Briefing Chat: 'External lungs' keep man alive for 48 hours until transplant

0:03Hi listeners, Benjamin here. Welcome to the Nature Briefing podcast, the Friday show where we talk about a couple of stories we've read in the Nature Briefing podcast. is, of course, Nature's daily email about the latest science. And we're recording this in Nature Towers once again, so you might hear the hum of folk working in the background, but we've got an exciting debut today. We've got a new member of the team, Maren Huntberger. Maren, how are you doing? Hello. I'm very excited to be on the pod. Thanks for having me, Ben. I am Nature's new senior multimedia producer, and I'm excited to be on The Briefing today.

0:36Well, very excited to have you here. And we've got a couple of stories to talk about. But say, Given that it's your first show, why don't you go first? Oh, thank you. I'm absolutely buzzing. A paper just came out in Cell that has the most amazing top line of the story. Man survives 48 hours without his lungs. How? Right. Please tell me. The answer is amazing technology. This is a new technology called a extracorporeal total artificial lung system, of course. TAL for short. Good. Nice and catchy. Yeah. And what happened is this patient came into the hospital because he had the flu, And this put him into what's called acute respiratory distress syndrome.

1:13Essentially, his lungs were filling with fluid and he couldn't breathe. So what do you do then? You put the patient on a ventilator. You know, many patients during COVID were put on ventilators because of this issue. Unfortunately, ventilators do come with some problems, including the potential of introducing a bacterial infection. Now, you and I are both former microbiologists. Ben, you've heard of Pseudomonas aeruginosa, the foe of medics and doctors worldwide. lied. It is really tricky to get off of a medical device and it is often antibacterial resistant. So it's very difficult to treat. So this poor guy, his lungs were totally failing and turning his entire body septic.

1:46So his blood pressure is tanking, his organs are failing. What do you do? You take the lungs out. And this is clearly a medical emergency and this is a drastic step. Absolutely. And it is something that does happen occasionally. So this is what's called a bridge technology to take someone from the point where their lungs have failed and get them to the point where they can get new lungs, where they can receive a lung transplant. So there is technology that has existed to do this, but it's pretty finicky and it has some problems. It's really difficult, as some of the researchers who have commented on this project, to, I don't know, keep the heart beating without the lungs, right?

2:17Yeah, they kind of go together, right? Sounds tricky. So the technology that already exists to do this is called ECMO, and it's been around since the 60s and 70s. It's used to keep a patient's heart and lungs alive and doing stuff while they're really struggling. but it's usually not used when the patient's lungs aren't in their body at all. So this is what this artificial lung system is able to do. It's able to keep the blood flow consistent and automatically modulate the pressure across the heart without the lungs in the body. Wow. Okay. And well, let's find out how did this person do them when they were hooked up to this system?

2:49Well, one of the most interesting things about this story, at least to me, is when they took the lungs out of his body, he immediately started to recover. So his sepsis goes away, His blood pressure re-regulates, his organs start to come out of failure. And it's all thanks to his heart still being able to pump and his blood still being able to be oxygenated by this artificial lung system. So that blood is being taken out of the heart and put into an external oxygenator and then pumped back into the heart on the other side so that it can then go to the rest of his tissues in his body. And so they take the lungs out.

3:17Over 48 hours, he starts to recover. He becomes well enough to receive his lung transplant. And now, almost three years after the fact, the paper just came out, but this did happen in 2023. Now, almost three years later, he's doing really well. His doctors say he's healthy and his lungs are functioning normally. Well, that's really good to hear. It is clearly a very, very extreme example of something that needs to be done to keep the patient alive. This is N equals one. Is this something that researchers are looking to make more widespread, do we think? Definitely. These researchers have made the technology and how it works.

3:48everything about it open access non-proprietary for anyone around the world who is able to use it because patients do often die waiting for lung transplant because their lungs fail before they're well enough to receive a transplant or before a transplant is ready. So the researchers are hoping that this artificial lung system will be able to bridge more and more patients to be able to get them to the point where they can receive a transplant. And you're right it is that weight that can really lead to very poor outcomes even death for people waiting for transplants and I can't help but think like kidney dialysis or even iron lungs as well as a way of mechanically keeping people alive or in a state that they can start recovering.

4:24And this is another one of those, maybe. Definitely. And definitely the most advanced version that we've seen so far. And one that does the best job of keeping the heart beating as it should with the proper pressure and the proper flow of blood between the chambers of the heart in order to make sure that, you know, this incredibly complex and risky goal of keeping someone alive without their lungs in their body has the best chance of success. So this is definitely the most advanced version of this technology we've ever seen so far. And that's one part of the story, Marin, of course. But you say there that the patient started to recover really quite quickly after his lungs were removed.

4:59Do we know why that happened? What was going on there? Absolutely. You're right. This is only half of the story. I think all of the headlines say artificial lung system, which is amazing. But the other half of the story is that they analyzed his lungs after they were taken out of his body. And of course, it showed the presence of both influenza virus and this bacteria that I mentioned earlier. And it also showed pretty much irreversible damage to his lung tissue. So once he had entered that ARDS, the acute respiratory distress syndrome stage, he wasn't going to be able to recover. Now, of course, this is only handy to know sort of in theory, because obviously it had already taken his lungs out of his body.

5:33But this is something that doctors have had lots of questions about for a long time. once a patient enters ARDS can they fully recover is it possible for us to just wait and put them on a ventilator or maybe even ECMO this other earlier version of the technology that I mentioned and just wait for them to recover and this is a new piece of evidence in saying maybe once a patient reaches a certain stage of that acute respiratory distress syndrome they will not be able to recover and they will need a lung transplant so this is new evidence that we haven't had before that that's the case that's what's happening inside the lungs during ARDS.

6:04Well, it's nice to start with a good news story. Do we know anything about the patient themselves? Have they said anything about how they're doing, you know, what they think about the treatment they underwent? Well, other than the reports from his doctors that say he's doing well and his lungs are healthy, this man has chosen to remain anonymous as much as we'd all love to know his thoughts. Well, if you are listening, very best of luck to you. Let's move on to our second story. And this is one that I read about in Nature based on a Nature study. And long-term listeners to the podcast will know that what I'm about to talk about is something that I have covered many times, namely how cancer cells evade the body's defenses.

6:39Like I think last year I covered how cancer cells can palm off their dysfunctional mitochondria into immune cells to kind of power them down, right? So a variety of ways to get around it. And this is another one of those. I mean, cancer cells are sneaky. They've got all kinds of methods for getting past the body's defense systems. Absolutely. And in this case, it seems to be that some tumors boost their own growth by commandeering a type of neuron called a sensory neuron and essentially hijacking its function. Whoa. And so these neurons, they're not just in our brain, right? We've got sensory neurons all over our body.

7:13Absolutely right. There are a variety of different highways that reach out to different organs, different limbs to get information back to the brain and vice versa. Now, nerve cells are known to reside in tumors but working out whether they have a role in the survival of said tumors has been difficult now there's a few reasons for this one is in the past genetic tools haven't really been sophisticated enough to tease out a neuron's activity right getting that signal from the noise but also neurons as cells can be really really really long right and generally the genetic material is kind of stored at one end at kind of the head and they have this kind of long fiber-like tendrils called dendrites and often it's these bits that plug into the tumors So when someone takes a biopsy, they might get the tail and not have the genetic information from the head, as it were.

7:59But in this case, the team have worked out a way to kind of get around that and inactivate specific sensory neurons. Now, they're looking at the vagus nerve. This is a really, really important sensory signaling highway that goes between the brain and many parts of the body, as we've said there. The heart, the lungs, the digestive system, all over the place, right? It's the biggie. Indeed. And this work, it has to be said, is done in mice, double-underline mice. But what they're looking at here is lungs and the nerves innervating lung tumours. And so what the team saw is when they inactivated neurons in this pathway, linking these lung tumour cells to the brain, what they thought would happen is this would switch off an important pathway, telling the brain, hey, there's a tumour here, let's get your defence on.

8:41They expected that to happen, but it was totally the opposite of that. When they inactivated the sensory neurons, they, quote, saw such a huge dramatic reduction, end quote, in tumour growth. The tumour growth halved, like 50 % reduction in growth. And this is where things take a turn. So what they think is happening is that ordinarily a signal is being sent up the vagus nerve to the brain in the mouse. But then another signal is being sent back to the tumour by a different neuronal pathway. way. And what this return signal does is it releases a chemical called noradrenaline that ultimately suppresses tumor-killing immune cells.

9:18So the cancer tricks the brain into turning off its own immune system. So once again, we have this very tricksy way that cancer cells can inhibit the immune system, or in this case, essentially just switch it off. Wow, that's really complex. And again, just one other way in their huge arsenal of tools that cancer cells are showing us they have to get around our body's defenses. A hundred percent. And what's interesting here is that it shows that it seems there is a neuronal aspect, a brain aspect to this as well. It's been a lot of work about how cancer cells interact with nerves, but working out that there's this pathway that goes all the way up and then all the way back down again is something that wasn't well understood.

9:58And there had been some debate in the field about this kind of a situation. But of course, Maren, there are caveats to this. As I've said, this is a mouse model. This is one sort of cancer. And whether this effect is seen across the board, whether it's relevant in humans is one of those things that we don't know yet. But we can chalk this up on the board of things to think about when we're trying to work out how to attack cancer cells. Yes. And just another tick in the column of like, look into this further, because we could be able to use some of these mechanisms or target some of these mechanisms with potential future treatments.

10:30100 % the mitochondrion thing that I talked about at the start researchers are looking at that to try and work out is there ways that we can stop this happening of course these are far far down the track but you have to start somewhere you got to start somewhere well two very interesting stories there Maren thank you so much for being here listeners we will put links to both of those in the show notes and a link where you can sign up for the nature briefing to get even more stories delivered directly to your inbox but for the time being I've been Benjamin Thompson Maren Hunsberger thank you so much for being here.

10:58Thanks so much for having me. And thank you listeners for having me in your ears. Thanks for listening. And we'll see you next time.