Movement Science: Devotion to Motion

Let’s turn our attention to some very relevant fast-moving science. Around the world, scientists are tirelessly working towards various Covid vaccines. We’ve heard about various candidates recently, including the Moderna vaccine, the Pfizer/BioNTech vaccine, and now news is out about the Oxford University/Astra Zeneca vaccine, whose “Phase 3 interim analysis including 131 Covid-19 cases indicates that the vaccine is 70.4% effective when combining data from two dosing regimens”. Gillies O’Bryan Tear from the Faculty of Pharmaceutical Medicine joins us to digest the recent announcements and what this actually means...

Gillies - The vaccine works by introducing DNA, which sends a message into the cells to make the spike protein from the coronavirus. Now in order to get into the cells, Oxford Virus sends the vaccine in using a vector, a carrying... if you like, a Trojan horse, which is in fact an inactivated virus which cannot replicate in the human body. It's sort of a weakened version of a common cold virus called adenovirus. Once the virus carries the DNA into the host cell, the human cells, the cells - our own body cells - start making, on the instruction of that DNA, the spike protein of the coronavirus. And the body then mounts an immune response to that spike protein, and the reason that disables the virus or prevents the virus from infecting the person who received the vaccine, is because the spike protein is what the virus uses to get into our bodies.

Katie - Who have they tested this vaccine on? Does it protect people who are actually most at risk?

Gillies - So far they've announced results of three phases of trials: the phase I trial; the phase II trial, which was published last week in the Lancet, a peer reviewed journal, in great detail - 560 participants in that trial, half of whom received the vaccine; and more recently they announced the interim results from the larger phase III trial, which has enrolled 24,000 people, half of whom received the vaccine and half of whom received a control vaccine, for meningitis as it happens. So in total they've enrolled tens of thousands of people, and they plan to enroll up to 60,000 people all over the world. And you ask whether they've enrolled people who are at high risk: the phase II results, in that study they enrolled people who were older, over 70, as well as younger people; and in a phase III trial they also enrolled people who are older. And because they've done the study all over the world, they've also enrolled a lot of people from different racial and ethnic backgrounds. As we know, the black and minority ethnic population are at higher risk from coronavirus, and elderly people are more at risk; that's well known. So they've made sure they've included in the trial those groups of patients, and encouragingly, from the phase II results we saw that the immune responses which the recipients of the vaccine mounted against the coronavirus were just as strong in the elderly people who were in the trial, over seventies, as in the younger ones. And that's significant because it's well known that older people have a weaker immune system than younger people.

Katie - Is this about preventing infection, or mitigating the consequences of getting COVID?

Gillies - The interim phase III results have shown both. It's been shown that it prevents COVID symptomatic illness in up to 90% of patients, depending on the doses used; but also it prevents severe illness, because no cases of severe illness were seen in the patients who received the COVID vaccine.

Katie - How safe is it?

Gillies - The phase II results have got very detailed safety data, and show the vaccine produces the normal side effects that most immunisations or vaccinations cause: a sore arm, sometimes a fever for a day or two, and a headache, which can all be treated with paracetamol. So it seems to be safe. There've be no serious adverse events reported on this trial.

Katie - So how well does this work? What's going on with these different response rates and different dosing regimens?

Gillies - Well, they enrolled patients at two different doses: a half dose followed by a full dose, and then another group received two full doses. Slightly counter-intuitively, they saw 90% efficacy in the first group who received a half dose followed by full dose, and a lower efficacy of 62% in the patients who received two full doses. Now vaccines are not like regular medicines, where the higher the dose, generally the higher the effect. And there may be one or two scientific reasons why this happened, but they are looking into that currently. But the important point is that even at the high dose-high dose regimen, they achieved very, very good efficacy; because if you remember, flu vaccination only vaccinates against 50% of cases. So it cleared the hurdle for an effective vaccine, and at the lower dose regime it was 90%; as effective as any other vaccines that have so far announced results.

Katie - What are the theories on why this half dose followed by a full dose seems to be better than full dose followed by full dose?

Gillies - One theory is that the body can mount an immune response to the vector. And if that's the case then it can reduce the efficacy of the vaccine, because its carrier is attacked by the body. Now it's possible that the low dose regime provoked a less brisk immune response to the vector than the high dose-high dose regimen. And that's one possible explanation, but they're still looking into this. There could be other explanations. AstraZeneca have said that the study was not initially designed to look at the lower dose, and that there was possibly some mishap that gave the patients a lower dose and they intended to; but first of all, a very large subgroup of patients did receive this lower dose, so it's a robust sample; and secondly, it probably doesn't matter in terms of the approval and the efficacy of this agent, because they've shown that it works very effectively and the regulators may choose to approve that lower dose because it has been shown to be more effective. We really await more results from the full publication and from AstraZeneca about what happened, exactly what happened.

Katie - Is it a fair question to ask you how this stacks up compared to other COVID vaccines in the making, or is it a bit too soon to be talking about that?

Gillies - It is too soon in the sense that all of these, the three announcements we've had, from three different programs, are all based on interim data, which is not the full data set, so that the numbers may change. However, I'd like to talk about the difference between efficacy on a clinical trial, in a very controlled setting, and effectiveness in stopping the pandemic, they're two different things, the Oxford AstraZeneca vaccine costs $3. It's very easy to transport and it's got very good efficacy. Even the blended efficacy rate is 70%. That is an extremely good efficacy rate. So even if it's got a slightly lower efficacy rate in clinical trials, doesn't mean that it's going to be less effective in containing the pandemic, because it's easier to get around the world. We need to stop this pandemic in all parts of the world, not just the Western world. So the fact that it's cheaper and easier to transport might mean that in the real world, it's the more effective vaccine. If you can understand that slight paradox.

Katie - What questions remain then? Because so far we haven't had a vaccine that's actually been approved by the regulators.

Gillies - Well, we anticipate regulatory approval before Christmas for at least two of these. I would imagine, at least an emergency use authorisation in the US for one or more of the messenger RNA vaccines. And the UK authorities are going to rapidly review the UK Oxford vaccine. And they'll be also reviewing the messenger RNA vaccines from Pfizer and Moderna. I think it's a very low probability they will not get approved. They will go through the proper review process though, looking at all the data. And secondly, of course, as I mentioned earlier, we've got unanswered questions about efficacy and safety. We need to see the full dataset. For example, how effective is the Oxford vaccine in the elderly? We know from the phase two results that the elderly have brisk immune responses, but does that translate into effectiveness, efficacy, in the big phase three trial? So there are a few unanswered questions still while we wait for the full results.

Do you know, nine months ago, we didn't even know if we could vaccinate against coronaviruses. Because we tried with MERS and SARS-1 and failed. And here we are nine months later, not only do we know we can vaccinate effectively, but in nine months we've got phase three trials of multi-tens of thousands of patients enrolled and we're nearing regulatory approval. It's an unprecedented achievement.

One of the remarkable examples of volcano eruptions has to be Pompeii - the Roman City that was destroyed by the eruption of volcanic mount Vesuvius about 2000 years ago. Pompeii is particularly interesting because the volcanic ash ended up preserving the remains of the city and many of its inhabitants, providing a rich resource for scientists and archeologists today. And recently, the preserved remains of 2 more people have been unearthed in Pompeii archeological park. Katie Haylor spoke to archeologist Emma Pomeroy and volcano expert Jess Johnson...

Emma - So what they found are the remains of two individuals, as you said, they're two men, one seems to be older, perhaps between 30 and 40, and the other one younger. So in his late teens or early twenties. Now what they've actually found is, if you'd like, the void left behind by these men's bodies, when they were covered in ash. And then the bodies rotted away, the bones are still there. And so what they do when they find these voids, is pour in the material to take a cast of that hollow. By doing that, they can then see the actual shape of those people's bodies.

Katie - And Jess, how does a volcanic eruption end up freezing a city in time like this?

Jess - Well, one of the most deadly hazards from a volcanic eruption is called a pyroclastic density current. This is kind of like a flow, like an avalanche, but it's made up of volcanic ash, and boulders, combined with deadly gases, all at thousands of degrees, and traveling at hundreds of kilometres an hour. Very large pyroclastic density currents can create tens of metres of ash deposits. And in Pompeii, Mount Vesuvius had a large eruption, creating these pyroclastic density currents. In this case, probably the temperature likely killed the residents of Pompeii instantly, but then they were very quickly buried in the ash, as was the entire city. And so that is what preserved them.

Katie - Emma, what information can actually be gleaned from findings like this about, well, about things like what life was like for people in this ancient city?

Emma - A great deal. I mean, what's exciting about these individuals is, like I said, you've got the skeleton within these casts that they've been able to produce as well. So not only can we see the skeletal remains, and analyse them to look at things like age at death, whether individuals were male or female, and aspects of their life. So were they healthy? Did they suffer arthritis? All these kinds of questions. But then because we've got sort of the casts of their bodies as well, we can look at other things like what were they wearing? And in this case, the older man was wearing a woolen cloak, it looks like. And we can perhaps look at things that we can't tell very easily from the skeleton, what people's build and physique was like. And then you've got all the other evidence that gets preserved. So there's really remarkable sort of, everyday objects that come from Pompeii, including things like wooden furniture, and the remains of food, still in the bowls on tables, in some cases. It's really a whole host of evidence that actually, usually we don't get preserved in the archaeological record.

Katie - Now, Jess and Emma, I want to put this to you because on our forum, Peter's been wondering about volcanic ash. He says, the excavation of Pompeii must remove enormous quantities of this ash. So what do you do with it? How do you dispose of it? He reckons it might have a purpose as a soil improver. Emma, you probably deal with moving dirt and things around as an archaeologist. What happens to the stuff?

Emma - That's such a good question. And I'm actually really intrigued to know now what happens with the material from Pompeii. So usually in an excavation, we're usually removing just normal soil and sediment. And typically, unless the things that we're excavating are going to be left exposed for displays, such as Santorini or Pompeii, we actually fill back in the hole that we've excavated, partly to make it safe in some cases, sometimes because there's going to be new building work that takes place over the top, or sometimes perhaps to protect the remains that we have found for future generations. So quite often we actually put the material back. It's also important to remember that many archaeological excavations are not on the kind of scale that we're seeing in Pompeii. You know, it's really an amazing project that's been going on for such a long time. So that's a brilliant question. And actually in the case of Pompeii, I don't know, and would love to know.

On our People on the Move show, we heard about science challenging our understanding of when our earliest ancestors moved out of the African continent.

Mathew  - This traditional idea of this exodus out of Africa at around 50,000 years ago, isn't entirely correct. There is growing both archeological and fossil evidence to suggest that we dispersed out of Africa earlier, all the way to Northern Australia by around about 65 - 70,000 years ago. The picture is just becoming much more complex. It appears that we left multiple times, that there were disposals back into Africa. It's adding to this much more complex picture.

That was Mathew Stewart from the Max Planck Institute for Chemical Ecology, talking in particular reference to the amazing finding of what they reckon are homosapian footprints in an ancient former lake in Arabia, dated to around 125,000 years ago. And this jars with the idea of an exodus out of Africa happening around 50,000- 60,000 years ago, as was previously thought. So to find out what else science is revealing about how our ancestors moved around our planet, Katie Haylor spoke to Cambridge University's Emma Pomeroy...

Katie - That was Mathew Stewart from the max Planck Institute for Chemical Ecology, talking in particular reference to these amazing findings of what they reckon are homosapien footprints in an ancient former lake in Arabia. Emma, let's go back to you. What is the broad picture as we now understand it about how our ancient ancestors came to move around the world?

Emma - As was mentioned in that clip, for a while we thought that we didn't really spread out of Africa, which is where we first evolved, until relatively recently - by which we mean 50,000 years ago. But actually we're getting various lines of evidence showing that humans did spread out of Africa much earlier than that. But the question is how permanent were those migrations? So we've got some early modern human remains, for example, in Greece now dated 210,000 years ago. So sort of four times as old as we were thinking before, but there's no other evidence then for some time. So perhaps these are early dispersals that aren't successful colonizations.

Katie - Wow. That's an incredibly long time ago, it's kind of boggling my brain a little bit. But how do our modern ancestors homosapians, how do they end up on different continents? Because I guess there's just walking places, but what if you've got a mass of water in the way?

Emma - Yeah. Humans get remarkably early to, for example, Australia, where some of the earliest evidence now is dating to 65,000 years ago. And of course there's multiple large bodies of water to cross to get there from mainland Asia. So we assume that they must have had watercraft of some sort. We don't have any evidence of that. They presumably were made of organic materials so haven't preserved and any depictions of watercraft only come much later, but it's really the only plausible explanation for getting to parts of the world like Australia.

Katie - What about the Americas?

Emma - We used to think that humans only really got to the Americas perhaps about 10,000 years ago or a little more. And that they got that crossing from Siberia over a land bridge that was there at the time. However, some of the evidence that we're now getting suggests that those dispersals might have been much earlier. There was a recent study of evidence from Mexico that was dated to 26,500 years ago. Now one of the routes that we originally thought people must've taken was down the so-called ice-free corridor. So at that time, the land bridge was covered in ice sheets. And there were certain times when a corridor opened up that people could have walked down. But given that we've now got these quite early dates another hypothesis is that people actually went along the coastline.

Katie - Once you've got humans all over the world, what about when people start to settle? Do we know much about the transition between having a more kind of hunter-gatherer lifestyle and when you start doing things like farming agriculture?

Emma - Yeah, we do. And there's some really interesting evidence again coming from the archeology, but supplemented with ancient DNA, particularly to really understand what these processes were like. So for example in Europe and Asia, the domesticated plants and animals that people come to rely on as farmers, came from an area called the Levant in Southwest Asia. For a long time there was a big debate, was this moving into Europe by diffusion? Or was it actually farmers moving from the Levant actually migrating into Europe, bringing their farming techniques with them? The genetic evidence has been showing some really interesting things. So it does suggest that actually there was a migration of people into Europe and in some places they almost completely replaced the existing hunter-gatherer populations. There was a study of remains from the UK and it suggested that perhaps 90% of the original hunter-gatherer population was replaced by these incoming farmers.

Katie - What about the other hominins that were around at the time? Because we're not just talking about homosapiens are we really.

Emma - If you'd have asked that question 20 years ago, we'd have said, well, it was just modern humans and there were then Neanderthals in Europe and Asia and maybe another species called homo erectus still in Asia. But there's been really incredible discoveries over the last 20 years. So we now have another species called homo floresiensis that survived to about 50,000 years ago. There's also homo luzonensis on the Island of Luzon in the Philippines. Homo naledi was still around about 230,000 years ago in Africa. We've got Vende Denisovans, this kind of enigmatic species that were identified only initially from DNA in mainland Asia. And then we've also got evidence that homo erectus were indeed still around in parts of Asia, like Java, until around 110,000 years ago. So yeah, when we're looking at that initial dispersal period, Europe and Asia and Africa were occupied by a whole range of species closely related to us. And it's only much more recently that we've become the only ones that are left.

Katie - So there's far more to hominin movement than just homosapiens then. Emma Pomeroy thanks ever so much.

A question in the collective consciousness recently has been around footballers heading balls, and consequences for their brain health. Last year, Glasgow University published research showing that professional footballers were three-and-a-half times more likely to die from neurodegenerative disease. And now, scientists want to build on this research with a long term study that looks at people’s brains over time. With evidence that women experience more concussion that men in the sporting world, what does this mean for female footballers and the risks associated with heading a ball? Katie Haylor spoke to Michael Grey who's leading this study at UEA...

Michael - So we think that heading a ball causes something called sub-concussive trauma. So if we take concussions, for example, a concussion is a mild traumatic brain injury. It has a number of symptoms like headache, dizziness, feeling like one is in a fog. And that's occurring because of a direct result of damage to the neurons in the brain. A sub-concussive insult occurs because we're getting a bit of a lesser hit that doesn't cause a full-blown concussion, but there is still damage. And the idea is that by heading balls day after day, year after year, the neurodegeneration that builds up in the brain eventually leads to dementia.

Katie - How do you know this? What evidence have we got at the moment?

Michael - The direct evidence will come from animal models. Typically in mice and rats, one can induce a head injury of different kinds. One can look at the behaviour of the animal, and then we look at the brain and we can actually see tau proteins in the brain. We can see amyloid proteins in the brain, and we know that there has been degeneration.

Katie - So these are buildups or plaques that seem to be associated with the degeneration you get in things like Alzheimer's or dementia. Is that right?

Michael - Yes, that's absolutely correct. So when a nerve is damaged, we have a process called Wallerian degeneration. So the nerve dies, it breaks up. And then there are components of the nerve called tau proteins or amyloid proteins that are not soluble. So they actually stick around in the neurons. They adhere to the blood supply, they stop the blood supply and they prevent nerves from functioning and they cause other neurons to die.

Katie - Okay. So there is a pretty decent amount of evidence between the potential long-term effects of heading a football and problems with the brain. But where does the difference in sex come in?

Michael - Yeah. So the difference in sex is we think really important and it has been under studied. I mean, it is a fact that most of the studies of concussion, of sport-related neurodegeneration, they're all done in men. So one of the areas of concern for us is if you look at the statistics of dementia, specifically - in the UK, 61% of the population of people with dementia are women. Now some of that is because women live to a longer age and because it's a disease, obviously, that is more prevalent, the older one gets. That explains some of it, but it doesn't explain all of the difference in that ratio. The other thing that we have to look at is concussions themselves. We know that women experience concussion to a greater extent than do men. And if we put those two things together, it just makes sense that women are more likely to sustain the effects of sport-related neurodegeneration than men. And that's why we really need to study it.

Katie - If you were a betting man, do you have an idea of the mechanisms behind the sex differences? Because I guess there's physicality, but are there sort of hormonal changes that may be involved here? What's going on?

Michael - If you look at the mechanism of injury, you have to think about the brain as some jelly in a bowl. If I smack the side of the bowl, the jelly inside will wobble around. And the nerves that are in that jelly, that is the brain, they are damaged. Now, if we have a much stronger neck, for example, you can actually withstand that bubble of head effect. And therefore there's less wobbling of the brain than if we have weaker muscles. And we know that women are, on average, less muscular than men, particularly in their neck. So that's one area.

And if we look at the physiology, we think that there's an issue with women's cycles. So with the hormonal cycles, we think that women may actually be more at risk of concussion and therefore potentially the effects of neurodegeneration, depending on their cycles.

Katie - How could this inform how sport is done in the future? Because I guess you can't eliminate risk can you? I guess it must be about mitigation.

Michael - No, you're absolutely right. This is all about risk mitigation. We need to understand the risk before we can actually do something about it. And the idea here is it's about exposure to the injury in the first place. So one of the biggest things we can do is reduce exposure to heading the ball. In children for example. Personally, I don't think young children should be heading balls. I think that we can be doing the training in a different way. We can be strengthening the neck muscles, for example, long before we start to head the ball. And we can do things like reducing the amount of heading in practice, increasing the time between practices, where one might head the ball. And I think just by doing that alone, we will be making a difference.