Antibiotics affect babies' vaccinations, and space miso
In today's news podcast, a study shows a reduced effectiveness of vaccinations in babies who have antibiotics treatments early in life. Also, the world's smallest, light-powered pacemaker, and we learn the secrets of the broadclub cuttlefish's crab-catching colour display. Then, we follow the journey of miso paste up to the ISS and back to Earth again, and hear what it tastes like!
In this episode
01:08 - Babies treated with antibiotics respond less to vaccines
Babies treated with antibiotics respond less to vaccines
Claire Waddington, Liverpool School of Tropical Medicine
A new study from Australia has found that babies treated with antibiotics as newborns have reduced immune responses to vaccines given later in infancy. They speculate that changes to the “microbiome” - the community of bacteria that live on each of us - underpin the effect. The findings have been published in Nature, and Claire Waddington - a senior clinical lecturer in infectious diseases at Liverpool School of Tropical Medicine - has been taking a look at them for us…
Claire - What this paper set out to look at was whether antibiotic exposure in early life could affect response to vaccines in young infants and essentially their bottom line was that it did indeed seem that infants given antibiotics when they were very young had different responses to vaccines subsequently.
Chris - They didn't respond as well, they were less well protected?
Claire - This study looked at the immune markers of what we think predicts how well the vaccines are going to work. They weren't able in this paper to drill down specifically to show that it had a negative impact. But what they did show was that the immune response looked less optimal in those infants that were given antibiotics in early life.
Chris - And just to be clear, these are vaccines for all sorts of infections, both bacteria and viruses. It wasn't just your ability to protect someone with vaccines against a bacterial infection and how that was affected by antibiotics, it was everything?
Claire - They did look at a range of different vaccines and these were the standard vaccines that you would give to most infants in most parts of the world. And some of those vaccines are targeting viruses like rotavirus and some of them are targeting bacterial infections like streptococcus pneumoniae. And they did find that the immune response and the impact of antibiotics on that immune response was different looking across the board at all of the vaccines that infants get.
Chris - And was there a window when exposure to antibiotics within that window is most likely to produce this effect? It must wear off at some point.
Claire - They looked at antibiotic exposure in infants through a variety of different routes. One of the groups they looked at was when mums get antibiotics in the late stage of pregnancy. And they also looked at infants given antibiotics in the early few hours or days of life. And then they also looked at infants that were exposed after they'd been born, but through their mum's breast milk.
The strongest effect with the infants that were given individually antibiotics in that early neonatal period, they were able to see that even if mums had antibiotics in the latter part of pregnancy, they could detect a difference in the infant's microbiome, so the bugs that make up the infant's gut. But because they were following these infants prospectively, they were able to show that that effect wore off by seven weeks of life. Whereas those infants that had antibiotics themselves still clearly had a difference in their microbiome at seven weeks.
Chris - And what do they propose is the mechanism by which you get this sort of legacy effect of early life exposure to antibiotics that then affects how you immunologically respond to vaccines later?
Claire - The suggestion in this paper is that the effect that we see on vaccine responses is probably mediated through the microbiome. It looks like early antibiotic exposure, particularly at the higher doses that we see in infants that get it themselves, seems to change the microbiome and that change in the microbiome is probably affecting the response to vaccines.
Chris - Does it go back to normal later though?
Claire - We don't have the direct data to show that at five years, they have different responses. And even in this study, what it was largely looking at was associations in the infants themselves. But what we do know overall is that very early neonatal period and early infancy is really important for subsequent health.
And that first 1000 days of life, as it's often termed, is absolutely crucial to health in the rest of your life. Vaccine responses are part of that equation.
Chris - What do you think, then, are the important questions we now need to answer? Or what should we consider changing? We don't want to make knee-jerk changes to any kind of protocols and policies and people don't get antibiotics for no reason, hopefully. But what should go through our minds then off the back of this and make us think differently?
Claire - I think one of the important strengths of this study and conclusions from this study is that there is something we could potentially do about this. And that namely is looking at the effect of probiotics in those infants that are at risk of having this muted response to vaccines. So those infants that require antibiotics for whatever reason.
There is probiotics that we already quite commonly use in neonates and newborns. And that gives us a potential real world solution to this. And if we can show that giving these probiotics is able to restore microbiome in these infants and that lets them get the best possible chance of a good immune response to vaccines, then that could have a significant impact in terms of all of life health as we were talking about.
07:32 - Scientists develop the world’s smallest pacemaker
Scientists develop the world’s smallest pacemaker
John Rogers, Northwestern University
During the recovery period after cardiac surgery, many patients will require a temporary pacemaker. This involves placing electronic leads near the surface of the skin, leading to a box of electronics, the ultimate removal of which is associated with risk of complications. But scientists in the United States have developed a temporary wireless pacemaker that is smaller than a grain of rice, and will eventually be broken down and absorbed - which means that potentially less invasive techniques can be used to place implants in patients. John Rodgers at Northwestern University is behind the device…
John - I guess the best way to think about it is it has a size somewhere between a single grain of rice and a sesame seed. In fact, it's so small, you can load it up into the bore of a syringe and just inject it in almost like a medicine. When it's illuminated with light from the outside of the body, from the skin surface, it turns on the pacemaker, thereby delivering pulses of electrical current to the surface of the heart to provide that cardiac pacing functionality.
Chris - So, the pacemaker is light sensitive and the light rhythm can drive the rhythm of discharge of the pacemaker, which in turn sets the rhythm of the heart.
John - Yeah, exactly. So we have a soft skin interface patch that you put on the surface of the chest, more or less above the location of this millimetre scale pacemaker. And that soft electronics patch has a light emitting diode integrated in it. The electronics then control the pulsatile flashing of that LED and the light that penetrates through the skin, through the tissue and illuminates the cardiac pacemaker then turns it on and off with a frequency that's matching the frequency of the operation of the LED.
Chris - I just want to say: “wow.” Enough light gets through that depth of tissue that you can do that.
John - Yeah, it's pretty interesting. The wavelength that we use is in the near infrared region of the electromagnetic spectrum. If you've ever played around with a red LED or a red laser pointer, you put it on the backside of your finger, your whole finger glows. It's at these wavelengths where tissue absorption properties are quite modest. They're quite low. And mostly what happens with light as it passes through the tissue, it's not absorbed as much as it is just scattered. And that turns out to be a nice thing because it means that we don't have to precisely align the position of our LED to be coincident with the location of the millimetre scale cardiac pacemaker because as light passes through the tissue, it kind of blooms out. And so you have a whole flashlight region of the heart that encompasses the cardiac pacemaker that gets illuminated.
Chris - And is the entire structure light sensitive then? So, it doesn't matter what orientation it's in in the heart tissue, it will see that light and it can detect it and respond to it.
John - It's oriented so that the light sensitive side is sort of pointing toward the skin, although that's not that critical because you have light scattering all around. So, you're basically illuminating a whole volume of tissue. But we do like to have that light sensitive side of the device facing up. And then the other side of the device is providing the electrical contacts that are needed to inject current into the cardiac muscle to initiate a cardiac cycle.
Chris - How does that bit work then? You've got these electrodes, what are they made of? So, how are they generating the electricity? And what's the processing that's going on inside to turn the light signal into those discharges?
John - Yeah, great question. So, it turns out it's the simplest possible battery you could imagine. We use two dissimilar metals for the electrodes. You need a pair of electrodes interfaced in the cardiac tissue to deliver the current pulses. We like to use magnesium and molybdenum or magnesium and zinc. And if you take two dissimilar metals like that and you connect them with an ionically conducting fluid, like the naturally occurring biofluid that's bathing the surface of the heart, that forms a battery. Now, the battery can't discharge unless the electrical circuit is completed. So, you need the backside to be electrically connected as well so that current can flow to balance the chemistry that's going on between those two metal pads. And that circuit is only completed when that photoactivated switch is closed. So, if the device is not illuminated with light, that switch is open. And it works really well for this application because it is simple. And so we can size reduce the entire system and still maintain enough current to stimulate the heart.
Chris - And is there enough current to stimulate a human heart? Because capturing a little tiny mouse heart, that's going to be a lot easier than something much bigger and bulkier.
John - Yeah, that's right. So when we engage in a project like this, animal model trials are kind of an essential aspect. But we progressed with human hearts, not in live human patients, but recently deceased individuals. We were able to demonstrate the ability to capture the cardiac rhythm at a human scale by using those donated hearts from organ donors.
Chris - And the thing completely dissolves away harmlessly.
John - Yes. So we've studied that again in animal models, not in human subjects. We're not there yet. But the materials themselves are not really exotic and just kind of orient people. Magnesium, molybdenum and zinc are all essential minerals for a healthy diet and a healthy metabolism. The photo activated switch is built around a very thin sliver of silicon, which is also a part of a healthy daily diet that doesn't in itself guarantee biocompatibility and harmless dissolution in the body. But I think it sort of makes sense that we're not observing any adverse effects because you need these materials anyway. And I guess if you had enough of these devices, maybe you make a vitamin tablet out of them, but you'd have to add up probably a hundred, you know, I'd have to run the numbers, but kind of on that order to make an impact at a dietary level.
Chris - And were the cardiac team impressed with your endeavors?
John - Well, yeah, I mean, we're an engineering oriented group, but most of what we do is in response to inbound requests from clinical collaborators, cardiac surgeons reaching out and describing this challenge that they have. The kinds of patients who need this temporary pacing span the full range of ages, but it turns out that it is most critically important for pediatric patients who've undergone a cardiac surgery associated with a cardiac defect. And there the ultra-miniaturized geometries are even more important. I mean, smaller is almost always better, but especially for these infants, you know, minimizing the burden, the device load on the body turns out to be a really important consideration. And so that's high on the list of priorities around where this kind of technology kind of moved the needle in terms of patient care.
15:42 - How cuttlefish dazzle prey with a moving skin pattern
How cuttlefish dazzle prey with a moving skin pattern
Matteo Santon, University of Bristol
But first, we take to the depths of the ocean to examine the remarkable hunting technique of the broadclub cuttlefish. These cunning cephalopods are frequently featured on marine life documentaries because of their remarkable ability to camouflage themselves, stupefying their crab prey in the process. It has remained a bit of a mystery - but Matteo Santon at the University of Bristol thinks he’s cracked the shell…
Matteo - What is unique about this species is that it uses a very special hunting technique. When it's approaching prey, for example, crabs, what this cuttlefish does is that it changes the appearance of its head to a homogeneous white colour, then it's stretching six of its eight arms forward into a tight cone, spreading, stretching laterally the remaining two arms with a flat surface pointing towards prey. And at that point, the cuttlefish starts passing highly contrasting dark stripes in a downward direction across the head and the arms, and it's approaching prey until the strike. And we were particularly interested in trying to understand why this species is doing this. And there have been a few theories that were put up by natural history documentary filming, and that was mostly saying that this was some sort of mesmerising or hypnotising display that was somehow thought to help the cuttlefish catch prey. In particular, as a visual ecologist, we were interested in trying to understand how this actually worked.
Chris - Does it reserve this particular technique specifically for certain types of prey, or is this its modus operandi, regardless of what it's hunting?
Matteo - So the cuttlefish is actually quite peculiar because it can use this one hunting display that we call the passing stripe display, but it can also use up to three other types. We are still trying to understand whether there's actually a way that cuttlefish chooses between this display, but what I can tell until now is that it's just using them interchangeably.
Chris - And what effect does that seem to have on the prey when they experience this? Obviously it works because the animals use it, and if it didn't work, they'd go hungry, wouldn't they? So what effect does it have on the prey? What effect does it appear to have on the prey items?
Matteo - It's interesting because prey items like crabs, they're very sensitive to approaching cues, to sort of looming objects that come towards them, and they would respond normally by running away, by escaping. Whereas what we can observe when the cuttlefish is hunting with this display is that crabs don't seem to do anything. They just wait until the cuttlefish goes and grabs them. And that's something quite interesting because to us this hunting display appears very conspicuous. And that's one of the reasons why I thought there's maybe something more going on here.
Chris - So what do you think is going on and how did you try and test it?
Matteo - We've been using three different approaches to try to understand this question. And the first one was working with crabs in lab. And what we've been doing is that we've been feathering crabs on a sort of treadmill, like the ones that humans use, or very similar, made of styrofoam. And the in front of a LCD monitor. And what we then did is that we started to display to crabs expanding predator stimuli, which could have either moving stripes passing on them, very similar, trying to represent what the cuttlefish is doing, or stimuli without moving stripes, static stripes, or stimuli without any stripes at all. And then we had a second approach, which was based on actually going to the field, using scuba diving as a method, and try to really film this type of hunting display in the wild, and try to describe them in detail and try to understand whether there was something in the way that this cuttlefish was doing the display that could tell us something that was particularly relevant on the function of the display.
Chris - And what do you think it is? How do you think it's working?
Matteo - What we found out is that crabs seem to be less sensitive to respond to expanding stimuli when they feature moving stripes, which is sort of hinting us that cuttlefish may be using this just to prevent the crab from seeing the approaching cuttlefish. And we also found, while being in the wild and filming cuttlefish, is that somehow we saw that the faster is the approach of the cuttlefish towards prey, then the faster the passing stripes had been moved across the head and the body, which somehow is telling us that there is some sort of link, clear link, between the strength of the approach of the cuttlefish and also the strength of the motion that is generated by the moving stripes. And we think that this is in fact telling us a little bit how this hunting display works. We think that in this display, threatening motion cues of the predator, of the approaching cuttlefish, are actually overwhelmed by the strong non-threatening downward movement of the stripes that a cuttlefish is producing.
Chris - I was going to say, do we, based on what we understand about the way that a crab's visual system works, do we have any clues as to the effect that this moving stimulus might be having on them? Is it a distraction? Is it that they're so fascinated by it that it blurs and sort of obfuscates the approach of a predator and their interest in the stimulus motivates them to watch it more? Is that how it works?
Matteo - What is important to understand here is that crabs, they don't quite see very well, so their world is very blurred and often not in colour. And what their visual system is really fine-tuned to detect is expanding predator motion cues, which is something that animals in general get scared quite a lot if they see something approaching them very quickly. So their visual system is really finely tuned to detect a radially expanding approaching motion. And instead, what the approach of this cuttlefish with a passing stripe does is that the visual system of crab would not detect a radially expanding predator approach, but rather a strong unilateral downward motion, which is generated by the stripes, and therefore not really respond at all to predator. So we actually think that the crab is not really detecting the predator approach and is somehow invisible to the visual system of crab, and therefore it doesn't respond to it. And somehow this will give cuttlefish a hunting advantage and enough time to go close enough and then catch prey.
22:25 - What does space-fermented miso taste like?
What does space-fermented miso taste like?
Maggie Coblentz, MIT
Miso is a staple of Japanese cuisine, but what happens when you try to ferment it in space? Scientists recently conducted an experiment aboard the International Space Station, creating what’s believed to be the first food deliberately fermented outside Earth. Maggie Coblentz at MIT is behind the culinary caper…
Maggie - Astronauts have these very interesting things happen to them in microgravity. They call it “space-face”, so fluids will rise in the body and it almost feels like you have a cold or you're stuffed up. So, food tastes different — it might not be as flavourful, it might not be as delicious.
So astronauts are known to use a lot of salt and hot sauce on their food to try and enhance the flavour. We thought we would use something like fermentation to create an alternative to their freeze-dried foods wrapped in plastic.
Chris - Of course, one of the things you can ferment is alcoholic beverages, but I presume that’s not what you meant.
Maggie - Correct — that is not what we meant. Fermentation is a very broad and diverse way of making food, but for us, we were using fermentation to create a new paste called miso, which is actually a condiment from Japan that could be used to flavour foods. But really, this was just a first pass at an experiment to see what's possible for fermenting in space.
Chris - This was literally: send the ingredients up there and then let them make the stuff in space on the ISS?
Maggie - That would have been ideal, but you can imagine that doing anything in space is very, very expensive — and that includes an astronaut’s time. So something as simple as an astronaut pressing a button on your experiment has a price tag attached to it. Our experiment was first produced on Earth and fit inside a box about the size of a microwave. Inside that larger box were smaller boxes the size of a shoebox, and we had our miso fermentation experiment inside one of those boxes that got loaded into a SpaceX rocket and then launched up to the International Space Station.
The fermentation was able to continue doing its thing as it would here on Earth, but in the space environment. After 30 days, the experiment was sent back down to Earth, and then we analysed the food product to see how it had changed.
Chris - So what's actually being fermented — and by what — to make this?
Maggie - Miso is a fermented, umami-rich paste usually made from cooked soybeans and koji. Koji is rice or barley fermented with the filamentous fungus Aspergillus oryzae, and salt. All these ingredients are mixed together, and then they begin their fermentation process.
Fermentation is what we call a metabolic process where these microorganisms convert sugars into either alcohol, gases, or acids. They’re really producing energy for themselves in the absence of oxygen. This process can occur naturally, and it can also be controlled by different environmental factors, like temperature. But in this case, we wanted to see what would happen naturally in the space environment.
Chris - Did you have a sort of parallel experiment — an identical rig that stayed on Earth while one went up to the ISS — so you knew you were comparing like with like and could see if there was any difference?
Maggie - Correct. We had two ground controls, so when the space miso came back down to Earth, we could actually compare it to these two ground control samples to see how they differed. Did the fungi mutate? Did any new acids grow or mutate in space compared to the Earth controls?
Chris - And did they?
Maggie - They did! What was really exciting about this project for us — from a food perspective — is that in addition to looking at how the microorganisms evolved in the space environment, we also did a full flavour chemistry analysis. We could actually test what volatile chemicals existed.
And in addition to the scientific analysis, we had to use people — because food is something that you actually eat, smell, and taste. So we had a sensory panel of people who knew what miso was — they had an understanding similar to how you might learn musical notes.
These people understand and can detect different flavours in foods. What came out was that people felt, on average, that the miso from space tasted more nutty and had a roastier flavour chemistry. This can actually be correlated to the microorganisms and the flavour chemistry from a scientific perspective.
Chris - Why do you think it’s different? What changed about its experience up there that led to that result?
Maggie - That is the golden question. I have to be honest — because of the constraints of doing space research, this was very much a foundational study. A first pass at a new way of producing food in space. There are so many things happening in space:
You're in a microgravity environment. You're potentially exposed to radiation. The temperature is going to be different. The microorganisms that are already living on the space station are going to be different.
All these things play into what makes that place so unique. My hypothesis is that the temperature fluctuations and environmental shifts were so much more dramatic for the space miso.
Being in space isn't just being in space — our miso actually had to travel all the way to space. It was sitting next to electronics that were heating up, turning on, turning off — before it even got to the space station. And then, for 30 days, it existed in this industrialised environment with lots of things happening.
So that’s a long-winded answer to say: we still don’t know exactly why. That could be part of a phase two experiment. And that’s what’s exciting about space research — you keep trying and trying again, making improvements so you can be more precise with your results.
Chris - Did you taste it?
Maggie - I did taste it.
Chris - And did you say it was out of this world?
Maggie - I don’t know if that was my direct quote, but there is something special about tasting something from a new environment — wherever that is. I have the same spark in me when I taste something from another country here on Earth, or somewhere I’ve never been. But indeed, tasting something from space did feel like it had a particular energy to it — that could be all in my head… But I run with that, and I embody it.
29:19 - What was the Wow! signal caused by?
What was the Wow! signal caused by?
Thanks to Donald for the question. In an attempt to unpick one of the mysteries facing astronomers over recent decades, James Tytko enlisted the help of former BBC science editor, David Whitehouse...
James - The Wow! signal was detected in 1977 at Ohio State University's Big Ear radio telescope. Astronomer Jerry Ehman observed an unusually strong signal originating from the direction of the Sagittarius constellation. On the printout chart, he circled the corresponding high numbers and wrote Wow! beside them.
And he was right to be impressed, as the phenomenon which might have caused such a reading has yet to be identified. To share more details and to address your question, Donald, here's former BBC science editor David Whitehouse.
David -Well, this wasn't a search for extraterrestrial signals or beacons, although that had been done many times before. This was an all-sky search, looking at the radio sky at the frequency of hydrogen. Hydrogen is the most common element in the universe, and it gives off characteristic radiation at 1420 megahertz, the H-line.
It had been suggested earlier on, 10, 20 years earlier, that because this H-line was so common and well-known to all astronomers, wherever they were, it might be a good place to put a signal that people would pick up. When this very strange signal turned up, and it was very strange, some people have suggested that perhaps this was a beacon, but they couldn't identify any particular object within the reception area. And that's applied ever since. We've looked at it with very deep telescopes, very precise observations, and we found nothing there.
James - To Donald's question, if it isn't a signal from aliens, are there any theories as to what natural phenomena might have been behind the signal?
David - There was a couple of years ago a survey done with different telescopes of dwarf stars, red dwarf stars, which occasionally give off explosions of radiation. And this was done with the Arecibo radio telescope, which is now collapsed. And they found similar types of signals, but much weaker, they thought, perhaps from excited clouds of hydrogen.
Something excited the hydrogen, caused it to what we call super radiate, almost like a laser, a microwave laser, and give a blast of very intense short radiation. But the trouble with that was that every example of that was a hundred times fainter than this particular Wow! signal. So, whether or not what we saw with the Wow! signal was that same type of event, but due to circumstances much, much stronger, we don't know.
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