

  OK, so your team found this fossil early in the pandemic.

• 12:42Speaker 03

  Yeah.

• 12:43Flora Lichtman?

  Set the scene for me.

• 12:44Speaker 03

  Yeah. In the spring of 2020, Dr. Salem and the team decided to take a break from COVID and spend some of the quarantine in the desert, specifically in the Sayyoun Depression in the western desert of Egypt. There, one of my colleagues spotted teeth sticking out from the ground and shouted excitedly to the rest of the team. It seemed like we had made a big discovery.

• 13:12Flora Lichtman?

  Teeth sticking out of the ground. Did you all know right away you had something big?

• 13:17Speaker 03

  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. Yeah, at that time, we, uh, yeah, we, we have really made a big discovery.

• 13:43Flora Lichtman?

  And what makes this fossil such a big deal?

• 13:45Speaker 03

  Yeah, um, it's a big deal because it's complete and it has new traits. So we, uh, we have a new genus to name.

• 13:56Flora Lichtman?

  Wow, new genus.

• 13:57Speaker 03

  Yeah. And we performed several phylogenetic analysis to get the life tree and to study the movement and migration of hyaenodont group throughout continents. So it provides us with a very impactful and interesting information.

• 14:16Flora Lichtman?

  So it's a hyaenodont. Should I be picturing a hyena? What does it look like?

• 14:20Speaker 03

  Uh, hyaen- hyaenodont, it's, um, a group of extinct, um, meat-eating mammals that lived all over the world, in North America, Europe, Africa, Arabia, and Asia, after the dinosaur extinction and before the diversification of the modern-day carnivora like dogs, lions, and cats.

• 14:44Flora Lichtman?

  It's like a pre-cat?

• 14:45Speaker 03

  Yeah, yeah, I like this, uh, expression.

• 14:50Flora Lichtman?

  How big was it?

• 14:51Speaker 03

  It weighed twenty-seven?

• 14:54Flora Lichtman?

  Twenty-seven kilograms?

• 14:56Speaker 03

  Yeah, kilogram, yeah.

• 14:57Flora Lichtman?

  Okay, so like, I'm just Googling. So like sixty pounds, about?

• 15:02Speaker 03

  Uh, okay.

• 15:04Flora Lichtman?

  Take my word for it.

• 15:06Speaker 03

  Yeah.

• 15:08Speaker 03

  So it's in the same weight of leopard or modern hyena?

• 15:13Flora Lichtman?

  Like a modern-day leopard. And was it the top of the food chain? Where? What was it eating? What was its life like?

• 15:20Speaker 03

  Uh, 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, um, as well as our monkey-like ancestor, Egyptopithecus.

• 15:36Flora Lichtman?

  Really, Egyptopithecus?

• 15:38Speaker 03

  Yeah, yeah, yeah. All of these fossil were discovered at the same site.

• 15:42Flora Lichtman?

  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?

• 15:50Speaker 03

  Yeah, it's amazing. If you one time go to Fayoum, you will see the logs of trees, the petrified forest. And you can imagine how old 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 Hyena Don. Maybe climate change has played a big role in their extinction. So it's like an analog for what's happening today.

• 16:32Speaker 03

  We, as Egyptians, are fascinated by our ancient Egyptian history. So we need to connect our natural heritage to our ancient Egyptian history.

• 16:45Flora Lichtman?

  You know, I think when Westerners think about ancient Egyptian heritage, they think about human civilizations. But I hear you broadening it beyond that.

• 16:55Speaker 03

  Yeah, before our ancestors were here to put their foot on earth.

• 17:02Flora Lichtman?

  There was this whole other world.

• 17:04Speaker 03

  That's completely different.

• 17:06Flora Lichtman?

  What name did you give this fossil?

• 17:08Speaker 03

  Bastet Don. Bastet Don, we named it after the cat-headed goddess Bastet in our ancient Egyptian history.

• 17:19Speaker 03

  It's like the symbol of the protection and the pleasure in ancient Egyptian.

• 17:24Flora Lichtman?

  Hmm. 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 vestedodon or other hyaenadons that may have inspired any of these depictions?

• 17:44Speaker 03

  Oh, that's, that's really a deep question. We found a lot of stone tools near the sides of the hyaenadon. 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 spoons before, but they didn't realize what they are.

• 18:15Flora Lichtman?

  They may not have known that they were a cat-like creature.

• 18:18Speaker 03

  Yeah, pre-cats.

• 18:20Flora Lichtman?

  Pre-cats, yeah.

• 18:21Speaker 03

  Yeah.

• 18:22Flora Lichtman?

  I loved hearing about this. Thank you so much for joining us today.

• 18:25Speaker 03

  Okay, thank you. It was nice being with you.

• 18:28Flora Lichtman?

  Sharuk Al Ashgar is a PhD candidate at Mansoura University Vertebrate Paleontology Center and teaches at American University in Cairo.

• 18:40Flora Lichtman?

  And that is about all we have time for. Lots of folks helped make the show happen, including

• 18:46Speaker 05

  Dave Petersman.

• 18:47Speaker 06

  Phyllis Samers. Emma Gomez. Jackie Hirschfeld.

• 18:51Flora Lichtman?

  I'm Flora Lichtman. Thanks for listening.