How do you save a species?: Breakthroughs from cheetahs, red wolves, and 'spicy' toads

0:00In 1972, the organization Wildlife Safari in Oregon began breeding cheetahs to address their declining population. And in the beginning, things were looking good. There were healthy litters, which was a promising start. But in 1983, a cheetah was brought in from another facility, unknowingly carrying a form of coronavirus called a feline infectious parotonitis. Soon after, the disease had infected every cheetah and led to the deaths of about 60% of that colony. What researchers would soon learn was that these cheetahs were vulnerable to the disease because of an event that had taken place around 10,000 years before at the end of the last ice age. Welcome to Tiny Matters, a show about the small science of big things.

1:01I'm Sam Jones and I'm joined by my co-host, Deboki Chakravarti. And today, we're talking with scientists about what it takes to conserve animals, particularly the red wolf, harlequin frogs, and, of course, the cheetah. When you think about conservation, there are some major things that have to be addressed at a systemic level, but there's also a lot of science. Here's Adrian Crozier, the carnivore curator at the Smithsonian Conservation Biology Institute in front Royal Virginia. It's a multi-faceted approach. Yes, we absolutely need to maintain our habitats. We need to address human wildlife conflict. We need to stop illegal pet trade. We need to stop poaching, snaring, etc. Depending on the threats that you're all given species is facing.

2:02But then we also have these other tools that are worthwhile to explore and help develop because there is a good chance at some points in the next decade or 40, 50 years. We will need these additional tools for some of our species. Today, we're diving into what those tools look like and what they tell us about the incredible diversity of our planet. So, getting back to the cheetah, you might be wondering what happened 10,000 years ago that made these cheetahs vulnerable to this virus. I mean, I was. I hadn't really thought about this before, but cheetahs were around at the end of the last ice age, which was somewhere between 10,000 and 12,000 years ago. Other large vertebrates like the Wolley mammoth, the sabertooth cat, and the dire wolf were going extinct, and the cheetah population was also going into sharp decline. This led to something called a bottleneck. A bottleneck results in a steep reduction in genetic variability. When you only have a small genetic pool to work with,

3:04inbreeding is inevitable, and that can lead to developmental issues and increased risk of disease. So, in the case of wildlife safari, it was a feline coronavirus that wreaked havoc. But cheetahs have also been known to be more susceptible to AA amyloidosis, a neurodegenerative disease that manifests similarly to pre-on diseases like mad cow. Cheetah males also have exceptionally low sperm counts and poor sperm morphology. To state the obvious, this is really bad. But how exactly did we find out that cheetah populations today are suffering because of a bottleneck that started at the end of the last ice age? Yeah, on the surface at least, that seems like a really tricky thing to pinpoint. Right. So, starting in the 1980s, scientists began uncovering some pretty fascinating and important stuff. One of the key studies was published in the journal Science in 1985, and it involved, of all things, skin grafts.

4:05Researchers found that 14 unrelated cheetahs could accept skin grafts from each other without rejecting them. This sounds like a good thing, but it actually pointed to a lack of genetic variability that you typically only see in identical twins or inbred lab animals. A genomic analysis ultimately showed that a group of genes called the major histocompatibility complex, or MHC, which is responsible for tissue rejection, is nearly uniform across the species. And to try to get a sense of when that genetic uniformity arose, in 1993, scientists looked at well-known, rapidly-beantating genetic markers, using them as a molecular clock of sorts, which allowed them to date the bottleneck event to somewhere between 10,000 and 12,000 years ago. And since then, both genetic and other molecular studies have supported this timeline and given researchers' additional insight. This has huge implications for conservation efforts. Cheetahs are considered vulnerable by the

5:07International Union for Conservation of Nature, or IUCN, and some subspecies are considered critically endangered. While cheetahs today mostly live throughout sub-Saharan Africa, but in the past, they were found throughout the continent, as well as the Middle East and into India. Population numbers have decreased drastically. We've lost over 90% of the population just in the last 100 years. So numbers right now are less than 7,000 in the wild. Less than 7,000 cheetahs caught me off guard. I guess I just always assumed that there were more. Yeah, it's such a small number. And for many decades, scientists like Adrian have been working to increase species numbers, and at the very least, preserve the already low genetic diversity that remains. Well, before my time in this field, folks were working on biomedical sample collection, including semen samples from males and learning how to collect those samples and freeze them

6:12successfully for future use. We still do a lot of that in cheetahs. But beginning in the early 90s, scientists began working on the female side of the equation, starting with artificial insemination, and then learning how to harvest eggs, or O.O. sites, from ovaries. All of the techniques that we use have been developed in domestic species, cattle, you know, your farm species, a lot of lab species. But also we have a lot of the same fertility issues that they see in human medicine. So some of the things that we use, some of the tools that we use to combat our fertility issues are very similar to what you will hear being used in human medicine, like in vitro fertilization and serigate females to carry embryos and things like that. Adrian first began working with cheetahs in 2001. She was a postdoctoral fellow at the Smithsonian Zoo, based in Namibia at the Cheetah Conservation Fund. She spent more than three years there working to set up a genome resource

7:14bank for cheetahs, a long-term warehouse storing biomedical samples, including sperm. And shortly after I finished my postdoc in 2005, we started a large-scale study trying to understand the influence of age on female cheetah reproduction. At the time, they didn't know if cheetahs went through menopause like humans and at what age their egg reserve in ovarian health would decline. What they saw was oocyte and follicle numbers decreasing, which they'd expected, but there was also something that surprised them. We also learned that females start to develop pathologies in their uterus as early as six years of age, especially if they have not had a litter. One of those pathologies is endometrial hyperplasia, a condition where the lining of the uterus becomes incredibly thick, making it hard for an embryo to implant. The condition can also lead to bacterial infections in cancer. It could be hard to manage reproduction in captivity because there isn't enough space

8:18for the potential offspring, but still learning about this pathology meant scientists knew they had to reach females in the early part of their lives. Today assisted reproduction, insemination, and IVF, for example, are important tools for increasing both cheetah numbers and genetic diversity, but the success rate is pretty low, in part because it's hard to time things due to their estrus cycle being unpredictable. Their cyclicity is, I'll just say wacky, they don't have normal cyclicity, it's kind of all over the place, but they're not seasonal. And so with an animal whose oocyte readiness is hard to predict, some scientists are asking, what if you could have those oocytes develop outside of the body, which brings us to our next conservation story, the Red Wolf. These are truly America's wolf. They are critically endangered, caned species, native only to North America. That's Jen Nagashima, a reproductive biologist with

9:21the Smithsonian's National Zoo in Conservation Biology Institute. So they used to be all the way across like the South Eastern United States, but unfortunately in the 1970s their numbers are really, really steep decline, combination of different factors, but ultimately they ended up in really, really small population like Louisiana and Texas, and at that point the Fish and Wildlife Service stepped in and took the animals under human care for breeding, purposes to save the last of the species. Since then there have been ongoing efforts to breed Red Wolves for future reintroduction. Right now there are about 25 animals in the wild and just under 300 in human care in over 50 facilities across the United States. 7,000 cheetahs seemed like a really small number, but like this is tiny. Yeah, but before researchers can address the critically endangered Red Wolf, they started with a species closer to home. Dogs. So dogs or canids more generally are like cheetahs

10:26in that timing reproduction is quite difficult, but cheetahs can be fertile a number of times throughout the year. Dogs only go into heat about twice a year, and while cheetah o-sites can be fertilized just after ovulation, dog o-sites that have been ovulated still need to mature for two to three days inside the reproductive tract before they can be fertilized. That's wild. Yeah, they can also make conservation efforts for canad species really hard. Folks have been trying to work on this for for decades. They made progress in terms of fine-tuning some of the protocols. The scientific community is a whole, right? But something was still not working. I actually was a brand new graduate student and my supervisor at the time was like, okay, basically if this is not working, we need to take 10 steps back, go all the way back to the basics. Either it's the sperm, the eggs, or your actual culture conditions. So on the sperm side, there had been basically a culture media

11:26used for handling dog sperm after ejaculation that had been developed in the 1970s. And it works quite nicely. The sperm are still alive and modal. But one of the things is that in the years between 1970s and when we started the project, a lot of research had been done in other species about how sperm develop the capacity to fertilize. When Jen picked up the project in the early 2010s, scientists had learned that magnesium was needed to break down the energy-carrying molecule ATP and power sperm movement. So we went back and re-added a different version of magnesium to our culture medium and saw that they responded much more robustly to our culture conditions in a way that indicated that they would be able to fertilize. They could do their last stages of puberty or maturation, which is really it's called capacitation and sperm. Okay, so sperm optimization check.

12:27Next, the egg. Scientists realized that if they waited to collect the egg four days after ovulation, giving it more time to mature, they had a much better chance of successful fertilization, leading to viable embryos. At that point, we had to figure out what we were going to do with the embryos because we weren't basically fully controlling the dog's reproductive cycle, so we didn't have surrogates ready to go to transfer those embryos back into. And so to be able to time everything correctly, we ended up cryopreserving the embryos at pretty early stages of development between four and eight cells and then waited until we had a surrogate that was at the same stage of her cycle before transferring those embryos. And then they had to wait until the dog was ready to give birth. I was kind of a mess. Yeah, I'm trying to remember all the slurry of emotions, but once everyone

13:28was out breathing healthy and mama dog was recovering, that's when I started feeling the full joy of the moment. And it was pretty funny because they were born on the Friday before I defended my thesis on the next Tuesday. And so I spent that entire weekend and most of that Monday before, as I was supposed to be finishing up my last finishing touches on my dissertation presentation, like on the floor with the dogs, because what else are you going to do? Yeah, I would have gotten nothing done. I would have not finished my dissertation, right? Also, Jen got to keep one of the IVF puppies and named him Cannon. Oh, that's adorable. Can you imagine keeping part of your research like that? Like not a thing that could happen. I know. He's named after Dr. Patrick Con Cannon, who was a Cornell researcher, who was a big, big time dog reproductive biologist, like pioneer in the field. And Cannon is the best dog. And my boss and I, my boss also adopted

14:34one of the puppies. We have a competition as to whose IVF puppy is the best. And so since I have a voice on the podcast, I will have to say that my dog Cannon is the cutest. Put that out there. Also, we have photos. We'll have them up on Instagram if you go to ACS podcasts. All right. So being able to use assisted reproductive technology in dogs is of interest for specialty working breeds, you know, guiding dogs or seizure detection dogs, for example, but Jen's motivation behind trying to make IVF work in dogs came back to Red Wolf Conservation. As challenging as it was to make IVF work in dogs, making it work for Red Wolves is even more challenging. I had mentioned that Canids only ovulate once or twice a year. Red Wolves only ovulate once a year, the adult females. So if you miss that event, and specifically the four days after ovulation,

15:40to get those fertilizable eggs, you've missed her breeding window for the entire year. It's already problematic enough for breeding efforts. However, we also unfortunately have times where an animal passes away outside of breeding season. So if she doesn't happen to pass away in that week of the year, we don't have mature eggs that we can collect from that female. Everything that we can collect in her ovary is going to be at a immature stage of development. It's rare, but sometimes a young female Red Wolve will pass away. Jen told us that to preserve her genetics, the conservation facility where she lived will ship her ovaries overnight so that they can be cryopreserved or frozen at super low temperatures, keeping the cells alive but in stasis, where they can remain for years or decades. But the idea is that at some point when we need those genetics back in the population, we'll take those tissues, thaw them out, grow them in our over

16:41in a chip, to the stage where we can get those eggs. Yeah, Jen just said ovary on a chip. I bet a number of our listeners have at least heard the term organ on a chip, which is a relatively new technology that helps scientists essentially construct mini organs in the lab. This is in contrast to standard cell or tissue culture, where you take cells or tissue, add it to a petri dish, cover it in nutrient-rich media, and stick it in an incubator with the appropriate temperature and gas levels. And every day or so, you remove the old media and add fresh stuff to keep the cells alive. And that's just not physiological. That's not what happens in your body, right? You have constant blood flow that's perfusing your organs with nutrients. It's removing waste products from your cell metabolism. It's delivering gas. And that's really where the organ on a chip technology sort of arises is that the combination of using microfluidics, so very small scale, fluid flow through a device or a chip to mimic that miniaturized version of that organ in your

17:47incubator. The ovary on a chip is designed to have a center chamber where the piece of ovarian tissue is placed. And then there are three inlets into that chamber connected to tubing. And this tubing in these channels basically represent in my mind blood vessels that are feeding that center chamber, feeding that piece of ovarian tissue. In our case, we had these three channels because I wanted to mimic at least two or three different hormones that are a part of a natural reproductive cycle. And specifically, we're looking at two hormones that you might have heard of from the human fertility clinic side of things, a follicle stimulating hormone, which as the name might imply, it stimulates ovarian follicles, which are the egg-containing units of the ovary, stimulates them to grow. And then the other one is luteinizing hormone, which is sometimes interchanged with a human-chorianic gonadotropin for like IVF clinics. And this is actually the

18:49trigger for ovulation. So this is the hormone that causes the egg to be released in the last stages of development. And so we wanted to recreate this increasing and pulsatile change in both of these hormones on our cells and tissues in that center chamber. All under flow that's delivering nutrients and getting rid of waste products and see how that affects cell function and also ultimately egg quality. This feels so futuristic, but also organs on a chip have been around since 2010. And researchers all over the world have been finding ways to optimize them to study organ development, disease, and drug efficacy. So although this is early days for Gen and her colleagues, they're already making progress on understanding how hormones are affecting ovary developments and fine-tuning their protocols. And hopefully one day they'll be able to mature and fertilize those oocytes and transfer embryos to female red wolves who can have pups.

19:54Also, something I wanted to mention is that in doing this work, they're not just getting samples from deceased animals. The majority of the time they're using cat and dog ovarian tissue donated by spay and neuter clinics. Typically that tissue would just be thrown in biohazard waste, but how cool that it's contributing to research that could help save the red wolf or other species like the cheetah. Where current reproductive technologies can't address the very difficult timing that comes with trying to keep the species alive. Okay Sam, so we're going to move away from mammals and talk about harlequin frogs, which are not actually frogs, so they're toads, more on that after a quick break. We have a podcast we want to tell you about that we've definitely talked about in the past. It's called This Guy Sucked and is a history podcast for haters by haters. Join historian Dr. Claire Aubin and a new expert every week to pull back the scholarly curtain on some of the world's

20:58biggest bombers. No dead person is safe. And the show's guests prove that the best part of understanding the past is criticizing it. From Charlemagne to Kroschmitt, every episode gives listeners all the ammo they need to win dinner table arguments over why history's main characters were actually kind of the worst. New episodes every Thursday, wherever you listen to podcasts. That's This Guy Sucked from the multitude podcast collective. Okay, Sam, we're back to talk about the harlequin frog, which again, it's actually a toad. Yes, it's a strong confusing start. Okay, but yes, please to learn more about these frog toads, we talked with Brian Gratwick, the amphibian conservation biologist at the Spitz-Sonia National Zoo in Conservation Biology Institute. I think harlequin frogs is a much more apt description because they're very brightly colored little gestures of the rainforest living on

22:03the sides of the stream and they occur all throughout parts of Central America from Costa Rica all the way down through the Andes and they're also found in Brazil and on the Guiana shield. This brightly colored, mostly poisonous diverse group of toads includes about 130 species. Brian told us that 94 had been evaluated for their conservation status by the IUCN and about two thirds of those were identified as being critically endangered. About 39 of them are possibly extinct. So they are as a group of animals, they're just highly, highly threatened. Even though we know now these are toads, we're going to keep calling them frogs throughout the episode because it's in the name. For Brian, the species that got him hooked was the Panamanian golden frog, a bright yellow frog with black spots. Many of these frogs were rescued from Panama when the Kitchard wave was making its way through Central America. The Kitchard wave describes the devastating

23:05spread of the water-borne pathogenic fungus, butreco-kitchrium dendro-batitis or BD, through amphibian populations. BD first described in 2000 attacks the keratin layer of amphibian skin. In frogs, this typically causes excessive shedding as well as red skin and discoloration around the mouth. As a disease progresses, the animals start to eat less and convulse. They also lose the ability to write themselves, should they flip over. It's a really heartbreaking demise, and it's often fatal. It's hard to find exact up-to-date numbers for this, but a few years ago, it was believed that the fungus had infected more than 1,300 species of amphibians globally, wiping out around 90 of them. So it's not just frogs or toads. It was predicted that these animals might be in the path of the amphibian Kitchard fungus. So they were the subject of a large rescue operation, where zoos and aquariums from the United States paired up with some

24:09Panamanian scientists at the Smithsonian Tropical Research Institute, and they went collected a founding population of these animals to take into captivity before the Kitchard fungus arrived. And then after the Kitchard fungus arrived, they did disappear from the wild. So this is a species that is thought to be extinct in the wild, but there are about 2,000 of them living in zoos and aquariums in the United States. It's lucky they stepped in. Many species didn't fare as well as the Panamanian Golden Frog. They're all very susceptible to the disease and had declined precipitously when the disease came through. So the very first Harlequin frog to disappear in Panama as a result of the amphibian Kitchard fungus was the Chirikii Harlequin frog. And that's right up on the border of Costa Rica when the Kitchard fungus first hit as it spread down from Costa Rica. And that one is considered extinct. So it's just a very sort of somber message to us

25:16that we needed to listen and pay attention because there were all these other species of Harlequin frogs in Panama where the Kitchard fungus hadn't hit yet when I started the Panamanian Phibian Rescue Conservation Project in about 2008. They began creating what are called captive assurance colonies of the animals, rescuing them from the wild and bringing them into captivity. In some cases, Bede had already struck and so they entered veterinary triage where they were treated with antifungals. Many survived which is incredible but there was a problem with trying to get them back into the wild. The frogs that had been taken into captivity had lost their poison or as Brian told us they weren't spicy anymore. The most analogous toxin to the one you find at Harlequin frogs is a tetradatoxin that you find in Fugupafifish which is like the sushi you get in Japan where you even mess up a little bit in the skinning and get some of that skin on the

26:16flesh of the fish and the person eating that sushi could die. That is a very potent neurotoxin. It's one of the most potent neurotoxins known. So the average Panamanian golden frog walking around in the forest and so wild golden frog would have enough toxin in it to kill about 1500 mice. That is a lot of mice. Yeah it is. But these frogs are toads. They need the toxin to defend themselves against predators. The issue is that researchers don't know exactly where it comes from in the first place making it difficult to know how you'd get the frogs to produce it again. We're not really sure if it was derived from microbes on the skin because we know that many microbes have evolved the ability to produce tetradatoxins or whether it is something that is derived from plants or something that invertebrates are eating and that then gets bioaccumulated by

27:19these frogs in their skin. The project to make the Harlequin frogs spicy again came about when the formerly captive frogs went back into the wild and the researchers soon witnessed them in the jaws of spiders and whips scorpions. Whips scorpions are a really interesting beast. They look a little like a scorpion and they have these giant chelousurai as its mouthpiece and they are barbed like giant clubs and they look very scary and they have these long sort of antennae like appendages that they point in the direction they're going to run and they can run very very fast. If you look up a picture they really are the stuff of nightmares. Take the image of a normal scorpion out of your brain because he's a way scarier. It's like if a scorpion had a nightmare about another scorpion. Yeah exactly. So that spawned our project to try and make the Harlequin frogs spicy again. That's a term that we coined just to kind of convey the idea that this would be

28:28very strong deterrent for predators and if we can restore these skin defenses then we are making these animals in a better position for rewilding. So they did the science equivalent of spoon feeding the toxin to the frogs. They took synthetic lab-made tetradetoxin and injected it into the larva of pantry mods and then fed those larvae to the frogs. They found that feeding a frog just one pantry moth larva pumped with enough tetradetoxin to kill 400 mice was basically equivalent to the natural toxicity of a panamanian golden frog and the frogs had no complaints. They gobbled it down and they were looking for more and then we also found that they were able to take those toxins and transport them to their skin and store those toxins in their skin. So we were able to restore their their spice level but if you can imagine the research safety protocols that you have to go through

29:32just to transport that toxin legally from the United States to Panama and then the handling concerns around something that toxic. It's not something you really want to have a bunch of different people having to handle that toxin. So they wondered if they could make these frogs spicy the natural way. In their most recent trial they released panamanian golden frogs that had been in captivity back into the wild in a semi-natural situation by putting groups of 10 frogs in outdoor cat enclosures. Sometimes called cadios. It's adorable. I'm just imagining my cat and a cadio surrounded by like billions of poisonous frogs and for some reason it's adorable. Yeah would it fashion be down to even go in a cadio? I don't know. He's like, I mean at this point he's scared of so many things but I think he would love it. I think you would enjoy it. Yeah. So these cadios, they're more or less a mesh tent that protect the frogs from predators but still give them

30:35access to whatever they eat in the leaf litter or detritus on the forest floor that might be leading to their spiciness. So we had a student who went through and collected all the little invertebrates that came off of that leaf litter to try and figure out if we analyze just the ants or the mites or the beetles which ones might have these tetratutoxins in them. We also swab the frogs to look at their skin microbiome to see if they might be beneficial skin bacteria from the environment that are colonizing these frogs that could produce this. So things were looking good. Data was being collected. They were getting one step closer to understanding what drives these animals toxicity but then everyone of the Harlequin frogs became infected with BD, the Kichrid fungus and 70% died within a few months. Just awful. Yeah that had to been just so incredibly disheartening. But Brian told us they were at least grateful to get those samples because it means they can still

31:40work towards answering the question of where Harlequin frog spiciness comes from. Is it coming from the microbiome? Is it coming from the bugs they're eating and how long is it going to take for them to get their spice back in a natural situation? So this is all just part of the basic discipline of conservation biology. It's hard work and you need to understand when you're reassembling these ecosystems that are missing their critical puzzle pieces. It's not just a case of oh well we'll just pop them back and there we go. We have to understand how do they function? How do we give them their best chance to succeed? Although there's still more that needs to happen before the Harlequin frogs can go back into the wild there is a happy frog story that Brian shared with us. We've been having some successes actually with other species of frogs that are

32:40not in the Harlequin frog family but with lemalee frogs. We released about 120 tadpoles into the environment and photographed the little metamorphs as they came out and we've just come back from the field a year later and found some of those animals that we released alive a year later and breeding. So that's very encouraging to us. Now they're looking to release some Harlequin frog tadpoles to see if they'll go through their natural skin toxicity development that will position them better to survive. Again B.D. is always a threat but Brian told us they're also seeing signs of resistance to the fungus in some animals so maybe they can selectively breed resistant animals and make them spicy again before putting them back into the wild. That would be so cool. One of the things that I have learned because I've been at this now for 18 years is that it's one foot in front of the next and it's discipline and as you learn more about these systems you uncover

33:47more information that you can then iterate and figure out how do we achieve our goal and our goal is healthy thriving populations of these beautiful animals in the wild. All righty let's try to show and tell. Yeah so Sam I have news about narcolepsy. Okay yeah so recently the FDA approved a new drug called Orzefull that was developed by Takeda Pharmaceuticals to treat type 1 narcolepsy. Yeah so the drug works by mimicking a brain peptide called erexin which people with type 1 narcolepsy don't have and so erexin as part of its overall process the way it works is by binding to two different receptors in the hypothalamus and so there are several

34:47treatments that work by blocking that binding but therefore insomnia. In this case they needed a drug because these patients with type 1 narcolepsy they aren't making erexin they needed a drug that could actually bind the way that this peptide does to these receptors and it took a while but researchers found one and I thought the way that they tested this was really interesting so researchers had the subject sit in a dim room for 40 minutes and they're like no books no TV who's like no talking and the goal is you have to try to stay awake for that whole 40 minutes and even for people who don't have narcolepsy like that is kind of a challenge yeah and so when they were testing out this treatment before treatment people would usually fall asleep within four to five minutes. Okay they did two late-stage trials looking at almost 300 patients between 16 to 70 years old who were taking either or zaeful or placebo for 12 weeks and with or zaeful they could stay awake for more than 20 minutes which is around twice as long as currently available medications. The pill has to be

35:52taken twice per day and there's still like a lot to learn about how the drug works how it performs and also this is another thing that I thought was interesting but I think it makes sense they're still waiting for the DE8 to figure out how the drug should be classified as a controlled substance and in the meantime other companies are working on similar drugs but I just thought this was really good news for people who are dealing with narcolepsy and will hopefully produce exciting new treatments that will will help them out. Yeah that's really cool I I actually until you said for narcolepsy type one I had no idea there were two types of narcolepsy. Yeah me neither and it seems like type one is worse than in a lot of ways like it seems more severe and like pretty awful I mean I would assume that it could be like at you know minimally very frustrating right but you know it's like these like sudden sleep attacks sleep paralysis like hallucinations

36:52when falling asleep just sounds awful so it's amazing that there's it looks like this is really promising for people who are dealing with this. Yeah yeah might be interesting to talk about narcolepsy in length more for a future episode that's what I was kind of thinking because I know I know some people who like have dealt with narcolepsy but I don't like know that much more about the disease so like going into this was like oh right like there's yeah yeah I don't know it was just interesting to like kind of learn a little bit more about some of the mechanisms and how people are working to treat it. Yeah absolutely. Okay well I have something really different we're going to space Deboki of course. I learned a lot of things in reading about this. Do you know about the the giant impact theory of how the moon formed? I kind of knew I mean like I had a sense of this but is this like the idea of like the moon was formed from the impact on something else like the moon is actually like made from the impact of like you're like a thing that came off of an impact on another planet. Yes so like I I generally knew about this but I didn't really understand

37:57much about it. So the giant impact theory is the theory that 4.5 billion years ago the moon formed after a Mars-sized body called Thia collided with Earth and so now researchers have actually done a new simulation to try to account for more than they did in the past. So in the past I guess they were thinking of Earth and Thia as these fluid-like masses and they weren't taking into account physical strength and geology of Earth and this Mars-sized body. This is like physics class like assume like around frictionless surface. Yeah yeah and so like temperature structural strength of these colliding objects one of which was early Earth would theoretically impact the outcome right? Yeah like if you have something that's hot it's going to behave differently than something that's cool and so some of the simulations did produce something that looks like the accepted giant impact

39:04theory where you have like a debris disk around Earth that gradually assembled into the moon but there are other simulations and the ones that it seems like the researchers are more a more psyched about I think because it's so different but these seem to feel more strongly about which is that an intact moon formed within five hours of this collision between Thia and the Earth. I know I'm also be excited about that too. Yeah I mean that's like a massive revision on what people believe. Can you imagine like you know like everyone's like you know like Rome wasn't built in a day but we could be like yeah but the moon was built in five hours. Right actually it's so funny that you said that because I just finished writing the newsletter for tomorrow and I actually have that line I'm not even kidding like I literally when I read about this I was like hold on maybe we're less built in a day. Yeah that's so funny but yeah so it is not definitive we're never I

40:06don't want to say never but like I want to say we're never going to know for sure how the moon forms but it's very cool that you know with time I think we've talked about this a number of times but science is never truly finished right like almost everything could be revised maybe gravity camp but hey I don't know there's like a lot of crazy stuff that's been revised in that world too so yeah I just thought this was really fascinating again it's not saying like this is definitively what happened yes the moon formed in five hours or whatever but it's cool yeah that's really awesome I think it's like one of those things where you're like it could form in as littlest five hours probably and even that is like really incredible to think about the implications of absolutely cool well thank you Sam and thanks for tuning into this week's episode of Tiny Matters a podcast brought to you by the American Chemical Society and produced by multitude this week's script was written by Sam who's also our executive producer and edited by Michael David and by me Deboki Charkavarti it was fact-checked by Michelle Boucher our audio engineer is Misha Stanton the

41:11Tiny Matters theme is by Michael Simonelli and the charts and leisure team thanks so much to Adrian Crozier Jen Nagashima and Brian Grapwick for joining us go right and review us wherever you listen and remember you can always email us tiny matters at acs.org we'll see you next time if following the news leaves you feeling like everything in the world is getting worse I want to recommend a podcast called What Could Go Right From The Progress Network the show looks beyond the constant stream of negative headlines and asks a simple question what if despite all the challenges we face humanity is actually making progress hosts Zachary Caribal and Emma Varvolucis explore everything from politics and the economy to scientific breakthroughs sustainability technology and medicine this show examines what's going

42:12right why it matters and aims to present a more balanced picture of the worlds so if you could use an intelligent counterweight to doom scrolling I mean I know I could and a reason for some cautious optimism search for what could go right wherever you get your podcasts