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In this episode of Tiny Show and Tell Us, we hear from a listener about her incredible grandma who’s a pharmacist in Venezuela (still, at 92 years old!) and has inspired her love of science and current lab work. We then talk about orcas spotted wearing dead salmon as hats, and what this fishy behavior may mean.

Transcript of this Episode

Sam Jones: Welcome to Tiny Show and Tell Us, the bonus series where you write in with your favorite science news or factoid, we read your email aloud and then dive deeper. I'm Sam Jones, and I'm here with my cohost Deboki Chakravarti.

Deboki Chakravarti: Hi, Sam. This is great. I'm excited to be here. I don't know why I said this is great. I'm making this sound like a very formal event, but really, we're just here to chat about really, really cool, fun science. Last time we talked about vaping, which I learned a lot from because I know so little about smoking so that was really useful for me to understand more about what makes vaping vaping. We also talked about life at high altitudes and how people adapt to them.

Before we get into all of the interesting science we have to talk about today, a huge thank you to Tien Nguyen for doing the research for this episode, and also, a reminder to all of you that we are looking for you guys to write into us so that we have all of this interesting stuff to talk about and learn about.

Sam Jones: Yeah, we need material.

Deboki Chakravarti: Yeah. Thank you to the people who've written and thank you to you who will probably write in the future, I hope.

Sam Jones: Hint hint.

Deboki Chakravarti: Yeah. So if you take that hint, as we would like you to, email tinymatters@acs.org or fill out the form linked in the episode description.

Okay, Sam, I'm going to get us started today with a question from listener Tammi, to quote Tammi directly. "What the heck?! Is that true? Why?? How???" And then Tammi included a link which includes in the URL, orcas start wearing dead salmon hats again after ditching the trend for 37 years.

Sam Jones: I have a lot of questions.

Deboki Chakravarti: Yeah, so this is a live science article for anyone who wants to read it, but we are here to talk about it because what do you mean? Dead salmon hats? So in 2024, scientists and whale watchers reported that they could see orcas around Washington state swimming with, yes, dead fish on their heads. And this is not the first time this has happened. In 1987, there was a female in a whale pod seen carrying a salmon hat, and it's been seen a few other times. Do we know why? No. We don't. So to quote an orca researcher named Deborah Giles at the University of Washington, Deborah said in an interview with New Scientist, "Honestly, your guess is as good as mine," which is what you love to hear from the experts. I feel like we should just spend the rest of this time speculating and just being like, yeah, why are they wearing it?

Sam Jones: Why are these orcas wearing dead salmon as hats?

Deboki Chakravarti: Yeah. And honestly, it just seems to be kind of a fad. They just seem to be-

Sam Jones: They have a fashion fad as well.

Deboki Chakravarti: Yeah, yeah. I think there was another scientist who said in the Smithsonian article, "Maybe it's to impress another member of the pod." It could just be they want to do it. There are of course factors that might make it more likely for the whales to do it. For example, there could have just been a lot of salmon in the area, and so maybe they were just like, "We've got excess salmon. We need to do something."

Sam Jones: We're showing off.

Deboki Chakravarti: Or it could actually be a way to save them. Sorry, not to save the salmon, but to store it for later, and this is supported by the fact that they will sometimes store fish under their fins to eat later so that's just a thing. My personal favorite explanation was from Andrew Trites, the director of the University of British Columbia's Marine Mammal research unit who said on CBC Radio West, because one of the best things about this is there's so many news sources with just different quotes from people speculating.

Sam Jones: I mean, because everyone wants to report on this and get quotes about this because it's so weird and fun.

Deboki Chakravarti: Exactly. How can you not? So Andrew Trites said, "Maybe they just like the smell of dead fish." Maybe it's just something they just want the perfume of. Maybe they just want-

Sam Jones: They just enjoy it.

Deboki Chakravarti: Must there always be a reason? And Tien also added that this is not the only example of animals that might wear their dead prey. There are bugs called assassin bugs that carry their ant prey as backpacks, and they're actually a way to fend off predators, so apparently jumping spiders are much less likely to eat them because they can't see the assassin bug hiding under the dead ant backpack.

Sam Jones: Carrying a dead carcass as a backpack is so dark.

Deboki Chakravarti: It really is. You don't watch Real World or The Challenge, right?

Sam Jones: No, I don't.

Deboki Chakravarti: Okay. There's a famous moment from The Challenge where basically one of the competitors wears another competitor as a backpack, not dead, but it is just the immediate image that came to my head of these bugs carrying these ants as backpacks, from this moment. But also, it's just fascinating that this is part of what animals have learned to do.

Sam Jones: Oh my gosh. And based on Tien's research, it seems like the assassin bugs will carry a bunch of dead ant carcasses.

Deboki Chakravarti: Yeah, because they have to be able to hide under it.

Sam Jones: Like a pile.

Deboki Chakravarti: Yeah.

Sam Jones: Essentially it's a pile of dead ants on their back and the spider's like, "That's weird."

Deboki Chakravarti: Yeah. Imagine hiding yourself under, I don't know, a pile of ground beef to hide yourself from predators. So gross.

Sam Jones: Yeah. I mean, I guess I would do it if I had to, but I wouldn't like it.

Deboki Chakravarti: No.

Sam Jones: Okay. Well, I'm going to take a very different turn. Also, I will say we do try and match these stories up so you get a very different flavor for each one, which I guess is a gross word that I just used because you were talking about ground beef, but whatever. It's fine. Okay, so this one from listener Oriana, who wrote in saying, "Since I was a kid, I always admired my grandmother. She's a recognized pharmacist in Venezuela and speaks Spanish, French and Latin. I often visited her pharmacy and learned everything about common pharmaceutical drugs, active compounds, drug efficacy, and played with some of her lab instruments. She nurtured me with an indelible passion for drug development and science communication." Which, that's so nice. Okay. Oriana continues, "Nowadays. She's 92 years old and still working as a pharmacist in my country. Unfortunately, I can't see her anymore because of the dictatorship we have. However, I can proudly say thanks to her, I got inspired to study protein-protein interaction modulations that are crucial for targeting neurodegenerative diseases and cancer. I aim to establish novel computational strategies to calculate in vivo drug efficacy for PPI stabilizer molecules. I hope the outcome of my research will continue the family legacy of helping the ones who need it most." That's so nice.

Deboki Chakravarti: Yeah, that's really sweet. I love this.

Sam Jones: Your grandmother sounds amazing, and it's so cool that she's been your inspiration. I want to talk about these protein-protein interactions, these PPI stabilizers, because it's something I actually knew so little about. Had you heard of this Deboki?

Deboki Chakravarti: No, I don't think so.

Sam Jones: Yeah, I feel like I should have.

Deboki Chakravarti: Well, that's what we're here for.

Sam Jones: Maybe I heard about it in a different context. So let's talk about what protein-protein interactions are more generally, and then we'll get into stabilizers and all this other stuff.

Deboki Chakravarti: Okay.

Sam Jones: So protein-protein interactions, or PPIs, seem to be really important. I know that's vague, but they seem to be really important for a bunch of different processes in our cells. So there are studies that show that what you'd call aberrant PPI's, essentially ones that are not functioning the way that they should be, are associated with a bunch of different diseases. You have infectious diseases, you have cancer, you have neurodegenerative diseases and so the idea is, okay, could we target these PPI's through drugs and then change the outcome, make the disease less likely? And so this has been a strategy for developing new drugs for a couple decades, actually, but it's very challenging.

So according to an article from 2022, in Current Opinion in Chemical Biology, the authors wrote that from a drug discovery perspective, PPIs are definitely attractive therapeutic targets, but they're challenging. Why are they so challenging? A lot of times with drugs, you're targeting an enzyme and you have really specific receptors on an enzyme or a protein or something that you're trying to target. But the tricky thing is that PPIs have these flatter, broader surfaces as compared to the pockets and grooves that you might see on an enzyme, for example. And so that just makes it more challenging to actually find where� can we find a molecule that's going to actually bind here? But it doesn't mean it's impossible.

So there have been some successes with small molecules that will target PPIs. For example, in the treatment of chronic lymphocytic leukemia, there's a family of proteins called BCL-II that's involved in that leukemia, and there's a PPI inhibitor that's called Venetoclax or ABT-199 that the FDA has actually approved. So although this is challenging, it's not like this is not a field where things exist.

So inhibiting PPIs, or the protein-protein interactions, that was approach one. But then more recently, we're talking about PPI stabilization, and that's what Oriana mentioned, and that has gained increased attention by the scientific community in more recent years. When I first read that, I was like, "Wait, but these are doing different things. I'm so confused. This is very confusing." So I'm going to break it down.

Stabilization, so this PPI stabilization, it allows for a targeted enhancement of a protein complex that's doing something good. You want it to be doing more of that thing, so it promotes a desired function within the cell, like something it's already doing that's good. Inhibiting a PPI disrupts something that you don't want to happen so it's just coming from different angles. So it's thinking about what do we want more of? What do we want less of?

Deboki Chakravarti: That makes a lot of sense.

Sam Jones: And so it's like, okay, well, I guess we could do both, but why are we more focused on PPI stabilization as opposed to inhibition? Well, first off, I'll say, I actually love this, in terms of stabilizers, the small molecules that will actually strengthen or stabilize this interaction, they're often referred to as just molecular glues, which I like because I think it's such a good visual. That interaction already exists, but then you bring in a molecular glue that makes it more stable and that can have an influence on disease.

So I guess that stabilization versus inhibition is a more promising approach, at least in some ways, because it can be more specific, and there are fewer off-target side effects because you're not disrupting anything. You already have a thing that's happening and you're strengthening it versus introducing some disruption that could throw off some other process somewhere else. And then Oriana was, of course, talking about her interest in targeting using these PPI stabilizers in neurodegenerative diseases and cancer. So according to a 2022 paper, in current opinion, in Chemical biology, the authors write, "As many of these molecules now enter the clinic, the expectation is that the concept of PPI stabilization and induced proximity will significantly enlarge the druggable proteome and add to our armamentarium to treat diseases like cancer and neurodegeneration."

So what that means is that they're figuring out how to target these proteins. They have a lot of potential molecules that are going to be able to do it so that they have more options for treating disease. Academic writing is rough sometimes.

Deboki Chakravarti: I'm looking up armamentarium.

Sam Jones: I know. I was like, I have never written out or said aloud the word armamentarium, but I had to include that quote because I feel like it was just such a thing where it's like, okay, so what you're trying to say is that, yeah, we're targeting these proteins now we have some options, and yeah, we think we can treat more diseases soon. I'm like, "Can you just write that?" But anyhow, I had to include the quote.

Deboki Chakravarti: Apparently armamentarium, one of the definitions is the medicine's equipment and techniques available to a medical practitioner.

Sam Jones: Whoa.

Deboki Chakravarti: Yeah.

Sam Jones: Okay. That's interesting. That's more specific.

Deboki Chakravarti: I respect it.

Sam Jones: I do respect it. All right. I take it back, but just for that. The rest of it was also-

Deboki Chakravarti: It was just a lot of words. Yeah,

Sam Jones: It was a lot. So I think the point of that is this is a very active area of research, and it sounds like Oriana is really interested in these PPI stabilizer molecules, but her interest is definitely in calculating in vivo drug efficacy, which is very cool. So her approach is computational, which I didn't even get into. But yeah, I think with this, people are approaching it from a bunch of different angles. It's cool that they were looking at inhibitors. Now stabilizers are coming to the forefront because it seems like there will be less off-target effects. How will computational biology really fit into that? I'm sure it's going to provide a lot more information on what molecules could actually help with that stabilization. So it's just cool, and I'm glad that Oriana wrote in because I had no idea. And this is just, yeah, it's a very hopeful, exciting area of research.

Deboki Chakravarti: Yeah. Thank you so much, Oriana. And I love the story with your grandmother too. It's just really sweet.

Sam Jones: I know. It's so nice. It's so nice. I also have a ninety-two-year-old grandmother, but she's not a pharmacist.

Deboki Chakravarti: My grandmother was definitely one of my scicomm inspirations too, because she was a chemistry professor and-

Sam Jones: Amazing.

Deboki Chakravarti: Even now, I've met people who had her as a professor and really remember her. It's really cool.

Sam Jones: That's so cool.

Deboki Chakravarti: Thank you to Tammi and Oriana for writing into Tiny Show and Tell Us, a bonus episode from Tiny Matters created by the American Chemical Öйú365betÖÐÎĹÙÍø and produced by Multitude. And a big thank you again to Tien Nguyen for doing the research for this episode.

Sam Jones: Send us an email to be featured in a future Tiny Show and Tell Us episode, at tinymatters@acs.org, or you can fill out the form that's linked in the episode description. We'll see you next time.

References:

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