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Covid-19 – The Trouble With Variants
Expressive Minds Media

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Sarah Fourcheraud (Producer): Welcome to Expressive Minds

Prof. Turi King: it’s a bit of a race that’s going on at the moment because the coronavirus is mutating and we’ve got vaccines that fits at the moment but it’s also why you hear about how some Vaccines might not be as effective against particular variants of the coronavirus, so it’s this whole idea of vaccinating just single countries but vaccinating people as quickly as possible whilst the vaccines work against these particular variants. 

Ron McCullagh (Presenter): Welcome to this special edition of Expressive Minds where experts share their deep understandings.

The full series of Expressive Minds begins in April, but our first guest has a tv series featuring her coming out this month, in March, called The DNA Family Secrets on BBC2 in the UK and to coincide with this, we thought you should hear her insights into Covid-19 right now.

Professor Turi King is Professor of Public Engagement and Genetics at the University of Leicester. She is best known for her role in identifying the skeleton found in 2012 in a car park in Leicester as Richard the third no less.

But Turi’s expertise in Genetics and communications has given her a grandstand view of scientists’ extraordinary battle with Covid-19 and what it’s teaching us about the future of mankind, which she shares with us now.  Enjoy.

Prof. Turi King: A Coronavirus is actually quite a simple organism. It’s actually a piece of genetic material that is wrapped in a coat, it’s actually a lipid layer, and it’s got little protein spikes that stick out and when you look at that underneath the microscope it looks like a crown which is how it gets its name, Coronavirus, and actually there’s a lot of debate as to whether or not viruses are actually living things because they can’t carry out metabolic processes themselves, they are essentially what seems to be sort of a bag of chemicals and it’s not like they can actually… they can’t replicate, they can’t survive unless they get into a host so they’re really interesting things and they’re sort of at the edge of chemistry and life.

Ron: So all they actually want to do is to replicate.

Turi: Yes, that is it. That’s the virus’s goal in life, so to speak.  It wants to get into a host  to replicate, make more copies of itself to then go on and infect other hosts, that’s it’s sole purpose in life.

Ron: So as I understand it, there are two ways a Coronavirus can replicate.

Turi: The main way that Coronavirus replicate is that they will get into a host, they will latch onto the cells within the host and then from that they get absorbed into the host cell and then it is replicated, it basically acts like an overlord, it takes over the cell’s mechanisms. Our cells are always transcribing, reading, RNA to make proteins and basically what it does, it co-opts our cells’ mechanism to do that for it, and it replicates, it makes copies of itself and then it comes out of the cell when it goes on to infect other cells or other individuals.

There’s other ways you can get… Coronaviruses could sometimes mean that if it infects into a cell, that cell is already infected by another virus. You can get things where viruses sort of swap bits of material and that can create a different form of virus or even a new virus. So there are those sort of two different ways that you get Coronavirus as I suppose changing and altering.

Ron: These two viruses are coming together and they’re sharing their DNA, that sounds awfully like sex to me!

Turi: (Laughs) A little bit. With humans you get half your DNA from your mum and half your DNA from your dad. It’s not not quite like that because you don’t necessarily get an equal half and half sort of split but you can get this swapping of bits of genetic material so you might have one section from one virus and a little section that’s from another virus and so this is how you might get new viruses evolving.

Ron: And therefore the variants that we are hearing about right now…

Turi: Variants that we are hearing about right now are actually typos. So when the virus gets into the body and it’s being copied to make new viruses, I always say it’s a little bit like having a bunch of typists and we know that the SARS-CoV-2 virus that causes Covid-19 has got about 30,000 letters long so it’s a little bit like a bunch of typist having to copy out those 30,000 letters and of course, you get typos that happen. Now there are actually mechanisms within this virus which are supposed to go back and proofread and make sure that there aren’t these little mutations but mutations always slip through and this obviously then creates different forms of the viruses and you can have this happening within an individual, if somebody’s chronically infected, in fact we know that this has happened and the individuals where they have been chronically infected by a virus and you can actually watch the virus mutating within a single individual. Or it’s that viruses are being copied in the cells and you’re getting little typos and those typos go on to form the virus particle which then goes on to infect somebody else so viruses actually love the fact that if we are getting in close contact and the viruses gets into a number of different people this virus can replicate with more and more mutations, the more people it goes into.

Ron: You say that we’ve actually seen this in one individual, can you tell us more about that?

Turi: This was an individual in Cambridge who was a patient in Cambridge who was chronically ill with Covid-19 and they could actually see the mutations that were occurring over time within this individual because every time the virus is replicated, you get these chances of these mutations occurring, and so they were able to actually watch this happen in this individual over the several months that they were actually infected with Covid-19 and sadly they subsequently died from it.

Ron: So they were doing similar tests to the one we are familiar with where they were taking swabs for the back of the nose looking at the Coronavirus seeing the changes.

Turi: Yes, they can take samples on a regular basis and they could actually see over the course of these months so they are getting new mutations arising. The really interesting thing about mutations is that you can have mutations that arise in the virus RNA sequence and they have no effect whatsoever. The ones that people are really interested in are ones that cause a change actually in the protein itself, in particular the protein spikes are of particular interest because that’s how the virus actually latches onto our cells and gets in. 

One of these mutations occurred it seems really early on in the pandemic and it’s known as D614G, the D bit actually stands for Aspartate and the G stands for Glycine and we know that what’s happened is that there’s been a mutation in the DNA which has meant that the amino acid which is one of the building blocks of proteins has changed from Aspirate to Glycine because of this mutation that’s occurred within the genetic sequence of the Coronavirus. It was found to be one that was starting to be found all over the world and when people looked at it I mean the first kind of thought is so is this a founder effect?  Is it that the reason why we see this in a particular part of the world is it just happened to be that somebody with that particular mutation travelled for example in the early stages of the virus from China to Italy or Germany and they happened to have that particular variant and so that’s the one that spreads through the world, or is there something about that particular mutation that allows this virus to transmit more quickly, more easily to replicate more quickly and what they were able to do was look at this particular mutation and see that actually it was found in China in… at least in January 2020 and it does seem to be one that increases transmissibility. It is causing more shedding so this is where you get a sort of higher viral load is going on in the nose or when you cough this kind of thing and it means that you’re shedding more virus particles. Now that’s fantastic for the virus because it then means it can infect more people and go on to reproduce itself more and more.

And it’s interesting because when we talk about the virus we talk about it being a living thing with a mind and this is what it wants to do, but it’s not, it’s just randomly accumulating mutations and some of these mutations will do things that will increase it being transmissible, maybe it can replicate faster or maybe it can evade the immune system better so those are the kind of mutations that we are worried about, if it gives an advantage, a sort of selective advantage in terms of being able to transmit to further people.

Ron: And the more people it transmits to the more chance there is of more variants.

Turi: Absolutely, so the more times, it’s just a case of the number of replications. So, if it’s in a very small number of people who get over the virus then it’s only replicated a certain number of times but if it’s spreading to more and more people then it’s replicating more and more and more and that gives you more and more mutations some of which might make it so that it is more virulent or it’s more transmissible or it’s able to avoid the immune system, this kind of thing, so this is why we have lockdowns, because you can break that transmission. So what this virus needs is other people to go and infect. So you may have somebody for example who over the course of them having the virus there’s a mutation that causes something that’s quite serious but if they’re not in contact with anybody that’s not going to go anywhere so this is why there’s this whole thing about keeping a 2m distance, wearing face masks, washing your hands, everything that can be done to stop the virus hopefully from jumping from person to person.

Ron: There is this strong sense that this is a virus that feeds off human sociability and if we can stop being social we starve the virus.

Turi: That’s absolutely true, I mean that is the thing about viruses, it needs people to be able to to jump from person to person to be able to replicate, make more of itself and so the fact that we are very social means that, particularly in the early stages where you don’t have lockdowns, it can go from person to person much more quickly which is why we have all these things in place about please don’t have gatherings of more than a certain number of people because that is absolutely perfect for the virus to be able to jump from person to person.

Ron: This idea that you’ll have more variants with more infections is presumably the reason why vaccinating just one country’s population isn’t enough; there’s a need then, a scientific requirement if you like, to vaccinate everybody, even in those countries where they can’t afford vaccinations.

Turi: Yes, so, you are absolutely right. The idea of just vaccinating one country just doesn’t help because people are still travelling around. The other thing that’s really important to do is that you need to vaccinate people as quickly as possible, because at the moment the vaccines we have out there are able to cause a response in people to do with the Coronavirus that’s out there now. As it’s mutating it may get to the point where the vaccines that we have currently, they maybe still provide some protection, but it’ll get to the point where the vaccines aren’t suitable; it’s like the flu virus, so every year we have to have a different flu virus because the flu virus mutates such that the vaccines, the antibodies that it causes the body to generate don’t fit the virus anymore. It’s a bit like jigsaw puzzle pieces, so the spike protein that sticks out of Coronavirus at the moment has got a particular 3D structure and what the vaccines do is they get your body to make that 3D structure and so your body goes “Oh, I don’t recognise this” and it will make antibodies to that 3D structure, but if the virus is mutating such that that protein structure changes the antibodies that you have might still latch onto some of it but not so well and so this is why you might then need to change the vaccines. So it’s a bit of a race that’s going on at the moment because the Coronavirus is mutating and we’ve got vaccines that fits at the moment but it’s also why you hear about how some vaccines might not be as effective against particular variants of the Coronavirus. So one of the big things with vaccination is it’s a way of giving us herd immunity. So this is something which has been talked about a lot in the news. Now if herd immunity arises naturally, that’s through people getting the virus and either surviving or dying, and one of things is that obviously some people have been surviving and have been getting things like Long Covid, so this is not the way you want to do this. What you want to do is to give people herd immunity is vaccinate them because that does the same thing, it exposes people to the virus but in a safe way such that they develop an immune response, and this is also again why it’s so important to vaccinate just not in our country but in countries around the world; it gives us a global herd immunity.

So I think there’s… it benefit us on a number of levels; not only does it give us this global herd immunity which allows us to kind of get over this Coronavirus as early as possible but as I say, there is this kind of moral imperative to do that because you want countries themselves to have this herd immunity with them within them. If we leave countries to be where they don’t get vaccinated and they don’t get this herd immunity, that then means that the virus is still replicating there and potentially coming up with more and more harmful mutations which then the vaccines that we’ve been given, already, don’t give us any protection against as well, so that’s another thing to consider.

Ron. And if we can’t do that quickly enough, then the variants will come along at a quicker pace and we won’t be able to keep up in producing vaccines to meet that variant.

Turi: The more the Coronavirus spreads the more variants that you get so it’s a combination, what you want to do is have people practicing social distancing essentially whilst also vaccinating them. As the vaccines change, because these are MRNA vaccines… ok, so what is MRNA? Ok, so it’s actually really straightforward, so when the body is like right, ok, we need a protein being made, what happens is that it goes to the little section of DNA that codes for that particular protein and it builds something known as RNA, it transcribes it across, and that then goes out of the nucleus and into the rest of the cell where it is then translated into a protein, that’s what messenger RNA does, it acts like a recipe to be able to be translated into a particular protein that could be made in the body so this is how this vaccine works and as I say, messenger RNA is something we create in our own bodies, it’s how DNA is read and then it is transcribed and then it’s edited and then it goes out of the nucleus where the DNA is and it goes out into the rest of the cell where the cells, the little mechanisms, they read it and they generate the proteins, that’s exactly what’s happening, the Coronavirus RNA is going into our cells and being read so if you give the body, in the form of the vaccine, a little section of the messenger RNA that codes for the proteins to make that spike protein, then your body starts making that spike protein.

So because these are largely MRNA vaccines there’s also a vaccine where it’s actually you’ve got a bit of the spike protein genetic material is put into a virus which we know gives chimpanzees the cold but doesn’t hurt us, and it’s the same sort of thing you’re basically giving the body the recipe to make the spike protein. So you can change that recipe, you can tweak it a little bit and so we should be able to keep up with this provided we keep… again, it’s practicing the social distancing, so you don’t get the variants arising super quickly.

Ron: But what concerns me is it takes time to not only create a vaccine for this new variant but obviously it has to go through at least three stages of testing and that can take, what, 3-months minimum?

Turi: That’s the thing that takes time. So the thing is…. the beauty about these vaccines is that once you know what the genetic code is you can put it into the vaccine but it does need to be tested and so obviously you have stages where… so, stage one is where you’re testing in a relatively small number of people who are healthy and then stage 2 is where you start to widen that up also to where you know people who might have underlying conditions like diabetes and so on, and you are also checking the dose with this as well but it’s not like we’re starting with a completely clean slate, we do know about doses and things like that and then obviously once you get stage 3, it’s lots and lots,  thousands of people, who are taking part in it. What they’ve managed to do with the Coronavirus is they have managed to run some of these stages alongside each other but being extremely careful all the way through and people are heavily monitored.  It has to go through this entire process. So yes, there is a few months lag whilst this is going on which is why we still have to be so careful.

Ron: So what defines whether we can win this with our abilities not only to create the appropriate new vaccine for a new variant but also our ability to test it in a timely fashion and to produce it in billions of doses?

Turi: So it’s money, as ever with many of these things. One of the really fantastic thing about this was that the genetic code was published in January 2020 and so the entire kind of genetics and immunology community comes together to work on this and you need money to do that because you have to start thinking about how you’re going to design it, you have to actually manufacture it, then you have to test it. So it’s money and time is what’s needed to be able to do… to be able to make these vaccines and do them very very quickly. I mean it has been an absolutely extraordinary scientific achievement what’s happened over the last year with this, being able to design vaccines and to get them to the point where you can actually give them to people, within months really…  I mean it’s just unprecedented and it makes me very proud, in awe, being a scientist to just see… you know, colleagues have been able to do this amazing work. I just think it’s absolutely extraordinary and also, we individually have parts to play in this because it’s absolutely crucial that we do our bit to, as much as possible, stop the spread of the virus, stop it from replicating, so it’s this combination of you know, science is able to do this work, but we also need to do our bit and that is by staying safe, keeping our distance, wearing masks and and this kind of thing.

Ron: This is ultimately the most extraordinary thing about our engagement with this virus is that if we were to close down, I mean completely lockdown for 3 weeks, theoretically that would be it; the virus would starve to death, it wouldn’t be anywhere.

Turi: We would have to completely lock down, I mean completely lock down, you have to absolutely stop the transmission and to some extent, that is simply not possible. We’ve got hospitals and police forces and this kind of thing, it is simply not possible to do that completely but we’ve seen in other countries, New Zealand is the one that’s held up regularly as kind of really being on this, that you know, anyone new who comes in, they have to be tested, they have to be quarantined and so that they can stamp on an outbreak, they can detect the outbreak as well so you have to be able to detect it, and then you have to stamp on it so this is why a full lockdown probably isn’t possible but as much as we can possibly do to stop the transmission is absolutely crucial.

Ron: Over 100 years ago just, we had the last pandemic, the so-called Spanish flu, and it sort of petered out didn’t it? and no one was completely sure why and I think no one’s completely sure to this day why. Is that possibly what could happen with Covid-19?

Turi: So yes, in terms of the Spanish flu dying out there seems to be a number of things going on there so herd immunity is one of them so it had spread globally and so by in large people had either already had it or had died from it and obviously people who are surviving have got some sort of immunity against it and the thing about herd immunity is that it means that even people who haven’t had it or haven’t been vaccinated against it, the chances of them getting it is low because it can’t spread, the virus can’t spread in the same way because people are able to fight off already because they’ve got that immunity… it protects people to some extent who haven’t got any immunity to it because they haven’t had it before.

Ron: You and your scientific colleagues, are they optimistic that we can sort this out? So far, as you say, it’s been a remarkable achievement of science to have managed to get a useful vaccine in such a short period of time.  Any sense out there that this is going to mutate faster than we’re capable of dealing with it?

Turi: So it really depends on what the mutations are. So again, the virus is mutating all of the time it’s whether or not the mutations arising are giving it a selective advantage and I know that there are scientists all the time who are keeping an eye on the virus, they are… and even predicting, so what mutations might be the ones that we really have to look out for, that would be really quite scary if it got this? But I think at the moment people are cautiously optimistic. We do have these vaccines, we are having these lockdowns and you can see that it absolutely has an effect, so I think people are cautiously optimistic. I don’t think it’s time to let our guard down, but I think people are cautiously optimistic that we can actually get some control over this. I mean one of the really beautiful things about this is that it has been a global effort, I mean a huge global effort and because people are carrying out scientific studies and they are publishing them, and the publishing process… it’s really been speeding and it means that people are able to put out discoveries and things as they are… as they’re coming up and the community spirit around it as far as I can tell, has been absolutely fantastic in terms of the huge global effort, global scientific effort coming into how do we tackle this. It’s been extraordinary.

Ron: After this is all over Turi, do you think there is a different scientific community that emerges from it, one that is more participatory, more sharing, more useful perhaps for human society?

Turi: Well I certainly hope so. I’ve always been very lucky in that the vast majority of scientists I have worked with have always been hugely collaborative, but I think what’s been really nice about this project is that, as I say, the sequence went online in January 2020 and the scientific community just completely swung into action, I mean it was really just extraordinary to see and I’m optimistic that what this means is that that’s in place already which means that should we confront something again, and almost certainly we will confront something again, that that kind of infrastructure is already there to some extent to be able to act even more quickly on this kind of thing.

Ron: An example perhaps of the type of collaboration necessary to curtail global warming…

Turi: Absolutely, when you bring people together from different fields of science to complement one another the results can be absolutely extraordinary… something I find in my research and it’s nothing on that kind of global warming… but it’s that bringing certain bits of expertise to the table makes a much greater whole and for tackling really big issues like global warming that is precisely what we need.

Ron: Thank you Turi. We’ll be launching a new series of six Expressive Minds podcasts in April. You will find them where you usually find your podcasts. Prof. Turi King will be back again to give us her inside story of digging up Richard III.

Sarah Fourcheraud: You’ve been listening to Expressive Minds presented by Ron McCullagh and produced by me, Sarah Fourcheraud.

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