Caesarean stops measles jab response, and quantum navigation

Plus, proof that last summer was the hottest for 2000 years...
17 May 2024
Presented by Chris Smith
Production by Rhys James, James Tytko.

MOTHER_&_INFANT

Mother & infant child in field

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In the news pod, geneticist Henrik Salje tells us about the relative ineffectiveness of the measles vaccine for infants born via c-section. Also, the incredible memory-making abilities of Eurasian jays with Nicky Clayton, and Ramsey Faragher relates how quantum-based navigation can overcome the vulnerabilities of GPS. Then, Ulf Buntgen explains how tree rings have revealed that the summer of 2023 was the hottest in 2000 years in the northern hemisphere, and Toby Wiseman explains the marvel of our working theory of everything.

In this episode

Baby

00:57 - Measles jab less effective after caesarean section

Doctors suspect differences in infants' microbiome may be responsible...

Measles jab less effective after caesarean section
Henrik Salje

Researchers at the University of Cambridge and Fudan University in China have found that the first dose of their measles jab is almost 3 times more likely to be completely ineffective in children born by C-section compared to those born vaginally. Henrik Salje, from the University of Cambridge’s Department of Genetics, suspects that differences in the microbiomes of babies born via the two different routes might be at the heart of it. As measles cases continue to rise around the world, it’s an important health issue to bear in mind…

Henrik - Measles remains a really big problem around the world. About 130,000 people die each year from measles, and we have a very good vaccine, but for some reason or other, sometimes when we vaccinate infants, they actually are not protected afterwards. That's always been a bit of a mystery. And so what we did was to try and understand why it is there are these infants, we think they're protected, they're vaccinated, but in fact they're not.

Chris - How did you pursue it?

Henrik - We worked with a cohort of children. What that means is, right from birth, a group of babies were followed up over time. What this team in China did is they collected blood at very regular intervals, they then noted down when these infants got vaccinated and, in the blood, we could then see whether or not they had protection to measles, including before and after vaccination. This allowed us then to identify those infants that actually failed to mount an immune response following vaccination, as well as to carefully monitor how antibodies in general change over time, including from maternal antibodies that are given from mothers at birth, and also then how your maternal antibodies post vaccine change over time.

Chris - Did any of the vulnerable individuals, the ones that you were documenting, an apparent absence of measles immunity, then go on to catch measles?

Henrik - No. So, in measles generally, it tends to have big outbreaks and then you have no circulation for long periods of time. In this case, there wasn't a measles outbreak. Fortunately, these individuals did not develop measles, so far that we could tell anyway. Also, very importantly, like most countries in the world, in China you have two doses of the vaccine and all the individuals who failed that first dose ultimately got protected with their second dose.

Chris - So it's not that you ruled out, if you get vaccinated and you don't respond, you're never going to, it's just a question of you having more and it pushes those stragglers over the immune line.

Henrik - That's exactly it. That's something we've generally always known is that, that second dose is often just to pick up those individuals who failed that first vaccination. That's certainly the case here as well.

Chris - So what we'd like to know is what's special about those people who were the primary first vaccine failures, what connects them, and what might we be able to do about it?

Henrik - Absolutely, yes. This is probably true not just for measles but for again many other infectious diseases. What we did is we just really looked at all possible reasons, hypotheses as to why some people may fail a vaccine and others not who otherwise look completely identical. The only thing that came out was the mode of delivery of those babies. What we found is, babies born through c-sections were around two to three times more likely to fail their vaccine compared to babies born through vaginal delivery. Even though the vaccine is happening many months later, it seemed to have this long-term effect on the ability for you to mount an immune response.

Chris - Indeed, we give that MMR vaccine at least a year or more, don't we, in this country at least. So why do you think there might be that connection to caesarean section then?

Henrik - That's completely true, and I think there's another whole group of people who maybe don't mount such a high immune response, and that's really to do with this reason: we'd wait for a year in the UK. That is, we have these maternal antibodies which are passed from your mother to the baby, and they're fantastic, they protect you, but they're also very good at stopping the vaccine from having its desired effect. So, what we do is we tend to wait until those maternal antibodies are very low, and that's where we wait for a year in the UK and in many other countries too. But this seemed to be something completely independent to that, and I think what we are slowly discovering more and more is something called the gut microbiome. What this means is all those friendly bugs which help you in all sorts of aspects of your daily life, including the development of immunity. What happens is that mothers have a vaginal microbiome which gets passed on to the infants at birth. If you're having a c-section, you're completely circumventing that, so you don't have that early microbiome that you would do otherwise.

Chris - Some people say that's the most important meal you'll ever eat, don't they? They say your first taste of life is a mouthful of muck, but it's absolutely critical for good health. But how do you connect then what the microbes are doing with response to a vaccine? Because you're still running into all kinds of other infections as a little kid and they don't seem to behave differently, or do they?

Henrik - That remains an excellent question and a very open question. We weren't able to really tackle that through this study. Certainly, it's something which we will need to focus on more: what is the mechanism by which all this muck which, as you say, we now have from the very earliest stage of life, really develops, or allows you to develop immune responses going forward. It seems to be relevant not just for measles, but really all those different vaccines and all the different infections. What's really comforting is that those individuals who are born through c-section failed their vaccine, they ultimately did respond. I think what's happening is it's taking longer for you to develop the appropriate microbiome. Certainly you don't want to be too worried that, in the long term, you won't be able to mount an immune response, but it just takes a bit longer. Another point to note is that in the UK we wait until three to five years for the second dose. We're having increasing rates of c-sections, about 3 in 10 babies are born through c-sections these days in the UK, so it might be that from a policy perspective we might want to consider shortening that for infants born through c-sections

Chris - Because epidemiologists have connected other health outcomes to caesarean section as well, haven't they? Things like, a greater risk of allergy in later life, more risk of getting gastrointestinal problems as you get a bit older. There does appear to be something going on. How are you going to try and pursue this, then? Are you going to try and get underneath what that connection is between what's going on in the gut and how the immune system is maturing?

Henrik - That would be wonderful. I think there are a number of ways you could continue this study and we will certainly do so. One is better characterisation of this microbiome, both in the mother and the baby, and seeing how that develops in the first few weeks and months of life, seeing how it changes then following vaccination, following infection. I think that will give us a more complete picture. At the moment, this is really, ultimately, an observation. We see some babies that failed their vaccine and we just see how they're different from ones that don't. But now what we need to do is do some more detailed studies that really try and understand why.

Eurasian Jay

08:10 - Crow family make memories like we do

'Episodic memory' has often been considered a uniquely human ability...

Crow family make memories like we do
Nicky Clayton, University of Cambridge

Eurasian jays - members of the crow family - are able to remember incidental details of past events. The findings - which have just been published in PLOS ONE - suggest that these brainy birds have memories not dissimilar to our own. To find out more, Chris Smith went to Clare College to meet Nicky Clayton, professor of comparative cognition at the University of Cambridge…

Nicky - A long time ago now, I showed that jays are able to experience the past. That is, they don't just remember information about what's happened, they're able to project themselves - in self and time - to remember what happened, where and when. That was the first demonstration of what scientists called episodic memory. You could think about it as experiential memory. You don't just know a fact about Clare College, the second oldest college in Cambridge, you will have an experiential memory of our conversation sitting in the SCR, in Clare, on this gorgeous sunny day. That's an experiential or episodic memory.

Chris - That would be like, every time I come to Clare College, the sun shines. So, next time I go to Clare College, I won't take my raincoat and I'll wear a T-shirt. That would be an example of that kind of associated planning for the future based on an experience in the past.

Nicky - Absolutely. That's exactly what it's about. If you think about it, as Lewis Carroll said in the series, Alice in Wonderland and Alice Through the Looking Glass, it's a poor sort of memory that only works backwards. If you think about it, it is. What's the point in remembering things if you're never going to need to use those memories again. But really, experiential memories, not facts about the world, these experiences evolve with the future in mind because you use them in the here and now to think about the past in order to plan for the future. Hence your example of the sunny day and no need for an umbrella and just wear a T-shirt.

Chris - So what have you done to push that further?

Nicky - So what the recent experiment is on is about jays memories of the past, their experiences. The first author on the paper is my PhD student, James Davies. The idea was to think about whether they could remember other aspects about the event, because one of the hallmarks of experiential memory in people is that we don't set out with an agenda of things to remember: we just experienced an event and then we remember things about it. And so the idea was that maybe we shouldn't just be asking 'can they remember what, where and when,' but can they remember other incidental features about the event?

Chris - I came to Clare College to see Nicky Clayton, I remember that, but I also remember I was wearing a red jumper at the time.

Nicky - Exactly that. Or that you were sitting on a red sofa, and there was no reason to remember that. It doesn't really help your memory of the event in any particular way, but it's just these unexpected things that you just happen to remember.

Chris - And you wanted to know, do the birds do that like we do?

Nicky - Yes. We wanted to know whether they could incidentally encode these features, not features that they deliberately needed, but whether they just happened to remember them by chance. And when I say we, I mean my PhD student, James Davies, my former PhD student who's now a professor at the National University of Singapore, Elias Garcia Pellegrin, and myself. I just want to make sure that they get credit, I don't want you to think it's all Nicky Clayton and nobody else is important. And of course I must give credit to the gorgeous Eurasian Jays because, without them, none of this would've happened.

Chris - How do you do that then? How do you get a bird to remember the red jumper as well as where I hid my lunch?

Nicky - Well, what we do is we give them various little pots that they can hide food in, or the experimenter can hide food in, but the pots have different patterns or colours or shapes on them. Those features are incidental to the task. They've just got to remember which cup had food, where, and how long ago. But these features are irrelevant during training, they're nothing to do with it. Then we ask them afterwards: but did you remember? So you might imagine rather than a jumper, there's a tray with particular patterns on it and the cups are on those. Can they remember the pattern on the table where the cup was?

Chris - And do they? Do they store that incidental information alongside the other things they were trying to remember?

Nicky - Yes, they do. So it's often called the unexpected question because they're not being trained that this is the question. They're being trained that they need to remember what, where and when, they're not being trained about your red jumper or the patterns on the cups or trays and they just happen to remember it. So that shows that this is another feature of experiential memory that they share with us. They seem to remember their personal past experiences in the same way as we do, and that's why it's important.

Chris - And apart from the fact that they appear to share that memory trait. What else does this tell us about how the birds are thinking?

Nicky - Well, it's just one more thing in this clever cognitive toolkit that these members of the crow family have. Their brains relative to body size are as large as those of chimpanzees, and they seem to be able to do all the same kind of cognitive feats; experientially remembering the past, waiting for a better future award, being able to imagine the future, and think about what others are thinking. That's why we call members of the crow family, including these jays and ravens and magpies and crows, feathered apes, because when it comes to their cognitive abilities, although they have feathers and not hands, they seem to be as smart as chimpanzees.

Phone GPS navigation in a car

14:52 - Using quantum mechanics to safeguard GPS navigation

More accurate and more sensitive, it's also less susceptible to 'spoofing'

Using quantum mechanics to safeguard GPS navigation
Ramsey Faragher, University of Cambridge

But first, when people say things are “up in the air”, that’s often a bad sign; but not this week because the UK has successfully completed flight trials of an advanced quantum-based navigation system that can’t be confused or jammed by hostile states. It’s so accurate it means that even if GPS signals are lost for long periods of time, it can still keep track of our location. To find out more, I caught up with Ramsey Faragher, a fellow at Queen’s College in Cambridge, and fellow at the Royal Institute of Navigation. First we talked about how present day GPS works, and how it can be vulnerable…

Ramsey - The main tool that we all use, whether we're a person on the way to the shops or whether we're a submarine captain or a fighter pilot, we rely very heavily on the global navigation satellite systems of which GPS is the most famous. These are a lot of satellites that orbit the earth. They transmit radio waves down to us here. We have little receivers in our smartphones, in our cars, and in our submarines and fighter jets that use those radio signals to work out where you are and when you are. They're a metre level accurate positioning system and a nanosecond accurate timing system.

Chris - And how does my GPS receiver, whether it's in a phone, it's in my car, how does it know where I am?

Ramsey - Fundamentally, they are atomic clocks in space that transmit the time and because the speed of light is constant, when you are different distances from each satellite, you get those copies of time at slightly different times. So you collect up these numbers from the satellites and you do a little bit of maths that calculates, in order for me to have picked up this particular sequence of the time from these particular satellites, I must be at this location on the Earth's surface. We've become very reliant on these signals and because these signals travel a very long distance to get to us, 20,000 kilometres to get to us, if you have a nearby jammer, which is just spraying noise out on the same radio frequency, it completely blankets the signal and it removes the ability to use GPS anymore.

Chris - Are they vulnerable as well? If someone were to create false signals, could it be fooled into thinking you are where you're not?

Ramsey - Yes, that's called spoofing. It used to be just the realm of Hollywood movies. There was a James Bond film all about spoofing GPS. Nowadays, unfortunately, it's possible to download software on the internet and buy a cheap little software defined radio and actually spoof your own GPS. People do this to cheat at Pokemon Go and to do research into GPS and to test GPS receivers in smartphone companies and car companies and things before they ship them in their products. So it's an unfortunate feature that in order to test these systems well before we give them out to the public, we design them so that they can be spoofed easily so that they can be tested well. It's a difficult catch 22 but, yes, it's easier than we would like for people to broadcast fake GPS signals into receivers and trick them into thinking that they are somewhere where they're not.

Chris - And the new system that they're now testing, what's the vulnerability that that's designed to protect against and how does it work?

Ramsey - So, because GPS can be jammed, it can be spoofed and it can simply be blocked. If you drive through a tunnel, for example, the signals can't penetrate through the tunnel covering. We use what are called inertial sensors to bridge those gaps. This consists of a little box containing accelerometers and gyroscopes. When the GPS signal is unavailable, the accelerometers measure your changes in acceleration. The gyroscopes measure your changes in heading, and you can keep adding up the measurements from them to work out how you've moved since your last GPS fix. Your smartphone has little accelerometers and gyroscopes in it as well that are predominantly used to play games and to make the screen turn when you turn the phone. But even the tiny cheap accelerometers and gyroscopes inside your phone can do a really good job of bridging GPS fixes for say, 10 seconds. So this new quantum navigator is a much, much more accurate and sensitive accelerometer and gyroscope set than we've ever had before. That means you can survive very big GPS outages, maybe hours.

Chris - How does it work?

Ramsey - It uses cold atom interferometry. A chap called Bose, who's less famous, and Einstein, who we all know, they wrote a seminal paper a long time ago on how, if you cool down atoms enough, they enter a new state that we call a Bose Einstein condensate. What happens is, all of the atoms of the gas collapse down to a single energy state, and they all now start to act as waves instead of particles. And so because they're now at the quantum limits where they can all be treated like waves instead of particles, you can do wave stuff with them, like interfere with them and defract them and make use of their wavelength. Atoms don't normally have the concept of a wavelength until you bring them down to this point. The wavelength of these cold atom systems is about ten to a hundred thousand times finer than the wavelengths of lasers, and so the laser based gyroscopes we've been using for years are about a hundred thousand times less accurate than these ones. So it's very exciting. That's why we're using the new technology. It's a whole new level of sensitivity and performance.

Chris - How big is it though, Ramsey? And is this easy to do, easy to build, easy to apply? Because the report I read was of a whole bank of material and equipment on aircraft.

Ramsey - Yeah. So I had the pleasure, about 15 years ago, to go and visit early work in Imperial College in London on these cold atom interferometers and I was pretty much standing inside the device at the time. I was inside a lab where the entire room was dedicated simply to trapping, cooling and using these atoms. There were lasers everywhere and power supplies and lots of tubing and piping, and it's still container sized from what I gather from some of the experiments that have been going on, but the aim is to get tabletop and eventually shoebox sized versions of these sensors.

Chris - Can they cope with going round corners really quickly, though, because aircraft, it's not the gentlest experience, and if you're a military aircraft, these guys are going to be pulling multiple Gs to take evasive actions and so on. How do their clouds of cold atoms cope with that?

Ramsey - Yes, that's a very good question. So the different designs, the different types of accelerometer and gyroscopes that we've used over the years all have different levels of sensitivity, accuracy, and dynamic range, which is how big a force they can survive and still operate. At the moment, the cold atom technologies don't have high dynamic ranges. It's literally a cloud of atoms, tiny little clouds of atoms that are being thrown up and down inside a tube. So, if you're midway through chucking these tiny little atoms up and down the tube, and then you give the tube a big kick, they all smash against the side of the tube and you can't measure them anymore. This is the current problem that they'll be working on overcoming. There are various ideas on combining the cold atom technologies with traditional technologies so that when the cold atoms are available you've got all of that accuracy and in high dynamics you free wheel on a normal inertial navigation system. These are the main engineering challenges, Chris. Us physicists don't worry about such things.

Trees in a forest

Tree rings prove 2023 was the hottest summer for 2000 years
Ulf Büntgen, University of Cambridge

We know the last few summers have been hot. But how hot? Ulf Büntgen’s team at the University of Cambridge have developed a way to extract climate data from the growth rings of trees, and even ancient fossilised wood buried in the Fens, that are allowing them to look back over thousands of years, and - critically - well before thermometers were invented...

Ulf - The main message of this paper is that the last summer, of the year 2023, is the warmest summer of the last 2000 years. We know that not from instrumental measurements, we are using tree ring data. So a tree is recording for us the temperature over the past 2000 years. You may now ask how do you get 2000 year old trees?

Chris - How do you get 2000 year old trees? No, I was just going to ask exactly that. So where did you get the trees from and how do the trees record temperature? I know you're saying you're looking at the rings, but what about the rings records the temperature?

Ulf - There are basically no trees, almost no trees, that are 2000 years old. So we take living ones from maybe the past 3, 400 years and then we extend the information of these living trees with relic wood, with that material. So we, for instance, would go into a college here in Cambridge, in the roofs, and take samples and collect material from historical construction timber. Or, we work together with archaeologists that have excavations where we get wood remains out, or for instance, just last week I was in the fenlands, North of Peterborough, where we collected subfossils, relic wood that comes out of the peat box. All these different wooden sources help us to build a continuous time series, we call that a chronology, that covers 2000 years for different parts of the world. And how do we do that? Or, in fact, how are the trees doing that for us? These trees are functioning like a thermometer. Small changes in summer temperature are reflected in wide or narrower rings. So the tree is suffering if it's getting too cold, and the tree is thriving and producing lots of wood under favourable conditions. Then we have an overlap where we have both the instrumental measurements. Whenever we have an overlap of what the tree rings are recording and what we measured with instruments, we can build a model. We are calibrating, we are trying to understand what does it mean if a ring is wide or narrow and how can we transfer that into temperature.

Chris - Could anything else though affect those tree rings? Is it just temperature and is that discreet. Or could, say, a very wet year make a difference, a very dry year make a difference and therefore other things could tweak the formula?

Ulf - You will be surprised about the answer. Everything affects the tree. So when a tree grows, it's completely affected by a lot of things in its environment and that is all recorded. But we are not relying on a single tree. We average the information for hundreds or even thousands of trees and then we cancel out the noise. Then what we emphasise is a common signal. If we see that a tree shows a narrow ring, let's say, in the European Alps, and at the same time in the same year in the same summer, also in Northern Scandinavia and so on, over a larger geographical region, then we know it can't be a local factor. It must be a larger factor and that is then temperature.

Chris - And how much bigger are the effects now? So the tree rings are saying it's warmer now than 2000 years ago. How much warmer?

Ulf - So trees are only recording something that happens during a growing period, right? That is the summer, let's say, from spring to autumn. So the northern hemisphere summer temperature of 2023 was roughly two degrees warmer than the pre-industrial period. Before our study, people just had information from 1850 to 1900, which we called the period of early instrumental measurements. That is where, in some places on our planet, certainly not everywhere, we had the start of early instrumental measurements. These measurements were also biased. They were not absolutely accurate. They still had to learn how to build up meteorological stations to fine tune it. Based on this period, before industry starts significantly in the 20th century, we would say we have this two degree warming trend. Now with the tree rings, we are able to provide and set the most recent anthropogenic warming in a much longer context. That is the main achievement of this study. It makes a huge difference if you say the last summer was the warmest summer of the past 150 years, or if you say the last summer was the warmest summer of the past 2000 years.

An alien walking with a backpack

Do the laws of physics stay the same wherever you are?
Toby Wiseman, Imperial College London

For this question of the week, James Tytko was tasked with finding an answer to Daniel's question on the human understanding of the universe. Luckily, cosmologist Toby Wiseman from Imperial College London was on hand to help...

Toby - Does physics change as we move around the universe? One of the fundamental tenets of cosmology is in fact that we don't live in a special location. All locations, all directions are the same, and that is absolutely what is observed when we look out into the universe. Our modern theory of cosmology uses our theory of particle physics, which we derive from collider experiments such as CERN on the Earth, and then our theory of gravitation, Einstein's general theory of relativity. Now, it isn't a complete theory, but if we are not worried about physics in the very earliest epoch of the universe, then the theory is remarkably good. We can understand everything that happens within this theory from way earlier than a second after the Big Bang. You start with this almost blank canvas of the Big Bang with little quantum fluctuations on it from what we call the theory of inflation. And those quantum fluctuations grow, cede structure because of gravity pulling structure together, and then eventually this forms the galaxies, stars and so on that we see today.

James - I think Janus' comment on our forum post for this question captures what Toby is saying about some of the unanswered questions we have and how they fit into our understanding of the universe very nicely here. They write, 'It would be possible for another civilization to have pierced the veil more deeply and have a better understanding of some of those principles than we do. This would not constitute a change in the rules, however, but just a better understanding of what they are.'

Toby - If you are sitting on a particular star somewhere, you may look down at your star and call it a different name, and you may look at the elements in it and call them different things. But this theory really predicts all of that physics. It has all of that physics in it, and we think of this theory, of the standard model of particle physics together with gravity, as something that we've discovered and uncovered rather than something we have constructed. The fact that we can write down the theory of all the forces and all of matter on a T-shirt and a couple of lines is astonishing, and it's a process of uncovering. We've got closer and closer, and the theory in many ways has got simpler and more elegant as we've honed in on it. It's very difficult to understand how that could be a human construct. This is the most accurate thing that's ever been predicted by any theory of anything, and it works. That's where my money is, anyway.

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