Flu Seasons to Solar Storms: Science Round Up

The UK government has its roadmap out of lockdown, and news that the vaccines seem to be working is more than welcome, but what is happening right now? Though he's usually the one doing the interviewing, Chris Smith spoke with Adam Murphy, as well as guests space scientist John Zarnecki and pharmacist Bahijja Raimi-Abraham, to unpack the most recent COVID stories...

Chris - Well, all viruses mutate and change as they go and grow through a population. So if you've got parts of the world where there are lots of cases of the virus, effectively that's lots of rolling of the genetic dice. The virus has many opportunities to change and evolve. And it will disclose variants. That happens just naturally. But if you've also got a situation where there are people with partial immunity to the virus, people who are immunosuppressed for some reason, or people who've been vaccinated, then you're putting in the way of the virus a new kind of challenge, an opportunity to evolve better under those circumstances. And so what we've seen from Brazil is an emergence of a virus that has a certain constellation of genetic changes. It overlaps with virus variants from South Africa, which carry many of the same constellations of changes. And we've also had variants here in the UK as well, which have similar constellations of changes. In other words, patterns of genetic changes that they're all being arrived at independently by the virus, but it's settling on those changes because they confer some kind of advantage to the virus. And in the case of the Brazilian variant, perhaps it's a difference in its shape or structure that means it's more likely to evade the immunity of the population. In the case of the South African variant, similar. In the case of the variant picked up in the UK, it's more transmissible. It's conferring an advantage on the virus. It's very important we keep an eye on these variants because they could ultimately lead to a virus that not only spreads better, but could bypass the protection conferred by the vaccine. And of course, that's where we're putting enormous emphasis at the moment as our route out of the pandemic.

Adam - And speaking of vaccines, there's a story out that perhaps we could see this, especially this Oxford vaccine, as something other than an injection. As a pill or a nasal spray. How is that going to work? I can't picture a vaccine that isn't a needle.

Chris - Well, it's intriguing, isn't it. And as scientists and researchers have quite accurately pointed out, the way in which we're administering these vaccines - a number of them are based on what we call viral vectors. They use a modified virus to deliver the genetic code from the coronavirus for its spike protein, which is the business end of the virus, which we want to trigger an immune response against. But the viruses that are being used to do that are cold viruses, adenoviruses to give them their proper name. And they don't naturally infect people through an injection into a muscle. They normally spread through the nose and throat through the air. So what researchers are saying quite reasonably is, "well, hang on a minute. Why don't we try presenting these things as an inhaled vaccine? Something you breathe in as a sort of mist of virus particles, or even package them up into a sort of pill?" That you would just pop a pill. And you'd basically infect yourself with these vaccines, which confer protection against coronavirus at the same time. So they're actively pursuing this because just imagine the prospect, if you had something that was inhalable or a pill, you wouldn't have to drag people to vaccination centers. You wouldn't have to basically ask people who are needle-phobic to have an injection. And that is a deterrent for many people. You'd have something you could mail out to people, far more convenient, far more likely that people will take up the offer and you won't be having to run complicated vaccination centers. You just need the postal service.

Adam - To come to you Bahijja, What factors decide what form a drug takes? If it can be a spray or a pill or a needle or what it has to be.

Bahijja - Yes, that's a really good question. And it's what pharmaceutical scientists and also even drug discovery scientists, they have to consider. You generally want to understand what we call the physico-chemical properties. So this is the solid state, the state of the drug. There are several different factors like its solubility. How soluble is it? So if you think of well was going to say, if you think of our bodies, but as humans, we are majority water, right? So we want drugs that are water soluble, but most drugs are actually poorly water soluble. So that makes it such a challenge to try and figure out what route is best for it to be delivered. And so when you're designing a medicine and thinking about where it should go, you're also then thinking about the patient, right? So you're thinking what is going to be easier for the patient. On top of all of that, you're also thinking about cost, right? It's just so many different things in one go!

If you're thinking about cost, then generally the cheaper methods or the cheaper manufacturing processes are those that have been long established for years. So that's why everything, most of the things, come as tablets, capsules. When we're thinking about vaccines, generally speaking, we just think injection, let's find a way to have it as an injectable. But as anybody who's had a vaccine or has to take injections, that's not pleasant. Some people have real fears of needles and things like that. So you start to think about other routes. And so this is where we start to think about the route that has the best patient acceptability is actually the oral route. But you've got to think of what else is going on in the mouth. So saliva, the enzymes that could break them down. So this is when people start to look at other routes such as the nose, because we breathe all the time. And you know, there are lots of studies about the nanoparticles, microparticles from pollutants that just in the atmosphere, can actually just from normal breathing, get into the deep lung and things like that. Ultimately, if you're thinking about what the patient would prefer, then it would basically be anything but an injection. Then the second option would be, oo, can we take it as a pill?

Adam - One other story that's come out is there's a big link between, is it death from Covid and the rates of obesity in the UK, which might go some way to explaining why there's so many deaths in this country. Can you tell us a little bit about that story and what it might mean?

Chris - Well, there's a report out literally in the last couple of days, looking at the prevalence of obesity around the world, and then asking, how does that marry up with the likelihood of a person getting Covid? And what you see are countries like the UK, where we are number three or number four in the world in terms of our obesity rate. In other words, if you pick an adult at random from the population, how likely are they to be obese? And then you ask, and how does that compare with the number of people who when they catch Covid, as in the virus that causes Covid, go on to develop life-threatening or lethal coronavirus infection? And the answer is there's a really strong correspondence. And one of the reasons being postulated for why countries like the UK have such a high mortality rate from coronavirus is because we have such a high obesity and therefore also potentially diabetes rate.

And many people often point to Taiwan or Vietnam or Thailand, and say, why is it that these countries, for example, have such low levels of coronavirus mortality? How are they controlling the virus? What are their public health initiatives that are so successful? And the answer is that some of their public health initiatives are so successful. Yes. But if you look at the number of people in the populations of those countries who are overweight, there are fewer than one in five. If you look at the number of people in the UK who are overweight, it's more like one in two, and this is the pattern that's repeating itself across the world. And really, we probably need to take this seriously because it's one thing to dwell on the coronavirus pandemic, but the pandemic we have all slept walked into in the last 20 years also is an obesity pandemic. And this is going to cause ultimately far more death, far more disease, far more disability than any pandemic from a virus. And that's an unarguable fact with maybe half the world's population now overweight. We know that that is a massive disease risk factor for all kinds of conditions. And so actually solving that one would immediately also help us to address the coronavirus problem. And it's interesting that the countries that do have very low rates of coronavirus death, so they're still catching and the still passing on the coronavirus, it's just that people aren't dying of it. In those countries there are far more interventions and initiatives aimed at helping people to maintain a healthy weight compared with countries like our own. And so we really do need to take a good look at ourselves and ask, what do we need to do in order to tackle this invisible but far more lethal pandemic that is creeping up on us?

Adam - We have the UK's plan to get out of lockdown in the next few months. And we should be back to - all things going well - some kind of normalcy by July. Do you think that's a reasonable roadmap out Chris?

Chris - Well, Boris Johnson thinks so. I don't think it's a coincidence that he announced in his press briefing last week that on the 21st of June, there would be no legal constraints on what people can do together. And the 19th of June is Boris Johnson's birthday. So I think he's got a big party planned! But more seriously, I do think that it's a reasonable road out of this. The vaccine success has really surprised even the people who thought it would work. And when you look at the data that we have now for asymptomatic transmission, for people who are in their older latter years, who are protected from coronavirus at outstandingly high rates, far higher than we had perhaps anticipated. And you see this being mirrored, not just across the UK, but in other countries, Israel, for example, it gives us enormous confidence now that in fact this is going to work. And I know not withstanding the worry over variants, we still think that the vaccines are going to provide defense against even variants of the virus. It just means that perhaps we might still tolerate a higher level of transmission of the virus through the population, but nevertheless, we will not see the mortality that we were seeing on the scale we were seeing it, thanks to this vaccine initiative. And that's an amazing thing.

And I think that does give us great reassurance and great confidence that in fact, this is our road out of it. And I felt more optimistic in the last couple of weeks having seen the data I now have, compared with, you know, many weeks before. So I think there's every reason to be very, very optimistic, but what we don't have yet is a solution for the rest of the world. And as Melinda Gates from the Bill and Melinda Gates Foundation said very, very presciently, right at the beginning of all of this, if there's Covid anywhere, there's Covid everywhere. Because at the end of the day, unless we sort the whole world's problem out, then it will keep coming back. It will remain a problem and it won't go away. And so therefore the job is not done until we've done it everywhere. And that's what we've got to remember. Otherwise, we're just in a gilded cage here in the UK. We fix our country, but we can't go anywhere and we don't want to be like that. We want the world open again.

Adam - And to come to you John, what are your thoughts on this kind of thing?

John - Chris, we hear a lot about modeling of the spread of the virus, but when you were talking about variants, I just wonder, it made me ask, is it possible? And does anybody try to model the development of variants?

Chris - Uh, yeah, they do. And they not only model the development of these variants and the likelihood they're going to arise, they also model the impact that they will have. Because when making models of disease, you take into account a number of factors, such as how many people have got it, how close those people live to each other, how many journeys they make every day. In other words, you know, how many shopping trips, work trips, the size of a household and so on. But you also take into account transmissibility. You also take into account the degree of immunity in the population. And so you factor in, if you've got a variant that you think might have the ability to bypass immunity, you programme that into your model, saying "well we think the immunity of the population will be successful at a certain percentage level". And you would adjust that accordingly to take into account the prospect of these variants arising.

Up to Mars now, And the new Rover that’s landed on the surface, Perseverance. What has Perseverance actually done up on Mars, and what’s it about to do. Matt Bothwell from the Institute of Astronomy in Cambridge spoke to Adam Murphy, as well as guests pharmacist Bahijja Raimi-Abraham and space scientist John Zarnecki, about the latest on the red planet...

Matt - It's been doing a few things. So one of the things that you would expect it to do is do all kinds of tests and calibrations of its systems. So once this thing lands on Mars, that's the end of a very, very long and violent journey, right? So since scientists last kind of tinkered with it, it has traveled hundreds of millions of miles through space, and come in and landed on a planet, starting at tens of thousands of miles an hour, and eventually has come down, resting safely on the floor. There's an enormous amount of checking that scientists need to do to make sure that all the systems and all the components are still working. There's also quite an important kind of software side of things, where there are different software programs that are involved in actually getting to Mars versus being on Mars. And so a big thing that the team has presumably doing right now is switching from those two modes. So going from "I'm traveling to Mars" mode to "I am driving around on Mars" mode.

Adam - And once it starts driving around, what's it going to start doing?

Matt - So, one of the biggest things is it's going to be looking for a nice site for the test flight of Ingenuity. The first helicopter, the first drone on Mars. I guess it's a nice link back to talking about use of drones in photography. There's now going to be a drone on Mars. And one of the things that Perseverance is going to have to do is scout out a nice place for Ingenuity's first flight. And that's going to involve using it's cameras, driving around and looking for a nice flat surface to take this test flight on.

Adam - And what are the other sort of big mission aims of Perseverance then?

Matt - Well, the ultimate mission aim is to look for signs of ancient life on Mars. Mars is one of the best places that we think there might have been life in the past, even though Mars is this dry desert, nowadays. Thousands of millions of years ago, Mars had water on it, it had liquid oceans and lakes and rivers. And given that life emerged on the young Earth in exactly these conditions, it’s a reasonable guess that there might have been life on Mars, billions of years in the past. And so Perseverance's main mission is going to be to look for signs of this ancient life. One thing that's going to do that has never been done before is take samples of the Martian soil and prepare them for return to Earth. So far our missions to Mars have just examined the soil, kind of in-situ, and radioed back to the results. The Perseverance rover is going to dig up some soil samples and then prepare them in a way that in the future and a mission might be able to actually bring them back for Earth examination, which is very exciting.

Adam - With all this. These are some lofty goals. Do you think it's going to meet them? Are you excited to see what comes next?

Matt - Well, I think the question of are we alone in the universe, which is what this is really about, it's a small way of getting at the question of are we alone in the universe? Obviously everyone has their fingers crossed for a positive answer, right? I mean, if Perseverance discovers life outside our planet, it will be one of the most momentous discoveries in the history of the human race. But this question is also very interesting because the results are fascinating, whichever way the answer pans out. If Perseverance gives us the green light and says, it has found evidence of ancient life on Mars, that's fascinating. And then we can all start kind of getting philosophical, and wondering what that life might've been like. But if the answer is that Mars is completely barren and always has been, that's also philosophically interesting. It means our Earth is much, much more special than we might've thought previously. And so that's going to give us a lot to think about as well. And so whatever way the answer pans out, I think we're going to have a lot of thinking to do.

Adam - Bahijja, what's a pharmacist's opinion on a Mars mission. This is very much not your usual wheelhouse.

Bahijja - I am so fascinated by Mars, just by astrophysics, just the world of physics. It's just amazing because , pivoting on what Matt said. If from this mission, we can find out that there's life, or has been life on Mars, there currently is, I don't know, it's just going to be so amazing to even just start expanding one's thoughts in this area.

Adam - John, is there anything else going into space, anything in the space missions that you're excited about coming up?

John - Let me just first say, I mean, it is a fantastic mission, but I've been involved with a mission which landed instruments on the surface of Titan, which is Saturn's largest moon. It took us seven and a half years to get there. So we rather look down on Mars as being, you know, in our backyard and rather easy and local, but joking apart.

Adam - It's just there.

John - It's well, you know, it really is in our backyard. It only takes a few months to get there. And only one probe has landed on the surface of Titan. But you asked me about other missions, I think, what am I getting excited about or interested in? Well, there are other missions at Mars, of course, several, and one from Europe is called TGO, Trace Gas Orbiter. It's actually a collaboration between ESA, European Space agency and the Russians. And that is trying to look for trace gases. That's gases in the atmosphere that exist in tiny concentrations, and in particular methane. So there've been reports over the years, both from space missions and from the ground of small traces of methane. And of course on Earth, one great source of methane is biology, is animals, for example. And so that's one of the reasons why this mission was developed. And this is more sensitive than any of the other missions or ground-based telescopes that have detected methane, or claim to have, and yet in a year or so of operation, it hasn't seen anything at all, despite the fact that it's working very well. So that's a bit of a mystery and, you know, not quite sure where that story is going to go. Otherwise, of course, we've got the James Webb space telescope. In some ways, the successor to the Hubble space telescope that is due for launch later this year. And I think every astronomer, whatever their interest is, is going to be watching that with bated breath.

Given the year that was 2020, you’d be forgiven for forgetting that the flu was a big deal, we’ve had a lot on our plate virus-wise. But rates of flu have fallen dramatically, perhaps because of lockdown and social distancing measures. And while that may seem wonderful in the short term, it can have some negative effects down the road. Derek Smith from the University of Cambridge spoke to Adam Murphy about the potential severity of the next flu season...

Derek - Adam, we don't know how bad it is going to be or not. Like with many situations with what's going on with COVID-19, we've just never been in this situation before in our lifetimes, and in times when there has been such good recording of data and really knowing what is going on. We may have a relatively mild season if COVID continues and there is still social distancing going on, or if COVID circulates and somehow manages to competitively exclude flu. Or we may be in a situation where people haven't had much flu circulating for a couple of years, and it comes back with a vengeance and we have to be prepared for the latter. It's important that people continue to get the vaccines against the flu if they are at risk, but the truth is we don't know what's going to happen.

Adam - How do we usually vaccinate against the flu, because it's a bit of a moving target, isn't it?

Derek - Flu is a moving target from a scientific perspective. It's absolutely fascinating to study because of that. But of course from a public health perspective, this makes it an extremely difficult thing to vaccinate against, yeah. The flu evolves to escape immunity that we have, so it has this seemingly endless capacity to incrementally change and evade the immunity that we might have built up with prior infections against flu or prior vaccinations against flu. And so for people who are at risk for severe influenza, this is why the recommendations are that these individuals are vaccinated every year, because in most years we change at least one of the four strains of flu that's in the flu vaccine.

Adam - If it's going to change so much from year to year, how do we pin down any kind of correct answer for what a vaccine is going to look like?

Derek - Yeah, there is a really astonishing global network of people working in hospitals and GP offices who are noticing people who come in that look like they might have influenza taking throat swabs, sending those to a so-called World Health Organisation National Influenza Laboratory in their country. Those swabs are analysed there to see whether or not they really are flu, and if they are, then those samples are sent to one of five WHO so-called Collaborating Centres across the world. There's one in London, one in the United States, one in Tokyo, one in Melbourne, Australia, and one in Beijing, China. And those strains are analysed in a great deal of detail in terms of the sequence and in terms of whether or not their phenotype has changed to escape immunity. This is happening in almost 140 countries across the world. Thousands of people involved. And yeah, it's an amazing global operation. And much of that infrastructure that has been built up in those countries is the same sort of infrastructure that has been leveraged for tracking COVID

Adam - The rates have dropped though, so does that mean there's a lot fewer samples with which to try and make a prediction? Could that end up being a problem?

Derek - Yes, that's absolutely right. We rely on all of that global surveillance to see what is happening with the evolution of the viruses worldwide. And in a typical year, there are a small number of millions of samples that are taken in this way that I described throughout the world, and the viruses that filter through to the Collaborating Centres as being representative of what is circulating. It's typically in the region of about 10,000 per year, and this year it's in the hundreds, not 10,000 or so. So the vaccine choice this year we made with a much smaller number of viruses. There's still a lot of surveillance that is going on looking for flu, so we really do know that there is very little flu that is going on, and it has made the choice of which strains should go in the flu vaccine much more difficult. Nevertheless, it has been identified that there are some variants of one of the types of flu, the so-called H3 viruses that have emerged in a couple of countries and have spread internationally. And indeed, so the H3 component of the vaccine has been updated for this year's recommendation that took place in discussions over the last couple of weeks. And that is the decision announced last week.

Adam - And what does that uncertainty translate to in practical terms? Does it mean that the vaccine could miss the virus entirely? Or is it how effective the vaccine is? What could the knock on effects be?

Derek - These are so-called vaccine mismatches, and they do reduce the effectiveness of the vaccine. It's never the case with any vaccine, just like we know with the COVID vaccine, not everybody is going to be protected who is vaccinated, but a large proportion of them are. And when there is a vaccine mismatch like this, when the viruses evolved after we make the vaccine choice until the vaccine actually gets used, yes, then that vaccine mismatch reduces the effectiveness of the vaccine, which means that some people who wouldn't have normally noticed that they would have gotten flu will get flu. But there's three main categories of how the vaccine protects. The same with the COVID vaccine. Whether or not it protects against people feeling like they're ill - so protecting against infection - whether or not it protects against severe disease, and then whether or not it protects against death. And even in years where there is a vaccine mismatch, even though more people might not be protected from infection with flu, it's still in many cases going to be protecting them from severe disease and from death.