Modelling and Microbes: Science of Birth

02 April 2019
Presented by Chris Smith, Katie Haylor.

NEW-BABY

Yawning baby wrapped in cloth

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Spring has officially sprung! There are newborn lambs prancing around in the fields in the UK, and we've recently celebrated Mothering Sunday. To celebrate, we’re taking a trip down the road of pregnancy and birth, stopping off along the way to chat with experts about some of the science involved in bringing babies into the world. Plus, the person who can smell Parkinson’s Disease, and a way to halve how much water plants need....

 

In this episode

Brain schematic

00:51 - Opening up the blood brain barrier

How do you get drugs through the blood brain barrier?

Opening up the blood brain barrier
with James Choi, Imperial College London

The brain sits cocooned behind a protective defense called the blood brain barrier. It’s there to protect the delicate neurochemistry of the nervous system and it bars the majority of chemicals - and critically drugs - from entering. Only very small molecules - like caffeine - can slip through. And this is a major frustration when it comes to developing treatments for diseases like Alzheimer’s, because it limits the repertoire of molecules that drug designers can work with. Unless, that is, you have a safe and selective way to temporarily open up the blood brain barrier and allow the right things in. Which is what James Choi at Imperial College London, and his colleagues have been trying to do. Chris Smith spoke with James to find out more...

James - Drugs have been developed over the past several decades and they work quite well in mice and in animal disease models but they can't get into the brain. What we're showing in this paper is a technology to get the drug into the brain.

Chris - But there are lots of drugs that do get into the brain extremely well - things like heroin, cocaine, nicotine, alcohol. They all do it, so what's the exception then?

James - So the exception is that those drugs, the bad drugs, are very very small, and so if you get a molecule small enough and put it into the bloodstream it'll get into your brain and everywhere else in your body. A lot of the drugs that are useful are bigger and so there's actually what we call a cut-off where we think with certainty that these drugs will not go across, and that includes antibodies, peptides.

Chris - And your challenge is to find a way to ease them into the brain and surmount this problem where at the moment they would struggle to get in?

James - Exactly. What we want to do is use a localised method to say ‘Hey, in this region such as your memory centre, which affects Alzheimer's disease, we want the drug only to go there.’ The way we do that, we inject tiny preformed micro bubbles - they're around the size of a red blood cell, and what we do is we apply a localised beam of sound onto the memory centre and the bubbles will then push the drugs from the blood into the brain.

Chris - But this is not new though is it, the idea of using injectable bubbles and then combining them with sound and directing that to the brain helps to dismantle this thing we refer to as the blood/brain barrier which keeps the blood space and the brain space separate, it does cause that to temporarily become permeable so drugs can go into the central nervous system. That's been done and that's been done quite a while ago, so are you doing it slightly differently then?

James - Yes. The current state of the art is to inject the micro bubbles and ping the bubbles with a very long pulse of ultrasound, and although they've done a lot of work to optimise it, the conclusion in the end is that the beam itself has some side-effects, and there's a list of issues. Two of the issues that we try to address is the distribution of the drugs. Within that beam the drugs accumulate in one area at a high concentration but it doesn't get to another area so it's a very uneven distribution. The second concern with long pulses is that it disrupts the blood/brain barrier for several hours and what that means is the blood/brain barrier can no longer do its original role which is to regulate what goes into the brain and what goes out, and so you allow a lot of the unwanted compounds into the brain.

Chris - A bit like jamming open the portcullis on the castle for longer than you'd like, so the good soldiers go in but then some other people sneak in behind them while the gates are still open?

James - Exactly. And so we want to make sure that we're disrupting the blood/brain barrier but do it in a very short time duration and so what we showed in this paper is that using short pulses of ultrasound in a very fast sequence we can get the blood/brain barrier open and then closed within 10 minutes.

Chris - And this works the same way does it? You're using the sound to shake the bubbles, the bubbles shake the blood vessels effectively and open up a temporary sort of permeability in this blood/brain barrier so that the bigger things that would normally be excluded can for a short while sneak in?

James - Yes, and the key thing here is to shake these bubbles gently.

Chris - And when you do this, how much can you enhance the delivery of a drug that would not previously stand any chance of getting into the central nervous system? How much more gets in if you do this?

James - A lot more. One of the model drugs that we tested does not go through the blood/brain barrier but with our technique it can then go in there so as a measure of how much more, that's really hard to decide if the original amount was very, very low. What we do know is that the level that we're delivering the drugs is at a similar dose to the long pulse sequences and a lot of work with the long pulses have shown that the dose is enough to have a therapeutic response against a disease such as Alzheimer's disease and Parkinson's disease.

this is a picture of some computer chips

05:60 - Spintronics makes computers more efficient

Electron spin-states can make computing less energy hungry...

Spintronics makes computers more efficient
with Ben McAllister, Naked Scientists

Scientists at the University of Cambridge believe they’ve come a step closer to revolutionising how computers work, and making them much more powerful and energy efficient. At the moment, chips work by pushing electrical charges through semiconductor materials like silicon to do calculations. But, as we shrink the sizes of the circuits to pack more onto a chip to increase computing power, it becomes harder to push electricity through them, and more energy is wasted. An alternative is to transfer information by using a property called the “spin-state” of electrons. But the challenge has been to design a material that can allow this information to be transmitted over a sufficient distance to be useful, but without messing up the spin information, and this is what the Cambridge team think they’ve done using materials called organic semiconductors. Here to explain how this works is Naked Scientist Ben McAllister...

Ben - It's a great question because it's something that is sort of difficult to conceptualise is this quantum mechanical property, the sort of bizarre thing subatomic particles have like electrons, for example, which is what we’re talking about here. They have this property known as "spin", sort of like intrinsic momentum that they have and it can take one to states: it has to either either up or down. And the fact that it has to be up or down means that you might start thinking about ways to use it in computing because anyone who has heard of binary before, which is the language that computer's speak and the language that they use to do their operations relies on a series of ones and zeros. You essentially need to states to do any kind of computing based on binary and when you have electrons that have this property that can either be up or down, you can make one of those one and one of them zero and then do computing that way.

Chris - How do you register the spin on the electron, whether it's an up or down spin?

Ben - So it kind of depends on the context that you're working in. In this case they're using something called the "inverse spin hall effect", another quantum mechanical process which basically means the spin creates a small voltage across some sensor that they can read out.

Chris - And the problem has been that you can impart this spin to an electron but you can't send it anywhere, over any meaningful distance in order to convey a message, and the Cambridge team are saying that's what they think they've surmounted?

Ben - Yeah. So specifically they’re talking about this class of materials called "organic semiconductors", and semiconductors are really important materials in computing, they're what we typically use to do computing. Typically we use what are called "inorganic semiconductors" so things like the silicon which is a chemical you find in sand and other things like that. If we want to use organic materials instead to make semiconductors, they're much cheaper and easier to produce, so there's been a lot of interest in doing that in recent years but yes, as you say, in these organic semiconductors that this team is working with, they've found that transporting the spins to use for computing is really difficult. They basically don't travel far enough and they don't stick around for long enough - they kind of defuse they call it.

Chris - And what's their solution?

Ben - So what they found, if you pump these organic semiconductors, if you put a bunch of additional spins in there it enters the strange regime where the spins start basically travelling a lot easier within the organic semiconductors. So they don't defuse as quickly, they can travel longer distances and they stick around longer inside the material as long as you provide this artificially increased spin density.

Chris - Is that a bit like if I was at a loud party and I just turned the music up that I did want to listen to a bit louder, the people in the room playing something different I drown them out. Is that it or is there something else to it?

Ben - I think it might be kind of similar in the sense that you're providing more of the things that you do want into the material, but it's really something quite strange and interesting going on in the material where if you provided enough spins seems that the way that they move around in the material actually sort of changes; it's like a mechanism for it. So it would be like if you turned up your music and when it reached a certain level all of a sudden you also got some headphones and then you could hear it a lot better.

Chris - Now when we design computer chips at the moment, one of the constraints is that we have shrunk the components, the transistors which are what are actually doing the logic, the noughts and ones of binary, to such an extent now that they are not much bigger than just a few atoms across and that means that obviously the energy that it takes to push electricity through there is very high. Also they're closely packed now that they begin to interfere with each other if we go much smaller so we've hit this silicon wall where we can't shrink them any further. What does this mean if we can pull off these new forms of semiconductors - these organic semiconductors - where does this take our computing?

Ben - It really is a completely new regime because we sort of would not necessarily need to think about using traditional semiconductor-based transistors and making them smaller and smaller and smaller because you wouldn't be using those transistors to encode your information and that's what's going on at the moment. Transistors that are either on or off, so that's how you read your ones and zeros and so you can only have as many ones and zeros as you can have these little transistors which are a few atoms across. If you were to use spins in these organic semiconductors instead they can be much, much, much smaller so we could basically keep scaling up the number of ones and zeros and bits you can feed into your chip. So yeah, we really could get around this problem that were having with miniaturisation.

Chris - What would the chip of tomorrow, using this technology, actually look like? I'm pretty comfortable with how a microchip at the moment works. It's got a leg or a pin and I can send some electricity in their and it finds way through all these various circuits inside the chip, so are these new organic semiconductors computer chips going to be completely different architecture?

Ben - Well the interesting is that those traditional semiconductors that you're talking about, the transistors that we use to do computing today, they're relying on transport of charge, so basically moving the electrons around inside them and then based on how much charge is moving around, how many electrons there are calling that one or a zero. This is actually reading something entirely different, which is the electron's quantum mechanical spin. So really the architecture, yeah is going to be quite different. It's quite a bit of a change of paradigms and I believe there is still quite a lot of work that needs to be done. It's really like getting these fundamental technologies sorted out, like chips that we can actually transport the spins around in, that's going to allows to figure out what the future looks like.

Chris  - And when people talk about quantum computing, is this it question?

Ben - So this is a good question. It's computing that relies on quantum mechanics. To understand how it works. We're talking about quantum mechanical properties like the spin of electrons. When people are typically talking about quantum computing, what they're really talking about using a different thing which is called a "qubyte" or a "quantum byte" which is a byte that exists in like a super position of being up and down at the same time. Then you can do all kinds of other interesting operations there that work a lot faster. In this context they're not talking about using them for quantum computing even though they are quantum properties that are being read out. So no is the real answer but it is kind of on the blurry line there.

this is a picture of a t-shirt

13:51 - Sniffing out Parkinson's Disease

Some people have an incredible sense of smell...

Sniffing out Parkinson's Disease
with Joy Milne; Perdita Barran, University of Manchester

It’s not everyday you meet someone with an incredible sense of smell that they can also use to detect disease, including even Parkinson’s Disease. Katie Haylor spoke with Joy Milne, who has this ability, and mass spectrometry Professor Perdita Barran...

Katie - Ever heard the phrase something doesn't smell right? Well, while smelling someone isn't a commonly accepted form of medical diagnosis it turns out that some people are capable of actually smelling Parkinson's disease, a serious and progressive neurological condition which causes brain damage over many years. Physical symptoms include a characteristic tremor, muscle stiffness and slowness of movement. Retired nurse Joy Milne, whose husband had Parkinson's, is one of these "super smellers".

Joy - My husband was 31, 32 and I began to smell a change in his basic male musk smell became quite different, it changed. I put it down to the fact he was a consultant anaesthetist in an enclosed environment, sweating and that and really he wasn't pleased about me going on about it so I was quiet and we just put up with it.

Katie - But now, University of Manchester scientist Perdita Barran and her colleagues have, using Joy's impressive nose, been able to identify a handful of biomarkers for Parkinson's disease which currently has no conclusive diagnostic test. First off, Perdita told me how her and Joy met.

Perdita - Well, Joy found us as she approached colleague of mine, Tila Kunar, at the University of Edinburgh, who's a basic scientists like me working on Parkinson's disease, and she told him that he should find out why people have Parkinson's disease smell differently. I have to say, we didn't really believe her at first. We thought that perhaps it was just an associated sense with the disorder movement of people with Parkinson's but we thought we better prove it, and we thought we'd better divorce the smell from the person and the motor symptoms. So we devised a test which got people who had Parkinson's and people who didn't to wear T-shirts and then the T-shirts were cut up and put into bags for Joy to smell way away from any patient. And, well Joy, you can say, she was right!

Joy - And yes, as a parting gesture I said you've cut them in half and I don't know which witch is which, will I put them back together again to the person? And I did.

Katie - Joy smelled 12 T-shirts: six were worn by people with Parkinson's and six were controls. And she got them all correct. What's more, she identified one control subject as having Parkinson's. This was labelled as a false positive but they actually got in touch later to say they'd received a diagnosis. So I asked Joy, what exactly does Parkinson's smell like?

Joy - It is a quite deep animal musk and it has quite a rancid smell in it when it's a little bit stronger.

Katie - Lovely. So having controlled for variables like sex or diet that could be separating the T-shirt wearers, and confirming that Joy really could smell Parkinson's, Perdita and the team took a closer look at where on the T-shirts these odours were actually coming from.

Perdita - So you might think it will be under the armpits; that's where we think people smell, but it wasn't. It was in the middle of the back underneath the hairline, and that's a region of our bodies where we excrete a lot of the oily substance called sebum. That's the place where when you're a teenager you get spots - face as well. So we then had to develop a test that could be applied to patients that would extract sebum from them and we would then waive volatile molecules from the sebum - that means the ones that go through the air - and so that's what we did.

Katie - Once Joy's sense of smell told them which molecules to look for the team were then able to put the sebum in a machine that essentially weighs different molecules, called a mass spectrometer, in order to define what molecules are there and in what abundance.

Perdita - We've been able to pinpoint four compounds, which are three of them upregulated and one of them is actually down regulated in people who have Parkinson's, and those molecules have been given back to Joy and she smells them and she smells the smell. So we now have four biomarkers that tell us whether someone has Parkinson's or not just from swabbing their skin.

Katie - The four markers in question are eicosine, hippuric acid, octadecanal and perillic aldehyde - quite a mouthful. These compounds are normally found in sebum but it's the quantities that could, the team hopes, mean these could form a diagnostic tool for Parkinson's disease. But could looking for the quantities of these compounds in sebum reveal anything about the severity of someone's condition?

Perdita - That's a really good question and I can't answer that now. There are definitely some patients who have a much stronger smell and much stronger signal than others. Definitely people at late stage Parkinson's the smell is stronger and the signal is stronger and we've really focused on people who are called "drug naïve". That means that they haven't yet been put onto medication for Parkinson's disease because we want to see how early we can diagnose it and actually those cohort have a very strong smell as well. So we think we will be able to go even earlier and that's where our research is taken us now, to see if we can diagnose people before the motor symptoms.

Katie - We don't currently have a cure for Parkinson's disease, but if we can pick up on it earlier the hope is that we might be able to make interventions to prevent the condition from spreading. But why should Parkinson's disease smell at all?

Perdita - We really don't know the answer to that. What we do know is that people who have Parkinson's do produce more sebum, and sebum is a nice oily environment which bacteria would certainly like to eat and colonise on. So it may well be that this is a signature based on the change in the microflora on the skin of people with Parkinson's, but why that smells I don't know.

Katie - And now to Joy. What's it actually like to have this ability?

Joy - It can be a curse but it in this instance it's a superb gift I’ve been given. And I feel that I really do have to use it because having lived with Parkinson's for so long I think now is the time. We have the science, we have the research, and with those together we could diagnose Parkinson's earlier and then look at the inflammatory process far before the motor symptoms come in. And I think that's so important.

this is a picture of a wheat field

20:50 - Halving the water requirements of crops

Scientists have found a potential strategy for minimising water loss in crops...

Halving the water requirements of crops
with Mike Blatt, University of Glasgow

Water is increasingly making headlines in many countries where, year on year, we’re seeing declines in rainfall resulting in shortages. Cape Town, in South Africa, was on the verge recently of having to turn off the taps completely. And in parts of Australia, farmers are weathering some of the worst drought conditions ever documented. And even where the rainfall is reliable, rising population - and therefore water consumption - mean that there may still be shortages. One of the biggest consumers, globally, is agriculture. So a breakthrough by Mike Blatt, at the University of Glasgow, that’s enabled him to halve plant water requirements, could be a game changer. He’s done it by adding a light-sensing gene to the guard cells that open and close pores on the leaves - these are called stomata - that the plant uses to absorb CO2 so it can grow. This modification means the plants can respond more rapidly to changes in light intensity, so they become much more water efficient. Chris Smith spoke to Mike, to find out more...

Mike - One of the biggest resource demands for plant growth is water. Every attempt people have made in the past to improve photosynthesis, carbon gain and biomass production of a plant, results in increased demand of water simply because the plants rely on small pores in the leaf surface, so-called stomata, for both CO2 entry, CO2 being used by photosynthesis to make sugars, these pores also are, unfortunately a pathway for water loss -  a bit like you and me breathing, we breathe in oxygen to carry out respiration but at the same time we have to breathe out, and when we breathe out we lose water.

Chris - So by virtue of the fact that they have to get the CO2 into the leaf and the inside of the leaf has a lot of water, by allowing the CO2 in, it’s an inescapable consequence that water is going to leak out and be lost and therefore the plant has to maintain a constant supply of water that it's basically throwing away to the atmosphere?

Mike - In a sense yes. Water loss in itself actually drives an engine of circulation within the plants, so it's not necessarily a bad thing but it doesn't necessarily have to be as extravagant as it is in some plants and that's particularly true of crops.

Chris - So what have you done here that you think can improve on this process?

Mike - What we've done is to show that it is possible to increase the water efficiency to the plant and also to increase the efficiency of carbon capture by introducing a new way for the guard cells that surround the stomatal pore to gain and lose solutes which is what drives their opening and closing. And by doing so we've managed to accelerate the rate at which they move, and that acceleration better matches the variation in photosynthesis that the plants see over the course of the day as clouds move overhead or will pass by and that means that the plants are more efficient in their ability to prevent water loss when they don't need to carry out gas exchange.

Chris - Now when you say these guard cells, when we look at these pores on the underside of the leaves down a microscope, you can see these cells that are literally like the gatekeepers which change their shape to allow the pore to open or close and therefore allow water out and carbon dioxide in, when they're open. You're saying that you can manipulate how those cells do their job to make them do it much faster, so that there literally tethering whether they're open or closed much more rapidly to the ambient conditions?

Mike - Precisely, exactly.

Chris - But how have you done that? What have you actually done to the cells?

Mike - We've introduced a synthetic ion channel. In this case we've introduced a channel which we've created to connect the activity of the channel to light, so the channel becomes active when the light is on, it shuts down shortly after the light is switched off so we basically providing a new pathway for solute uptake and loss from the guard cells, and it's that movement of solute in and out of the guard cells that drives the accelerated stomatal movements.

Chris - And how much of a difference does this make to the a) consumption of water and b) the rate at which the plant actually grows?

Mike - In terms of the increase in biomass that we see in the plants, is on the order of a factor of two, and likewise the water use efficiency improved more or less on the same order, a bit less than a factor of two.

Chris - Now could you easily confer what you've done on your laboratory test plants on important plants we grow to keep humans fed, things like soy, things like maize, things like rice, wheat, other cereals and so on?

Mike - In progress. We'll revisit this chapter in another couple of years. We're now looking to get the selection of very similar light dependent controls into a number of crop species including brassica and barley as a starting point. It will be very interesting to get into maize which is obviously tremendously important agriculturally, and also in rice.

Chris - And assuming this does work in those other species, what could be the implications of this?

Mike - If it actually works out it means that in crop species it means that we may well have a number of crops available to farmers in the course of the next decade or so that are substantially more efficient in their use of water, which means that the amount of water that agriculture demands in the field goes significantly downwards. At the moment, agriculture consumes 70% of all freshwater resources on the planet. If we can reduce that by even 20 or 30% that would be a very significant impact on agriculture and on our water use globally.

ECG Trace

27:37 - Imaging babies' hearts in the womb

How can scientists image the hearts of babies still in the womb?

Imaging babies' hearts in the womb
with David Lloyd, King's College London, Evelina London Children's Hospital

At various times throughout a pregnancy, women will be invited for scans to check how the baby is developing. These scans can tell us a lot - for instance how big a baby is, when it was conceived and what sex it is. But babies in the womb are tiny, with tiny organs, and there are some things we currently can’t see very well on existing scans. This is an issue if babies encounter problems during pregnancy, which we can’t pick up on before the birth. Chris Smith spoke to David Lloyd from King's College London and Evelina Children's Hospital, who has come up with a method of 3D modelling babies' hearts before they're even born. First up, Chris asked, how can we image babies in the womb currently?

David - So at the moment we use ultrasound and, as we just heard, ultrasound is used in a variety of ways. The primary one that most people will experience in their pregnancy is the screening ultrasound, so the anomaly scan which happens at around 20 weeks, and there we’re looking just to screen out major abnormalities in the baby. If we look at the heart - so if we suspect that there may be a problem with the heart then that patient will get referred on from the screening ultrasound to see a specialist so like a Foetal Cardiologist. So you’ll see a sonographer who's expert in scanning the heart with ultrasound, and a physician, a doctor who works specifically looking at babies hearts before and after birth. That's the sort of main way of doing that and actually ultrasound is still the same technique as we use for both of those scans.

But there are some limits, and even when you have those very expert operators, when you're in that very specialist environment of foetal cardiologists, there are some things that we can't necessarily see as clearly as we'd like. It's a very good tool for most things but when we get to things like the small vessels around the heart that can be very difficult to define accurately, and when you look at all the other ways we have to image postnatally and compare that to before birth, it's much more limited. So, things like CT scans that use radiation we can't use, MRI which is safe to use in pregnancy and has been used for things like say the brain for example, is very limited when it comes to the heart because it's very small and it moves very quickly. So we've developed a technique to use those types of MRI scans using lots of images that we acquire of the heart and then cleverly reconstructing them after the fact to produce these very detailed 3D images.

Chris - Cardiac abnormalities are one of the most common congenital things to go wrong, aren't they? Put simply then, you take a person who has for some reason been detected to possibly have some kind of abnormality in her developing baby's heart. You then put her in her pregnant state into your MRI scanner, and what, you just take loads and loads loads of images - slices, effectively through the pregnant uterus and then use a computer to recompile this?

David - Exactly. So, an MRI scanner works by essentially taking like a stack of photos through the baby from one side or the other side - we can choose where we want that to be - but each of those photos is just a two dimensional image. So what we do is even though the baby is moving, if you looked at those stacks of images that each image wouldn’t relate to each other so you can't actually go through that stack and make any sense of one image compared to the next image. So it's a little bit like someone’s taken a load of pictures and then just thrown them all around the room. They're all a shuffled up deck of cards.

But we still take all of those pictures, and we’ll get the woman in the scanner and we can take sometimes hundreds of individual pictures and put them into a very clever piece of software that will look for the little bit we’re interested in, and when it identifies that it will try and work out where that belongs in a three-dimensional space, and it will keep using all of the other pictures to support that sort of growing volume, as we call it, of the foetal chest and the foetal heart and eventually we'll end up with something we can interpret in three dimensions.

Chris - So this was more of a software problem, writing clever enough computer software that can sift through enormous numbers of slightly different images because there's been movement, and draw the common components back together so that you compile them to make that image? How good are the images?

David - The images are excellent. So we can resolve down to less than a millimetre in terms of the resolution, and actually one of the advantages of this technique is because we've got so much data, the dataset that we end up with is actually higher resolution than any other data we put in because it all overlaps with each other.

Chris - Presumably a surgeon then, when this baby's born, we can predict what problems it's going to have on the basis of that very detailed scan?  They could even rehearse in their mind what surgery they might carry out on that individuals anatomy in order to fix the problem before it's even been born?

David - Exactly, and usually that kind of thing, really understanding to that level of detail what's happening with that baby's anatomy, would have to wait until the baby was born for many conditions. So they can have a CT scan then they can have an MRI scan once they've delivered but not before, so all of that's on hold until the baby is actually here with us. What we can do now is bring that into the antenatal domain sometimes two or even three months before the baby's there, speak to the surgeons, they can counsel the family, we can plan for how that baby is going to be treated immediately after birth and ultimately improve the outcomes for those children.

this is a picture of a pregnant woman's stomach

32:46 - What is pre-eclampsia?

What exactly is pre-eclampsia, what causes it, and what can be done to help?

What is pre-eclampsia?
with Catherine Aiken, Cambridge University and Addenbrooke's Hospital

Many women have healthy, uncomplicated pregnancies. But this isn’t the case for everyone. Around 7 or 8% develop a condition called pre-eclampsia. This can be potentially very serious, and women who develop it will usually be monitored closely throughout their pregnancy. Catherine Aiken is an obstetrician and researcher at the University of Cambridge, and she spoke with Katie Haylor. Firstly, Katie asked, what exactly is pre-eclampsia, and how would women know they had it?

Catherine - So pre-eclampsia is a complication of pregnancy that's characterised mainly by the mother's blood pressure going up, and protein beginning to appear in her urine later on in the pregnancy, but it's not limited to that. Pre-eclampsia can affect all parts of the mother’s organ systems. It can affect her kidneys, her liver, it can affect her brain, and it can also affect the growth of her developing baby at the same time. And so many women present with initial symptoms; for example headaches, flashing lights in their vision, they might notice swelling.

And one of the difficulties with pre-eclampsia is really the enormous range of things that different women experience when they actually develop the disease, and that's why we spend so much time monitoring the blood pressure of women in the third trimester. It's why we dip the urine during antenatal visits, because we know that this problem is common. We know if we can pick it up mums and babies will do a lot better, but it can mimic so many things and that's why we spend so much time trying to identify who has actually got it and who is at risk.

Katie - You mentioned the third trimester there, is that when people tend to get it?

Catherine - It's when people tend to get it. We do see women who develop this very severe form of it earlier than that, but most mums will find it developing later on as the pregnancy progresses.

Katie - How much do we know about why it happens in the first place? You mention some symptoms, but do we know what it's caused by?

Catherine - What we know is that it's not primarily a disease of the mother or the baby but it seems to arise from the placenta. And the placenta is one of those really fascinating organs that seems to be the answer to quite a lot of those really major complications that we see in pregnancy.

And it seems that pre-eclampsia arises from the very very early growth of the placenta and so interestingly this condition arises way way before we see it, which is late in the pregnancy, at the time when the placenta's trying to plug in to the mum’s circulation in order to feed the baby and support its growth. And it seems to be in that initial phase that actually the vessels don't develop properly and that's when pre-eclampsia has its beginning, although we don't see the effects until much later on.

Katie - How can it be treated then, or managed? What do you with a lady who has it?

Catherine - Well, ultimately the only thing that will end pre-eclampsia is delivering the placenta; that course means delivering the baby. So often we're in a situation where it's too early for the baby to be born. We don't want to give the baby the problems of prematurity but we know that both mum and baby are at risk from pre-eclampsia, and then we've got a difficult balance between can we continue with this pregnancy where the mother is at risk from these complications? Versus do we deliver a baby that then will face the problems of prematurity. And so a lot of our management is making these really tough judgement calls about when the right time to deliver is, and in the meantime trying to control the symptoms in the mother, trying to control the high blood pressure, make sure that we keep her safe from all the things women can experience during this complication.

Chris - Now I happened to be reading what's been published this week Catherine, there's a very interesting paper with your name on it actually! We've talked very much about the mother's health here, but what about the unborn foetus if we don't treat or we don't manage pre-eclampsia properly? What are the consequences for the baby?

Catherine - Well, we know quite a lot about the immediate complications for the baby. We know that there at risk of being born small and we know that they're at risk of being born early and both of those things carry a lot of risk with them.

What we've been looking at is what happens later in life and that's the bit that we really don't have enough knowledge about at the moment, which is are those babies if we get them through the initial phase, do they catch up to their development, continue normally and so on?

We've been looking at fertility in the female babies of women with pre-eclampsia, and what we find in our animal model is they have actually got a lower egg reserve in their own adult life, and so their fertility may be impaired by this womb environment that they've been developing in.

Chris - So a baby born to a lady who's had pre-eclampsia will ultimately have fewer eggs in her ovary, when she comes to have her own children, she may therefore suffer a shorter reproductive life?

Catherine - Absolutely. That's what our works and the models that we've been looking at indicates, and that's really fascinating to us because we know that pre-eclampsia has all of these problems arise immediately, but we are only really beginning to see glimpses into the future of what it means in the longer term.

this is a picture of a new born baby gripping an adult's hand

Labour - our questions answered!
with Alberto Rodriguez-Cala, The Rosie Hospital; Andrea

Now we couldn’t do a show about having babies without hearing from someone who’s just had one themselves! Katie Haylor went to the Rosie maternity hospital in Cambridge. Her first port of call was midwife Alberto Rodriguez-Cala...

Alberto - I am the matron for the delivery, and the triage clinic, the high-risk recovery area and bereavement services. We are currently in the triage clinic of the Rosie maternity Hospital in Cambridge.

Katie - It sounds pretty quiet for a maternity hospital. Is this normal?

Alberto - This is not massively normal. It's good and always we try and keep the noise level to a minimum. This time in the morning it starts getting busy from now really.

Katie - So before you shoot off to deliver some babies, can ask you a few questions about labour? How does someone know if they’ve gone into labour?

Alberto - So generally speaking because they're experiencing painful contractions. Sometimes the breaking of the water without an awful lot of associated pain might be suggestive of women going into labour as well, but generally speaking experiencing contractions that are regular and sustained over a period of time is a most clinically recognised relevant sign of someone being in labour.

Katie - How long does it tend to last?

Alberto - Very variable. In general we’ll say that for a first-time mother labour will last, on average, about eight hours and unlikely to last more than 16/18 hours. For mothers that have given birth before it will be an average of 5/6 hours, unlikely to last more than 10/12 hours. But it is very variable depending on many different factors.

Katie - Are there any things that women can do to help themselves have the best labour possible? I'm thinking in terms of physical fitness, would that make a difference?

Alberto - Physical fitness as such does not equate to having an easier labour. However, being physically fit means that you're less likely to have and develop complications during pregnancy such as high blood pressure, diabetes or suffering with obesity or anything like that is likely to potentially impact on the care that you received during your pregnancy and in labour. But, in general, being physically fit means that you'll probably be able to be much more active, being able to be fitter for pregnancy itself hence minimising the risk of complications.

Katie - I guess it's important to acknowledge that we're here in a maternity hospital and lots of women give birth in hospital but some women don't.

Alberto - That's right. So for us in the Rosie it's about 1% of women will give birth at home. Sometimes it's planned and sometimes it’s unplanned because babies come whenever they want to come really. But we are a service that provides adequate care for women providing they've been informed about the different options that they've got and where to give birth.

Katie - A question we've had is about pain. Is it possible to have a pain free labour?

Alberto - I guess that's very individual question. I'm hoping it's not a tricky question for a man. Pain is a very subjective concept. In general we’ll say that pain is a common feeling women will experience through labour. Different women will have different ways and different coping mechanisms, different pain thresholds, but I will say in general having a pain-free labour is something that unless someone's a genetic mutation got where pain pathways are blocked, it's something that women will normally experience. But the pain concept in childbirth is very different to in other fields in healthcare because it's got a good outcome and something that's really exciting associated to it, so some women will experience birth with no pain relief but it’s still being a very pleasant experience despite being painful.

Katie - So a side pain being a subjective experience, are there aspects of labour or intervention that are pretty guaranteed to make things more or less painful?

Alberto - So there are certain things that definitely will make labour be perceived as more painful; induction of labour or any other medical intervention that might be clinically required. Those two things are likely to affect the length of labour and because it's an artificial form of labour being induced it might potentially, again, affect the way women perceive pain, making it feel as if it's more painful. We're currently in the Rosie birth centre now.

Katie - Is this birthing pool?

Alberto - That is birthing pool.

Katie - It looks like a jacuzzi -  I'm guessing it's not. Does it have bubbles?

Alberto - It doesn't have bubbles no.

Katie - So after someone has had a baby, hopefully they're healthy and the baby is healthy, what about recovery?

Alberto - Recovery from labour is very varied, depending on the circumstances and depending particularly on the type of birth a woman’s had. In general, about a week to 2 weeks for someone that's had a normal birth, a woman having had an instrumental or particularly a cesarean section involving significant abdominal surgery it might take longer.  But in general we’ll say that the woman's body tends to go back to prepregnancy state in about six weeks so the total recovery can last as long as that but depending on how little intervention or more intervention woman has had, then the recovery might take longer.

Andrea - I'm Andrea and I'm the Rosie birthing centre.

Katie - Congratulations. I see you've just had a little baby?

Andrea - Yeah, he's Barnabas.

Katie - First of all, how are you feeling?

Andrea - Actually surprisingly good. I think that somehow women are designed to do quite well after childbirth. The other halves don't tend to look so good on so little sleep actually. He's doing better this time but I remember him looking particularly grim after another baby being born when I didn't look bad.

Katie - How was the labour?

Andrea - Obviously it was labour so it wasn't very nice in the grand scheme of things and it was as tough as it had to be, and yet lots of things came together and we felt really blessed and then it went really well.

Katie - So I understand you’re off home in a minute and hopefully going to have some rest and enjoy yourself and relax as much as is possible with a newborn.

Andrea - Yeah, I'm going to try to. I think the adrenaline is still going so still feeling rather awake. So I imagine I'll crash in the next few days but enjoy what I’ve heard other people call the babymoon, so I'll enjoy that for a few days.

Katie - Have you had any sleep, or your partner?

Andrea - He was snoring away, as was my little one. I managed about an hour and a half. Again, I think the adrenaline pumping, very proud to have a new baby.

Katie - I'm going to let you go and get some sleep.

Andrea - Okay. Thank you.

this is a picture of some micro-organisms down a microscope

44:47 - Does how you're born affect your microbiome?

How could being delivered by C-section vs vaginally affect babies' microbiomes?

Does how you're born affect your microbiome?
with Peter Brocklehurst, University of Birmingham

It’s now well understood that we’re not alone in our bodies. Trillions of microbes collectively known as the human microbiome live in us and on us, and make a major contribution to keeping us healthy. But how do newborn babies acquire their microbiomes in the first place, and how does the way you are born, or exposure to antibiotics potentially affect things? Peter Brocklehurst is based at the University of Birmingham where he’s a consultant in Public Health and studies these questions as part of an initiative called the Baby Biome Study, and he spoke with Chris Smith. First, Chris asked, what's the Baby biome study seeking to find out?

Peter - Well, we know that mode of birth, particularly cesarean section when compared with vagina birth is associated with conditions in childhood such as asthma and eczema and possibly early-onset diabetes. And the mechanism that links those early exposures to those later outcomes could be through their microbiome. So we know that babies are born without any organisms on them or in them and their first exposure is at the time of birth. If those organisms that colonise the babies gut are different between a cesarean section and vagina birth then that may be the mechanism by which that risk leads to the late outcomes for the baby.

Chris - How are you doing the study?

Peter - So we've taken samples of maternal poo, we've taken samples of baby poo with taken cord blood and we've taken the vaginal swab samples, and then of course we've linked all of those together and we're following up those babies. So with analysed the poo samples, in particular taken at day 4, 7, 21 and between 6 and 10 months and then we are looking at the organisms that we find and linking those together, ascribing them to the mode of birth of the baby.

Chris - So at the moment the association that we know of, the one you mentioned is that you've taken people whom we know were born by cesarean section and we've said these individuals have an elevated risk of asthma, other allergies and intestinal diseases, but we don't know what role the microbiome is playing. Here you're saying you're going to follow these individuals having got a cross-section of the microbiome at these different ages to see if they develop those conditions and then we can actually ask whether one causes or is profoundly linked to the other?

Peter - Correct.

Chris - With your initial findings with the data you have so far, what actually emerges when you compare the microbiome of babies born via cesarean section and those born vaginally?

Peter - Well, for those born vaginally, perhaps not surprisingly, we're finding organisms - the initial colonising organisms to be very similar to those that their mothers carry because babies are born obviously with their mouth close to their mothers anus and that's probably where they pick up the organisms and get that initial colonisation. For babies born by cesarean section, we always rather hoped that the organisms they were first exposed to will be those on their mothers skin and their mother's breast, and those would colonise the babies gut.

What we're finding however is that those babies born by cesarean section have a very different microbiome pattern than those delivered vaginally, including a lot of pathogenic organisms which are those which you would find in hospital-acquired infections. Of more concern is that those hospital-acquired organisms appear to be persistent so even at 6 to 10 months we're finding high levels of those organisms, many of which are resistant to antibiotics so antimicrobial resistant organisms are persisting at 6 to 10 months. So that's quite a lot of concern.

Chris - Indeed, some people say that babies born vaginally their first taste of life is a mouthful of muck. Their mums muck but it's probably the most important meal there ever going to eat because it does seed to their microbiome in this way. I suppose it's worth considering that if you've got a cross-section of microbes that aren't quite the ones that ought to be there, as in you've got hospital superbugs and things, they might be there at low level for what they might be doing is suppressing the growth of other microbes that you do need and which are beneficial to your health so it's not just the physical presence of some bacteria, it might be also that they're causing an absence of other critical ones?

Peter - Well I'm not sure that's true. We are finding obviously babies who are born by cesarean section do digest proteins in milk, whether it's breast milk or formula milk, and so there are organisms in there doing the activities that they're supposed to do. It's a very complex system of organisms living in the gut. The issue about which are the initial colonisers however is that babies are born without anything, without any organisms inside them so the first one is a become exposed to they recognise as being normal and they don't get rid of them and therefore they can become persistent. So even if they're only there in low levels, if they've got antimicrobial resistant pathogenic organisms, those could cause disease disease for them for other people later in life - we just don't know that yet.

And one of the reasons we don't know that is that, until quite recently, we used to give all women, we give all women now who are having a cesarean section broad-spectrum antibiotics to limit the risk of them developing a wound infection. We used to give those antibiotics after the baby had been born by cesarean section after the cord had been cut, so none of those antibiotics got through to the baby. Because their recent evidence suggest that by giving the antibiotics earlier we might slightly decreases the woman's risk of wound infection. We're now giving high dose, broad spectrum antibiotics before the cord is clamped, and so though babies are being born not only by cesarean section but with high-dose of antibiotics on board. So that may have a double whammy if you like in terms of their exposure to organisms, again selecting out the antibiotic resistant and abnormal bacteria which can become established as normal.

Chris - Since you brought up the subject of antibiotics, may we therefore venture into the territory of a baby that’s born the normal way but develops some kind of infection or is exposed to something that means it ends up needing a big dose of antibiotics in the first year of life. Are you also looking at that and what might be the consequences because that too could distort the microbiome considerably couldn't it?

Peter - Yes, and we know that it does. So again, from epidemiological studies, we know that children who are given antibiotics within the first six months after birth, compared with those given after the first six months but within the first year, those given it early are at a much higher risk of developing childhood obesity than those given later antibiotics. Again, the mechanism for all of this is not clear, it's thought to be the microbiome and we do know that antibiotics have a profound effect on the microbiome development.

For you and I, if we are given antibiotics it does affect our microbiome but over time that microbiome will drift back to the state it was before because our bodies are used to and tolerate the organisms that we have in our gut because we recognise them as normal.

One of the theories is for newborns until they've developed that tolerance, you can knock the trajectory in a completely different direction by giving them antibiotics early, killing of some of the bacteria and allowing others to grow and therefore you send the baby's microbiome in a completely different trajectory and it never gets back to where it was before.

But we're really in the very early days of understanding this and it's a highly complex ecosystem in our gut so I don't want to make too many assumptions about what we're going to find, but I think there are concerns about the very widespread use of antibiotics around birth and early life, that could have quite severe consequences which might not manifest for many many years to come.

Chris - Indeed. One has to be conscious of the fact that antibiotics save lives don't they and we owe them a great deal, but at the same time we must not become too profligate because there may be unintended consequences?

Peter - Exactly. And if a baby absolutely needs antibiotics, it needs antibiotics. We don't want women getting lots of infections because we’re not using antibiotics appropriately, but I think the balance between using enough antibiotics and not using too many is quite a difficult one, and we need to get that balance right. So we limit our use of antibiotics to where it's absolutely essential and limit our exposure to when it's potentially quite nice to have, we think, but it could be potentially harmful. And it's that balance that is quite difficult to achieve.

Chris - So what can health professionals do? Because there are reports in some countries of investigations about the possibility of seeding babies that are born by cesarean section with what we dubb the right sorts of microbes by taking swabs from the mum and then spreading them into the baby's mouth as one way, perhaps, to get the baby colonised with the right sorts of microbes early?

Peter - Yes. And lots of people are doing that. It's mostly driven by women and parents rather than health professionals. I think, in general, health professionals are quite anxious about this procedure. Everything I've said about the microbiome is still theoretical. We are finding these interesting effects in the microbiome, but we don't know yet that they will inevitably lead to disease or problems.That's the hypothesis and we want to explore that further.

But in the meantime we are concerned that vaginal seeding could introduce one particular organism which about 1/4 of all women carry in their vaginas, which is group B Strep, which can be extremely serious. It's very rare that it causes disease but when it does these babies can get very sick and die very rapidly.

So we feel uncomfortable suggesting that women should do vaginal seeding because, of course, if that causes a baby to get sick and die as a consequence of addressing a theoretical impact on the microbiome, then that will be catastrophic.

So we do need to understand the processes better, we do need to understand the mechanisms, and we need to understand if we're going to get to the stage of using bacteria therapy in babies born by cesarean section, that we use the right bacteria in the right way, in a more controlled way, so that we don't make things worse, we make things better. But that, I think, is quite a long way in the future.

this is a picture of some orange carrots and some purple carrots

54:49 - Does eating purple carrots turn you purple?

If eating too many orange carrots can affect your skin colour, can purple carrots?

Does eating purple carrots turn you purple?

Naked Scientist Jack Tavener crunched down on the science of carrots to answer Aidan's question...

Jack - Fellow Naked Scientist, Katie, is with me.

Katie - I do feel a bit like a guinea pig, because I’ve got loads of carrots sitting in front of me

Jack - Yeah...You’re still happy to eat as many of these as you can, and then see if it’s made a difference?

Katie - I mean it is a hard life, isn’t it? In the name of science I’m going to basically have a snack.

Jack - Ready? Go!

The carrots Katie is eating make a tasty snack and are packed full of nutritious goodness. One component of this is beta-carotene, an organic pigment your body can use to make Vitamin A, which boosts your immune system and, whilst they may not help you see in the dark, it can help you maintain healthy vision.

This beta-carotene is what makes orange carrots appear orange. Purple carrots on the other hand get their colour from anthocyanins, which are the same compound that makes red wine red. And just like with red wine, you might find a purple carrot might stain your tongue, but this doesn’t necessarily mean that it also discolours your skin or that your urine turns red, like when you eat lots of beetroot - that’s yet another type of pigment. What happens to the purple colour all depends on what happens to the anthocyanins from purple carrots when your body processes them.

It turns out that your body is really good at processing anthocyanins, so none builds up in your skin and only a tiny amount comes out in urine - it means you don’t turn into a human grape, but purple might not be the colour to worry about...

Surprisingly purple carrots can have levels of beta-carotene similar to orange ones! So ironically, even the purple ones could turn your skin yellow, something Kryptid also suggested on the forum.

So how many carrots, orange or purple might you need to cause this? A lot depends on the size of the carrots, how much beta-carotene is in each and the individual eating them. But from what we’ve found, what is key seems to be the consistently high levels of intake. At least 5 carrots a day, every day, over the course of a few weeks would start to cause a change, with the carotene being stored under the skin and most visible on the palms of the hand, soles of the feet or on the face's laughter lines.

You looked completely stuffed Katie, how many have you managed?

Katie - I’m on number 3, and I’m still going.

Jack - That’s pretty good. Any effects you’ve noticed yet? Your hair seems to have gone ginger.

Katie - Oh ha ha, my hair’s always been ginger, thank you very much.

I’m not sure I’ve exactly noticed any yellowing or anything like that of the skin, I do feel a bit weird having eaten so many carrots though!

Jack - Don’t worry, even if you did turn yellow, you’re totally fine. You just have to stay off foods like carrots, tomatoes, sweet potato and even spinach, which contain a lot of carotenoids, for a few weeks or months until the colour goes away.

But just before we go, some fun facts that we learned from our friends at the World Carrot Museum, who helped with some of the research we’ve mentioned - carrots aren’t only great as food, but can also be used to make lasers, antifreeze and even to reinforce concrete… so even if purple carrots are more likely to turn you yellow than purple, that’s not the only surprising thing about them.

Next time, we’re taking to the skies, with this question from Seán

Seán - Why is it that when you directly at small faint stars, they disappear, but when you look at a point near it, you can see it again?

Comments

Hey, I've just listened to the section of the birth of babies. My question is regarding about the use of ultra-sound scans and the accuracy of these scans. I want to know how accurate it is at assessing the gender of the un-born baby. the reason is that I had a baby boy on the 28th march, but was told by the sonographer at my wife's 20 week scan that we were supposed to have a baby girl (with a percentage of 95-97%).

Can someone explain this for me?

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