Jab to alleviate asthma attacks, and amber in Antarctica
In the news, a potentially game-changing new injection to ease the suffering caused by asthma attacks shows success. Also, who should fix the gas leak on the International Space Station? Then, fossilised footsteps fuel speculation over interactions between early human ancestors, and we find out what the presence of amber in Antarctica reveals about the history of this now desloate land...
In this episode
01:03 - First new treatment for asthma attacks in 50 years
First new treatment for asthma attacks in 50 years
Richard Russell, King's College London
A new study has found that an injection given to people who suffer from asthma and COPD - chronic obstructive pulmonary disease - attacks is much more effective than the current treatment with steroid tablets, which - alarmingly - fails three quarters of the time. The new therapy - an injected antibody that targets a population of white blood cells called eosinophils, which drive the inflammatory response that causes many asthma attacks and COPD exacerbations - is called benralizumab. And the authors say it could be “game-changing” for millions of people. Here’s Richard Russell at King’s College, London…
Richard - We know people have these attacks. These attacks occur and they affect individuals. They cause loss of lung function. They make them feel really sick. They lead to hospitalisation and indeed, in some cases, lead to death. The treatments we've had have not changed for over 50 years. We give these people oral corticosteroid treatments, anti-inflammatory therapies. We were then aware that these treatments themselves, 1) are not very effective. 2) have got side effects; osteoporosis, diabetes, obesity, skin thinning, bruising, cataracts. We needed to think can we find a better treatment? We identified, over 15 years ago now, that there are groups of patients who have attacks of a particular pattern of inflammation, we'll call it eosinophilic inflammation. Now what was really exciting is that, in the last few years, we've developed new treatments which are specific to reducing this pattern of inflammation.
Chris - But what are eosinophils and why are they uniquely bound up with these particular patterns of attacks?
Richard - Well, that's a really great point. Eosinophils are part of your immune system. They're white blood cells. They are relatively uncommon in our blood in comparison with other blood cells. Historically, we believe they've been associated with particular things like allergy and indeed asthma, but also worm infection. We've now recognised that these eosinophils are really important in our guts and in our lungs, particularly at monitoring what is going on in the immune environment. We recognise these cells are actually really important and what happens is, when you have an eosinophilic attack, you have an increase in breathlessness, increasing in cough and sputum, and in your blood we can measure an increased level of these eosinophils. That's what we're targeting with this new treatment.
Chris - The rationale being then that if there's a lot of these cells and they're linked to attacks, if you reduce the number of them, you should have fewer attacks.
Richard - Absolutely correct. That's exactly what we did. We designed a study using a treatment called benralizumab. Benralizumab is an antibody therapy given by injection which specifically targets eosinophil production and migration into the lungs. We compared this with standard therapy oral corticosteroids, and indeed we had a third arm, which was a combination of the two treatments together.
Chris - How many people did you look at and who? Who were the patients?
Richard - We looked at 158 patients. These patients were all comers, whether they had asthma or COPD, that had an attack. If you were a patient out there on the street and you had a worsening of your condition, you would come along to us. We would do a blood test at that moment. If your eosinophils were raised, we would then randomise you into the study. It was everyone with asthma and COPD who had this raised level of eosinophils and we followed them for three months, 90 days. Our primary outcome was what we call treatment failure, meaning: did your treatment work or not? If your treatment failed is defined by needing more treatment or having to go to hospital or even dying. We were comparing the failure rates of standard treatment with the failure rates of this new therapy.
Chris - And how did they compare?
Richard - What we demonstrated was a couple of things. One, if you have eosinophilic exacerbation attack (from asthma or COPD), you have got with standard therapy around a 74% chance of your treatment not working. Now, that should shock the audience today because I think that's where we are right now. That is standard therapy. Is that good enough? Absolutely not. But what we demonstrated was that, with the new therapy, we were able to reduce that rate to around 44%, which is a 74% reduction in treatment failure.
Chris - Is it practical and is it cost effective? Because that's the thing that NICE are very keen on. We have drugs that might work, but if they don't work well enough to return a good bang for their buck, they won't say we can use them. Where do we sit on that line?
Richard - There are two points there. Let me put the first one to bed: is it practical? Yes, absolutely it is. We have technology which can allow for point of care testing of your blood with an answer within seconds, if not a couple of minutes. That is available right now and indeed our standard therapies in hospital can give you a blood result within a few minutes. It is absolutely practical. The injections are given, can even be given by the patient themselves, but certainly are very easy to administer, and the side effect profile is extremely good. We've got experience with these over time. The practicality I think gets a big tick, absolutely. Cost effect is much more difficult. Steroids are very cheap but, hold on, steroids fail 75% of the time, so what the heck are we doing with this? We're exposing people to side effects and risk, so we need to do a bigger study, a phase three, larger scale multinational study, and then we can do some cost effective analysis which will make the argument, I would hope, to use these treatments. This is a one-off treatment, not recurrent treatment. If you end up being admitted to hospital, or even worse, you end up being admitted to intensive care, you are looking at a cost of 2, 3, 4, 5,000 pounds a day. This treatment costs around a thousand pounds. So, although it is expensive, if it's saves intensive care and even death, that will end up being cost effective.
07:17 - The row over a leak on the International Space Station
The row over a leak on the International Space Station
Richard Hollingham, Space Boffins
The International Space Station has been a great source of collaboration between the NASA and Roscosmos space agencies for decades. But the extent of a five-year-old leak on board the ISS has put Washington and Moscow loggerheads. Here’s Richard Hollingham from the Space Boffins on what we know about the leak…
Richard - It's months or years old and no one quite knows exactly where it is or what caused it. It could be around the welds in the structure of this section of the space station, or it could just be in the integrity of the metal as well. This section, it connects the Russian spacecraft to the station itself. They have this little tunnel, you have the progress freighters, which are uncrewed spacecraft, they dock with the station, they go into this tunnel to get all the stuff out, and they put all the rubbish in and they send the freighter back to burn up in the Earth's atmosphere. It's quite a crucial module, but right now they can close the door, so although it's leaking it's not affecting the integrity of the rest of the station.
Chris - What's the scale of the leak? How much are they actually losing in gas terms?
Richard - It's really not a huge amount. It's not like there's a *hiss* of air going out. It's just a gentle leak over time, like a slow puncture, I guess, on a car or a bike. This module is really old. This has been in space since the year 2000. These were actually built before then, so it's really getting on in years. It's got this harsh environment, it's got pretty much constant bombardment by micro meteoroids, little tiny space rocks, the risk of space debris also hitting the station too. It's reaching the end of its life and it looks like this is the first section to really be showing that. It could have happened to another part of the station as well. When you look at the actual fabric, the basic whole structure of the station, this is not thick metal. This is centimetres thick. It's not a massive structure because you have got to launch it into space and then it doesn't have to be particularly thick once it's in space. But that does mean any leaks or any welds, anything like that is going to deteriorate over time.
Chris - Why are NASA and Roscosmos having argy-bargy about it?
Richard - Russia never seems to admit a problem with its side of the space station, or with any of its space programme. We see this on the ground of course as well. Very thin skinned, I would say, are the senior officials of the Russian space programme. I do think it's extraordinary that, if you think about it, 400 kilometres above our heads on the International Space Station, the Americans and the Russians are cooperating. Meanwhile, on the ground, there's a proxy war between NATO and Russia in Ukraine. I think it's almost extraordinary they've been cooperating for so long, but there's just this constant pushback on things. Meanwhile, in space, actually the crew get on really well because they're in this harsh environment. Everything's safety critical, they have to get on well! They're all astronauts.
Chris - So what happens if they just carry on rubbing along as they are and they don't fix this?
Richard - It'll probably be fine, until it's not. That's the problem with these things, particularly as they haven't actually identified what the specific problem is, where the leak is. All the time now they're closing the door to this section of the space station. If the leak gets worse, they will have to close that door permanently. If that happens, that means they will not be able to dock the progress cargo spacecraft to the station. They'll be then solely probably relying on the American SpaceX. They need to fix it. They need to find the leak and fix it or decide, well, is it fixable? Is there a pinprick there, is there a failed weld, or is this something they're gonna have to live with? If it is a faulty weld, and there was some sort of knock to that or it suddenly gave, then you are in a potentially very dangerous situation if that hatch is open. They've got to keep the space station alive working for another six years or so. That's the plan at the moment, till 2030, which means this stuff has got to limp on. It would've been in space operating with people on board for 30 years. That is extraordinary.
Chris - Can you repair stuff in space in the same way? If that was a blow up boat on the ocean, you'd put a patch on it, wouldn't you? Is that sort of thing feasible in space?
Richard - Exactly the same. In the past, when there was the Mir space station, you may remember, in its dying days, there was a massive collision with a cargo module when it hit the space station. That was a catastrophic loss of air with the crew having to really shut the hatches to stop it. They went outside, they repaired it. You can use tape! There is a lot of tape used on the space station to hold stuff to walls and things. You could just stick some tape over it. It will be absolutely fine. So it is fixable, the issue seems to be, with this particular leak, they don't know exactly where it is or what it is, and no one seems to be investigating to find that.
13:40 - Were different species of early humans neighbours?
Were different species of early humans neighbours?
Craig Feibel, Rutgers University
But now, researchers say they have found the 1.5-million-year-old criss-crossing footprints of two different species of early human ancestors preserved in mud at the same spot in Kenya. Nearly half a century ago in the same geography the famous British palaeoanthropologist Mary Leakey made a similar discovery of footprints dating back over three and a half million years. Those footprints were some of the strongest evidence at the time that those ancestors walked on two feet. The international team who’ve made the new discovery, which actually also includes one of Mary Leakey’s descendents, say their findings prove that at least two different ancient hominins were near neighbours and possibly even friends. Here’s Craig Feibel at Rutgers University…
Craig - This is a trackway from one and a half million years ago that represents a beach on an ancient lake. On that beach surface, we have the trackways of not only a lot of birds and other animals, but two of our ancient cousins; one walking along the beach and one at some point crossing that trackway. We can see two different trails on this surface.
Chris - And are these two different species, effectively? They're two different branches of life's evolutionary past.
Craig - For the first time, I think we can actually distinguish individual footprints and begin to tell that at least they're different, that there are two different forms here. We can tell them apart. That's really the novelty of this particular discovery, I think, that we can recognise that they're in the same place, maybe not at exactly the same time, but that they passed across the same beach probably within a few hours or a couple days of each other.
Chris - You're calling them cousins, but what were the two groups that you think made these footprints?
Craig - One of them is the lineage that leads directly to us, so our direct ancestor. That would've looked very much I think as we do today, a very long bodied, tall form. But the other cousin was very, very different. It was a shorter, stouter, more robustly built cousin. Perhaps the main distinction between the two is that we think our ancestors were already into scavenging for meat and marrow and having an omnivore's diet, whereas this other stockier cousin was perhaps still more of a vegetarian.
Chris - We often think of the timeline of evolution as, one thing turns into the next, turns into the next. But what this is saying is actually something quite different, which is something we've suspected. That these things were all going on and around in an overlapping way. They were around simultaneously. It's like nature was doing an experiment with lots of different forms alongside each other.
Craig - In this particular time span, one and a half million years ago, there was quite a bit more diversity than we have in the world today. Not only were there different kinds of giraffe or different kinds of antelope, even in our own group we had cousins that were very similar to ourselves, but were different species. Today we're the only surviving species, but we had a number of these cousins who have all gone extinct over time.
Chris - How did you find these footprints? Where are they? And how do you know, just on the basis of a footprint, that one is homo, our lineage, and the other is this other group which are a bit stockier, a bit shorter and into eating vegetables and so on?
Craig - The footprints are found in northern Kenya, up towards the Ethiopian border on the Eastern side of Lake Turkana. They're in deposits that represent an ancient lake where a river was coming in near the shoreline of the lake. That would have been the setting for this particular several days of fossil record. A number of different birds and animals were wandering along the beach, and all of their tracks are preserved on this surface. Footprints preserve very nicely in damp sediment, and that's part of the story here. They're very nicely formed in the soft sediment and then a nearby river gently buried them and preserved them to the present day.
Chris - And that enables you, with the detail you've got there, to say, well, these are definitely the footprints of one group and these are definitely the footprints of the other.
Craig - That was the surprise in this discovery. In part the technology and our understanding of feet and how feet operate, the locomotion of human ancestors, has advanced a lot. Looking at the details of these feet, it was very apparent that there were two different ways of walking here, two different kinds of getting across the landscape. That made these two sets of footprints quite distinctive.
Chris - It's interesting, isn't it, because that part of the world has form for this kind of thing. Mary Leakey made her name and put it on the map, this area, this part of the world, for this very reason.
Craig - This is one of the richest places in the world for fossils from the last few million years time. Over the last 50 years there has been extensive exploration and discovery there. The way in which these footprints were found, Mary Leakey's granddaughter Louise Leakey now runs a team of fossil hunters who prospect the landscape and search for fossils there. They had actually found some very interesting bones on the surface at this locality. When you find bones on the surface, you're often curious if there's anything still in the ground still buried. They were starting an excavation to see if they could find more of those bones, and that's when they stumbled across the footprints.
Chris - And just for clarity, how do you know how old they are?
Craig - We managed to date these sites because there are volcanoes that are very active in the Rift Valley at that time. In some of the materials that are thrown out of the volcano, volcanic ash, and particularly pumice, they have some crystals in them that originate with that eruption. Those crystals can be dated by radiometric decay to give us an age for that particular eruption. Then, we can relate those to where the fossils are found.
Chris - What do you think the main learning point here is to emerge from this?
Craig - One of the most interesting things we've learned from this is that these two forms were actually on the same part of the landscape. The problem has been that, when we find the fossil bones, they're not always in the place that the animal lived. Bones can be transported by water, or often carried by a carnivore or a scavenger. We knew there were two different species present, but we really had no idea if they would've ever encountered each other on a given day. This tells us that they're very much in the same space.
Chris - Were they friends or were they enemies, do you think?
Craig - It's very hard to say. They probably recognised each other as we recognised any other animal on the landscape. They may have seen the similarities, but they were probably very different in their lives, not competing with each other and so probably less likely to have interacted very actively.
21:31 - Why the discovery of amber in Antarctica matters
Why the discovery of amber in Antarctica matters
Johann Klages, Alfred-Wegener Institute
Sticking with ancient fossilised relics from the past, scientists in Germany say they have discovered the first documented deposits of amber in Antarctica. It means that the resin has now been found on every continent on the planet, and it paints a picture of a heavily forested Antarctic continent millions of years ago. Here’s Johann Klages at the Alfred-Wegener Institute…
Johann - We found for the first time amber in Antarctica. Fossilised resin that trees exude when they try to seal injuries, for example. That was really the first time in Antarctica. So far, on all continents, Amber was found and discovered, but not in Antarctica. That was really exciting for us.
Chris - Where did you find it?
Johann - We found it in a marine sediment core, which is very unusual because normally you don't find these things in a marine sediment core, but at the time, when the resin deposited, it was a terrestrial ecosystem, so on land. And therefore it is a direct indication and direct evidence for us that a forest must have existed in the location where we drilled.
Chris - You don't think the amber could have got there via another route? Perhaps an animal took it, or currents took it, something like that?
Johann - No, because we know exactly what this environment was about because we published another paper in 2020 where we reconstructed a temperate rainforest in the same location, and sediments were completely undisturbed and pristinely preserved. We have a root system in there. We have pollen and spores from these plants back then. So we know that the sediments were pristinely preserved. We looked a little closer in the particular layer of that sediment core, and there we found this amber. The first direct evidence for the presence of resin producing trees in that particular location.
Chris - Critically, when does that date from, then?
Johann - In between, let's say, 93 to 82 million years. This is the time the dinosaurs lived. We call that the mid Cretaceous, which is about 90 million years ago.
Chris - Why was Antarctica so different then compared to how it is now?
Johann - Interestingly, the location of Antarctica was not so much different. The location where we drilled today is on 73 degrees South, which is pretty far South, but back then it was on 82 degrees South, so only 900 kilometres away from the South Pole. But, and this is a big but, the continent of Antarctica was still connected to the other continents in the Southern hemisphere, so South America, South Africa, and also Australia, New Zealand. There were land connections in between those continents and it was the final breakup of those continents from Antarctica, the final days of the super continent, and we call that Gondwana, and that was about 90 million years ago.
Chris - Why though is it now so cold, and back then it was much warmer, despite being in the same geographical position, warm enough to sustain a big rainforest?
Johann - That is a very good question, and we know exactly why that is. The continents were connected back then, also ocean currents and atmospheric currents, winds, were able to reach the Antarctic continent and transport warm water and air masses towards the continent much further south than can be done today. If you go back further in time, 34 million years before, then we had a time where those continents of South America, Africa and Australia were already very far away because of continental drift from Antarctica. Therefore an ocean current could evolve in between Antarctica and the other currents and we know that today as the circumpolar arctic current. Not only that, also at this time, 34 million years ago, the CO2 content globally in the atmosphere dropped significantly. Those two things together, and they're of course also connected to those things, they led to a significant cooling of the entire planet.
Chris - If Antarctica was connected to these other continents to create not just those climate effects, but also to allow other things to get there, does that mean there were animals down there as well then in much greater profusion than just the very specialist species that we see today?
Johann - Definitely. From the Antarctic Peninsula we have much evidence for the presence of, for example, dinosaurs. We also have evidence for insects and also frogs a little bit later in the Eocene. But still, it must have been a very diverse environment down there. Just imagine, on 82 degrees South, we had a temperate rainforest environment that could survive in those conditions, even though we also back then of course had almost four months total darkness because of the polar night.
27:27 - How do parasites recognise their hosts?
How do parasites recognise their hosts?
Thanks Kate. Parasites are organisms that live in or on other organisms. These freeloaders are dependent on their hosts for their survival, causing harm to benefit themselves, offering nothing in return. That’s why they have to come up with all sorts of tricks to evade the immune systems of their hosts, developed over generations of co-evolution.
You’re right to point out that often they can go on some extremely complicated journeys to reach what’s known as their primary or definitive hosts, where they will become adults and reproduce. Here to tell us about some of them is Professor of Parasitology at the University of Cambridge, Catherine Merrick. She spoke to James Tytko…
Catherine - There are at least two primary sets of cues that parasites rely on to know that it is in the right place. Firstly, the general environment: reacting to changes in temperature and pH and so on.
For example, many food and water-borne parasites have a resistant cyst form that survives in soil or water, shielding them from damage. These cysts only emerge and replicate when chemical signals from the host’s gut - like the low pH of stomach acid or bile salts in the small intestine - prompt the parasite to activate.
Notable examples of this include Cryptosporidium, which caused a major diarrheal outbreak in Devon this summer, and Toxoplasma, one of the most common parasites, which is spread through cysts found in cat feces.
Temperature is another common signal. The reproductive cells of malaria parasites transform and rapidly mate when the temperature drops from the human body’s typical 37°C to the 20°C inside a mosquito.
James - This is what we’re competing with in the biological arms race against malaria. Research has also shown that malaria parasites will sync up with our body clocks to help their development, another part of their ingenious life cycle. What about the second set of cues parasites use, Catherine?
Catherine - The second cues involve a more specific interaction with the host itself. Toxoplasma, which I mentioned earlier, is also interesting here. It will emerge from its cysts in the gut of any warm-blooded animal. However, if it detects that it is inside a cat, it reacts differently. In the cat's gut, the parasite undergoes sexual reproduction and produces new cysts, which are then excreted in the feces and can infect others. In other hosts, such as humans, Toxoplasma behaves differently: it burrows through the gut wall, remaining dormant in body tissues until a cat consumes the host.
The exact mechanism that enables the parasite to distinguish a cat’s gut remains unknown, but what’s interesting is that we see a similar fussiness in malaria parasites. For instance, malaria parasites that infect mice cannot invade human blood cells, and vice versa. This specificity is due to the interaction between proteins on the surface of red blood cells and those on the parasite: without the precise match, the parasite cannot invade. Such specific interactions are of great interest, particularly as potential targets for vaccines.
James - Indeed. The World Health Organization recently approved a new malaria vaccine that works by injecting malaria proteins into the bloodstream, along with an adjuvant to kickstart the body’s immune system. This process leads the body to develop antibodies so it’s ready for next time it comes across this specific protein,
Thanks so much to Catherine Merrick, Professor of Parasitology at the University of Cambridge for helping with that one.
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