Why it pays to scratch that itch, and science at the start of the second Trump administration
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This is the Science Podcast for January 31st, 2025. I'm Sarah Crespi. First up this week, we catch up with the editor of our policy section, Science Insider. That's Jocelyn Kaiser. She talks about changes at the major science agencies that are coming about with the transition to the second Trump administration.

Next, producer Kevin MacLean talks with researcher Dan Kaplan about why it sometimes pays to scratch that itch. It turns out scratching may be our body's end run around pests and pathogens stealthily attempting to steal blood or invade the body.

We're just wrapping up the first week of President Trump being back in office. We're recording on January 27th, which is a Monday, and there's just this tsunami of science news to get to. Jocelyn Kaiser is the editor for Science Insider, our policy and government news section. She and science news staff have been furiously gathering news about policy and government in the past week, and hopefully not too much will change by the time this releases on Thursday. Hi, Jocelyn. So glad you could join us. Hey, Sarah.

Okay, so I think we should start with the last few pieces of news that have come out on Science Insider, and then we'll talk about the intersection of science and government that you'll be keeping an eye on in the future. Sure. First, I think this story was kind of very early, which is the United States leaving the WHO, the World Health Organization, which I found from the news article could take a whole year to do. Is that right? That's my understanding. And Congress could block it. So has this happened before? Has the U.S. departed from WHO before? Yeah.

Oh, gosh, I believe they did. We started to during the previous Trump administration, but I think Biden overturned it pretty quickly.

What are some of the likely consequences of this departure? One big consequence is that the United States contributes one-fifth of the budget of the World Health Organization. So that will be a big blow to lose that funding. And another is that the U.S. will no longer have a voice in battling infectious disease outbreaks around the world, the important work that the WHO does. Yeah, that coordination across the globe is important for anything that's spreading continent to continent. That's right.

Okay. So let's move on here to a second story that you're following and it's still developing. So this is something we've written on multiple times in the past few days. This was a freeze at NIH, at the National Institute of Health, which is the largest funder of research in the United States and probably in the world. That's right. In the world too. This is a pause on external communications, travel, meetings, hiring.

And now we're starting to hear also about purchasing. What does this all mean for people who are in NIH who are trying to work and trying to push science ahead?

Yeah, it kind of boils down to that everything NIH does is in effect frozen right now. So they do two things. One is they have researchers on the campus who have labs and run clinical trials and do that work. And they cannot buy new supplies right now. They can't travel to meetings. They can't

They can't communicate with outside groups like patient groups to bring them in for clinical trials. They can't even buy animal feed. They're going to have to rely on whatever supplies they have. And then the bigger part of NIH, like 80% of its budget, is money that goes out to

medical research institutions around the country. And that part, what's happened is that these, they're called peer review committees or study sections that review the grant proposals that researchers around the country send in. And they meet regularly to assess the science and whether it's worth funding. And those meetings have been put on hold, which is going to have enormous implications, even if it's just

a couple of weeks. It could be as short as till February 1st, but people were on their way to meetings and they had to cancel their trips. I think some of them even landed in Bethesda where NIH is and had to be turned away and online meetings were paused. Nothing has happened ever like this in the memory, I think, of the community. And so it could have enormous implications for science.

Do we know why this is happening? I mean, as you said before, maybe a couple of days after administration takes over, there might be a pause on certain functions, but they resume pretty quickly. What's the thinking here? Yeah, it's a little bit confusing, but from one memo that we got a copy of, somehow the lawyers at the Department of Health and Human Services interpreted this pause on communications to include any

interaction with the outside world by NIH staff. And so they concluded that that affected even these study sections, even though they meet in private. And what about submitting papers to journals or being a reviewer for a journal? That's something that NIH staff scientists might do or people on grants.

I haven't actually heard anything about reviewing papers, but as far as submitting papers go, apparently some people at NIH are being told they can submit papers if they're about research, but they can't submit any sort of commentary or review or editorial. It has to be, it's going to have to be reviewed first. Others have not gotten clear guidance. You know, NIH is a big place, so. So we don't have any timeline right now for when this might be over or what steps are going to be taken before the freeze is over. Yeah, the communications, Paul,

memo says that it goes through February 1st, but we don't know for sure that it's going to end then. So, yeah, unclear. I wanted to touch on a few other executive orders that came about at the beginning of

this presidency that, you know, they apply to all agencies, including suspending diversity, equity, and inclusion efforts requiring in-person work. What do we know about how those initiatives are playing out in the scientific agencies? So we do know, like at all federal agencies, that agencies like NIH and the National Science Foundation are taking down their pages on

On the DEI topics, their offices of DEI are, at least the outside world, being dissolved. We've heard people are being transferred to other jobs.

But what we're all watching for is when it's going to start affecting research projects. And we are kind of just starting to get information on that. There's a lot of speculation that if you have something that's labeled diversity, that it's going to be canceled. And we don't really have, I mean, we're reporting on that today, trying to figure out what's happening. There's a lot of questions on that. Is it just, you know, mentioning it in your proposal or is it how you design your project?

your work, right? We don't know what's going to happen. That's right. And yeah, in some cases, it's more explicitly a diversity project that's trying to help bring more underrepresented groups into science, like a training project. And then in other cases, I think that a lot of agencies require a DEI plan as part of a just regular research grant. So we're kind of expecting that's all going to be stripped out, but that's kind of playing out right now. Yeah.

One other science-related item that came across at Transom last week was one of the executive orders basically redefined sex and gender by executive order. And this can have serious ramifications across government, across citizens. There's not a lot of scientific support for the way that these terms are being changed by the government.

That's right. I'm not sure that we've done that story specifically, but yeah, viewpoint of scientists, there's big problems with how the Trump administration is saying that there are only two sexes, male and female. And NIH funds a lot of research that a reporter found that there were a thousand grants with gender in the abstract, and we don't know if they're going to be canceled because they've got gender in the abstract or what they're going to have to do or change the research.

And then there's something like 400 grants that involve studies of transgender people or gender fluid people or non-binary. And so there's a big question about what is going to happen to that research and researchers are really worried. Well, there's so much going on. I really appreciate you talking to me, Jocelyn. Is there anything else you want to touch on that you're going to be looking at in months to come? Well, I think that the main thing is we're going to be watching for what happens to these research grants and whether there can be any sort of legal challenge involved.

especially any effort to cancel grants that already been awarded. There may be reasons why that's not so easy to do, but we haven't really found out exactly what might happen. All right. What about appointments for some of the heads of this agency? That's something that we typically cover in Insider. Do we know anything about how that's progressing? Right. Well, the one agency that we're watching closely, well, I guess two agencies, is the

Department of Health and Human Services, Robert F. Kennedy Jr. is the nominee, and he will appear before two Senate committees this week. And as we all know, he has some very controversial views about vaccines. He's a skeptic of vaccines. And then the Trump nominee to head NIH is named Jay Bhattacharya. He's at Stanford University, and he is controversial too. He had a lot of contrarian views about the COVID-19 pandemic measures.

but he is a scientist and an NIH-funded scientist, but he should be coming before our Senate committee before too long, and there will be a lot of questions asked about his positions too. Okay. All right, Jocelyn, thank you so much for talking with me. I really appreciate your time. You're

You're welcome, Sarah. It was good. Jocelyn Kaiser is the editor for Science Insider, our policy news section. You can find links to the story we discussed at science.org. Also, as I was checking out the stories on Science Insider, I found out you can sign up for alerts to anything new that we posted on Science Insider. That's definitely something you might want to consider as we see this cascade of science policy news in the coming weeks. So please do check out Science Insider.

Stay tuned for itchiness and scratchiness. Producer Kevin McLean and researcher Dan Kaplan discuss the benefits of scratching where it itches.

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The urge to scratch is a powerful one. You feel that little tingle on your skin from a bug bite, a healing cut, or sometimes nothing in particular and you just want to scratch it. But we're always told to leave it alone or we'll make it worse. I've definitely caved and scratched my skin raw, which I'm sure is an open invitation to pathogens, but a paper in Science got me thinking about this itching and scratching in a different way.

While looking into mechanisms that drive this itching and scratching cycle, Dan Kaplan and his colleagues posed the intriguing question, if scratching feels so good, it can't be all bad, right? Hi, Dan. Welcome to the Science Podcast. Hi, Kevin. Thanks for having me. Glad to have you. So what got you interested in studying this sort of cycle of itching and scratching in the first place? Well, the lab had been working for a number of years on

on how neurons that sense pain can trigger inflammation in the skin. Pain sensing neurons are really important in triggering inflammation and can also affect the response to pathogens as well. So we started thinking, well, what about itch? And as you just mentioned, if you think about itch, you know, there's some unusual things about it.

Like for instance, why do we itch? What is the purpose of itching? And particularly itching causes a lot of damage to the skin and can often make rashes a lot worse. Yet at the same time, scratching and itch is incredibly pleasurable. So it's a reinforced behavior. So we figured there had to be some benefit to scratching.

It seems like there's probably a lot of different directions you could have gone with this, but what specifically were you interested in investigating? The question we wanted to address is what are some of the mechanisms leading to scratching in allergic contact dermatitis, which is often called eczema. Those two words are the same. It's a kind of eczema that you get when your skin comes in contact with something that you're allergic to.

A classic example of this is poison ivy. Most people are allergic to poison ivy, and when you come in contact with it the first time, you generate an allergic type immune response. But then on your second encounter, you can get a pretty exuberant rash on the skin, which is characterized by a lot of redness, a lot of inflammation, and a lot of itchiness.

But of course, this is not, you know, confined to just poison ivy or other plant-based allergens. There are a wide variety of these allergens that can be contained in leathers and rubbers and cosmetics and soaps. And it's actually a whole branch of dermatology to basically sleuth out exactly what is the offending compound because really the best treatment is avoiding these compounds. Right.

So we used a mouse model of allergic contact dermatitis where we put small allergens, also known as sensitizers, on the mouse's belly. And this basically immunizes the mouse to this small molecule. And then we come back a few days later once the immune response is established and we put a small amount on the ear and then we can measure inflammation in response to this allergic compound based on how thick the ear is.

And so we tried a couple of different compounds. Yeah, you tried these different compounds that cause both the scratching and the inflammation. And it sounds like a couple of them were known already to trigger the immune system in order to cause that inflammation. So what did that indicate to you about the scratching? So that led us to think that maybe scratching was somehow part of the pathogenic process.

Right, because we'd always thought of scratching as just being a sort of a disagreeable outcome of having inflammation in the skin. But we were wondering if maybe it was actually part of the process. So the scratching might actually stimulate the response that your body needs. Exactly.

So how do you go about figuring out how important scratching really is? We repeated these same experiments of giving allergic dermatitis to mice, only this time we put these small Elizabethan collars around the mouse's neck. You might know these as cones of shame that you give to your dog when they come back from the vet. And the mice are fine. They can eat and they're not bothered by it, but it prevents them from scratching their ears and head.

And what we found is that if the mice can't scratch, they developed a greatly reduced amount of inflammation in the ear. And so that got us thinking that scratching seems to be really important in the development of inflammation in eczema. If they're scratching and it produces that inflammation, then that also means that the immune response is happening? Yeah, exactly. So now the tough part was to figure out, like, what is the mechanism that's driving all of this? The big clue was that

We only saw this dependence on scratching in the models which were also dependent on IgE. So this made us think that IgE activation was somehow important.

And we should note here that IgE is one of the antibodies in our immune system that responds to allergens, in this case on the skin. So what's going on there mechanistically when the compound is applied to the skin of the mouse? In the skin, IgE is pre-balanced to its receptor, the FCX1 receptor. It's expressed on the surface of mast cells,

which are present in, well, most tissues, but certainly in barrier tissues. And there's quite a bit of it in the skin.

And, you know, we know quite a bit about how mast cells work. When mast cells are activated, they do so many things. There's such an interesting and I think still enigmatic cell type. But one of the cheap things they do is they release a lot of small molecules. An example would be histamine that can then do a number of things. One is a lot of these itch sensing neurons are quite sensitive to histamine. So that is a direct trigger of itch.

And so by looking in this model, we found that, yeah, mast cells seem to be really important based on timing. And we did some genetic analyses on how this all works. Okay. You see these receptors on the skin in action. The mast cells are getting really activated. But then how does scratching do its part? Scratching is known to release a lot of cytokines and alarmins from the skin. That was our first idea. We didn't really see any effect with this.

But what we didn't see is that scratching also activates pain-sensing neurons. And one of the known factors released following activation of these pain-sensing neurons is called substance P. And it turns out that substance P is a well-described ligand for this MRGPRB2 receptor. And this is a different receptor than what we were talking about earlier, the FC-epsilon receptor. So we've got two...

two different receptors that are getting triggered, basically. We know FC-epsilon is part of IgE and mast cells and everything. So what does the combined action of these two receptors do? So the idea then is that if you have a rash that ends up

activating mast cells through this classic FC epsilon receptor. If you also have scratching, that will release the substance P from the pain sensing neurons. And together, those two signals kind of super activate the mast cells. And now you get a big inflammatory response. And so we demonstrated this in vitro using, you know, small molecules. And then we also did it in our in vivo models

by disabling various different parts of the pathway in loss of function models. Okay, so you knocked out certain parts of that process in the mice? Exactly. But I think one of the coolest experiments we did is that, remember, if you put the collars on the mice, they can't scratch and you don't get the inflammation.

So we repeated those experiments. We left the collars on so the mice couldn't scratch. But now we just activated those pain-sensing neurons by putting capsaicin on the skin. Like from peppers, right? Yeah, exactly. It's the active ingredient in chili peppers and activation of these TRPV1 pain-sensing neurons. That's what causes the burn from chili peppers. So we had these mice who had the Elizabethan collars on so they couldn't scratch and they won't get inflammation.

But if you do the exact same experiment, but now you just add a little bit of capsaicin, just dribble it on the ears, you get full restoration of inflammation. Oh, so the same inflammation that would have occurred if they were scratching, you can trigger it by activating these pain neurons? Exactly. Okay. Right. And so I think that was a really nice demonstration that this mechanism really does require these pain sensing neurons. Oh, interesting. Yeah.

How closely related are the pain-sensing mechanisms and itch-sensing? Are they different neurons? I got to say, that's a question that is like a burning argument in the field. Really? Oh, yeah, yeah. So there are different types of neurons that have sort of been ascribed as pain-sensing and itch-sensing, but I think it's a lot more complicated than that. And it gets into this concept of

of whether there is like sort of like each neuron specifically encodes one sensation or whether the context will lead to a particular sensation. I'll just say this is still a fairly contentious area of study. It does seem to be clear that some neurons have the capacity to promote certain types of sensations, but

but it's not 100% a one-to-one link. So it's probably going to end up being a combination of the both. Okay, got it. I guess sort of zooming out a little bit, we've got this pain pathway that can trigger inflammation and also the itching pathway. Is there any sort of advantage of having two different pathways to cause this inflammation? So if you imagine a situation of

of a pathogen that has evolved to avoid triggering pain. Think like an arthropod bite, like a helmet or a tick. And if these actually triggered pain, then they would, the person or the host that is being attacked would notice it and take care of it promptly. So there's a strong evolutionary pressure to avoid pain. And so

If these challenges are avoiding triggering pain sensation, then they're also avoiding a lot of inflammatory activation as well. So one idea is that by activating itch and the resulting scratching behavior, the host is able to now activate these pain-sensing neurons through an independent mechanism.

And in the case of arthropods and helminths, one of the factors they need is to release proteases, you know, to get through the skin or to efficiently have a bite. And then the proteases can trigger a whole series of protease-sensitive receptors, many of which are expressed on itch-sensing neurons. So the idea then is that these pathogens that have evolved to avoid triggering pain sensation

end up triggering itch sensation. And then the resulting scratching behavior now links in this neuroinflammatory pathway triggered by the TRPV1 pain-sensing neurons. Okay, so like when you get a bug bite, like a mosquito or a tick or something, when it's biting you, it's suppressing the pain sensation. So you're not feeling the bite as it happens, but then that ends up triggering this itch pathway? That would be the idea.

And I hope to have the parasitologists weigh in and tell me how wrong I am. So what are you interested in doing next? What are you interested in answering in the future? What I'm really excited about is by identifying this sort of synergistic two-hit pathway in mast cells, it provides, I think, a pretty exciting target for therapies to suppress inflammation in the skin.

And so, you know, in other work in the laboratory, we've actually found that glutamate released by other neurons can suppress mast cell function. And we've developed some studies and used available small molecules to show that we can actually inhibit inflammation by targeting these pathways. So I'm really excited to try developing therapeutics that can target this. Okay. Well, so this might be sort of a weird question, but

When I was reading through the paper, I felt itchy just thinking about itching and scratching. Does that still happen to you? Or do you talk about this stuff enough that you're kind of immune to that effect? I have to say you're not alone in that. So...

Andrew Liu is the MD PhD student who did all this work. He did an absolutely fantastic job. Every time he presents the seminar or when I present the seminar, I look out into the audience and I see people scratching. So you're definitely not alone in this. I don't know. I think I've thought about it long enough that it doesn't affect me anymore. Yeah. But I have to say the power of suggestion is pretty powerful. Yeah.

Well, thank you so much, Dan. This has been so interesting to hear about. I'm really glad that we were able to have you. Thank you very much, too. This was great. And thank you for having me on. Dan Kaplan is a professor in the Departments of Dermatology and Immunology at the University of Pittsburgh. You can find a link to the paper we discussed at science.org slash podcasts.

And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at [email protected]. To find us on podcasting apps, search for Science Magazine or listen on our website, science.org/podcast. This show was edited by me, Sarah Crespi, and Kevin MacLean. We had production help from Podigy. Our show music is by Jeffrey Cook and Wenkoy Wen.

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