Motor neurone disease, and a gut microbe-brewery

Plus, a new find from the James Webb Space Telescope provides insight on the formation of Earth-like planets..
07 June 2024
Presented by Chris Smith
Production by Rhys James, James Tytko.

RUGBY-TACKLE

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In the news this week, after the death of rugby legend Rob Burrow, we explore the mechanisms of motor neurone disease with John Ealing from the Manchester MND Care Centre. Also, we hear from Alexander Forse at the University of Cambridge who has helped to develop a carbon sponge which can suck CO2 out of the atmosphere, and Inga Kamp from the university of Groningen explains why a new finding from the JWST could reveal the secrets of how Earth-like planets form. Plus, the intriguing story of a non-drinker who couldn't stop getting drunk... 

In this episode

Motor neuron

00:57 - Managing motor neurone disease

Rugby star Rob Burrow's passing shines a light on the condition...

Managing motor neurone disease
John Ealing, Manchester MND Care Centre

First this week, we were devastated to learn of the passing of rugby legend Rob Burrow, who has just died from motor neurone disease.

But, winding back a bit, nobody had expected Rob Burrow to make it as a professional rugby league player. He stood at 5 '5'' and, more often than not, happened to be the smallest player on the pitch. But he defied his size and used his brilliant rugby brain - and majestic pace - to outthink and outpace his much larger opponents…

Rob Burrow - I went in the room and he told me and I had a bit of a shock and, maybe it's the athlete in us all, we don't want to lie down and just take it. I'm taking it as a challenge. I don't intend to lie down. I want to get stuck into it, a bit like my career.

John - MND stands for motor neurone disease and it describes a condition where the motor nerves, the nerves that connect your brain to the muscles that you move, die off. They die off prematurely. When those motor nerves malfunction or die, the muscles that they connect to become weak and so you can no longer move the muscles that you want to move on a daily basis. That could be muscles of your tongue or the muscles of your arms or legs or hands. All your voluntary muscles can be affected and ultimately it can affect your breathing muscles, which are also under voluntary control.

Chris - Who tends to be affected and at what age?

John - It occurs more commonly in men than women, but it definitely occurs in both sexes. It occurs in all areas of the world. It tends to be more commonly seen in people who are older, and it can also occur in people where there's a family history of the disease. That's the thing we've learned recently quite a lot about.

Chris - Let's build on that then. What do we understand about the mechanism of the disease? What's actually happening to make those nerve cells die off? And how does that then translate into the syndrome we see for the patients?

John - I suppose that's where we still are struggling a bit. We see individuals in whom the disease has already started and we could look at tests and those individuals and know that those motor nerves aren't working very well and some of them have died off. To understand more fully what sets off the process, I think we need to do a lot more work. We know that the nerves that we're talking about are incredibly sensitive to minor changes. If you imagine what a motor nerve does: it's often about a metre in length, it goes from your brain all the way down to the bottom of your spinal cord, and it has to control your muscles over the course of a life of 70, 80, 90 years. It's probably lots of little things that just push it toward becoming damaged that lead to motor immune disease. Age, being a bloke, maybe having some genetic factor, but also environmental factors that we don't fully understand.

Chris - How might a person tell that there's something wrong? What would they notice that this might be coming on?

John - It usually presents with weakness, which often starts asymmetrically: it starts in one part of the body, one side of the body. It might be a weak foot or a weak hand or weak speech. For example, somebody's speech might become slurred and that progressively gets worse over a number of months. In contrast to a stroke, for example, which comes on suddenly and often slightly improves over time. The history, the trajectory of this gradually worsening disease is over months where patients become weak and or wasted with their muscles, without any numbness or tingling. It's very much a muscle disease as opposed to a sensation disease.

Chris - Most of the people who present with this are older people, but there are notable exceptions who are younger people. Stephen Hawking from Cambridge, classically, we know about him very well. He was very young when he developed something that resembled motor neurone disease. And poor old Rob Burrow who's died, he's very young indeed as well. What do we think's going on there? Is this a different disease in these younger people or are they just prone to develop it at a younger age for some reason?

John - I'm sure they are prone to develop it for some reason. I suppose my view over the years is that I've thought of MND not really as a single disease. It's a combination of many different diseases that ultimately end up with those motor nerves dying prematurely. We now can split the disease up into different genetic forms where there's a faulty gene which caused the disease in one family but not another family. Then, there are the additional factors, the environmental factors, and other ones we don't fully understand. People have thought about environmental factors such as toxins in the environment and, particularly with cases in young sporting people, whether or not exercise or head injuries that we get with repeated head trauma for rugby or football may play a role in damaging the motor nerves and just pushing them more toward damage than repair, leading to them dying prematurely.

Chris - So is there a generally accepted association then between people who are taking a lot of severe exercise, pushing their body very hard, and having a higher risk of developing this? Or is it that those sorts of people tend to be notable characters and it makes a huge impact on their career so they tend to get talked about a bit like Lou Gehrig, for example, the famous baseball player.

John - I think the jury's out on that one. I mean, you're absolutely right, those young, relatively famous people who develop the disease are people that we all think about and they get lots of press. Rob Burrow and his colleagues have done huge amounts to raise the profile of MND. I'm uncertain. I think the evidence is still uncertain as to whether or not exercise per se damages motor nerves, or whether the head injuries damage motor nerves, or whether they are just genetically predetermined to get the disease at an earlier stage. We have a lot more work to do. What I wouldn't want to do is to give the impression that exercise is bad for people, because we know that exercise is generally very good, either psychologically good for us or good for our heart, good for our blood pressure. Exercise has many positive sides to it. I think it'd be wrong to blame exercise per se for MND at this stage.

Chris - And when you see people who've already got this in your clinic, what can you do for them? What's the prognosis and how do we aim to support people with this? How long is this going to go on for them?

John - It's the question I'm often asked: what's the prognosis? How long have I got doctor? And actually it's very difficult to know that. The disease is hugely variable. Yes, you can read the literature which says that a certain amount of people will be dead in a certain period of time, but I think in an individual it's quite difficult to extrapolate what's going to happen to that individual. It may be involving their other frailties, how old they are, what other medical problems they have, where the diseases first affected them. For example, if it's affecting their speech, their swallow, their breathing muscles early, then that's clearly something which is more worrying to me as a medic than if it affects an arm or a leg. I suppose we try to individualise our care, so we listen to the individuals that we are seeing, we try to understand where they're coming from, explain the disease in terms that they can understand, and then see how we can help. So if, for example, they have a problem with their speech, well what can we do to maximise their understanding, the clarity of their speech? If it's swallow, can we do something to help improve their swallow? Do they need a gastrostomy tube to help overcome a difficulty with swallowing if they have breathing muscle weakness? We have a clear intervention called non-invasive ventilation which we know both prolongs life and maintains quality of life. We can also start people on medication, so although we have no cure for the disease, we do have a tablet called riluzole, which is licensed, which we know is a benefit. Although it provides a relatively small amount of benefit, we feel that most patients do benefit from this drug with minimal side effects. We can also talk to them about the counselling, the support they need, or what support they and their family need to keep as independent for as long as possible. There's a lot we can do in the clinic, although at the present time we don't yet have a cure, I'm afraid to say.

A Forse carbon sponge

10:01 - Carbon sponge sucks CO2 out of the air

Used in countries with plentiful renewable energy sources, it could help combat climate change...

Carbon sponge sucks CO2 out of the air
Alexander Forse, University of Cambridge

To chemistry now, and researchers at the University of Cambridge have developed a low-cost and energy-efficient way of making materials that can capture carbon dioxide directly from the air. The method is not dissimilar to charging a battery - but instead uses activated carbon sponge. To find out more, I went to meet Alexander Forse at the University of Cambridge…

Alexander - So here I've got some of our new sponge material, a black piece of fabric-like material that's a couple of centimetres square, here. This is what we've developed in our lab over the past three years. We effectively take these cheap carbon sponge materials and we charge them just like how you charge a battery. After we've done that, we find we're able to suck up carbon dioxide with the material directly from the air around us.

Chris - It's really thin and it looks like the material might stitch into the lining of a coat, for example. It's jet black. What's it made of? Is it just sponge?

Alexander - It's a layered carbon material. We've got sheets of carbon, like what you've got in a pencil which is graphite, except in this material there are spaces between the layers of the carbon, very tiny pores which give it its sponge-like properties.

Chris - It's bendy and flexible isn't it? But you are saying you can also charge it or you have charged it. So what was that process and how does that work?

Alexander - We take this carbon material and charge it up. The sponge here is one of the electrodes in a battery and when you charge it up, you store ions in the tiny pores of the sponge and these ions are going to become important later when we try to bind carbon dioxide.

Chris - When you say you charge it up, you literally put electricity through it? And what are the ions that go in then?

Alexander - Yeah, so in this case we charge in hydroxide ions. This is an alkaline species. Those hydroxides go into the tiny pores of the carbon.

Chris - So you'll get something which is a carbon matrix and the holes are filled with these hydroxide ions, the alkaline substances, and that's now stable? It'll just sit there until you want to do something with it?

Alexander - Yeah, exactly. Overall this material on the solid is positive, but then we've got these negative ions, the hydroxides, sitting in the pores.

Chris - And how does that make it do what you want it to do?

Alexander - What we want it to do here is to suck up carbon dioxide from the atmosphere. These hydroxides can directly bond with carbon dioxide very strongly and thereby remove it from the air.

Chris - What does that make in the sponge, then, when that chemical reaction happens?

Alexander - We looked at this with a technique similar to MRI that's done in hospitals. We do a type of spectroscopy where we see the kinds of bonds that are forming and we can see that we actually form a bicarbonate. So a little bit like baking soda you've got in your kitchen, it's a similar kind of chemical forming inside the sponge.

Chris - And how much carbon dioxide will it soak up and how quickly can it do that?

Alexander - This material can take up about one gram of carbon dioxide per 100 grams of the material. It's quite a small amount, but what we can do is wring out our sponge and get it ready for repeated use so we can potentially do a hundred cycles in a day of absorption and collection of carbon dioxide.

Chris - It's fully reversible? You can expel or push off the CO2 again and it's reset back to reuse?

Alexander - Yeah, exactly. So when we want to collect CO2 off the material and get the sponge ready for another step, we heat it up and that releases the carbon dioxide collection and gets our sponge ready to go again.

Chris - How can you heat it? Because is that not quite energy hungry, potentially? This is all about trying to pull down CO2 from the atmosphere and rescue the planet from climate change and part and parcel of the cause of that is us using too much energy.

Alexander - This process of sucking up CO2 from the atmosphere does use a lot of energy. Our new materials can be reactivated or regenerated at quite low temperatures of around 100 degrees C compared to some of the existing materials where you need to use much higher temperatures approaching 1000 degrees C. We're trying to cut down the amount of energy you'd need to use here. Also, our materials are conductive, so we can heat them up in a way similar to how your toaster works. If you flow current through a resistor, it heats up and we can do that in our material to heat the material very rapidly and regenerate it for another step.

Chris - That's neat. So rather than having to take the material away, do something to it to chemically reset it, it could all be done in situ. You could have a system where you just reverse the cycle, put a current through it, it gets hot, CO2 comes off, you grab that and you're back ready to go again.

Alexander - Exactly. All we need is to be able to plug in to the wall with electricity and then we can heat the material very quickly.

Chris - So where would you use it then? Where would you see this being deployed?

Alexander - Currently there's only a relatively small amount of CO2 being sucked out of the air. A lot of that activity is based in places where you've got very cheap renewable electricity. For example, there's a plant in Iceland that's capturing around 5000 tons of CO2 per year from the air. You really want to make use of cheap electricity, but also you need to be close to places where you can store that carbon dioxide. In Iceland they've got favourable rock formations where CO2 can be stored and permanently trapped in the rock.

Chris - It's all very well grabbing the CO2, but you've got to do something with it once you've caught it. What's the plan there?

Alexander - Either store it in the ground in a way that's safe, where it's permanently stored, or make something useful out of the CO2. Currently we produce so much carbon dioxide, around 40 billion tons per year. The big potential here is to store the carbon dioxide in the ground because if you start making stuff out of it, you end up making a lot more stuff than people would actually need.

Chris - Can you take it a step further and do this for other gases?

Alexander - I think so, yeah. To take one example, during the Covid pandemic, we needed oxygen supplies in hospitals and there were big shortages that were well documented. Things like separating oxygen out of air, oxygen from nitrogen, is really important. We've got a new way to make materials now with this charging process, so maybe we can extend it to some other areas like that.

Hubble Telescope image of distant stars showing diffraction artefacts.

16:57 - JWST finds hydrocarbons likely to form Earth-like planets

Orbiting a young star, the molecules could give us insight into how Earth formed...

JWST finds hydrocarbons likely to form Earth-like planets
Inga Kamp, University of Groningen

The James Webb Space Telescope has observed hydrocarbons in a disk surrounding a young star. To find out why it matters, Will Tingle has been speaking with Inga Kamp at the University of Groningen…

Inga - In our observing programme we focused on a number of well-known discs around stars that have masses like the sun, but also what we call very low mass stars, so masses of about a 10th of the solar mass. Our goal was to actually characterise what the discs' chemical composition looked like in the inner few astronomical units where we know that rocky planets could be forming right now.

Will - The idea is then that if you can tease apart the chemical composition of this area that's closer to the sun, you might be able to work out how rocky planets such as Earth may have formed.

Inga - Yes. That is the basic idea. It's very hard to observe the planets themselves. I mean, first of all, they are still in the stage of forming when we look at these objects because the discs we study are typically a few million years old, maybe a million years old. A rocky planet typically forms over much longer timescales, so at the moment we are observing these discs, maybe such a rocky planet has assembled about half of its mass at most. We are actually studying these environments at a moment where the planets are actively assembling.

Will - And this particular disc that you found that's orbiting a young and very low mass star has revealed abundant hydrocarbons. Is this particularly rare? Because when we talk about carbons out in the universe, people do get pretty excited because, well, our life is carbon based.

Inga - Yes. That's true. However, when we look at space, and certainly when we look at the clouds of gas and dust from which young stars are forming, usually we see more oxygen than carbon. So what we most often see is water, carbon dioxide, OH. This is also what we typically see when we look at young discs around solar type stars. But what we see in this particular study is very different. So this is a disc around a very low mass star, 1/10th of the solar mass, and here we see abundant hydrocarbons. This is very unusual. The Spitzer Space Telescope had actually seen one particular strong emission feature which was due to acetylene, but we did not expect to see so many hydrocarbons in this disc. So that was really, completely unexpected, and I have to say that the infrared spectroscopy itself is very difficult to carry out. There are instrument artefacts, for example, that need to be corrected. When we saw this spectrum and we were convinced after some time that all this ringing, all this up and down that we see in the spectrum is actually due to molecular emission due to small hydrocarbons, this really blew us totally away.

Will - Do we know then, if this is such a rare occurrence, how those hydrocarbons got there?

Inga - Well, that is something we are still trying to understand. I think the most interesting thing is that with the James Webb Space Telescope, we can really look so deep into these discs that we see all these abundant hydrocarbons. Because if you see only one molecule, it's very hard to piece together: why is it so abundant? Why is it so dominant? Why don't we see water? But if we now see all these hydrocarbons, we have a new view into these inner disc chemical factories, and we can hope to decipher how did these hydrocarbons originate there. We can piece together the chemical pathways that led to their formation in the warm inner regions, and I think that is the power of the new James Webb Space Telescope compared to what we had earlier, that we can really see these minor species as well. We need all of these species in order to get the full, complete picture of how these discs evolved into what we see right now, namely, this very carbon rich gas signature.

Will - Since these discs then eventually go on to end up forming planets, do we anticipate anything different happening to a planet that is formed with these hydrocarbons?

Inga - Well, that's an interesting question. First of all, there are different types of planets that could be forming in these discs. There are rocky planets, and then they're predominantly made out of solids, but there are also maybe gas rich planets, maybe around the size of Neptune or a little bit smaller. Of course, if that gas that we see now in the molecular emission in the infrared, if that ends up being part of a gas planet, it will make a very interesting gas planet because we don't know of any of these in our own solar system. We do have Titan which has a very carbon rich atmosphere as well. But in terms of the normal planets, Jupiter, Neptune, and Saturn, they do not look like this.

A pint of beer.

22:05 - Woman whose belly brews its own alcohol

It took seven trips to the hospital before the mystery was finally solved...

Woman whose belly brews its own alcohol
Rahel Zewude, University of Toronto

Now, I'm sure many of us have claimed to have had an upset stomach when we’ve had a few too many glasses of wine. But that is literally the case for some people with a very rare condition called auto-brewery syndrome. It happens when a person’s digestive system produces alcohol through the fermentation of ingested carbohydrates and - if not managed properly - it makes them drunk. To find out more, we put in a call to Rahel Zewude at the University of Toronto. One of Rahel’s patients developed the syndrome that led to dangerously high blood alcohol levels, way over the drink driving limit. She’s written up the case in the Canadian Medical Association Journal…

Rahel - So this patient is a 50-year-old woman who had intermittent presentations throughout two years leading to seven emergency room visits with slurred speech, gait imbalance leading to multiple falls, and was found to have high blood alcohol levels at her emergency room assessments despite her being adamant that she was not consuming any alcohol.

Chris - So what did the casualty officer, the attending physician, conclude on those occasions when the woman was seen?

Rahel - So in her six emergency room visits the conclusion was that she was indeed intoxicated with alcohol and she was not being forthcoming about her alcohol use. She was evaluated by three different psychiatrists during those visits. Despite her being consistent and her husband also providing the same history of no alcohol use, she was discharged with a diagnosis of alcohol use disorder and advised to stop drinking. But on her seventh visit, the emergency room physician gave her the diagnosis of probable auto brewery syndrome.

Chris - And what's auto brewery syndrome?

Rahel - Auto brewery syndrome is a syndrome characterised by endogenous fermentation of alcohol that occurs in the gut. So most typically fungus in the gut starts to convert carbohydrates into alcohol and result in high blood alcohol levels that then lead to intoxication.

Chris - And when you say high blood alcohol levels, how high were the blood alcohol levels in this lady? Would she be done for drink driving if she was behind the wheel of a car, for example?

Rahel - Oh yeah. She was absolutely way over the limit, the legal limit for driving in Canada. The highest level was 61 millimoles per litre. And to sort of give you an estimate, when you get to 86 and over millimoles per litre of blood alcohol level. That is considered fatal levels of blood alcohol.

Chris - So she was almost at the point of lethality with alcohol that she'd effectively brewed in her own belly? Why did she end up with an abdomen capable of intoxicating her?

Rahel - The currently understood pathophysiology for this syndrome involves multiple factors. The main one is disruption of gut microbiome. So we all have bacteria that live in our gut and fungus also as part of our healthy gut flora. But in auto brewery syndrome, these alcohol fermenting fungi overtake as the predominant pathogens in the guts of the patients. That also has to coincide with other factors that can put them in a situation where they are having ineffective gut motility, so things like gastrointestinal diseases like inflammatory bowel disease, short gut syndrome have been implicated. Certainly, things like liver disease and a potential role of genetic predisposition, that could affect their ethno metabolism. So when all of these things line up perfectly in a metabolic storm and the patient is also ingesting high carbohydrate diet, then it could lead to auto brewery syndrome.

Chris - And how was she managed once you realised this was what was going on? How did you sort her out?

Rahel - After the diagnosis, the patient was referred to our clinic and the gastroenterologist clinic. She was treated with antifungal medication called fluconazole and started on a low carbohydrate diet with dietician assessment and follow up. She had had a few episodes of relapse, particularly in the context of increasing her carbohydrate intake after she finished the course of antifungal. But we had given her an additional course of antifungal which led to symptom resolution and she's now doing well without any medication, but continuing with a low carbohydrate diet.

Chris - So have you managed to rebalance her microbiome? Has she got the right spectrum of bugs in her guts now so that she's less at risk of this happening?

Rahel - We do suspect that because we did organise an oral glucose challenge and she did have an undetectable amount of glucose after ingestion of this 150 grams of glucose. So at that point, we felt that there was not any gut fermentation happening. But again, in light of how the pathophysiology of this disease involves multiple factors, we do still think that she continues to be at risk. So we try to minimise any empiric antibiotics and anything that could disrupt her gut microbiome again which could cause a relapse.

Chris - And how does she feel about all this? Because obviously she wasn't taken terribly seriously for the first six trips to casualty. It was only on the seventh a very bright person said, could something else be going on? So has she forgiven the doctors for dismissing her?

Rahel - She's very happy with the seventh emergency physician who believed her and helped her identify the diagnosis, and then all of us who had been looking after her from infectious disease, gastroenterology, dietician to ensure that she continues to have a relapse-free life. But of course, on our first assessment, she was very emotionally distressed to even hear that this is all real and there are several reports of this and patients who have had this syndrome described across the world.

Blood smear, blood cells

How does the body replace its cells, and how often?

James Tytko took on John's question with the help of Nadia Rosenthal from Imperial College London...

James - Thanks John, you’ve touched on the fascinating phenomenon of cell regeneration. This is a critical biological process across all living organisms, and it’s my pleasure to introduce Professor of cardiovascular science Nadia Rosenthal from Imperial College London to explain further…

Nadia - Thanks James! Cells, like any complex machine, wear down over time: their DNA accumulates mutations, their component parts become damaged, or they are naturally lost in the process of bodily functions.

James - It follows, given that these cells wear out over time, we need to replace them somehow. Just take the 500 million skin cells sloughed off the body each day, for example.

Nadia - Exactly. Replacing aged cells is one way to ensure that there is a constant replenishment of old or dysfunctional cells with young healthy cells so they can continue to perform cellular functions properly.

Most of the 37 trillion cells in our bodies maintain the capacity to replace themselves by producing daughter cells from small populations of progenitors set aside for this process.  

Cell regeneration also happens if we've suffered an injury. Daughter stem cells may possess the ability to form a whole range of different cell types depending on what the body needs to replace.

James - Given the amazing variety of functions cells are responsible for in the body, not all of them regenerate in the same way: skeletal muscle cells last for decades, while your nerve and heart muscle cells are the same ones you had as a child. 

Nadia - Indeed, healthy cells only divide when necessary and the process is tightly controlled. Otherwise your arm wouldn’t keep its exquisitely choreographed functions – imagine if the overall blueprint was lost and it slowly turned into a cauliflower!

We don’t yet fully understand how this perfect replacement process works – but we know when it goes wrong, either in the case of cancer (uncontrolled cell proliferation), spinal cord injury or dementia (where no replacement of lost nerve connections occurs) or heart failure (in this case, lost heart muscle cells are replaced with scar).

Other animals such as starfish or salamanders do a much better job at regeneration and can grow back a whole arm, wouldn’t we love to know how to do that!

James - Thanks Nadia. To recap, as cells get older, they incur more damage which can lead to more mutations and more likelihood of things going wrong. Luckily, most of our cells have the ability to produce daughter cells from within, allowing us to maintain our critical bodily functions and adapt to changes in our environment.

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