Science Friday - Zoonomia Genetics Project, Telomeres, Mutter Museum. May 26, 2023, Part 1

Episode Date: May 26, 2023

Orcas Are Attacking Boats Near Spain. Scientists Don’t Know Why This Thursday, the Supreme Court restricted the scope of the Clean Water Act pertaining to wetlands, in a 5-4 vote. This could affect the Environmental Protection Agency’s power to protect certain kinds of wetlands, which help reduce the impacts of flooding by absorbing water, and also act as natural filters that make drinking water cleaner. Justice Brett Kavanaugh joined the court’s three liberal members in the dissent, writing that the decision will have, “significant repercussions for water quality and flood control throughout the United States.” Plus, earlier this month, three orcas attacked a boat, leading to its sinking. This is the third time an incident like this has happened in the past three years, accompanied by a large rise of orcas attacking boats near the Strait of Gibraltar. Scientists are unsure of the cause. One theory is that these attacks could be a fad, led by juvenile orcas in the area, a documented behavior in this subpopulation of the dolphin family. They could also be a response to a potential bad encounter between boats and orcas in the area. Science Friday’s Charles Bergquist talks with Sophie Bushwick, technology editor for Scientific American, about these and other stories from this week in science news, including a preview of a hot El Niño summer, an amateur astronomer who discovered a new supernova, and alleviating waste problems by using recycled diapers in concrete.     A Famous Sled Dog’s Genome Holds Evolutionary Surprises Do you remember the story of Balto? In 1925, the town of Nome, Alaska, was facing a diphtheria outbreak. Balto was a sled dog and a very good boy who helped deliver life-saving medicine to the people in the town. Balto’s twisty tale has been told many times, including in a 1990s animated movie in which Kevin Bacon voiced the iconic dog. But last month, scientists uncovered a new side of Balto. They sequenced his genes and discovered the sled dog wasn’t exactly who they expected. The study published in the journal Science, was part of a project called Zoonomia, which aims to better understand the evolution of mammals, including our own genome, by looking at the genes of other animals—from narwhals to aardvarks. Guest host Flora Lichtman talks with Dr. Elinor Karlsson, associate professor in Bioinformatics and Integrative Biology at the UMass Chan Medical School and director of Vertebrate Genomics at the Broad Institute of MIT and Harvard; Dr. Katie Moon, post-doctoral researcher who led Balto’s study; and Dr. Beth Shapiro, professor of ecology and evolutionary biology at UC Santa Cruz, who coauthored the new study on Balto and another paper which identified animals that are most likely to face extinction.     The Long And Short Of Telomere Activity Telomeres are repeating short sequences of genetic code (in humans, TTAGGG) located on the ends of chromosomes. They act as a buffer during the cell replication process. Loops at the end of the telomere prevent chromosomes from getting inadvertently stuck together by DNA repair enzymes. Over the lifetime of the cell, the telomeres become shorter and shorter with each cell division. When they become too short, the cell dies. Telomere sequences weren’t thought to do much else—sort of like the plastic tip at the end of a shoelace. Writing in the Proceedings of the National Academy of Sciences, researchers now argue that telomeres may actually encode for two short proteins. Normally, those proteins aren’t released into the cell. However, if the telomere is damaged—or as it gets shorter during repeated cell replication cycles—those signaling proteins may be able to leak out into the cell and affect other processes, perhaps altering nucleic acid metabolism and protein synthesis, or triggering cellular inflammation. Jack Griffith, one of the authors of the report and the Kenan Distinguished Professor of microbiology and immunology at the UNC School of Medicine, joins SciFri’s Charles Bergquist to talk about the idea and what other secrets may lie inside the telomere.   Philadelphia’s Mütter Museum Takes Down Digital Resources Robert Pendarvis gave his heart to Philadelphia’s Mütter Museum. Literally. He has a rare condition called acromegaly, where his body makes too much growth hormone, which causes bones, cartilage and organs to keep growing. The condition affected his heart, so much so that a heart valve leaked. He had a heart transplant in 2020. Pendarvis thought his original heart could tell an important story, and teach others about this rare condition, which is why he was determined to put it on display at the Mütter Museum. The Mütter Museum is a Philadelphia institution, a medical museum that draws hundreds of thousands of visitors to its rooms filled with anatomical specimens, models, and old medical instruments. The place is not for the squeamish. Display cases show skulls, abnormal skeletons, and a jar containing the bodies of stillborn conjoined twins. Pendarvis thought it would be the perfect home for his heart — and more. To read the rest, visit sciencefriday.com   To stay updated on all-things-science, sign up for Science Friday's newsletters. Transcripts for each segment will be available the week 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 Flora Lichten. I'm a host and managing editor at Gimlet Media, and I am very happy to be co-hosting the program this week. And I'm SciFri producer Charles Bergquist, and we're so happy to have you back. Later in the hour, we'll talk about new research into yourselves telomeres. We'll also talk to researchers compiling a zoo's worth of animal genomes. And talk about a museum's dilemma around displaying human remains. But first, a five to four Supreme Court decision delivered yesterday, will restrict the scope of the Clean Water Act, specifically as it relates to the nation's wetlands.

Here to tell us more about that decision and other science news of the week is Sophie Bushwick, technology editor at Scientific American here in New York City. Welcome back to Science Friday. Thank you. Okay. So we've talked about this case before while it was pending, but remind us of some of the details here. So this is a case called Sackett v. EPA, and it deals with restrictions to building and modifying wetlands under the Clean Water Act.

And part of what I've been reading on this is that this decision comes down to a sort of technicality-sounding thing, a difference between the words adjacent as opposed to adjoining. That's right. So a five to four majority declared that only wetlands that are adjoining a larger stream or lake would get these federal protections. So previously, it's just if it's a wetland, it's protected. These wetlands are often next to a larger body of water. But the new ruling says if it's next to it, but there's not a continuous connection, it doesn't count and it's not protected under the scope of this act. And this means a lot of wetlands are going to lose federal protections. And why is that significant? Why should we care? Wetlands, they're not only these really interesting ecosystems in their own right. They also play a big role in things like flood mitigation because they can take in. take in some of those waters and slow down flooding in the nearby areas. They also improve water quality because they can absorb runoff from farms and other sources. So they play this important role in our health and in the quality of the water we drink.

And removing the protections means they could be more vulnerable going forward. I see. Speaking of bodies of water, a curious case of orca behavior off the coast of Spain and Portugal. Orcas are grouping up somehow to attack boats and are even sinking some of them? That's right. So in the past few years, killer whales have started attacking boats. And sometimes these are only minor encounters. You know, there's hundreds of cases of whales kind of swimming up to the boats and then maybe exploring around them and then going away. But in about 50 cases in 2020, the orcas made contact with the boat. And in the past three years, there have been three boats that have been so damaged by orca attacks that they actually sank.

Wow. I get this mental image of, you know, some sort of jaws-type chomp right in the middle of the boat. But it's worse because they're all ganging up together. You know, one of them might go for the rudder, another one might scrape its teeth along the hull, and they can really do damage. Wow. We keep saying attacking, but do we know whether this is aggression or are they playing with the boat or we don't know? We don't know. They don't seem to be attacking the humans. They don't seem to have a problem with the humans on the boats. It's the boats themselves. And so there's a couple different theories for why are they doing this. So one group has an adult female in it, one of these groups that they've noticed attacking. So it's possible that

she had a negative encounter with the boat and now sees the boat itself as a danger. And so has her group attacking it. There's also a group of juvenile whales that have attacked some boats. And so some people say, well, maybe this is a fad. Like a teenager taking on this cool, you know, Orca equivalent of a TidePod challenge. And this has happened before. So Orcas can experience fads. There was a previous case where Orca started wearing, I don't want to call it a hat, but essentially hats made out of dead salmon.

They would be swimming around with this dead fish on their head, like a fashion statement. And it seemed to be a trend that multiple different individuals were picking up. All the kids are doing it. All the cool kids wear dead salmon. Do we know why it's happening now? Has there been an increase in boat traffic or anything? Or it's just it's one of those weird nature things? It's probably just one of those weird nature things. Maybe one particular whale had a really bad encounter with the boat and started attacking them. And other whales were like, this looks fun and joined in. Maybe a group of juveniles just decided to do it for fun one day. And then others, again, started spreading the behavior. It's pretty unclear. But it's fascinating. Okay, in some medical news this week, a group of American women contracted fungal meningitis after getting some surgeries in Mexico. What happened there?

So fungal meningitis is an infection where a fungus can attack the brain and the area around it. And this can be deadly. One of the individuals has died from this fungal infection. And infections are, it's hard for them to get to the nervous system. There's a lot of safeguards in the human body. But in this case, it seems that all of the surgeries involved in epidural. So this is where you have an anesthetic injected into the area around the spinal column. So it's possible that that carried a fungal infection that affected these individuals.

Yeah. I mean, is this just a cautionary tale for medical tourism? Or is there something deeper that we should be taking out of this? So this kind of outbreak isn't limited to this. particular clinic. There have been other cases, so it's not necessarily that this is due to the medical tourism, but it does shine a light on the issue of medical tourism, on the idea that some Americans travel out of the country for cosmetic procedures or for other health care because they can't afford it in the U.S. And so by going out of the country, they're no longer in

our familiar system of regulations. And so it can be risky. Gotcha. I heard that an amateur astronomer has discovered a star that went supernova from his backyard. Why are scientists excited by this? This is really cool because this amateur astronomer who's amateur but not new to this, he has discovered almost 200 supernovae since 2000. Wow. So he spotted this supernova pretty early in its development. This is what's called a type 2 supernova. So what's happening out there about 21 million in light years away in galaxy M101, the pinwheel galaxy, is this big start, maybe eight times bigger than our sun, is collapsing into itself. And it's in the process of becoming a neutron star or a black hole. And in doing that, it's throwing out all this matter as well as electromagnetic radiation. And

it's really cool for researchers and scientists to be able to measure and observe this supernova as it progresses. So as it gets brighter and then starts fading again. And while they're doing that, amateur astronomers with even a backyard telescope can also take a look at it. So it's something the rest of us could see, too, if we went out to our backyards this weekend? Yes. So you're going to want to look near the end of the handle of the constellation known as the Big Dipper or Eursa Major, and the supernova will be a bright spot there. And part of what's cool here is that this amateur was able to catch it much as it was happening or this is just happening. Yes, totally. That's why scientists are really excited. It's not the first time that they've heard of such a supernova or observed it, but this gives them the

chance to make continuous observations of it as it progresses and changes. And because it's in a popular corner of the sky, so to speak, they could look at what this area looked like before the supernova happened and then compare it to what it looks like now as the supernova is happening and afterward. So there's lots of data for them to collect. Yeah. And while we're saying, as it's happening, as it's happening 21 million years ago. Yes. Yes, exactly. Because this is 21 million light years away, it's 21 million years in the past, but we're just seeing it now. Whoa. I'm looking forward to doing some stargazing this summer, but forecasters are saying that it seems we might be due for an El Migno year for the first time in 10 years. Remind me what those are and how they factor into this whole trend of warmer summers that we've

been seeing lately. So in El Nino is a phenomenon, a weather phenomenon, where the waters of the eastern Pacific get hotter than usual. And then this has a sort of butterfly effect on the rest of the planet. That extra heat changes the air flows and circulates around the world. and it also ends up increasing overall global temperatures. So an El Nino makes a hot summer, what might have already been a hot summer, even hotter. And the fact is that our summers are getting hotter. We're seeing more heat records broken. There was a heat record just recently broken in Western Canada for this time of year.

And it wasn't just broken by a few tenths of a degree. It was broken by about 12 degrees Fahrenheit. So it was 12 degrees above the highest previously measured. temperature, but it was also 40 degrees above the average temperature for this time of year in that area. Yikes. How does this affect different parts of the country differently? So in places that are used to hot summers and hot weather, there tends to be a lot of air

conditioners installed. There tends to be an infrastructure in place that is built to deal with the heat. But in places like the Pacific Northwest or Western Canada, which was affected in the recent heat wave, they don't have that same kind of infrastructure in place. So people are less likely to have air conditioners. People are less likely to be familiar with what they can do to mitigate that heat when it hits. And so it's more of a shock to the area. And it tends to kill people.

So finally, an infrastructure story of a different kind using recycled diapers instead of sand in concrete. I love this idea. So researchers in Japan found that you can shred up, dispositions. diapers, which are often made of, you know, wood pulp, cotton, even absorbent polymers, all of these ingredients can be used in concrete. So they washed the diapers and shredded them and used them as an ingredient in concrete. And they were trying to figure out just how much of the sand in concrete can you replace with diapers before it starts to lose some of its strength and ability to be used in buildings. And I mean, that leads to the obvious big question. I mean, can I have a tower

castle made of recycled diapers. So this is another interesting thing. Concrete is used in buildings in different ways. So if it's used as a structural element, you've got to have a pretty low proportion of diapers because these structural elements like columns and beams, they need to be very strong to support your proposed castle as opposed to architectural elements. If you're using it for like a wall panel or a brick, you can use a higher proportion of diapers up to 40 percent because it doesn't need to be.

as strong. So for instance, let's say you're building a one-story house. You could replace about 27% of the sand and the concrete with diapers. But if you want just a three-story house, not that crazy, you can only use 10% diaper in your concrete. And I imagine if you want a castle even bigger than that, the percentage would continue to drop. Very good information to have. I will keep that in mind for this weekend. For your house building. Yes. Thank you so much, Sophie. It's always great to talk to you. too. Thanks. Sophie Bushwick is a technology editor for Scientific American based in New York City. After the break, Flora Lickman talks to researchers who studied the genomes of hundreds of animals, including the sled dog turned movie star, Balto, to get a fuller picture of mammal evolution.

Stay with us. This is Science Friday. I'm Charles Bergquist. And I'm Flora Lickman. Do you remember the story of Balto? In 1925, the town of Noam, Alaska was facing a diphtheria outbreak. Balto was a sled dog and a very good boy who helped deliver life-saving medicine to the people in the town. Balto's twisty tale has been told many times, including in a 90s animated movie in which Kevin Bacon played Balto. Which way, Balto?

Which way? Which way? Uh, this way. But last month, scientists uncovered a new side of Balto. They sequenced his genes and discovered he wasn't. wasn't exactly who they expected. This study was part of a project called Zunomia, which aims to better understand the evolution of mammals and our own genome by looking at the genes of other mammals from narwhals to Ardvarks. Here to tell us more of my guests. Eleanor Carlson is an associate

professor in bioinformatics and integrative biology at UMass Chan Medical School and director of vertebrate genomics at the Broad Institute of MIT and Harvard. She's based in Boston, Massachusetts. Katie Moon is a postdoctoral researcher at UC Santa Cruz in Santa Cruz, California. Beth Shapiro is a professor of ecology and evolutionary biology at UC Santa Cruz in Santa Cruz, California. Welcome all to Science Friday. Thanks for having us. Katie, you were the leader of the pack on the Baltos study. Were there any surprises that jumped out of Balto's DNA?

Yeah, I think not surprising, but I think, you know, you never really know when you sequence something's genome, what you're going to find. And I think what was cool about Bolto is that we had some ideas about what we'd find. And a lot of those were confirmed with the genomics. But we also found some really neat other things, which we didn't predict. One of my favorite things is that we were able to predict his physical phenotype from his genotype. So everything from his coat color to his eye color to, you know, skin thickness, you know, muscle development, things like that. You know, that was really cool because you can imagine why a dog like Bolto would have needed.

needed those things where he was living. So he had genes that might have made him better adapted to pulling a sled in very cold conditions? Exactly right. You know, body weight things, joint formation, coordination, things like that. You know, so that's exactly what you would expect from Bolto and his population, you know, the larger group of sled dogs, you know, that were pulling these large weights through icy conditions 100 years ago.

What about Balto's pedigree? How does he compare to modern sled dogs? One of the really cool things about looking at a genome from an animal that lived 100 years ago is that we can't really think of it as what of today's breeds are in Balto because Balto lived before today's breeds existed. So he is kind of that ancestral population and his ancestry, parts of his ancestry, have also contributed to the ancestry of what we think of, as dog breeds today. So it's kind of a hard question to answer what breeds is he because it's

not really the right question to ask. He lived before the breeds. So he's kind of representative of all of them together. So one of the things that I got really excited about looking at Balto and Balto's data was that Balto was actually called a Siberian Husky. And his, you know, epic sled run in Alaska is one of the things that might have inspired them to establish the Siberian Husky breed. So having an opportunity to look at Balto's DNA and compare that to Siberian Huskies today and try to figure out what their actual relationship was was something that I was quite curious to find out. And what we saw was that, you know, when you establish a sled dog breed, like a breed like we do today, you create these closed populations of dogs. These are dogs where only Siberian huskies only

get to have puppies with other Siberian huskies. And so we found two things. We found one that Balto had a lot more genetic diversity in his population than it is in the modern sled dog breeds today, including the Siberian husky, and also that it looked like he was probably had fewer changes in his genome that might have been damaging to his health. So it might have been kind of overall a healthier population as well. Katie, how did you fetch Balto's DNA in the first place? Great pun. Well, so he's actually on display at the Cleveland Museum of Natural History.

And, you know, you can still see him today. And his taxidermine remains, they're in a glass case. So we actually grabbed a little piece of his underbelly skin. We gave him a little tummy rub and extracted the DNA in our clean lab here in Santa Cruz. So, you know, we have a clean lab where no modern DNA goes into and we keep everything spick and span. And we extracted it, you know, with some in-house preparation. You know, we've made a lot of leaps forward with ancient DNA extractions and preparation techniques. He actually ended up being quite well preserved and not as damaged as you would expect.

But certainly more damage than if we were to get DNA from a dog that's alive today. We know that as soon as an animal dies or a plant, the DNA in all of its cells starts getting chopped up into smaller and smaller pieces until eventually they're so small that you can't recover them or make use of them. So even though Balto was only about 100 years old, his DNA was chopped up into really tiny fragments, like only about 60 letters long or so compared to modern DNA that might be hundreds of millions of letters long after you extract it, which is why we had to use that special clean facility that Katie was talking about. So he was really well preserved compared to the things like mammoths and giant bears that we often work with, but not as well preserved as the dogs that Eleanor gets to work with. Yes, yes, I know, Beth. Your life is so much harder than mine is with your DNA. Eleanor, the Balthos study used Zunomiya data as well.

Will you tell me more about that project? What is the mission? Yeah, so the Zunomia Project is a big project where we sequence the genomes, the DNA, from hundreds of different mammalian species. So we had 240 different species of placental mammals in there. We didn't include all the crazy mammals from Australia that are marsupial. because they're basically just too weird. They're too far away.

So we were focused on the placental mammals. Things are reasonable. You know, you don't want to get too crazy. And so we sequenced their DNA, and lots of other people did too. We basically took advantage of these big public data sets. And then we aligned all the genomes. And what we do, by aligning all the genomes, it means that we can look at a given position in the DNA.

So you take a human, a human's genome is about 3 billion bases or letters long. And once we've aligned it, we can actually look at a given position in the human genome and see what it looks like in every other species in our data set. So we can see what that position looks like in a dog, looks like in a bat, looks like in a mouse. And that allows us to kind of understand how things are changing over evolutionary time. Has Zunomi revealed any, like, hidden superpowers of animals that we didn't know about before? I'm getting more and more interested in superpowers of mammals, but I hadn't really thought about hidden ones. We sort of actually go the other direction where we've observed that animals have amazing superpowers and we're like, how do they do them? The biggest challenge in genomics is that we've gotten very, very good at sequencing DNA.

We can sequence, you know, every individual very easily. We can look at all their A, Cs, Gs, and T's, figure out what order they go in. We can even do it for ancient DNA like mammoths and balto. The problem is, is we don't actually understand what most of it means. We don't know how to read out that string of aces, Gs, and T's and actually say, hey, that's what this piece of DNA is doing, and this is why it's important. And so by sequencing the genomes of a lot of species and then also going and studying those species and understanding how they're different, we can start analyzing those two things together,

the phenotype of the animals and the sequence of the genome and try to figure out which parts of the genome are actually giving them those exceptional abilities. Beth, what about DNA from extinct animals? Is there any plan to incorporate ancient DNA into Zunomia? Absolutely. So I think one of the really awesome innovations that comes from Zunomia is this alignment, the lining up of all of the genomes from these various. different mammalian species. So what is on chromosome one from a human is not necessarily on the same chromosome from a bat or from a bear or from a cat. And so you have to use really sophisticated statistics to be able to line them up so that you can compare these sequences because they've been

shuffled around the genome by evolution, recombination over the many tens of millions of years of mammalian evolution. So now that we have this base alignment of all these different things, can start sticking in other species that we don't have. And that could include extinct species where we can generate genome sequences from things like mammoths and saber tooth cats and giant bears and begin to ask where they are different from their closest related living species using this same sort of structure that Eleanor has been talking about, but also filling in some of the gaps that aren't there. You know, I think it's been pointed out several times now. And Eleanor, you really do have to explain yourself. There is no raccoon, for example, in the way.

the Zunomiah alignment. I know about the missing raccoon. Actually, it's really funny, because we didn't even think about the raccoon until the press conference that Eleanor had, and people kept bringing it up. And I've just been teasing Eleanor about this ever since. I think a bunch of people have as well. So why people are so fascinated by the raccoon, I don't understand, but it's not there. Are there animals on your bucket list? Yeah, I don't know. I mean, I'm interested in species that are struggling. So species that are on the, endangered species list and how we might be able to use the sort of resource to identify species that we should be focusing conservation efforts on. And so I think that it would be useful to

generate genome sequences from species that we often don't think about, those that don't immediately come to mind because these are the ones that maybe we need to be focusing on from a preservation of biodiversity perspective. I don't know, Eleanor, do you have a bucket species? The ones I'm most interested in are the ones that we don't know anything about. So what are the things I learned working on this project was that, you know, you'd think that sequencing a whole lot of mammals would be really easy. You just go down to the zoo and you work with the zoo people and you get a sample of DNA and then you sequence it and then you've got your genome made. And it turned out what I discovered during the course of this project was that most species, including most mammals,

don't tolerate being kept in captivity. They don't do well. They don't reproduce. They don't have babies. And often they just can't survive. They just don't do well in that environment. And that includes, includes, for example, like most bats. Except for a couple of fruit bats, most bats just don't do well in captivity. And so in order to actually study these species, somebody's got to go out to where they're living and find them in the wild and get samples from them. And I'm really curious to know what's out there that we don't even know that we're missing yet. Beth, you mentioned conservation work. How can this genetic data tell us about whether a species is in trouble? How does that work? It's a great question. One of the papers, there were actually 11 papers that were published together as part of this Zunomiya package, and I was fortunate to be involved in a few of them. One of those was to ask whether if we just had one genome sequence from one individual, we could learn something from that one genome sequence that would help us to prioritize our focus of conservation. Obviously, we're in the midst of a biodiversity crisis and extinction crisis, and there is not enough.

money, resources, and time to go around to focus on all of the species that we need. And there are many species that are listed as data deficient, where we just don't have the ecological survey data, the genomic data, of any knowledge about these species as to whether they might be endangered. And it's easy to imagine how if you had a bunch of genomes from a bunch of individuals, you could ask how much diversity is in that population, or is that population really in trouble? Are they inbreeding? Are there mutations at these sites that see, seem to be important for other reasons. But with just one genome, we were curious, is there, is there any information in there that can really help us to focus, do triage for this conservation

prioritization? And the answer we were able to figure out is yes, in the absence of any other information, we can use certain features of a single genome, things like whether the two chromosomes, because every animal has one chromosome from mom and one chromosome from dad, if they're the same as each other for a long time in that genome, that means that there's an inbreeding going on, recent inbreeding, the population size is small, and that can hint that there might be a problem. Or if there are mutations that are happening in these parts of the genome that are identified, as Eleanor was talking about before, as constrained, where mutations don't normally happen. If we see mutations accumulating there that change genes and potentially change functions,

then this is, again, a signal that that species might be in trouble. and we should invest some more energy and trying to figure out what's going on. Wow. So without survey data, you can tell from the genes of one individual whether that species, the whole species might be in trouble. Yeah, it's really impressive. And, you know, it's not enormously powerful as an approach. I mean, it would be more powerful to go out and collect a lot of data or to do the survey data. But it is possible to use this as a first step in conservation triage. We can identify populations that we need to go and spend some time and money,

potentially to see if they really are in trouble. Yeah, it's really fascinating that this is, this is possible from one genome. This is Science Friday from WNYC Studios. Eleanor, this is a very human-centric question. But does this data give us new insight into ourselves? Does it, does it tell us anything about what it means to be human? Well, I can tell you that the press conference about the papers told me that we're very interested in that question. Everybody wanted to know the answer to that question. We're apparently very excited about ourselves. What is it that makes humans different? The first part of that answer would be not nearly as much as people think that we're different.

You know, for the most part, humans are animals and do mostly the same things as all other animals do. But we had a few hints at things that might be different in humans. So we had two different papers that looked at the question of what's special about humans. There was one that looked for parts of the DNA that were basically constrained, meaning that they seemed to be doing something important across all of the mammals, and then started changing much more quickly within the human lineage, meaning that for some reason that important part of the DNA was changing in humans such that it was different from the other animals.

And then there was another paper that looked for things that were, again, constrained across all of mammals, but then deleted just in the humans to try and figure out what it was doing. And both of those papers seemed to point at changes in part, of the genome that regulate the expression of genes in our brains. And we don't know exactly what they're doing yet, but we could sort of guess that they're taking the mammalian brain. You know, there's a lot of similarities across all of mammals, but somehow in humans, it's just tweaked a little bit, maybe so that we have more neurons or we have more connections between neurons, or maybe the sizes of different parts

of the brain are changing. We don't know exactly what effect these changes are having yet, but now that we found them, now that we can say that out of the 3 billion letters that are in the human genome, or 3 billion bases that are in the human genome, these are the ones that seem to be having a functional impact on how things are regulated in human brains, we can start to go back and see what it is that they're actually doing. That's fascinating. You know, the space between figuring out that something is important and then figuring out what it does is it's a very long road. It's quite impressive. But when you've got 3 billion bases that you're starting with, at least knowing that you're looking at the right thing at the beginning of all that,

it makes the whole thing a lot easier. I think that's the perfect place to leave it. Thank you all so much for joining me today. Thank you. That was fun. Thank you very much. Thanks, Leah. Dr. Eleanor Carlson is Associate Professor in Bioinformatics and Integrative Biology at the UMass Chan

Medical School and Director of Vertebrate Genomics at the Broad Institute of MIT and Harvard. She's based in Boston, Massachusetts. Dr. Katie Moon is a postdoctoral researcher. at UC Santa Cruz in Santa Cruz, California. Dr. Beth Shapiro is a professor of ecology and evolutionary biology at UC Santa Cruz in Santa Cruz, California. Up next, Charles talks with a researcher who says that longstanding views of part of your genetic machinery could be wrong.

Stay with us. This is Science Friday. I'm Flor Lichten. And I'm Charles Bergquist. At the end of each of your chromosomes is a repeating chunk of six DNA letters called a telomere. It's often described as being sort of like the plastic tip on the end of a shoelace, a thing that protects the more important part of the strand, but doesn't do much else. And as your shoelace or chromosome gets older, those ending tips get worn down and damaged.

But recently scientists reported that instead of being just silent placeholders on the chromosome, telomeres may actually encode for small proteins. And proteins do things. They change things, perhaps helping your cell run normally, perhaps promoting diseases such as cancer. Dr. Jack Griffith is the Keenan Distinguished Professor of Microbiology and Immunology at the UNC School of Medicine in Chapel Hill, North Carolina. He's one of the authors of a report on the finding in the proceedings of the National Academy of Sciences. Welcome to Science Friday, Dr. Griffith. Thank you so much, Charles. So if telomeres can encode for these two small proteins,

do we know what these proteins do in a normal cell? We don't. And this is all so new, and I might say paradigm shifting or shocking that the field is really, perhaps reeling from this discovery. And we're going ahead as much as we can to find out what these two proteins do. Because telomeres were discovered 80 years ago with some mysterious element at the end of the chromosome, which keeps two different chromosomes from sticking end to end. but nobody knew how that was done until six decades later when my colleague Tisha de Longa the Rockefeller and I showed the end actually isn't an end, it's a little circle, a loop.

So it's an endless end, and that keeps the chromosomes from sticking end to end, and we call these T-loups. But it was assumed that this DNA, as you mentioned, is rather boring T-T-A-G-G-G-G-G-over. and over again, and it wouldn't encode RNA or proteins. And that's been the dogma. As you say, this is surprising because these sequences weren't thought to do very much beyond act as this buffer. So how did you find this? Well, in 2007, a group in Switzerland showed that telomeres actually do something, and they're transcribed into RNA. And it turns out this RNA is like Velcro. It sticks to chromosomes. It kind of globs up the ends of the telomeres,

and it never, never, never gets out into the cytoplasm. But again, because it's a simple repeat, it doesn't look like a protein coding sequence, and no one thought it would do that. But in a Star War analogy, in a galaxy far, far away was the world of repeated nucleotide diseases, like ALS, frontal temporal dementia, mitani dystrophy, fragile X. And there's two fabulous scientists in that galaxy, Laura Randem and Maurice Swanson, and they discovered that the ALS disease involves an RNA that has six repeats, CCG, GGG,

and that by an unusual mechanism, can be turned into proteins. And since I know those people very, very well, I lived in that galaxy years ago, I wrote down CCG, GG, and then underneath it, TTA, G, GG, and said, wow, if the ALS RNA makes these two very toxic kind of proteins that they discovered, what would telomeres do? It looks like it makes the same thing. So telomeres make two proteins, one's very hydrophobic and makes little preon, like. like rods and amyloids, the other is very charged, by and nucleic acids.

And in the ALS world, they're different amino acids, but they're basically the same, very hydrophobic, and it was very charged. And so that was a shock 10 years ago. And we made the proteins chemically, looked at them in my electron microscope, did as much as we could, but it was not until 2020 that I was able to

recruit a fabulous postdoctoral fellow, Dr. Tugred Al-Turkey, who had done her graduate work at Colorado State and had expertise in light microscopy. And so he made an antibody to one of the two proteins. Togrid took over, and due to her fabulous work, we have been able to show that this one protein in particular is present in all human cells that we can detect. It's much higher in a number of cancer cells. It's higher in cells from people with certain telomere diseases. And recently, we're finding it higher in serum from people with some cancers. So that's really quite exciting, but very new. Yeah. So as cells age and divide, the, the, telomeres get shorter, does that shortening process alter the protein that you found at all,

or make you produce any less of it or more of it? I think it actually makes more of it, because as the telomeres shortens, it's kind of a self-immolation of the telomere as you get older and older, older. Eventually, the telomere gets so short, it cannot make our little tel loops. And now the telomere is called dysfunctional. And now this RNA that is very carefully kept away in a nucleus can get out into the cytoplasm and make these two proteins signaling proteins. And so those proteins can then shut down cellular processes.

We think that they may turn down protein synthesis. They may get out into little things called exosomes that are shed from cells. And they could communicate the kind of distress that cell A is. undergoing to cells BC and D all around them. Researchers have talked about telomeres as being a kind of marker of cellular aging. Does finding these new proteins teach us anything about aging in general? That's actually a question that we're starting to think about in detail because we have reason to believe that these proteins are actually shed into our blood in a serum.

And so we're working on our big effort in the laboratory right now is to work on a blood test for these proteins and serum. And our guess is that as you age, that level would slowly, slowly, slowly get higher and higher and higher. The older you get, it would go up and up and up. The cells go into senescence, become inflamed and so forth. But in certain cases, like, say, younger people who do not know that they have a disease, called idiopathic pulmonary fibrosis, which is a disease of telomeres, and they have very short telomeres, but it makes more of this telomereic RNA. Those people might have a big spike of this VR protein that were assaying early in life. And so if you discovered that, you could then identify

those people, and they would know they're at risk, and so there's certain things they could do during life to ameliorate the symptoms of that disease. So even normalizing for age, all human telomeres aren't the same. My telomeres may have started off at a different length from yours. That's absolutely true. So people have different telomere lengths and they change during their lifetime. And it may be in part inherited. I just had lunch with one of our veterinary pathologists who was talking about having

cloned pigs. And they cloned pigs from another pig that was somewhat older. And now they've discovered that their new cloned pigs are dying very early because their telomeres are getting short. And they just started out kind of short change. The baby pig, the piglets were short change because they started out with short telomeres. And so there are probably people who start out that way. There are also rare diseases you find in children. that are also involved in defects in the telomereic machinery. And these people often pass away at an early age because their telomeres just are not functioning or are unusually short.

We keep talking about problems associated with extra short telomeres. Is there any harm or any disadvantage in people that have super long ones? Yes, there's been a big, big studies of that. that one of the best studies was in Denmark, where they have the ability to look at a whole nation's worth of people. And they found that on average, people that have shorter telomeres tend to have trouble with cardiovascular disease at an earlier age because the heart muscle cells are now dying at an early age. Whereas people who have very long telomeres have less susceptibility to cardiovascular issues, but I have higher risk for cancer. Because our most fundamental

barrier against cancer are the telomeres getting shorter and shorter and shorter and then the cells quit replicating. And it's only those few cells that jump over that barrier become cancerous. So if you have a really long telomere, there's more chance that those cells will divide and then become cancerous than if you start out with shorter telomeres. So in some cases, it's advantageous to having almost a kill switch for an aging cell. Absolutely. Yes. Interesting. So as you and your colleagues work to try and figure out what these two proteins may do, is this just sort of another strike against the term junk DNA? Oh, yes. Yes. Togrid and I keep laughing in the lab because this RNA, that makes these proteins in the literature

is called a long non-coding RNA. And it's in all the papers. And we keep saying that we have forced the field to get rid of that term for this RNA. And it's going to take time. I have colleagues that are still, maybe, maybe not, they wanna see more data. And we really appreciate that,

but we have a series of three papers right now kind of outlined that I think going to put a lot more meat on the story. And that's what science is all about. You come up with a new idea. People, well, maybe, maybe not, but you just keep piling on more and more findings, and hopefully it will turn into an exciting story. There are no stories that are important that are to start and finish in one paper. Well, I wish you good luck with your future research. Dr. Jack Griffith is the Kenan Distinguished Professor of Microbiology and Immunology at the UNC School of Medicine in Chapel Hill, North Carolina. Thanks so much for being with me today.

Well, Charles, it's all my pleasure. This is Science Friday from WNYC Studios. Charles, you grew up near Philadelphia. Do you remember visiting the famous Mooter Museum as a kid? Yeah, it was definitely one of the more unusual class field trips. Right. It is no ordinary museum. It's a medical museum chock full of unusual items. Yeah, but I remember most was the scary-looking antique medical tools. But there are also skeletons from people who had rare bone diseases, livers of conjoined twins. In the pantheon of museums, it was kind of creepy. Well, the museum has been under a microscope recently because of a dilemma it faces around

displaying human remains. joining me to talk about this story is my guest. Alan U, science reporter for The Pulse from W. H.Y. Public Radio in Philadelphia, Pennsylvania. Alan, welcome to Science Friday. Hi, thank you for having me. So there have been conversations in the museum world for a while about the ethics of displaying human remains. How is this playing out within the Mooder Museum? Yeah, so the Muzer Museum, like any museum that has human remains in their collection,

has obviously had to think about these issues, right? They've always, to my understanding, tried to look for the provenance of where their specimens come from, at least in recent history. They've also tried to find living donors, so talk to people who can clearly consent to having their bodies

or parts of their bodies displayed in the museum. And so it's an ongoing process for them, and one that, you know, did not begin recently. They've always had to think about this. But recently you discovered something odd. The Mitter Museum has deleted a lot of its digital presence, including videos from its very popular YouTube channel. So what happened?

Yeah. So at first, it wasn't quite clear what happened. And so I talked to the current museum leadership, and they said that this is part of a reassessment that they're doing. They're basically going through everything the Muta has, both in their physical collections and in their online exhibits. And in their words, they want to make sure that it is respectful and appropriate. And in the meantime, they've made the decision to unlist all of their YouTube videos and also take down all of their online exhibits. And they said that this will continue until they finished reassessing their entire collection.

And they don't know how long this will take. You spoke with a person who donated his heart to the Mooder Museum after he received a transplant. Will you tell me the story? Yes. So this is a gentleman named Robert Pandarvis, and he has a rare condition called agro-megaly. And the simple explanation is that his body makes too much growth hormone, and so his bones, his cartilage, his organs will keep growing. And this affects his heart as well, so much so that one of his heart valve actually leaked

and he had to have a heart transplant. And before he had his transplant, he had actually been to the Mutu Museum and saw some of their collections and exhibits about his condition. And he thought that his heart could tell a very important story here and educate more people about this condition. And so he was quite determined that after he had his heart transplant,

he wanted the Mutuum Museum to put his old heart on display. and he said that he actually, whenever he meets new doctors and new medical providers, he tells them to Google the YouTube video that the Mutum Museum did about him and they interviewed him. And he found out that the Mutu Museum had unlisted all their videos when he went to a doctor and then he couldn't find the video anymore. And so he was actually quite upset about this. I mean, I did have to sign legal paperwork saying it belonged to them so they could do it, they wanted to do with it, but for them to bury it in their archives so soon after I gave it to

him would really be an injustice. And he was very much set on this. He said that even if he had died, he would want the museum to have his skeleton, because that's how much the education means to him. And so since I published my story, the Mutim Museum said that they're aware that this has created concerns among supporters and that they take these very seriously, especially the concerns that taking down the online exhibits make the museum and the exhibits less accessible. And they said that in the coming months that they will host a series of discussions about the future and encourage people to share their ideas. And so that's where they left it. Alan Yu is a science reporter for The Pulse from W. HYY Public Radio in Philadelphia, Pennsylvania.

Thanks for joining me today, Alan. Thank you very much for having me. Pleasure to be on. And that's all we have time for this hour. Sandy Roberts is our education program manager. Annie Narrow is our individual giving manager, and Ariel Zitch is our director of audience. B.J. Leaterman composed our theme music. If you missed any part of this program or would like to hear it again, subscribe to our podcasts or ask your smart speaker to play Science Friday. I'm Charles Bergquist. And I'm Flora Lichtman. Thanks for listening.