Camden Bay Dr 4 (1)

Megan and Debbie, real-life scientists, discuss a lab mix-up story on gender differences in multiple sclerosis research. Male mice had a genetic mutation worsening MS, while female mice were protected naturally. Testosterone triggers a protective immune response in males, but not in females. Researchers aim to develop targeted treatments without hormone side effects. This mix-up led to new insights in MS research. Hi, I'm Megan. And I'm Debbie. We are real-life scientists, and we want to share some science-y stories about our gender-bent, sometimes mutated, and occasionally beneficial, but with an AdLib twist. You are listening to LabLibs. Okay, Debbie, today I'm going to tell you a story entitled, Mousy Mix-Up. Ooh. Okay, so you've filled in some blanks. Uh-huh. Which I do not have. Oh, hang on, I'm happy. In advance, and I'm going to fill you in. I'm going to tell you when there's a blank coming up in the story. Okay. Here. Okay, so the whole thing started with a pretty innocent mistake at a medical lab at Northwestern Medicine, Northwestern University. Where's that? I don't know where Northwestern. It says Chicago here. Oh, okay. So maybe it's Chicago. So the first AdLib coming up is this story highlights how important it is to study a blank type of differences in medicine. So you said age. Okay. Do you think it's going to be right? I haven't told you that yet. I don't know. Mice? I don't know. No, probably not right. Okay, no, it wasn't right. It's actually sex differences in medicine. Okay. Okay, so they were MS. Oh, I gave away the sex AdLib. I knew that one. I knew that one. Okay. Okay, so I went a little bit out of order, but it's important to know right away because that's what the whole story is about. Right. So the AdLib blank was a type of autoimmune disorder, and Debbie actually got that one right. She said multiple sclerosis. Okay. So MS is a disease that affects the brain and the spinal cord, and it's the result of dysregulation within your immune system. Okay. So this lab was using a mouse model that was common for MS research in which they only use female mice because when they use male mice, sometimes they don't get sick at all. But when they use female mice for multiple sclerosis, all of the mice get sick pretty much. So it's easier to do the research because it's more consistent. So that's pretty common already in this type of research. And they were trying to study these types of cells that in male mice protect against the disease, and in female mice they don't. What was this they were trying to find? They're studying this certain kind of immune cell. Oh, a cell. Okay. Yeah. Okay. So the mix-up part of the study happened because there was a lab assistant or a graduate student who was assisting in the experiment. Right. And because she had some not very much training, I said that she couldn't tell this type of body part apart from the males and the female mice. Oh, boy. And you said arms. Do you think that's right? No. Do you think that she couldn't tell the arms apart? No. No. What do you think? What? They're like sex organs? Yeah. So there are very minute differences in mice genitals, and that's how you tell them apart. I've heard a lot of animals. It's like, I don't know, man. It was an honest mistake. She accidentally used, instead, all male mice instead of all female mice. Right. So I mentioned that when the female mice are used, they mostly always get sick, whereas the male mice, when they're used in these MS studies, they sometimes get sick and they sometimes don't. Okay. This correlates with humans with MS as well, and I asked you for a number, and that number is representing that women, female humans, are blank times more likely to get MS than men. What do you think? You said seven. I said seven. Seven times more likely. Do you think that's right? No. No. It's actually more? No. What? It's actually four. Four times more likely. Four. Okay. Okay. So females are four times more likely to get MS than males. Right. Okay, so this is a little bit complicated. It took me a while to wrap my head around it, too, so I'm going to try to talk about it without getting confused, but bear with me. Okay, so basically there is this type of immune system. Keep in mind that MS is your own immune system attacking you. That's a type of autoimmune disorder. That's how they all work. Your own immune system is attacking you, okay? Correct. So there's a certain type of immune cell, an innate lymphoid cell. Okay. Okay? It's activated, and it protects male mice from MS. Oh, okay. But in females, they have the cells, but they remain inactive. Doesn't do anything. And they don't do anything. Right. Okay, so basically the study was trying to study why. Why is that happening? But they accidentally used male mice. All male mice. And they were very surprised at the results because the male mice, which usually don't get MS very badly in these studies, they had this genetic mutation that, hold on, let me look it up here. Like all of these males ended up having this mutation? They had this genetic mutation that prevents the development of several different types of immune cells. And when they had this genetic mutation, the male mice actually got more sick. Okay. So in their original study, they were using female mice. They were expecting the female mice to be protected because they were giving them this immune system mutation. Okay. So their immune system wasn't working right, which helped their MS not be so bad because, again, MS is your own immune system working against you. That's why they give people with autoimmune diseases immunosuppressants. Exactly, exactly. You can imagine that that would cause a lot of problems. It would compress that part of your body attacking itself. Right. So this genetic mutation, they were thinking, would decrease the immune system enough to protect against MS, but not so much as immunosuppressants. Right. That's why they were studying it. Okay. So then this shocking thing happened, that they thought it was going to make the mice not get MS as much, but they actually used the male mice, and now they actually got sicker. Okay. Okay. So here's the last Madeline. Here's the second-to-last Madeline. Okay. I said to give me a verb. Okay. And it's that they blanked the experiment, and they have the surprising results. You said they ran the experiment, which is pretty close. I was going to say, I mean, you can run the experiment. I don't know. They ran the experiment again. They repeated the experiment. Oh, they ran. They repeated the experiment. They repeated the experiment. Okay. So, you know, that's pretty much what all kinds of seriously- With the same exact? With male mice on purpose now. Yeah, okay. Okay, and they got the same results. The male mice got sicker with the same mutation that the female mice got. It helped them. Yeah, it was beneficial for the female mice. And so this prompted them to start asking a whole new host of questions. Just from that simple mistake by that grad student, they started, instead of asking why are females getting more sick, they started asking what is protecting male mice from getting sick. Right. So I'm going to tell you a little bit more about MS in a little bit more technical detail to explain the last MADLIB, in which I asked you to think of a type of cell. Yeah. So let me look at my notes here. I imagine the type of cell is like the myelin. Yeah, actually, yeah. You took the words out of my mouth here. That's exactly what I'm going to say. I know that it attacks with the myelin sheath in the brain of humans, so. But I was way off with squamous cell anyway. You were way off with squamous cell. Yeah, you were way off with squamous cell. I'm trying to find this particular part. Oh, here it is. Okay, so in MS, the immune cells are attacking the myelin sheath, a membrane that wraps around nerve axons. That's the one I was looking for, nerve cells. Nerve cells, okay. Yeah. Okay. Within your brain and within your spinal cord. So their immune systems are attacking these sheaths, which are supposed to insulate and assist your nerve signals being sent from the brain and the spinal cord throughout the rest of your body. So this damage interrupts the normal nerve signals and can result in a bunch of different symptoms, sensory disturbances, loss of motor function, cognitive deficits. Okay, so due to this study with the male mice now and further researching why this genetic mutation would harm their ability to fight off the disease, they found out that it's the testosterone. So the testosterone is kind of like a key that activates a certain type of protein. Okay. So the testosterone causes another type of immune cell, a mast cell, to produce a certain protein that's acting as a guardian in male mice. Okay. CK33. And it triggers all these chemicals that prevent yet another type of immune system cell being produced that is the one directly attacking the myelin sheath. So it's like a cascade of testosterone. Building blocks. Exactly. Testosterone is affecting the mast cells. The mast cells make another type of molecule. That molecule triggers another type of immune system cell to be created, and that attacks the myelin. Right. So because women don't have as much testosterone, this entire cascade of steps is happening. Right. It doesn't matter if they have, you know, this type of immune system capable. There's no testosterone to make it happen. Right. There's no activation going on. Right. So because of this one small mix-up, they're now going to be studying specific targeted ways to activate this immune response that's protecting males, but not females, and create medicines that do that. Instead of shutting down the immune system, they want to have that much more targeted, just twisting it a little bit, just changing how it works. Because one other solution, actually, to MS is you can give women with MS testosterone. Well, that's what I was just about to say. Okay, so what's stopping us from just giving them testosterone? Trans men who have MS, I guess, are in luck because they can decrease their MS symptoms by taking testosterone. Right. Okay. Wow. But lots of women don't want to do that because it has a lot of undesirable side effects for them. Right. So they're trying to trigger this without having to give women testosterone to trigger it. Right. Yes, exactly. And they're trying to do it for all sexes, all genders, in a more efficient way as well. Instead of just relying on, maybe you don't have the right testosterone levels just by happen chance for this to happen, regardless of what gender you are. Okay. So they could use that. And they're also using the same type of research now, looking at the similar immune responses in other autoimmune disorders as well. Okay. So it's kind of opened up this whole new autoimmune disorder medical category. I don't know if you know the answer to this, but how is this distributed? Is this like a, I don't know what it would be called, like a stem cell? You mean how is it given to them? Yeah, like for humans or whatever. How are they going to target it? I'm not sure. Like what are they going to give them, medicine? I'm not sure. Okay, so the mutation basically causes, specifically, N8 lymphoid cells. And they've been used before to promote allergic inflammation. Oh, okay. So they're used to study allergies, basically. Yeah. And it's the first study to show that these cells exhibit sex differences in how they are active within the body. And it's the first time they have ever been known to protect against autoimmune diseases. I don't know how they're being distributed. Like it's a mutation, so maybe it's like an RNA virus type of thing. I don't know. Do they – I have no idea. I just made that up. I can't remember what the other – There must be some way. They're probably giving the mice the mutation in vitro. Yeah. I don't know how they would – I think maybe they would inject this type of cell rather than try to give you the mutation. Like I said, is it like stem cell type thing or – I don't know. It says type 2 N8 lymphoid cells. I know. I'm not sure. So I'm just trying to think of some sort of like – what's that called, like infusions or something when you go and like sit there and – Yeah, like they may be trying to completely flood your immune system with these cells. Correct. Yeah. Mm-hmm. That's what I would think. It doesn't sound like it's something that like a medicine is going to be able to do. Mm-hmm. Okay. I don't know that there's – You're right. It doesn't say medicine. Actually, it says a drug therapy. Uh-huh. So it could be some sort of – It's going to have to be something like that. Injection. Yeah. Infusion. Infusion. Therapy or something like that. Yeah. But then instead of just using like a chemical compound or something is going to give you what it's looking for. Yeah. Yeah. And then if you're curious, I should have said this earlier, but this was research done by Melissa Brown. She's the lead author of the study and a professor of microbiology and immunology at Northwestern University Feinberg School of Medicine. Okay. And – And the studies are like ongoing, I'm guessing. The studies are ongoing, yeah. They've been published in the Journal of Immunology. Oh, it's a type of white blood cell. Maybe that's it. Yeah, that's it. Infusion of white blood cells. Yeah, it's got to be something like that. Yeah. And then her PhD grad student – not the one that made the mistake. They don't list that person's name. That person's not in there, huh? Is Abigail Russey. Arguably, my grad student, though. Yes, she did get credit. I mean – She really should. Would they be where they're at right now if it wasn't for her? I don't know. All right. Well, I guess – I mean, it's interesting, very, very interesting. I'm glad that they're, like, finding – especially, you know, like, obviously, you know, I have an autoimmune disease, so – but – And it even specifically mentions lupus and rheumatoid arthritis. Rheumatoid arthritis. As avenues that they may be able to continue this research on in other ways. That's what it sounds like. But I know that people with multiple sclerosis, like, suffer really badly in a lot of different ways. It sounds like it causes a host of – It's awful. Really awful. Yeah, yeah. It's really, really awful. Yeah. I mean, I'm glad they're focusing on that right now because, you know, it's such – it's terrible, you know. Mm-hmm. So – Well, with that being said, join us next time. We'll see how well Megan fills in the blanks. Thanks for listening, guys. Bye. Bye.