Vaccines, squirrels with leprosy, and exoplanet atmospheres
In the news pod, the nanotechnology enabling the production of a new vaccine to immunise against future coronaviruses. Then, how we can use psychedelic treatments without giving patients an unwanted trip, and how it was discovered that squirrels and humans were both living with leprosy in medieval England. Plus, what does the latest exoplanet discovery tell us about how far the closest habitable planet might be?
In this episode
01:02 - Vaccines for viruses that haven't even evolved yet
Vaccines for viruses that haven't even evolved yet
Rory Hills, University of Cambridge
Researchers at the University of Cambridge have developed a new vaccine technology which they believe could provide protection against a range of new coronaviruses, including even those that may not even exist yet. It’s hoped that the discovery could help curb future pandemics. It works by glueing key pieces of the virus outer coat that are shared by many different viruses onto injected nanoparticles; these train the immune system to recognise them. Here’s Rory Hills from the University of Cambridge’s department of pharmacology…
Rory - There are a variety of other coronaviruses in the same family that are lurking in bats and pangolins and other mammals that have the chance to cross over to humans. Our vision is to have a vaccine that can protect against those before they've actually crossed over to humans.
Chris - One scientist scarily told me during Covid that there are probably as many as 5,000 members of the coronavirus family, quite a high fraction of which might jump the species barrier. You're pushing on an open door, I'd say. How do you do it?
Rory - We use a protein nanoparticle as the basis of our vaccine and then we attach parts of different viruses to that same nanoparticle. The trick is we create a mosaic of all these different viruses and when you immunise with that, you train the immune system to go after the parts of those viruses that are shared. If we can train the immune system to go after those shared parts, we can protect against all of those viruses we have on the vaccine, but also against ones that aren't present and are just related.
Chris - Because those things, even though you've not seen them, have still got that same core part that those other things you did train the immune system on had and so you make a response that indirectly protects you against those?
Rory - Exactly right.
Chris - Didn't some people argue that during Covid that was naturally happening in the sense that there were some people who didn't get the virus or didn't get it badly and they made the case that those individuals had perhaps had one of the other common coronavirus infections and made a response to it that happened to protect them because they'd made a response to some of the bits that those other common coronaviruses share with the SARS-CoV-2 virus that causes Covid?
Rory - That's my understanding. Of the seven coronaviruses that infect humans, four of them cause the common cold. There are regions of those spike proteins on those common cold coronaviruses that can provide protection against SARS-CoV-2.
Chris - When you're trying to make your vaccines, how do you spot the bit that you're going to put onto your nanoparticle? How do you say, well, I'm going to have that bit and that's going to be a really good bit to go for.
Rory - We have been very conventional in that approach. We've just used the receptor binding domain of the spike protein, the RBD, and that's the tip of the spear...
Chris - This is on SARS-CoV-2?
Rory - SARS-CoV-2. Yes. We've taken that same protein on all of the other coronaviruses, and then the trick is we haven't necessarily gone through and tried to pick out the parts that we're trying to target. Just by the nature of having these eight different proteins on the nanoparticle, we train the immune system to go after the parts that are shared. So we don't have to know going in what those parts are.
Chris - Does it work?
Rory - It works remarkably well. It works better than we were initially anticipating. When we immunise animals with our vaccine, we end up getting responses that are neutralising against the viruses included and then also viruses not included. In fact, I've created a version of our vaccine that doesn't have Covid, doesn't have any closely related viruses to Covid, and we're still able to get a very strong response against Covid with that vaccine.
Chris - You mentioned you vaccinated animals. You put this in and they presumably make antibodies. How do you then make sure they're protected against this range of viruses?
Rory - There are three main outputs. The first one is the easiest one: that's just making sure that the antibodies that they make bind to the proteins that the virus produces. We use something called ELISA for that. The second one is called a 'pseudo virus neutralisation assay.' So we have essentially a modified version of the virus that's not dangerous, it just carries the single protein from a coronavirus, and we look at that ability to infect human cells in a dish when we add serum from mice that we've immunised with our vaccine.
Chris - That's got the antibodies in it that serum. You're then able to say, well, if that blocks that then, were that in the animal for real, they would be protected.
Rory - Exactly. And the third way is that we take the actual COVID-19 virus and look at its ability to infect human cells in a dish. We look at the protection that is conferred by the antibodies that we've raised in mice.
Chris - And that works?
Rory - It works brilliantly. I think if we think much more long term, the vision is that you could have a library of preexisting vaccines that protect against a group of viruses, have them validated for safety and efficacy and on the shelf ready to go in case of future pandemic.
Chris - People have been trying to do this for flu for decades. When I was a medical student, people were trying to do this and make the 'uni flu vaccine.' Can you now turn this on to challenges like flu?
Rory - That's certainly something that we're really interested in and I think it's something that we definitely want to strive for. A universal flu vaccine is a very substantial challenge. Flu has been with us for a very long time, it's diversified incredibly, and it's not just a matter of getting antibodies that bind, we also want to have them actually able to neutralise the virus.
Chris - You're saying flu is a harder nut to crack?
Rory - I think so.
06:52 - Psychedelic toad venom chemical could cure depression
Psychedelic toad venom chemical could cure depression
David Nutt, Imperial College London
In 2022, the US National Park Service urged people to please stop licking Sonoran desert toads. The warning came about because the amphibian - which is frequently called a Colorado River toad - secretes a venom from glands on its back that can provoke an hallucinogenic experience. Biologists think the toads make the chemical to ward off predators. But now a new study published in Nature suggests that a modified version of the venom may prove effective for treatment-resistant depression and anxiety symptoms that don’t respond to traditional antidepressant medicines. Up to one person in three meets this definition. But not everyone can tolerate the hallucinogenic effects. The researchers suspect that the toad chemical is activating two brain pathways: one that produces those hallucinatory experiences, while the other is the depression buster. They’ve modified the molecule to lock onto just the desirable one. David Nutt, a professor of neuropsychopharmacology and the chair of Drug Science at Imperial College London, works on very similar research in his lab, so we asked him to take us through the new results…
David - There's a great need for new treatments in psychiatry. There's been very little innovation from pharma companies over the last 20 years. The biggest and most exciting development has come from academics like my own group using psychedelics. There's really good evidence now that these can lift depression where other treatments have failed. Now, there are different sorts of psychedelics. There are classic ones that people have heard of, like LSD, but there are others popular with aficionados but not so well known. One of them is a molecule called 5-MeO-DMT which comes from, amongst other sources, the Sonoran Desert toad. The toad secretes this molecule, probably as a deterrent to other animals eating it because they get quite powerful hallucinations. Now, 5 MeO-DMT has been known for some time to be a powerful hallucinogen in humans and, like other serotonergic psychedelics - LSD, psilocybin, DMT - it has a potential utility for the treatment of depression. But there is a lot of concern amongst investors and to some extent amongst some patients that a psychedelic trip might be challenging, particularly in depressed people. In fact, it is, there's no question. So there is a feeling that if we could get the therapeutic benefit of psychedelics without the trip, that would be a major advance, which of course it would.
Chris - Do you think it would be possible to divorce the two? Do you have to have the psychedelic element to get the therapeutic depression busting element, or are they mediated through two different routes in the brain and it's just because the molecules activate both you end up with both, but you don't need both?
David - Well, that's the hope. My own personal view, and certainly our own research supports this, is that the magnitude of the psychedelic experience is predictive of the outcome, but I cannot prove that. One thing that is clear is the pharmacology of psychedelic drugs is not just at the serotonin 2A receptor, the psychedelic receptor. There's also an activity through another serotonin receptor called the 5-HT1A receptor. We've long known that this receptor is involved in the brain circuits relating particularly to stress and in fact it's very likely that the antidepressant effects of classic antidepressants like the SSRIs are mediated through enhancing activity at the serotonin 1A receptor. It is a different kind of antidepressant effect with some unwanted deleterious actions like some blunting of emotions, but it's unquestionably a target for antidepressants.
Chris - So what did they do here to try to shed a bit more light on this?
David - What they're trying to do, as many groups are, is to try to get an antidepressant effect through these current hallucinogens, psychedelics, without having hallucinatory effects. They have taken this five methoxy dimethyltryptamine molecule and they have put it through a very sophisticated, very beautiful, series of in silico receptor interactions, looking at how the molecule and predicted chemical variance of the molecule will interact with the protein structure of the receptor. It's extremely high quality, which you might call molecular chemical pharmacology. From that they've come up with a couple of molecules which have specific activity at the 1A receptor, but without activity at the 5-HT1A receptor. So, they have taken the toad venom and turned it into something that is not hallucinogenic, but they believe may still be an antidepressant.
Chris - And is this purely still in the mind's eye of a computer, or have they actually got the molecule and have they put it into a brain yet?
David - Well, they've definitely got the molecules and they've definitely put them into mice and they've definitely shown some impact on tests of depression and anxiety. They have shown that.
Chris - The next step I suppose then is to go the sort of route that you and others have gone, which is to start physically testing this in real life patients to see if you still get this therapeutic effect without the scary hallucinogenic effects?
David - That is the next step. The problem is the compound they have invented is very similar to a compound that was made by Duphar, a drug company that's no longer with us, with exactly the same theory 30 years ago. It didn't work very well in depression, had quite a lot of side effects. So I think it's pretty implausible, frankly, that their new molecules are going to have any real clinical benefit. But of course, it has to be tested, and I may be wrong.
Chris - And of course there are people who don't rely on pharmaceutical companies. They go to the source itself because there is a trend of people licking toads and have done for centuries possibly to get these effects. That's true, isn't it?
David - That is true. But I want to say please don't ever use 5-MeO-DMT from a toad. People seeking out '5 MeO' as we call it, should not source it from the toad. It can be sourced from plants. Please do not use the toad, otherwise the toads will be extinct. The second thing is, people using 5-MeO-DMT are doing so because it produces a very powerful, rather strange, slightly different hallucinatory effects to psilocybin and LSD. We are currently studying that. No one's actually ever done a brain imaging study of the 5-MeO yet. We are starting that at Imperial literally this week. We'll find out whether it does have the same signatures in the brain as other 5-HC2 agonists. You can't get, from a toad or anything else, any other living species, the molecule that they're testing. This is a fluorinated molecule. It's not made in nature. It has to be made in the lab.
14:44 - Leprosy transmission between squirrels and humans
Leprosy transmission between squirrels and humans
Sarah Inskip, University of Leicester
But first, archaeologists have found that, during the Middle Ages, leprosy was transmitting between red squirrels and humans. It was revealed following a study of squirrel bones and human remains in the English city of Winchester. I’ve been speaking with Sarah Inskip, a bioarchaeologist at the University of Leicester and a co-author on the study…
Sarah - About eight years ago, people found that modern British red squirrels were infected with a strain of leprosy that had infected humans in medieval England. We were really interested to try and find out how these modern British red squirrels effectively had a strain of a disease that hasn't really been seen in England for about two to three hundred years. In order to answer this question, we needed to go back.
Chris - Where did you go back to and how far back?
Sarah - We went back about a thousand years, and in particular we looked at medieval Winchester. One of the reasons as to why we chose Winchester is because it had a large leprosarium. This is a hospital that was set up to care for individuals that had the disease. At the same time, we also knew that within the town there were fur trader streets where there were the archaeological remains of lots of red squirrels. We picked this place because we had circulating leprosy in humans, and then we had the opportunity to look at, well, is it also circulating in the red squirrels at this time? Is there possibility for transmission between the two?
Chris - Were squirrels very much part of the fur trade back in those days then?
Sarah - Yes. It's actually really strange. We don't think of squirrels as being important for animals, but they were really important for over a thousand years in England in terms of lining garments. People would line them up, the white to the grey, to make these very pretty fur lined trims. It was far more important than I even thought was possible.
Chris - So your theory would be that the squirrels are brought in and the leprosy is in the squirrels that get used for their fur, or just the fact that they are around humans and humans have got leprosy, it got into the squirrels from us. Do you know which way round it was likely to have been?
Sarah - This is one of the really important questions and actually we don't know which way round it would have occurred because people kept them as pets as well. At some point, someone would've been working with live squirrels to get the skins processed and then people would've been working with the skins to make it ready for a garment. Each one of those would allow transmission in both directions as well. We still want to try and find out.
Chris - So what did you have to work with from ancient Winchester and how did you study it?
Sarah - From Winchester, we had access to the individuals that had leprosy within the leprosarium, and it's quite big. It has individuals that span a number of years and we were able to extract their teeth and look in the pulp chamber where you have the blood that circulates in and out of teeth. We were able to look for the DNA of the leprosy causing pathogen within that chamber from the humans, but from the squirrels we were limited to a furrier pit. A furrier pit is a fur trader's pit where they're processing the fur, they remove bits that they did need and that was the hands and feet that often get stuck to the fur. The human side was fine, we had plenty of material, but we only had hands and feet of squirrels to do this. And for us it was phenomenal that we were able to recover the bacteria that causes leprosy infection from these tiny, tiny bones. We were really, really lucky.
Chris - You were looking for the DNA of the mycobacterium leprae, the bacteria that caused the disease.
Sarah - Yes, exactly. Leprosy is caused by a bacterium and that is mycobacterium leprae. We were specifically looking for the DNA of that organism to be able to show that that person or that animal was infected with that bacteria.
Chris - How does that prove - the fact you've got the genetic code - that one organism was giving it to another, i.e. the squirrel was giving it to the human or vice versa?
Sarah - We can look at the DNA and you can think a little bit about family trees, for example. We can look at specific segments or parts of the code to see how similar they are between the bacteria that's in the squirrel and the bacteria that's in the human. We can compare that to all of the other published strains of leprosy bacteria that exist. What we found is that the codes were so similar between the medieval squirrels and the medieval people of Winchester, that we can say that there is the same sort of strain circulating between the squirrels and the humans. What was really interesting is that, when we looked at the bacteria that's infecting the modern squirrels, it was distinct enough that there is a difference between them. That actually suggests that it was a different transmission event, that modern squirrels have the leprosy from. So, for us, it was really cool because we were able to show that not only has this transference happened between human to squirrels, squirrel to human, it's happened more than once because there are enough differences in the code between the modern and the ancient squirrel.
Chris - I suppose as well as there being an important historical message in this, there's also a modern message because we see very similar things with bird flu and with coronaviruses, don't we? Where there's a possibility of a two-way street, a trafficking of infection between animals and us.
Sarah - There is a precedent for this. Leprosy was not present in the Americas until the Europeans went over there and it got into armadillos where it is still today. But we also know from work on the genetic material from those infected armadillos and the people that do pick it up that they have picked it back up from armadillos. There's been enough change in that code in armadillos and then appearing in humans, but we know in that case that it's certainly gone from human to armadillo and back to human. In our research, we show this potentially with squirrels. The key message here is that, perhaps in places where leprosy is proving difficult to eradicate, we need to maybe go and look at some of the animals that are in the local areas to see if they are acting as hosts for the bacteria so it is able to keep coming back into the human population, or the human population reciprocally can keep infecting them as well. You have a circular dynamic that goes on.
Chris - There's something like a quarter of a million cases of leprosy around the world every year, isn't there? Everyone thinks it's gone away, but it is still prevalent in some places. And you think that perhaps it's worth a look in nature because there may well be a reservoir, something like a squirrel might be harbouring it and injecting it back into the humans locally?
Sarah - Yes, absolutely. For a long time, leprosy was thought to be a human only disease, with the exception of armadillo. They have a slight quirk in their biology that seems to make them susceptible. The fact that we've found them in effectively wild squirrels potentially does suggest that, okay, it does infect more animals than just us and they may act as a reservoir for this disease. It could be other rodents, it could be other mammals. So it's certainly worth exploring these areas where there are eradication efforts, but perhaps it's proving to be persistent.
22:34 - First rocky exoplanet found with an atmosphere
First rocky exoplanet found with an atmosphere
Matt Bothwell, University of Cambridge
Up into space now and a new study using the James Webb Space Telescope has found a so-called exoplanet - in other words a planet orbiting a star outside our own solar system - with what looks like a thick atmosphere around it. This is the first time anyone has discovered a rocky planet with an atmosphere like this. To find out more, I went to meet Matt Bothwell, Public Astronomer at the University of Cambridge, and asked him to take me through what the paper shows…
Matt - Astronomers, for the first time, have found an atmosphere around a rocky planet using the James Webb Space Telescope. It's orbiting a star called 55 Cancri in the slightly ridiculous naming system astronomers use. The planet is 55 Cancri e. It's about 40 light years away or so.
Chris - What do we know about the planet itself?
Matt - It's a terrible place to live. We know that for sure. It's a super Earth, about 10 times the mass of Earth. It's a roughly rocky planet, although rocky is probably the wrong word to use. It's so close to its parents star, this planet is certainly a molten blob of lava. It's about 1/25th of Mercury's distance to the sun. This thing is so close to its star it whizzes round once every 17 hours. It's a planet that's made of rock, but think of a molten blob of lava whizzing around a sunlike star.
Chris - How do we know it's got an atmosphere, then?
Matt - That's a good question. The team used this very interesting technique called a secondary eclipse. So listeners might have heard of planetary transits. That's when the planet goes in front of a star and from the missing starlight that tells you about the planet. In this case, they use the planet going round the back of the star and the way that can tell us about the planet is that if you imagine the planet just to the side of the star, our telescope will pick up the combined light of the planet and the star all at once. Then, when the planet dips behind the star, at that point we only get the star light. By comparing the before and after, the planet plus the star compared to just the star, we can subtract one from the other and get our best guess out: what the light from the planet is doing.
Chris - So how does that light tell you there's an atmosphere there and how does it tell you what's in the atmosphere, and indeed can it?
Matt - It can. I think the answer is to do some quite complicated modelling. Traditionally, in astronomy, when we look at things, we are looking for spectral lines, these characteristic fingerprints of particular atoms and molecules. That's not what's been done here. Here, the team have made some complex models of this planet's atmosphere and tried to reproduce what they saw in this planet's light using this secondary eclipse technique. The best model that fit to the data is a complex mix of carbon dioxide and carbon monoxide. We think that's what's going on.
Chris - I understand why you said it's not a home from home now. Not only is it roasting hot and hot enough to melt metal, it's also got an atmosphere that sounds pretty horrible. Why then should we be excited about this discovery?
Matt - Well, I think it's still incredibly cool that we have been able to find an atmosphere around a rocky planet. The holy grail for this whole area of science is of course discovering life living on an earth like planets. A big step in that direction is the ability to find atmospheres around rocky planets. Even though this one might not be your ideal holiday destination, I think it's a huge step in the right direction.
Chris - It's also not that far away in the sense that, 40 light years away, which is where we think it is, is in space terms just around the corner. Does that give us any clues as to the likelihood of finding planets that fit the bill that you've just outlined: how likely it will be, how frequently they are out there?
Matt - That's a very good question. It's one of the hot things that exoplanet scientists talk about a lot. I think the best guess right now is somewhere between 30 and 50% of stars have something roughly earth-like. Proxima Centauri, for example, our next door neighbour in space, has a pretty Earthlike planet. I think the good news is that these things are pretty common.
26:45 - Why do some plastics go from bendy to brittle over time?
Why do some plastics go from bendy to brittle over time?
Phillip Broadwith, Chemistry World
James Tytko took on this mind-bending question from listener Jimmie with the help of Chemistry World's Phillip Broadwith.
Phillip - Plastics are polymers. That means they have molecules that are long chains inside them. If you want those polymers to be flexible, those chains need to be able to move over each other when you apply a force. They don't stay still. You can do that in a few different ways: you can either make the chain molecules branched and twiggy, that means they can't pack together so tightly which means that there's a bit of space between them for them to move as you apply a force. Or, some polymers, like silicones, have bonds between the chains which change how rigid they are. If you think about silicone, you can have it as almost a paste or liquid when you squeeze your bathroom sealant out of the tube. But then, as it cures, what's happening is there are more bonds being made between the chains, so the polymer gets harder and more rigid into a kind of rubbery state. But for the same polymer, if you take it even higher and make more links between the chains, you can make it into a completely rigid polymer. That's called cross-linking. The more cross-linking you have, the more rigid the polymer is going to be. The other way that you can do it is to add an additive called a plasticiser which sits in between the chains and acts almost like a lubricant. There's lots of different types of plasticiser, but the most common one that people will encounter is in PVC. If you think about window frames, they're made of unplasticised PVC; they're quite rigid. There's not very much plasticiser inside them. But if you think about softer PVC, like the fake leather that you might may have clothes or furniture made out of, or things like Barbie dolls with its kind of soft PVC, that will have a lot more plasticiser in it.
James - Now, under our forum post on this question, over at nakedscientists.com/forum, user Alan suggests that exposure to heat and UV radiation can change bendy plastics to brittle over time. Is he right to say that and, if so, why?
Phillip - That's exactly what's happening. Environmental conditions, heat, light, oxygen, all cause chemical reactions within the polymer. Those chemical reactions might break the chains down, which might make them more rigid or crumbly. It might make more cross links between the chains which is going to make them them more rigid, or it might evaporate or leach out the plasticiser molecules. We had a feature in Chemistry World recently about preserving Barbie dolls which are made of PVC which has a plasticiser in, and they have all sorts of problems with the plasticisers coming out or the materials degrading. So if you want to then preserve those plastics, it's quite a challenge.
James - Are all plastics susceptible to this loss of bendiness over time?
Phillip - Most flexible polymers will tend to become more rigid over time because they will age, but sometimes that's not the problem. Sometimes you can go the other way, the way the polymer degrades will make it more sticky or more flexible in some ways. There's quite an interesting story on that which is, in the 60's and 70's, there was a musical instrument called a clavinet. A favourite of Stevie Wonder. If you know the song 'Superstition,' that riff at the start, that's a clavinet. The hammers that hit the keys in that instrument - it's a keyboard - were tipped with a rubbery polymer. Over time, that polymer would become more sticky and that changed the sound of the instrument. It went from more hitting the strings to a slightly sticky plucked sound, which sounded slightly different. There were various jazz musicians and some people who really preferred that kind of sticky, plucked sound so they would start to seek out instruments where the hammers were degraded enough to make that sound.
Comments
Add a comment