Pod Insights Science Friday An Animal’s Size And Its Cancer Risk | Bastetodon, A 30 Million-Year-Old Apex Predator About this episode 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.
Transcript Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:00 Speaker 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.
0:18 Flora 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.
0:38 Flora 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
1:21 Flora 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.
1:48 Speaker 02 Thanks so much for having me.
1:50 Flora Lichtman? Okay, is Peto's Paradox like a hot topic in cancer circles?
1:54 Speaker 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.
2:23 Flora Lichtman? And is it debated still, or is it sort of accepted as gospel?
2:28 Speaker 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.
3:03 Flora Lichtman? Okay, so does Peters paradox hold up? Do big animals not get as much cancer as smaller animals?
3:10 Speaker 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.
3:32 Flora Lichtman? Well, what explains that? That's kind of interesting.
3:35 Speaker 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.
3:53 Flora Lichtman? Do we know why they have that higher protection level? Like, why do they have that tumor suppressor gene in higher levels?
4:02 Speaker 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.
4:46 Flora 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?
4:55 Speaker 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.
5:12 Flora Lichtman? Do we understand the mechanism though, linking those things?
5:15 Speaker 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.
5:37 Flora Lichtman? Love naked mole rats. Yeah.
5:38 Speaker 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.
6:16 Flora 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?
6:33 Speaker 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.
7:05 Flora Lichtman? So you mentioned the elephant's protection. What are some of the other adaptations that might protect against cancer?
7:11 Speaker 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.
7:53 Flora Lichtman? Hmm. How do you think these findings could be adapted to human health?
7:59 Speaker 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,
8:38 Speaker 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.
9:09 Flora Lichtman? How has your paper been received? Are people like up in arms and banging, banging their desks about it?
9:17 Speaker 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
10:00 Speaker 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.
10:24 Flora Lichtman? Thank you so much for taking the time to talk.
10:26 Speaker 02 Absolutely. Thanks for having me.
10:28 Flora Lichtman? Dr. Sarah Amund, Associate Professor of Urology and Oncology at Johns Hopkins University Medical School in Maryland.
10:37 Flora Lichtman? After the break, a 30 million year old fossil from the Egyptian desert.
10:42 Speaker 03 One of my colleagues shouted excitedly. It seemed like we had made a big discovery.
10:48 Flora Lichtman? Don't go away.
10:55 Speaker 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
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12:05 Flora 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.
12:36 Speaker 03 Thank you. It's nice to be here with you.
12:38 Flora Lichtman? OK, so your team found this fossil early in the pandemic.
12:42 Speaker 03 Yeah.
12:43 Flora Lichtman? Set the scene for me.
12:44 Speaker 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.
13:12 Flora Lichtman? Teeth sticking out of the ground. Did you all know right away you had something big?
13:17 Speaker 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.
13:43 Flora Lichtman? And what makes this fossil such a big deal?
13:45 Speaker 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.
13:56 Flora Lichtman? Wow, new genus.
13:57 Speaker 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.
14:16 Flora Lichtman? So it's a hyaenodont. Should I be picturing a hyena? What does it look like?
14:20 Speaker 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.
14:44 Flora Lichtman? It's like a pre-cat?
14:45 Speaker 03 Yeah, yeah, I like this, uh, expression.
14:50 Flora Lichtman? How big was it?
14:51 Speaker 03 It weighed twenty-seven?
14:54 Flora Lichtman? Twenty-seven kilograms?
14:56 Speaker 03 Yeah, kilogram, yeah.
14:57 Flora Lichtman? Okay, so like, I'm just Googling. So like sixty pounds, about?
15:02 Speaker 03 Uh, okay.
15:04 Flora Lichtman? Take my word for it.
15:06 Speaker 03 Yeah.
15:08 Speaker 03 So it's in the same weight of leopard or modern hyena?
15:13 Flora 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?
15:20 Speaker 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.
15:36 Flora Lichtman? Really, Egyptopithecus?
15:38 Speaker 03 Yeah, yeah, yeah. All of these fossil were discovered at the same site.
15:42 Flora 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?
15:50 Speaker 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.
16:32 Speaker 03 We, as Egyptians, are fascinated by our ancient Egyptian history. So we need to connect our natural heritage to our ancient Egyptian history.
16:45 Flora 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.
16:55 Speaker 03 Yeah, before our ancestors were here to put their foot on earth.
17:02 Flora Lichtman? There was this whole other world.
17:04 Speaker 03 That's completely different.
17:06 Flora Lichtman? What name did you give this fossil?
17:08 Speaker 03 Bastet Don. Bastet Don, we named it after the cat-headed goddess Bastet in our ancient Egyptian history.
17:19 Speaker 03 It's like the symbol of the protection and the pleasure in ancient Egyptian.
17:24 Flora 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?
17:44 Speaker 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.
18:15 Flora Lichtman? They may not have known that they were a cat-like creature.
18:18 Speaker 03 Yeah, pre-cats.
18:20 Flora Lichtman? Pre-cats, yeah.
18:21 Speaker 03 Yeah.
18:22 Flora Lichtman? I loved hearing about this. Thank you so much for joining us today.
18:25 Speaker 03 Okay, thank you. It was nice being with you.
18:28 Flora Lichtman? Sharuk Al Ashgar is a PhD candidate at Mansoura University Vertebrate Paleontology Center and teaches at American University in Cairo.
18:40 Flora Lichtman? And that is about all we have time for. Lots of folks helped make the show happen, including
18:46 Speaker 05 Dave Petersman.
18:47 Speaker 06 Phyllis Samers. Emma Gomez. Jackie Hirschfeld.
18:51 Flora Lichtman? I'm Flora Lichtman. Thanks for listening.
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