Science Friday - FDA Approves A New, Non-Opioid Painkiller | Deep, Multi-Layer Oceans On Uranus And Neptune?

Episode Date: February 17, 2025

It’s the first FDA approval for a pain medication in 25 years. How does the drug work, and who is it for? Also, non-mixing layers of water and hydrocarbons thousands of miles deep could explain the icy planets’ strange magnetic fields.The FDA Approves A New, Non-Opioid PainkillerIn January, the Food and Drug Administration approved a new pain medicine called Journavx (suzetrigine), made by Vertex Pharmaceuticals. It’s the first time in 25 years the agency has given the green light to a new painkiller. Notably, it’s not an opioid and, according to the company, it’s not addictive. Unlike opioids, which act directly on the brain, Journavx instead blocks nerve endings across the body that transmit pain.Host Ira Flatow is joined by Dr. Sean Mackey, a professor of anaesthesiology and pain medicine at Stanford University and chief of the Division of Stanford Pain Medicine, to discuss how the new drug works, who should take it, and what its limitations are.Might Uranus And Neptune Have Deep, Multi-Layer Oceans?We’ve got a pretty good idea about what’s beneath the surface of our nearest planetary neighbors, like Mars. But as you get farther out into the solar system, our knowledge becomes scarce. For instance, what’s inside the so-called ice giants, Neptune and Uranus?Recent research based on computer simulations of fluids hints that the planets could contain vast multi-layered oceans, as much as thousands of miles deep. A layer of water that is on top of—but doesn’t mix with—a deeper layer of hydrocarbons could help explain strange magnetic fields observed during the Voyager mission.Dr. Burkhardt Militzer, a professor of earth and planetary sciences at UC Berkeley, wrote about this idea in the Proceedings of the National Academy of Sciences. He joins Host Ira Flatow to explain his theories.Transcripts for each segment will be available 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 Ira Flato. Today on the podcast, could Uranus and Neptune have deep, multi-layered oceans? But first, we'll dive into the science behind the first new kind of pain medicine in over two decades. The difference between the drug and placebo was, ah, mild. Last month, the Food and Drug Administration approved a new pain medicine. The first time it's done so in 25 years, it's called Jernavik. made by vertex pharmaceuticals. And the big headline here is that it's not an opioid and it's non-addictive.

So how does it work? Who should take it? Does it signal a new era for pain medication? Here to help break down, this new pain killer is Dr. Sharn Mackie. He's a professor of anesthesiology and pain medicine at Stanford and chief of the division of pain medicine at the university. Dr. Mackey, welcome to Science Friday. Hey, thanks for having me on board.

You're welcome. Okay. In a nutshell, how does this drug work? Well, in a nutshell, we need to first understand that pain all comes about from signals that are transmitted on nerves. And we have specific types of nerves that will ultimately transmit those pain signals. Now, those signals are generated by an electrical impulse. So when you get an injury, when you undergo surgery, those nerves are stimulated. that stimulation is caused by, in part, sodium channels. So what this particular drug does is it blocks those sodium channels. What's kind of cool about it is that, as you know, we've got nerves all over our body, our brain, our heart, every organ has got nerves.

And the last thing you want to do is give a drug that blocks the nerves that are serving particular vital functions, like our heart beating, like our brainworking. What's cool about this particular drug is it targets only the sensory nerves out in the periphery of our body. Specifically, a channel called NAV 1.8, NA, if you remember from, you know, your high school. N.A. Yeah, there you go.

N.A. It's sodium. So it's a particular sodium channel. That's how it works. I get it. So it stays away from your brain, in other words. That is the idea of it. And they've spent decades pharmaceutical companies to try to make this thing happen, and it looks like this company has pulled off a win with it. How is this medication different from an opioid or something like Tylenol?

So this medication works specifically on the peripheral nerves. It targets them with a laser-type focus on a particular receptor and blocks it. Opioids, on the other hand, predominantly are working in the spinal cord, the brain stem, and the brain, and the central nervous system. And think of them as turning the volume down on pain. So a completely different location for where they're acting and a completely different mechanism of action. Tylenol, we're still trying to figure out exactly how Tylenol works. I think it works, yeah, after all these years, it is a drug that works also centrally. It works in the brain. And it works by, you know, turning down some of these signals, if you will, in the brain.

Now, you add on the other common drug that we use, which are inseds, non-steroidal anti-inflammatory drugs, like the ibuprofen's, the naprisons. Those, interestingly, are not really pain relieving medications per se. It's sorry for the jargony word, but what it really means is they reduce inflammation. Right. That winds up pain. And so the key is, if you can imagine, once again, our job, typically in pain, is to attack those pain pathways at different points and ideally identify where the source of the signals are coming from, where the injury is, go after that specifically with the drug of choice. Okay. Now, how effective is it?

compared to, let's say, an opioid? And would it be a substitute for it? Yeah. And that is the big question. What this study showed that they published in the New England Journal of Medicine back in 23 is that when they compared it against a placebo, that the highest dose beat placebo statistically. The lower doses did not.

They did not in the paper make a nice head-to-head comparison against a. an opioid. And the difference between the drug and placebo was, ah, mild, rather mild difference. It met statistical significance, but it's not a hit the ball out of the park major effect. So what's the big excitement about then, if it's hardly better than a placebo? I think the big excitement is, one, this is the first new compound that's been introduced in decades that gives promise for targeting different pain pathways than what we've done before. Two, as has been mentioned, it's non-addictive. Most likely there's no chance that you're going to get addiction to this particular medication.

Three, it does provide some benefit. And remember, when they do these studies, they look at averages of people. The thing is that we don't treat an average. We treat a person. And so within this study, there was undoubtedly people who got a pretty profound effect, a benefit, and there were others who probably didn't get much of any. For those people who maybe they shouldn't be taking an opioid, they've had problems with opioids from either side effects or otherwise, this is going to be a nice tool.

to be able to use. And in addition, the message that we've been saying in the pain space for years is there's probably not a single magic bullet, meaning it's going to be, if you will, a cocktail of different approaches. So maybe it's using this drug with another medication where you're going to get the real big effect sizes. So you'd have to test it out, I don't mean literally on people, but say, try this, see if it works. Yeah, I mean, that's the nature. of how we practice pain medicine right now, right? It's, you know, it's kind of frustrating for patients and for the docs. Right. But is it almost, it sounds to me like a proof of concept within anything else. You know, the sodium channels, we can block them and it works.

Well, first of all, it is a real, a plecable drug with real utility. And you're right, it demonstrates a proof of concept that by targeting a specific type of sodium channel, you can provide pain relief, and it doesn't look like there's significant side effects. What I'm particularly hopeful about this medication is that it may provide an additional tool in the future for use in chronic pain conditions. Right now, it's only FDA approved for acute pain. This drug was strutted for post-surgical pain. after surgery. But one could also see it being used after trauma, but they do have phase three

clinical trials ongoing in diabetic peripheral neuropathy. Stay tuned. Stay tuned. And so we should stay tuned not only to see how this works, but what might come after it. Where does the research, I guess, where does it go from here? Yeah, I think there's a number of companies out there that are developing new agents that are going to be working in different places along the pain pathways. There's a company right now that are in late stage clinical trials focusing on what's called the trip V1 receptor, which is the Capsacin receptor. You know, the receptor that causes red hot chili peppers to be hot. Right. And so they've developed a drug that blocks that capsaicin and it's injected locally. And they've shown some long-term,

benefit after surgery and providing pain relief. So, you know, imagine you start to add, you know, a new drug like that, assuming it gets FDA approved with a sodium channel blocker like this, all of a sudden you start adding up to some real significant improvements in people's pain control. Right. You know, we've heard about personalized cancer treatment. Are we also talking here then? Personalized pain treatment. Well, now you're really talking to me because this is, is a big focus of my research and a lot of others in the country is to advance this notion of personalized pain medicine. So our lab focuses on developing objective biomarkers of pain so that we can ultimately identify the right pain treatment for the right patient and the right circumstance.

And, you know, you could say that oncology has been our muse. We've watched them for the last several decades, advance this space and do amazing work in personalized cancer care. And we're all sprinting to try to catch up with what they've done in cancer. And I'm particularly optimistic that we're going to get there. Getting back to this drug here, and I know that you treat patients, and do you plan on using this as a clinician? I think the questions for drugs like this are always, how effective is it? And we've got one published study showing it's got mild effectiveness and has some clinical utility. Two, what are its side effects? We spend a lot of time thinking about how drugs are going to impact people. This seems to be pretty mild and three costs. So on one hand, if you have a drug that

you know, is the same cost as Skittles, well, are you going to use it a lot? On the other hand, if it's priced as, say, a chemotherapy infusion, it's thousands and thousands of dollars, then we're going to be very selective with it. Yeah, because as you say, if the studies show it doesn't work much better than a placebo, then what's the sense, right, until you try it out? Yeah, I think one of the key things to note is this study that was done was done on a few hundred people. It's also a rather homogeneous set of people. What I mean, it's almost all women in these studies. We do know there's sex differences in responses to pain, men and women. We don't yet know if this will work the same in men as we do in women. It probably will based on what our understanding of the

physiology. Right. But until we get it out there and start applying it in thousands, tens of thousands, hundreds of thousands of people we're not going to know. We're also going to, in this process, get a lot more experience with what other potential side effects are. Just take a look at the GLP1 agents as an example. These are the drugs that cause weight loss, the azempic, the drugs that have been used to treat obesity. And people are seeing these used for many other indications, but now once you expose a public at large numbers, you now start to see potential side effects and the downsize to these medications. And it's only when you use them in those large numbers that that comes to bear. Very interesting, Dr. Mackey. I want to thank you for taking time to be with us today.

Thank you so much for having me on. And good luck to you in your research. Dr. Sean Mackey, Professor of Anesthesiology and Pain Medicine at Stanford University. After the break, you want to do some diving? Consider the oceans of Neptune or Uranus. So the upper layer is actually 8,000 kilometers steep. It's really, really thick. You could put the whole Earth in this layer. We've got a pretty good idea about what's beneath the surface of our nearest planetary neighbors, say, Mars.

But as you get further out into the solar system, our knowledge becomes scarce. For instance, what's inside the so-called ice giants of Neptune and Uranus? Recent research based on fluid simulation, hints that the planets could contain vast, multi-layered oceans, as much as thousands of miles deep. Joining me now to talk about that is Burkhard Militzer, Professor of Earth and Planetary Sciences at UC Berkeley. He wrote about this idea in the proceedings of the National Academy of Sciences. Welcome to Science Friday. Hello, it's good to be back.

Nice to have you. Why is it so hard to know what's out there on these planets? I think the main reason is they're far away, and we have not visited them very much. We had just one spacecraft that flew to Uranus and Neptune and measured the magnetic field, and this single measurement told us they have weird magnetic fields. So that was the starting point of the study, which we haven't been there at all. So you made computer simulations to figure out why they're strange magnetic fields? Yes, we've done this for quite some time, and we put materials at high pressure,

and we don't do lab experiments. That's what my colleagues do. I just pretend to do these things, and put it on the computer, and then study. What do the atoms do in this case? And in this particular case, when I put water and methane and ammonia in one box, It's really high pressure? The water mysteriously separated from the rest of it. That was the starting point of the study,

because the water seems to not like at these conditions, the carbon and the nitrogen system. And that gave us a clue what's probably going on in these ice giant planets, we call it. And I have an image in my head of oil and vinegar and my salad dressing separating. Is that sort of the same thing? That is pretty much true. That's the way you should think about it. But the problem is planets are hot in the interior.

And if you were to make the water and the vinegar really hot, it would mix. So what we're proposing that they don't mix or face separate, that is sort of radical. Nobody has done this before. But we think it's real because it gives us a good explanation for the field. Okay. Now draw me a picture then. If your theories are correct, what might be on these planets describe them for me? Yeah, so the traditional view is you have hydrogen and helium, which is a top layer,

and it has a little bit of methane, and it gives both of those planets a bluish color. So then the conventional wisdom was that there is this thick layer of water. So we're not saying we're the first one to say there's water there, that's the conventional wisdom. What we are saying that this thick layer, which we call the mantle, if you like, is split into two different layers. Just the upper layer is water, and then there is the carbon and the nitrogen that actually below. If you like, the oil is actually deeper at these things, and then there is rocks at the center of the plant. So what we're proposing in you is that this middle layer, which people thought is just water, in fact, has two separate layers.

The upper one is water, and the one below is carbon and nitrogen. And how deep is this upper layer of water? So the upper layer is actually 8,000 kilometers steep. It's really, really thick. So that is, you could put the whole Earth in this layer because these planets are bigger. They're about four times the size of Earth. And therefore, everything, all the different layers are proposing, they're very, very thick. So 8,000 kilometers, 8 times 6 is like 4,800 miles, something like that.

Yeah, that's right. Yes, yes. All right. Now, if this idea is correct, we check off, as you say, this question of why Voyager didn't see a magnetic field on these planets. Explain that a little bit more, why there would be the absence of the magnetic field. So do you pretty precise, we did see a field, but we didn't see the type of field were expected. So if you look at Earth, it has a well-defined magnetic north pole and a magnetic south pole. And you find this on Jupiter and Saturn, and then you fly to Uranus, in 1986, and the field is weird.

It looks like many small north and south poles, and it doesn't have this well-organized structure that we see you in the other plants. And that requires an explanation. Why is the field weird? And the proposal was, well, if you make this field just in a thin layer, rather than in the thick mantle,

a thin layer would actually make such a disorganized field, but people didn't know what those thin layer might be. So the proposal we're now saying this thin layer is this water layer that is not super thick because there's other layer underneath that doesn't make the field. So that's the novel interpretation which we hope is right, but we don't really know it's right until we have another probe that tests these things. Yeah. Are there other possibilities for why there's this weird magnetic field? I'm sure there are, but the moment we are the world,

One explanation that is we find very plausible. Other people just said it's just water all the way through in this mantle until you hit the rocks. And we find this implausible. I would say at the moment we have the most plausible explanation, but there could be others and we don't really know until we get more data from a future spacecraft. Now, other spacecraft were there. We're talking about Voyager and the data that came back many years ago, right?

Why has it taken so long for your simulations to yield some results? So we struggled with us. We had this idea, we pursued it in 2015, and we never saw this phase separation directly in the simulation. And the reason we now think was because we couldn't simulate enough atoms. So that we only had 100 atoms, but then machine learning methods came along, and I could simulate 500. And five hundred and ironically, it turned out

be enough that the system were actually phase separating two separate layers. Wow. Now, I know that some researchers have theorized that these planets might have other weird things like reigning diamonds. Oh, yes. Oh, yes.

I know Marvin Ross, we overlapped in Livermore. He was a good colleague of mine. That happens. But the question is whether it happens at high pressure. There are lab experiments that showed it. The question is whether this is actually happening in Uranus and Neptune. And the simulation that I've done is diamond would not rain out because it's too hot.

Ah. So at least that's what we differ from the older theories. Yes. I get it. Now, of course, the only way to test this would be what, to send another probe out there? Well, there are two things. So first of all, I talked to my colleagues at the Center for Matter Atomic Pressures, and they do lab experiment.

They should just take these materials, shock it with a laser to reach these extreme conditions, and see if they see the face upward. That's a good test. And then the other test is actually to fly a spacecraft. And they will probably measure all sorts of things. And NASA is in the process of preparing a Uranus orbiter and probe mission. And I'm just advocating you should bring the right instruments to detect such a novel two-layer structure on the mantle. That's what we're advocating for.

Ah, what instrument would that be? So it would be something that measures the oscillations of a planet. So it's been done for the Earth. We call this three oscillations on normal nodes that oscillate. You do this like the seismology, and you're done for the sun. You just look at the sun. You can check these vibrations. And now we want to do this for Uranus and Neptune.

If the vibrations have the right frequency, then we can tell. So the frequency is a little bit like you're listening to a bell that you can tell, and that helps you understand what the bell is made of, for example. It's like when we detect earthquakes, we look for traveling through the earth, right? The waves going through. Yes, so that our seismology colleagues, they do two things. When they won't understand the earth, they look for earthquake waves that travel through the earth and some travel to the mantle and some through go to the core.

And if you know how they travel, it tells us what's in the interior. But there is a different type of wave. And the earth is sort of vibrating, but on its own, without it triggering earthquake. And these are these re-ostulations. And my seismology colleagues use both of those data sets to understand there. Dr. Militzer, I'm going to give you my blank check question. If you had a blank check, you had all the money you needed, would you want to actually not land, but send, let's say, a diver probe, a submarine, something like that, into these planets?

Well, yes. But you have to look back what you need with other probes. So if you have a solid surface, then you can actually land on these things. When Neuron is in Neptune, most likely they don't have a solid surface. And you end up in this situation like with the Galileo probe that was dumped into Jupiter, and it had no mechanism to slow down. So it was flying in there, it was getting hot very quickly, and it sort of got too hot at the modest pressures of 22 bars.

So basically, most likely we'll have another, there is an entry probe. It will measure something, maybe 200 bars. But if you have any way to slow it down, then you could make cool measurements. But the moment this is the way it's going, it's probably there's no way to slow it down, and therefore it will just die if it enters the atmosphere.

Wow. Well, how soon do we think this probe might get out there? Well, that's a sad story, actually. honestly, because if NASA is really fast and gets everything together and Congress provides all the money we need, we might get there by 2050 and get measurements. And if I think about where I will be at 2050, I will most likely be retired. So I'm helping getting this off the ground, but I will not be the person who does the analysis for sure. You and me both, Dr. Millitzer. I guess so, yes. We'll meet back here.

Thank you for, this sounds fascinating. Thanks for taking time to talk with us today. Thank you so much. Burkhard Militzer is a professor of Earth and planetary sciences at UC Berkeley. That's about all the time we have. For now, a lot of people help make this show happen. Jordan Smudjik. Rasha Riedi. Charles Bergquist. Shoshana Buxbaum.

I'm Ira Flato. Thanks for listening.