transcript

Speaker 1:
[00:00] Hello, I'm Tom Whipple, and welcome to Inside Science from the BBC World Service. How do you make a vaccine for a pandemic that hasn't happened yet? And a venerable fossil named after a venerable man. All that, and we have non-venerable fossil Lizzy Gibney, senior reporter at Nature, here to chat through the other news. Hi, Lizzy.

Speaker 2:
[00:23] Hi, Tom, thanks for having me.

Speaker 1:
[00:25] Somewhere, perhaps in a live food market, a virus jumps from an animal to a human. A stallholder gets sick. The virus, a virus that for years has infected mainly birds, has mutated slightly. The stallholder passes it to his family. His children pass it to other children. The virus has found a way to spread in humans. The world now knows how this story goes. It is another pandemic, an avian flu pandemic. Except, this time, will it be different? This virus does not, in a sense, even exist yet, not in a human pandemic form. But we already have some stockpiled vaccines against it. Now, a new trial is starting in humans to get better ones, using mRNA technology. With Covid, we made a vaccine in a year, the fastest ever by far. One of those vaccines came from the company Moderna. With the next pandemic, will we have another vaccine ready to go? Joining us is John Tregoning, Professor in Vaccine Immunology at Imperial College London. John, let's start with the basics. What is avian flu?

Speaker 3:
[01:41] So influenza virus is the virus that causes flu disease. There are lots of different versions of influenza virus. There are some that infect humans, but actually there's many, many more that infect birds. And so avian influenza refers to all of those strains that can infect birds more than it can infect people.

Speaker 1:
[02:03] And so why are we particularly worried about these? I mean, lots of animals get sick in lots of different places. And is the one in particular that we are worried about?

Speaker 3:
[02:12] Yeah, there are two avian influenza strains that we're particularly concerned about. They're called H5N1 and H7N9. And those letters and numbers refer to the proteins on the outside of the virus, the bits that the virus uses to get into our cells.

Speaker 1:
[02:30] Why? Why are we worried about them? Of all the diseases in all the animals, why these?

Speaker 3:
[02:35] We know flu is highly infectious, it can spread very quickly. These two strains have been shown to sometimes jump into people. And when they do jump into people, can be very, very severe. So H5N1 has a very high case fatality rate. Not many people get it, but if you do get it, you get very, very sick.

Speaker 1:
[02:57] So what is it that we're concerned is going to happen? Because people have been getting sick for a while, but this hasn't been a pandemic. This has just been people with close contact with poultry have got sick mainly, isn't it?

Speaker 4:
[03:07] Yeah.

Speaker 3:
[03:08] So the virus, basically the virus adapts to the type of animal it wants to infect. So to be a good bird flu virus, you need to be good at infecting birds. And birds and humans diverged millions of years ago. And the way that are the kind of cells in our airways that flu likes to grow in, are different to bird cells. So the virus would need to change its ability to infect bird airway, to be able to infect human airway. So there are changes and that is what would enable the virus to move from one to the other, simplistically.

Speaker 1:
[03:42] We're now trying to make a vaccine in preparedness for this event that might happen where you get one that can transmit in humans.

Speaker 3:
[03:52] The recent history of kind of pandemic preparedness has shown us that you can make vaccines in advance of a pandemic happening. So if we think back to 2009, there was the swine flu outbreak and the outbreak was declared in mid-June, but there was no vaccine available for months and months afterwards. And that raised the concern that actually if something takes off very quickly and it's very severe, lots of people will die before the vaccine is ever given to anyone. And this was re-emphasized during the Ebola outbreak in West Africa. But by that time, it was seen that actually there may be a different way of thinking about vaccines. And we used to have an approach where you said one vaccine would match one disease. And that's still the case. But it was noticed that you could start using what are called platform approaches. So to use a very old analogy, if you imagine a cassette player, you could take one cassette which would say flu for humans, and you could take it out and you could put in a new cassette that says bird flu, and your factory starts making the new vaccine in much faster time. And this is where the IRNA technology is really advantageous.

Speaker 1:
[05:10] This is the thing that I find interesting though. We're talking, you've just said that if this H5N1, if this comes into humans, it's going to have had to significantly change in order to affect us efficiently. So we're making a vaccine for this virus that doesn't exist in this form yet. How can we possibly think that we're going to get something that will be effective?

Speaker 3:
[05:31] So I think what this is, is a proof of concept that you can use a mRNA technology to make a vaccine that would work against a bird flu. And yes, you might need to change it a bit for the next round. But what's helpful about RNA vaccines and flu is that RNA vaccines, you can act like a 3D printer, so you put in the cartridge, you get whatever you want out of it. But with flu, we know what should give you protection against the infection. And this is called a corollary of protection. This is based on data from the 1970s, where a thousand volunteers were infected with flu, and they measured their blood before the infection. And what they saw was that if the antibodies in the blood, so that's the proteins you make to kill viruses, were above a certain level, people didn't get infected. So what we can do is something called a bridging study, where we can say, we'll take the data from this 4,000 people study, and learn that we can make those good antibody responses. And then when the new flu strain emerges, we change the cassette, the code, the thing in the RNA printer, much more similar to the one that's circulating. You can do a much smaller clinical study because you know the target number you're trying to hit. And then from there, you can move into production very, very rapidly.

Speaker 1:
[06:56] And is that why this one's exciting? Because we do have conventional vaccines ready for an H5N1 outbreak, but presumably those for the very reasons we've gone through won't be terribly specific to whatever emerges.

Speaker 3:
[07:10] They will probably be good enough. If it's an H5N1 outbreak relating to the kind of circulating strains, one that's close enough is going to be better than no protection at all. But RNA gives us the thing of being able to match it absolutely perfectly and much, much closer, so you get even better protection. And you have that speed of being able to do it, and the scalability of being able to make lots and lots very quickly.

Speaker 1:
[07:36] And these correlates of protection, because a lot of people, we all feel we're experts on this sort of thing, having followed COVID. And during COVID, the phase three trial worked by you, you gave tens of thousands of people the vaccine, you gave tens of thousands of people the placebo, you waited for a certain number to get infected. And from where those infections came in the placebo versus the real thing, you determined whether it worked. We're not going to be able to do that at all in this phase three trial because it's not circulating.

Speaker 3:
[08:03] Correct. And that's why we use these very highly validated correlates of protection. The assay is called hemagglutination inhibition, or HAI. It has been used for a very long time, 50 years. The decisions about what strains of flu are put in the vaccine each year, so not bird flu, the normal seasonal flu, is based on the HAI titer, this level of antibody in the blood. We know from millions of pieces of data that HAI is a good measure. It's not a perfect measure because it's biological sciences. There's so much variability in everything, but it's a good enough measure to be able to predict the efficacy of a vaccine against influenza.

Speaker 1:
[08:46] Does this mean we've solved pandemics?

Speaker 3:
[08:49] No, because the next pandemic, it will be something that we're not expecting. The whole COVID-19 outbreak, some of the challenges were we were expecting a flu pandemic and we got a coronavirus pandemic. If we're training for an influenza pandemic, we may get something completely different again. So solving pandemics is not possible. We can move to a state of better preparedness. You don't ever want to have to need your seatbelt, but you want to know that it exists. Having a platform that can make a vaccine in quick time and closely match to the virus that is emerging, gives you better protection against what could come in the future.

Speaker 1:
[09:30] Thank you very much. That's John Tregoning, author of the book Infectious and also Professor of Immunology. Now over to Roland Pease, who's been diving back in time and into the Cretaceous oceans.

Speaker 5:
[09:44] I bring you giant octopuses from the Cretaceous last age of the dinosaurs, the top marine predators of their time, according to their Japanese discoverers in Science Magazine this week. Hideous kraken that may have been up to 19 meters long, head to tentacle tip. If so, they comfortably outstripped giant squid of today, up to 12 meters in size. Though, as Christian Klug, a specialist in cephalopod fossils, who knows the new work, he warns, in this case, the Japanese team found none of the fleshy bits, the mantle or tentacles, just the remains of hard mouthparts.

Speaker 6:
[10:23] First of all, we have only the jaws. So this is, of course, already a little bit of an obstacle. How do we know just from the jaws, which are actually comparatively tiny in proportion to the whole animal, especially if you compare it to other predators of the Cretaceous, like mosasaurs, which have quite gigantic heads and huge jaws, huge mouths. So that's a big difference.

Speaker 5:
[10:46] So the jaw is in the sense that the hard bit, which can survive fossilization process, is that right?

Speaker 6:
[10:51] Yes. I mean, there's also the gladeus, which sometimes fossilizes. But for some reason, we hardly have any gladeuses from the Cretaceous of Japan. We do have soft-tissued fossils from the Cretaceous, from Lebanon, for example, which are wonderful, which show all the arms and the mantle and jaws and eyes and whatever, but these are usually rather small species.

Speaker 5:
[11:14] So in this case, is it the point that the jaw part is, I don't know, twice as big as known modern ones and therefore the whole animal is thought to be twice as big? Is there some kind of relation like that they're working with?

Speaker 6:
[11:26] Yes, exactly. So they use the ratio of the size of the jaws to the body to then extrapolate what size might have been. And they say, mantle length ranged between 1.5 and 4.5 meters, which sounds of course much less dramatic. But of course, if you know the morphology of these colloids, you know they had arms. And then the size range of the whole body of the animal would probably range like 8 and 19 meters, right? But 8 meters is still a big critter. So I mean, when you go diving and you have a colloid, like a kraken sitting in front of you, that's 8 meters long, it can be intimidating. Yeah.

Speaker 5:
[12:09] And if it's 19 meters, I mean, that would be way beyond anything we know today, I guess. What were they feeding on?

Speaker 6:
[12:15] That's a good question. And that's actually one interesting thing about the study because they studied the wear of the jaws. The problem, of course, is if you look at the wear of these jaw elements, you see all these scratches. And there's not a signature that says, aha, this was a fish, this was a small reptile, this was a crayfish or so. But you see the scratches. So the safest way to know what an animal ate would be having a stomach content in the fossil record. And we do have that sometimes, even in fossil colloids. I have, for example, on my desk, I have a relative of modern octopuses from the Jurassic and it has inside its stomach, it has the jaws of ammonites. So we know that this little squid actually, or not squid, octopus-like animal, ate ammonites back in the day in the Jurassic.

Speaker 5:
[13:02] I suppose the reason I'm wondering what it was eating, this giant octopus, was it eating bigger things? And did it need to be big? I can't quite work out why one huge organism is evolutionary better than lots of smaller ones.

Speaker 6:
[13:19] So that's a good question. But of course, if you look at large animals today and also in the fossil record, I mean, if you look at Tyrannosaurus, it was a big predator probably eating big animals, right? But if you look at today's baleen whales, if you look at the whale shark, the basking shark, they're filter feeders. So they actually, instead of eating big animals, they ate basically zillions of tiny animals like plankton, right? So this is two strategies that help you to grow big. But in this case, with the big jaws and so on, I would expect that did eat like moderately big animals, like maybe fish, maybe other kephalopods, anything that was in reach. I mean, I wouldn't exclude that because for example, if you look at the giant Pacific octopus that lives in the Pacific Ocean today, and it has an arm span of up to 5.5 meters, there is videos showing how this octopus actually catches small sharks that are about a meter, a meter 50 long, and they can perfectly do that. So I wouldn't exclude that they ate big fishes that are like a meter or two long. Why not? I mean, with their tentacles and their suckers, they could perfectly hold on to such an animal and there is no escape. So the Pacific octopus can hold up to 20 kilos with one sucker and has 2,000 suckers. So this is a lot of weight lifting if you want. So you can hold on to fairly big animals with that and there is no escape really.

Speaker 5:
[14:49] I've sort of asked you the obvious questions that someone who's not a scientist might ask sure about this thing. How horrifying is it? I mean, for you, are there particular things that are striking about this discovery or that you want to know more about?

Speaker 6:
[15:04] So, I mean, of course, I would like to know the whole animal, right? So it would be amazing if we could find a locality that preserves soft tissues like we have in some localities like in Lebanon. And then we would see, aha, that's the actual arm proportions, that's the shape of a mantle, that's what its fins are like and so on. And if we were very lucky, then we would have a stomach content, which would even greater than we could even reply to that question. So what would be kind of the cascade of food in the food webs back in the day in this ocean? And were there maybe even bigger animals or were the animals that maybe not that big, but would still be eating those big kephalopods? So to address the questions, are they actually the apex predator or did maybe mosasaurs eat those big kephalopods? So there's a lot of questions linked to that. And of course some of them depend on exceptional fossil discoveries, but you never know what will turn out in the future, you know. Maybe you find a mosasaur and you find the exact same jaws in its stomach, then we can say, aha, OK, so this mosasaur ate this huge kephalopod.

Speaker 5:
[16:12] Christian Klug, Professor of Paleontology at Zurich University, with A Taste for the Monstrous.

Speaker 1:
[16:18] Thanks, Roland. You're listening to Inside Science from the BBC World Service. Tell us what science you think we should be investigating. Our email address is insidescienceatbbc.co.uk. It is time to move on to something that is very, very, very extinct. We continue our tour of new species of flora, fauna and fossils that are all very different, but all of one very specific thing in common. Their link to a man celebrating his 100th birthday.

Speaker 4:
[16:57] Father of the Night Guest, judging from the loudness of their calls, and 30 feet up in the tree.

Speaker 7:
[17:03] Fresh new shoots draw animals from great distances. There is plenty to eat, but getting to it can be a little uncomfortable. Never before have we had such an awareness of what we are doing to the planet. And never before have we had the power to do something about that.

Speaker 1:
[17:27] This week, a 560 million year old fossil called Aurora Lumina Attenburyi.

Speaker 8:
[17:33] There was basically no debate about who we should name this fossil after. And we named it after David Attenborough because he has done a huge amount to promote the significance of the fossils from Charnwood Forest in Leicestershire, which is where Aurora Lumina was described from.

Speaker 1:
[17:50] That's Dr. Frankie Dunn, senior researcher at the Oxford University Museum of Natural History. She got into the fossil business because of the David Attenborough documentary First Life, some of which was filmed at Charnwood Forest in the UK, the place where years later she would describe her own fossil.

Speaker 8:
[18:09] So Aurora Lumina looks, I think, a little bit like the Olympic torch, which is where the genus gets its name. So Aurora from the Latin for Dawn and Lumina from the Latin for Lantern. And coming from the top of this lantern torch structure, we can see a slame of tentacles. We all immediately knew this was something very different. We wanted to make sure that we did her justice. So we took her time with it. And we read around the literature, looking for any organisms that might bear some similarity to Aurora Lumina. And ultimately, we came on the Nideria, which includes today sea anemones and jellyfish. And jellyfish also go through a phase in their life when they look a little bit like a sea anemone. We would call this the polyp stage. And we were really shocked because Aurora Lumina actually looks a huge amount like the polyp stage of living jellyfish. So we built like a tree of life for all Nidarians. And we put Aurora Lumina into this data set. And what it told us was that Aurora Lumina was an ancestor to all of the diversity of jellyfish today. So Aurora Lumina really changed our understanding of what we thought animals were doing in the Ediacaran period. If you're interested in the origin of animals, there are two geological periods, which I'm sure you'll have heard of. The first and most famous is the Cambrian. And there is a very famous geological event known as the Cambrian explosion during which pretty much all of the modern ways of being an animal appear in the fossil record for the first time. So if you peered back through geological time into the Cambrian period, despite this being more than 520 million years ago, you would actually be able to recognize most of the life around you, which I think is a really profound thing. This also tells us that the origin of animals is consequently more ancient than this. And so we need to go back to the preceding geological period, the Ediacaran. And when we do that, the world is very, very different. And again, if we were to peer back through time and look at the Ediacaran seafloor, you wouldn't be able to recognize most of the forms around you. So we have this gap between the strange, extinct Ediacaran world and then the much more familiar Cambrian world. And this is why the discovery of a raw Illumina was so important because it's an Ediacaran aged fossil which we can look at and immediately recognize not just as looking like a group of animals which has made it to the present day, but actually being a direct relative of those animals. So it extends the evolution of animal body plans that we would recognize by, you know, almost 40 million years back through time.

Speaker 1:
[21:08] Thanks, Dr. Frankie Dunn. Lizzy Gibney is with us and she doesn't just have views on Martins. She is senior reporter at Nature, the world's most famous scientific journal. So she is on top of the other biggest stories of the week, we hope. Lizzy, what may have passed us by that we need to know about?

Speaker 2:
[21:27] Well, we had a paper in Nature about a ping pong playing robot. So I thought this is really interesting because we get a lot of hype about robotics at the moment. People might have seen there was a humanoid robot marathon that happened in Beijing last week. But a lot of the time robots are being teleoperated, they're kind of remote controlled. And actually doing robotics is incredibly difficult. And this paper showed how you could make one and it's not a humanoid, it is a robotic arm. But yeah, play table tennis. And that is a big challenge. You've got like the balls fly up 20 to 30 meters per second and they're spinning like a hundred revolutions a second. And the robot has to factor all of that in and then obviously has to know how to respond. So it's really impressive, but also shows us that there are still a lot of challenges to face in robotics.

Speaker 1:
[22:16] I mean, I watched it and it's sort of mesmerizing. It's like this sort of cyborg Forrest Gump going backwards, bash, bash, bash, bash, bash. I guess the thing that struck me is we're being told with the AI revolution, the lawyers might go, but don't worry, you can still be a plumber or a carer. This is kind of a concerted international attempt now to try to make really good functional robots that can live in our world as well, isn't there?

Speaker 2:
[22:43] There absolutely is, but from all of the stories that I've written, people have spoken to, it is still a big, big step to have robots in the real world. And this is why this is quite a nice kind of stepping stone, because we have robots in factories, that's a really controlled environment. And a game like Table Tennis is also very controlled, you've got your court, you know exactly the rules, there's only a certain number of moves that are allowed at it, that's so different to the messy, real environment of a house, say. So I think the scale of the challenge for a robot to be able to do just this one thing, okay, very difficult thing, but this one thing very well, shows you, I think, also how far away we are from a robot that can do your plumbing.

Speaker 1:
[23:24] Yeah, this is fab, but you've got something, I think, out of this world for our last story.

Speaker 2:
[23:30] This is, we're going super nerd now. This is big G. Do you know what big G is? It's not a limestar.

Speaker 1:
[23:36] F equals big G, M1, M2 over R squared.

Speaker 2:
[23:39] Very good. So it's the gravitational constant. So the number you need to calculate the gravitational pull between two objects. And yeah, it dictates the motions of satellites and stars. But what I find amazing to know is that actually researchers don't know it very well to any great precision. And a real like standout black sheep among fundamental constants out there in the world. It's about three significant figures we know it to. When if you think about another fundamental constant like light, the speed of light, C, that's like nine significant figures. And actually has now been fixed that that is the number as a constant. This efforts to measure big G have like scattered everywhere. We can't come to a consensus value. It's just really, really hard to calculate.

Speaker 1:
[24:17] This is astonishing because it is this is one of the first constants that you learn about at school. It's really important. You're saying we only know it to three significant figures.

Speaker 2:
[24:26] Gravity, the gravitational field strength is very, very small. So even compared to the weak nuclear force, which has the name weak in it, this is trillions of trillions of times weaker. Like I can pick up my water bottle and I've defied the gravity of an entire planet. And also you can't shield from it. So any experiment you're doing, you're trying to calculate the pull between two objects. But of course, you have the pull of everything else also affecting it. So someone told me for this story that this is actually the hardest lab experiment in the world. And I believe it.

Speaker 1:
[24:56] And so what is it? What have they been doing?

Speaker 2:
[24:58] So the result this week, published in Metrologia, and that I've been writing about for Nature, is a 10 year replication study. So to try and get to the bottom of this mystery, they shipped the experimental kit from a lab in Paris over to NIST in the United States to try and replicate this experiment. It's masses on a rod and it's hung by a wire. And these masses are attracted to another mass. And you measure the kind of twist on the wire. It took 10 years, they blinded it, so they didn't know themselves what the masses were. So they couldn't cheat themselves by subconsciously trying to work towards the number they knew it should be. And I'm afraid to say the result is that not only did their figure not match the study they were trying to replicate, but it didn't match the universal kind of consensus figure that the world has agreed upon as the best estimate. So there is some good in it in that they've figured out perhaps why it doesn't match well with the previous experiments and ways in which the previous experiment may have gone wrong. But overall, it just still shows us we're not there yet. This mystery continues, why it is so, so, so hard to still pin it down. And Stephen Schlamminger, who led this study, he said, it's like Everest. You know, we, why do people climb Everest? Because it's there. He was like, it must be possible to measure this number. And maybe, hopefully it will be, but we're not there yet.

Speaker 1:
[26:12] Well look, we may not know big G to any accuracy, but we do know the schedule of inside science. This week's episode has ended, but next week's will come, we will return. Until then, goodbye from Lizzy Gibney.

Speaker 2:
[26:26] Goodbye.

Speaker 1:
[26:27] And goodbye from me.