MRSA, The Metaverse & Medical Milestones

With the new year kicking off, join us for the science behind the latest headlines.
11 January 2022
Presented by Chris Smith
Production by Julia Ravey.

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We are looking into the science behind the headlines in the first week of 2022 - including a medical update on omicron and how this variant impacts disease severity, a review of some of the top games and gadgets to look out for in the year ahead, a celebration marking 100 years since the first use of insulin to manage diabetes, and a behind the scenes preview of the new Sir David Attenborough documentary, 'The Green Planet'.

In this episode

A cartoon of the Earth as a coronavirus particle.

01:02 - Does Omicron Cause Milder Disease?

The numbers behind the rapid rise in Omicron cases and how this variant impacts disease

Does Omicron Cause Milder Disease?
Christina Pagel, University College London and Luke O'Neill, Trinity College Dublin

Cases of coronavirus have been hitting record highs in the UK due to the highly transmissible Omicron variant. But levels of severe illness seen in previous waves have not been replicated. Does Omicron cause a milder form of disease? Or are we just seeing the vaccine taking effect? Chris Smith interviews mathematician and disease modeler Christina Pagel and immunologist Luke O'Neil to get some answers about this variant...

Chris - First let's kick off with COVID. Now it's been a pretty turbulent few weeks since the emergence of the Omicron variant, that spooked policy makers, the general public and the media.

BBC News - Let's begin with a full update on the new Omicron variant of coronavirus. The world health organization says it would have severe consequences for some parts of the world if it spreads. The World Health Organisation says the overall global risk related to the new variant is assessed as 'very high'. Health ministers from the G7 group of rich countries have met and say, the global community is faced with the threat of a new, highly transmissible variant of COVID 19, which requires urgent action.

Chris - But is it turning out to be the threat that some claimed it would be, and what's likely to happen in the weeks ahead? With me are immunologist Luke O'Neil, he's from Trinity College, Dublin, and mathematician and disease modeler, Christina Pagel, who's from University College London. Christina, let's start with yourself. What are the numbers looking like at the moment?

Christina - They're higher than they've ever during the pandemic. The official case counts that we're getting every day at the moment aren't telling us that much because there's been a lot of changes in testing over Christmas and New Year, plus we know that testing is maxed out at the moment. But the National Infection Survey released its latest numbers today, and they showed that up to the week ending at new year, the 31st of December, 6% of England had COVID, which is two to three times higher than we've ever seen before. And that was 10% in London.

Chris - Do we know who that 10% in London or a couple of percent of the population on the whole are? Are they any particular groups in society?

Christina - Pretty much every age group is higher than it's ever been. It is still concentrated in younger adults and school aged children. What is quite concerning in the infection survey is that over 2% of over 70's now have COVID, which again is quite high. Now, luckily that group is highly vaccinated, so it shouldn't lead to new admissions, but cases are certainly going up quite steeply in over 50's now across the country.

Chris - Because people were saying, 'Look this is a mild disease' and if we look at South Africa, there doesn't seem to be the same rate of translation of cases into severe consequences, like there have been with other variants. Could that be just a function of the fact that younger people were getting a lot of these, or were accounting for, a lot of these cases initially, and later, we're going to see it filtering into more older people who might become more unwell? Or are we pretty comfortable it is a mild disease across the age spectrum?

Christina - Certainly in South Africa, the average age is 20 years younger than in the UK. We do have an older and more vulnerable population. Part of it is that Omicron does seem to be intrinsically a bit milder than Delta. It doesn't seem to cause the same kind of lung disease that puts people on a ventilator, but because it's so infectious and it's infecting so many people, it is still causing a big burden in hospitals. Although now that burden is more on the ward than in intensive care. You've got a combination of stress on hospitals from a really big backlog of people trying to get treatment, along with lots of new COVID patients coming in and then also loads of staff being off sick. 10 to 15% of NHS staff are off sick. That's just creating these big bottlenecks. Loads of hospitals now are declaring crises, the military is going in to help, ambulance services are taking hours and hours to get to urgent cases. We are in quite an overwhelming situation just because of the amount of infection that is around right now.

Chris - So it's more a problem of 'what it's doing to our ability to run services' than actually 'what it's doing to people' per say, at the moment. Luke, bringing you in here, what are the experiments that scientists are now doing telling us about whether or not this is a more severe illness or not? Do we know yet whether it's just a function of who's getting it or whether there really is something fundamentally different about the biology of this Omicron variant that means we are weathering this storm better?

Luke - We're learning a huge amount Chris, the amount of immunology going on all over the world about this variant is startling in many ways. What we're learning on a day by day basis is lab-based. That means 'does it translate into the real world?' is one question. There's a couple of things that we're pretty confident about. One is that, as Christina said, it doesn't really affect the lungs as much as the upper airways. There's lab-based experiments, including in animals, to support that the change in the spike protein means it seems less able to latch onto your lungs. That's good because the lung infections cause severe disease. It is able to infect the upper airways massively, as much as 70-fold increase compared to Delta, for example, so something's changed there. If it stays in the upper airways, it's less of a concern for the person who's caught it unless it becomes severe, and that's a good thing. That seems to be consistent with the clinical course of this disease, with regard to Omicron and we hope that holds up. The second thing that we're more confident about is the T-cell responses holding up. The immune system has two key parts: the B-cells that make the antibodies, and the T-cells. The T-cells are still able to recognize parts of Omicron. In other words, parts haven't changed that much compared to Delta,. T cells are very good at stopping severe disease, their job in fact is to stop severe disease. It's like plan B for the immune system in a way, plan A is antibodies that can stop you getting infected and limit the spread in your body. If that fails, the T-cells kick in and they heal the virally infected cells. Therefore, the virus can't really grow very much. The evidence at the moment suggests that T-cells can still fight Omicron. That gives us hope that the clinical data, which says 'it's less severe' may be true, because we have these two aspects of the immune system that our bodies can use.

Chris - We are waiting really to gather that real world data aren't we? Which we're doing in real time. One question that's surfacing quite a bit is people are saying, 'if the vaccines haven't changed to reflect the fact that we have this new Omicron variant, why do they work at all? And why would a third dose work better than the two you've already had?' What's the immunology of that?

Luke - You learn as you go along, some vaccines are four shots. The tetanus vaccine needed four shots. That was discovered empirically by just testing it. It's now clear that this is a three shot vaccine. Why would that be? The immune system is a fascination. Every time you challenge it's almost like it's exponentially better every time. You train the troops, and train them again, and then a third time. The third time really trains them.

Chris - Have you escaped infection so far, Luke?

Luke - No, I caught COVID about four weeks ago. I was in close contact with someone, four days later I tested positive. Now, luckily it was very mild, I had three days with a bit of a sniffle and a bit of a cough. Ironically, I tested positive the day after I got my booster. It's no surprise you can get infected after you're vaccinated because the vaccines don't really work in the nose. It's very hard to get the immune system up into what's called the mucosa. So it's no surprise that you might pick up a bit and test positive. The beauty is, if it goes to your lungs, the immune system kills it. That's why vaccination is so important.

Chris - Just to finish, Christina, there's been a bit of negative press around the whole maths modelling and prediction side of what's going on at the moment with the pandemic. Now it was Neils Bhor, who was the forefather of quantum mechanics, who said “Prediction is very difficult, especially if it's about the future.” This is no different, is it? How did they manage to get it so wide of the mark? Because there were numbers that were being produced such as 6,000 deaths a day, 10,000 people going into hospital every day. We are a long way from that at the moment. Is it just that we haven't got there yet? Or was this a "worse case scenario on steroids" as one minister put it?

Christina - I don't think they have really got it wrong. What you do with modelling is you take the best available information at the time, you put it in and you see what would happen under different scenarios. Now the best available information at the time, which was early December, was that Omicron had the same kind of severity as Delta. Under that scenario, when you have the number of infections we've got now, which is 3 or 4 times higher, and you know that it can evade the vaccines, then you're in a situation where that could have been a possibility. Now it then turned out, it is a little bit milder. They updated their models, the deaths came down and what they said is, 'okay, well we still have really high hospitalizations'. And so far hospital admissions are running within their range. In fact, if anything, slightly higher than what was predicted by the SAGE models. I think what people forget is that what SAGE does is it says, 'Under this scenario, this is what we think might happen.' Then if the government says, 'Actually I don't want that scenario, so I'll change what I'm going to do.' that scenario never happens and the predictions don't come true. That's what happened, certainly in the first wave and also last December. I think people have to remember why you're modelling. Modelling is to inform policy and if policy changes, then what you modelled won't happen. It doesn't mean the model was wrong. It means it's done its job in informing policy.

Chris - Christina, thank you very much. That's Christina Pagel and also with us, Luke O'Neil. Thanks to both of them and Luke's book, which is called 'Keep Calm and Trust the Science -  An Extraordinary Year in the Life of an Immunologist.' is out now. He can also now write the sequel; 'What it's like when an Immunologist gets COVID.'

A woman gaming outdoors with a VR headset

11:40 - Gadget and Gaming Trends for 2022

The most anticipated gaming & gadget releases for the coming year.

Gadget and Gaming Trends for 2022
Zoe Kleinman, BBC & Chris Berrow, Naked Gaming

As 2022 begins, our technology for gadgets & gaming progresses with it. Chris Smith talks with BBC's Zoe Kleinman & Naked Gaming's Chris Berrow about these latest developments and trends...

Chris Smith - First though let's talk tech and find out what were the top tech trends in 2021 and what is on the way in 2022. Zoe Kleinman is the BBC's technology editor. Zoe, what has tickled your tech fancy in 2021?

Zoe - I asked a few people about this, 'what has been their top gadget of 2021?' The answer that kept coming back was Apple. It's no surprise is it that they've just been named a $3 trillion company? We had the iPhone 13 that lots of people were waiting for, we've had the air tags that have been a big hit. Apple really does still have the golden touch when it comes to launching products. That said, let's not forget that we've had this crazy backdrop of a global shortage of computer chips. It's causing big supply problems. I suspect a lot more people would've got their hands and a lot more gadgets if there'd been more chips to have made them within the first place.

Chris Smith - I was a victim of that as well because I tried to go and buy a Raspberry Pi. I wanted to build a project, and I was shocked to see it sold out across the board. Further investigation shows that they're also a victim of the global chip shortage.

Zoe - It's in all sorts of things. What really struck me is how many chips these devices need, especially cars. There's a big problem with the car industry at the moment. Turns out cars are more computer than vehicle these days, they have dozens and dozens of these chips and they're just not anywhere to be found. The other problem is you can't just set up a chip making factory overnight; It takes two years. While all over the world countries are scrambling to get production up to speed, it's taking ages. They're saying that possibly even towards the end of 2022 we'll still be playing catch up here.

Chris Smith - One other big story, which came in the latter part of the year was Facebook. This rebranding of the entity as 'Meta' and Mark Zuckerberg setting out his vision for what he dubs the "metaverse". What actually has he got in mind for Facebook?

Zoe - 'The metaverse' is one of these things that you're gonna hear loads about in 2022, but it doesn't yet exist. It's not going to exist in 2022. It's going to take years to build. It's going to be one of those things we're going to talk about a lot and you're going to sit there and go, 'Okay, well when can I actually see it?'. And the answer is possibly 5 to 10 years time. Think about it as a really extreme virtual reality where you are living inside the web. You're navigating various worlds using an avatar, you're not looking at a screen, you're actually part of the action. It's what some of the tech giants are seeing as the next evolution of the web. The first one was kind of us looking at very static information. The second one has been us using platforms to share our content. The third one is instead of looking at our content, we're actually being in it. It sounds crazy. It sounds very ambitious. Facebook is very influential, it has thrown a lot of money at this and has rebranded itself accordingly. Zuckerberg obviously thinks this is the future. Will consumers go and vote with their feet? Well, I think it'll be interesting to watch VR. Is this finally the big year of VR? We've seen virtual reality grow in popularity over the years, but it's never been the sort of ubiquitous big thing that we thought it was going to be. Could this be the year? I hate to bring up Apple again, but they are rumoured to be bringing out a VR headset in 2022. Apple just tends to do things well. Could it be that that product becomes the breakthrough product that gets a lot more people on board?

Chris Smith - I was watching, over new year, a rerun of 'Johnny English Strikes Again' when he dons a virtual reality headset and accidentally ends up in the street, and then beats up a café owner, pushes the lady out into the street and another bloke off a bus. Do we really want this? I'm not sure the idea of sticking a modified ski mask over my face and pretending I'm in a meeting with my colleagues is going to be any nicer than just going and meeting my colleagues. Why do we want this?

Zoe - Yeah, I agree with you. I think the hardware, the actual headset, has really held it back. It's clunky, it's uncomfortable. Lots of people get nausea, get sickness. I get sickness in VR after a while. I can't do it for that long before I start to feel quite queasy, which is embarrassing. I think in a way you are right, I don't think it will replace meeting people face to face. But if we've learned anything in the last two years it's that actually, we sometimes have to meet online. It's easier to meet online and it's better for the planet to meet online than to be jetting all over the world. It's not long before you get that zoom fatigue, and you start thinking, 'You know what? I like you Chris. Do you play golf? Why don't we go for a virtual round of golf while we're having this chat?' Would that be more interesting? Would that be more fun? Would it help us to connect better? Yes, possibly it would.

Chris Smith - We've moved the conversation onto the question of gaming. There was a new game demo called 'The Matrix Awakened' to show off the 'Unreal Engine 5' that came out. It's basically the original matrix film remade, but all CGI - absolutely amazing to some people's minds. Someone we got to play it said this about the demo.

Alex Rhodes - Unreal. It's supposed to be unreal. Oh, here come the agents. Bit of slow-mo going on. It does look very good.

Chris Smith - Bottom line is that they were creating all of the footage in a computer. It's not a film anymore. It's basically computer generated, but good enough to fool Alex Rhodes, who is the correspondent asked to review that for Chris Berrow from 'The Naked Gaming' podcast who is with us. He obviously liked it.

Chris Berrow - It's one of those tech demos which gives you a flavour of what the future of gaming could be. What was amazing about this particular demo is that it was like you were watching 'The Matrix' film with the classic Matrix footage, and then you'd press a button and you'd see all the underlying graphics that go into building all the models of the characters and the buildings and things like that. You realise that this video game simulation of the film, it's like another kind of matrix. Then the game demo drops you into the game and you can walk around the city which you've come to know and love from the film. It's unbelievable. The scope and the scale of what they can do. Obviously it's only a tech demo. It's not a proper game, but it gives you an idea that actually, let's say you've watched a new Marvel film, the new Spiderman film, or maybe they could just scan that into the Unreal Engine 5, and you could be running around as Spiderman using those buildings to swing around. It's an amazing tech demo and Alex was quite impressed, as I think you heard there.

Chris Smith - The thing is that the games industry is actually a value prospect and value proposition is actually much bigger than Hollywood in terms of its turnover, the amount of money that flows through it. Games have gone from very, very basic 20-30 years ago, to things - as you are hinting at - that could rival Hollywood. Are we at risk of losing the message in the medium, because you're employing armies of artists, you're employing a huge, great computing power to make something that looks all glittery and sparkly. Are we actually losing something the essence of why people wanted to play games?

Chris Berrow - Yeah and I think that that's a very good point that there are certain genres and styles of game. And some people like Leigh Milner, who co-presents the podcast, she hates games that are like films because she thinks that it is losing the essence of what gaming is, which is to have control to jump around, to lose yourself & to collect coins. She loves those old school games, whereas like this Matrix game demo, and like some of the huge releases from 2021 'Ratchet and Clank Rift Apart' - it feels like you are playing a Pixar film. It feels that you're running around in that incredible world, but for some people it's just too much. I dread to think what it's like to be a games developer starting up in this day and age, because how on earth can you have the budget to create the sort of games, the AAA games that are running on the PlayStation 5, the Xbox One and PCs now that are so incredible. You just can't do it, so you see start-up companies are going back to creating old school games. 2D side scrolling platforming games. Once they've done that, they then reinvest their money into their next big release. I totally agree; there is certainly a danger of losing what gaming is compared to watching a film, but some people love that. And you know what, if someone really wants to essentially watch a film, but press a couple of buttons here and there, there's a market for that as well and it can be very relaxing to do that.

Chris Smith - Zoe, is the huge demand that this is putting on computing power from gaming, driving the industry or is the industry and what we can do enabling gaming. Do we know? Or is it both?

Zoe - I suspect it's a bit of both. I think there's nothing more frustrating for a gamer than their kit not being up to scratch, whether that's your broadband connection being too slow to download the game you want, or Microsoft has an amazing game where, where you are basically a pilot and you are flying around the world. The graphics are beautiful, it's stunning. But your average computer won't be able to manage it, so you need a sort of proper kit to be able to do it and I think that does cause some frustration. The Unreal Engine is just a phenomenal tool that's been developed by Epic Games who are probably best known for the game 'Fortnite'. But the Unreal Engine is a really interesting part of their business. This idea of being able to virtually create an entire world so realistically is incredible.

Chris Smith - To finish, what would you be playing in 2022 Chris? Your eagerly awaited release?

Chris Berrow - You've talked about the semiconductor chip shortage. I was trying to buy a VR headset, but I can't get hold of one yet, because they're just not in stock anywhere. I'm looking forward to 'The Legend of Zelda -  Breath of the Wild 2'. I think that's probably a lot of people's most anticipated game. If you really like the 'Zelda' series, you're gonna be really looking forward to that on the Nintendo Switch. The first one was just incredible. There's a new console coming actually, which is super interesting just to quickly mention, called the 'Steam Deck'. If you've always wanted to play computer games, but you can't afford a hugely expensive computer like myself, if you just don't have space, this Steam Deck console will actually play all of those Steam games, which are traditionally based on a computer. We're looking forward to the release of that early on this year to just give it a go because it's super interesting how powerful handheld consoles can now be.

Chris Smith - What are you talking about - can't afford it, Chris? it's all on The Naked Gaming budget. Thank you for joining us. Tech journalist, Zoe Kleinman, and also 'Naked Gaming's Chris Berrow.

Artist's impression of the James Webb Telescope

23:12 - James Webb Telescope Unfolds in Space

The much delayed space telescope finally has lift off, helping us to view the universe like never before.

James Webb Telescope Unfolds in Space
Matt Bothwell, University of Cambridge

The James Webb telescope has just been launched into space. Chris Smith interviews the University of Cambridge's star public astronomer Matt Bothwell about what the telescope is and what information we hope to gain from its production & successful launch...

Chris Smith - Now, on Christmas day, you may well have been tucking into your turkey dinners, but, in South American space, scientists had some much bigger fish to fry.

James Webb Launch clip - (in french) 5. 4. 3. 2. 1. Lift off

NASA commentator - Lift off. From a tropical rainforest to the edge of time itself, James Webb begins a voyage back to the birth of the universe.

Chris Smith - Now that was NASA's coverage of the launch of its Arian-5 rocket that was carrying the $10 billion James Webb space telescope which, we are told, will enable us to see the universe like never before. Here to tell us what is in store for us is the University of Cambridge's public astronomer and author Matt Bothwell. Matt, was it Turkey for you or telescope? Were you watching it?

Matt - I was watching; it was all about the telescope for me. I was glued to the TV and, to everyone that was passing by, I was frantically showing them the exciting things happening. It was amazing. Did you watch it?

Chris Smith - I was enjoying my turkey too much. But it did get off the ground.

Matt - It did and it got off the ground absolutely beautifully. I think one thing that me along with all the other astronomers in the world were hoping for was a really successful launch, because the more fuel remaining for James Webb, the longer its potential lifespan. It turned out that the launch went so perfectly, it's going to massively exceed its 10 year lifespan. We're going to get a very long time of exploring the Universe with James Webb.

Chris Smith - How does it work? And what's it actually going to do?

Matt - The telescope is an infrared telescope, so it gets compared to the Hubble space telescope quite a lot. I think a better comparison with it is the Spitzer space telescope. It's a bit less well known, but it is an infrared telescope that's going to be taking photos of the universe in these long wavelengths of light. The difference between James Webb and Hubble is that James Webb is much further away, while Hubble is orbiting around the earth. James Webb is going to be beyond the moon, about 1.5 million kilometres away, where it's nice and cold and dark to get this very good infrared view of the universe. It's going to spend 10 years or more exploring all kinds of things from the atmospheres of exo-planets to the first stars that switched on in the universe.

Chris Smith - There's no risk of it being broken? Its predecessor, the Hubble, was launched and then, unfortunately, it was discovered to have some flaws that required a space walk to fix. We don't think that's going to happen here?

Matt - Hopefully that won't happen. I wish there was no risk of it being broken. Unfortunately, James Webb has an awful lot of potential failure points that might end up with a non-working telescope. The problem is, of course, it being so far away and not orbiting around the Earth: there's no chance to fix it. Luckily, at the time of recording, about 75% of all the risk involved in James Webb's deployment has been passed with flying colours. We are well on the way to a perfectly working telescope, but we're not out of the woods just yet.

Chris Smith - Speaking of working, when are we going to start to see data come back, some images that we can analyse?

Matt - It's going to be a little while to be honest. So James Webb is going to spend the next few months cooling down to operating temperature and then hopefully, by spring or summer 2022, we'll start to get some nice, pretty pictures back.

Chris Smith - And what are the big questions they'll be asking with it?

Matt - James Webb has a few different science goals. One of them is to explore the atmospheres of exoplanets and look for various things including what we call 'biomarkers'. These are signatures for potential organic processes going on in these exoplanets. Another one, which is very near and dear to my heart as it's my own research area, is the study of very, very ancient galaxies that existed early in the universe. James Webb is designed to see some of the first stars that ever lit up the dark in the cosmos. It's something we've never seen before. All kinds of things that are just completely on the cutting edge. It's all incredibly exciting.

Chris Smith - Well, let's see when we get you back this time next year; you can tell us what has been seen so far. It's a pleasure to have you on the program. Thank you very much, Matt Bowell, Cambridge University's public astronomer.
 

Insulin pump

28:27 - Insulin: 100 years of diabetes treatment

Tracing the history of this remarkable medical breakthrough.

Insulin: 100 years of diabetes treatment
Kersten Hall, University of Leeds & Charlotte Boughton, University of Cambridge

Chris invites history of science expert Kersten Hall to discuss the first insulin treatment in 1922 before welcoming Charlotte Boughton, a Cambridge University endocrinologist, to tell us what future medical interventions for the condition could be...

Chris - For people who live with type 1 diabetes insulin is a lifeline because, as we know, people with the condition can't make any of the crucial hormone themselves. Insulin tells our cells to pick up the sugar glucose in the bloodstream. Now, if this doesn't happen, our cells run out of energy and levels of sugar in the bloodstream climb dangerously. Long term, this can damage blood vessels, nerves, our kidneys, and also our eyes. Historically, type 1 diabetes was a fatal condition until this week a century ago doctors began injecting the hormone and saving lives. The story of diabetes can actually be traced back much further than a century ago, though. In fact, to 1776 and a certain doctor, Matthew Dobson, who boiled the urine from someone with diabetes and noticed something peculiar:

"There remained, after the evaporation, a white cake, and this cake was granulated; broke easily between the fingers. It smelled like brown sugar. Neither could it, by taste, be distinguished from sugar except that the sweetness left a slight sense of coolness on the palate."

Chris - Luckily not something that we do in medical school these days. With us now is Kersten Hall who's written the book called 'Insulin - The Crooked Timber', which documents the history of diabetes. Bit of an unconventional technique these days, Kersten. Take us back to a hundred years or so ago and tell us a bit more about how diabetes was actually discovered and what insulin's role was found to be.

Kersten - Happy new year, Chris. Thanks very much for having me on the program. Actually, the oldest reference to diabetes is on an ancient Egyptian scroll from about 3000 years ago. I think the Ebers Papyrus talks about a medicine to drive away the making of too much urine, and that's a reference to what I think is probably the most common symptom of the onset of diabetes: frequent passing of water as the kidneys go into overdrive to clear all this excess sugar that's in the blood. By the 19th century, it was known that the pancreas was central to diabetes. Two researchers, Minkowski and Meren, noticed that when you surgically removed the pancreas from a dog the poor animal became diabetic. Researchers began to speculate that maybe the pancreas produces some hormone that controls blood sugar levels and so the hunt was on to find that hormone. The person who is credited with having found it was Canadian scientist Fred Banting. In the summer of 1921, Banting and a younger colleague, Charles Best, who was a final year honour student, had been removing the pancreas from a dog to make the animal diabetic. Then, they'd been making pancreatic extracts and injecting those into the diabetic dogs to see whether that would bring down their blood sugar levels. And then, of course, the time came to test this on a human patient. So, January the 11th, 1922, young Leonard Thompson had been brought into Toronto general hospital. He was 14 years old. He'd been diagnosed with type one diabetes a few years earlier, and when his father brought him into Toronto general hospital he was pretty much at death's door from diabetes because, prior to the discovery of insulin, a diagnosis of type 1 diabetes was pretty much a death sentence. There was nothing really that could be done for the patient other than to put them on a starvation diet to basically delay the inevitable. So, January the 11th, 1922, Leonard was injected with some of Banting and Best's extract.

Chris - Is that from a dog, Kersten?

Kirsten - No. By that time they were making the preparations from bovine pancreas.

Chris - They realised that you could go to another animal and the analogous organ would work? So it was a reasonable step to then say, "well, let's take this because it's a bigger animal, big pancreas, lots available", and try injecting that?

Kersten - That first injection on January the 11th was actually not considered to be a clinical success. The reason was, yes, sure, Leonard Thompson's blood sugar levels fell, but he was still producing ketones in his urine. These are toxic compounds that are produced in diabetic patients. But the most serious result of all was that Leonard had suffered an adverse reaction. Two weeks later, January the 23rd, 1922, Leonard was injected for a second time. This time it was a success. His blood sugars dropped and there was no toxic adverse reaction.

Chris - And how did they achieve the improvement? Did they filter it or clean it up in some way?

Kirsten - Well, what had changed was that second batch of preparation hadn't actually been made by Banting and Best: it had been made by their colleague, James Collin. What he'd been able to do was work out exactly how you could use alcohol to clean up the pancreatic preparation to remove those impurities that were causing the toxic reactions.

Chris - Did he continue to receive these things? Because there've been these sad stories in the history of science and medicine where people invent amazing remedies - and I'm thinking, of course, of Fleming and Florey's penicillin - where people's lives were initially saved but they couldn't sustain the production and people then died because they couldn't keep treating them. What happened here? Was the story a happy ending?

Kersten - Well, Leonard, I think, continues to be treated. He died very young. In folklore, he died in a motorbike accident: that's not actually true - I think he died from a pneumonic infection in the end. But what happened with insulin was, very quickly, word got out about this discovery. The thing is Banting and Best and the Canadian researchers had the media on this. They had two key factors: They had the media on their side, the newspapers, and they also had industrial clout because, of course, it's one thing to make a discovery like this at the lab bench, but to get it scaled up, to get it purified, to get it into patients, you need industrial backing and they had that in the form of Eli Lilly. Insulin is an interesting example in the history of medicine because, by early 1922, this stuff was being put into patients in clinical trials. The problem was production was the rate limiting step and there were stories about patients coming and camping out in order to try and get hold of this stuff. The issue really was how: "How do we make enough of this stuff and how do we make it fast enough to start getting it into patients?" The other issue, as well, was I think the clinicians at the time were concerned about the media trumpeting this as a miracle cure for diabetes because the clinicians at the time knew it was nothing of the sort. What it does is it transforms what would be an otherwise fatal condition into a long term chronic one that can be managed. There was a very eminent American diabetes specialist at the time, Dr. Elliot Joslin. He was concerned about patients suffering depression if their expectations were ramped up beyond what could realistically be expected.

Chris - This is the perfect opportunity to introduce the other person we have here today, Charlotte Boughton, and she's a diabetes and endocrinology researcher at the University of Cambridge. She's been part of a team who in the past have come up with the organ that you've been referring to, the pancreas, in an artificial form so that we can try to treat diabetes better. Charlotte, you better tell us what was in your mind. I mean, how does this work?

Charlotte - Thank you. An artificial pancreas is actually three bits of hardware: unlike the pancreas, which sits in the body, all the bits of hardware are on the body or nearby. It's all external and it comprises a glucose sensor which measures the glucose levels in the fluids surrounding the cells in real time, an insulin pump which delivers insulin just under the skin, and both of these components are commonly used by people with type one diabetes. The clever part of an artificial pancreas, or a closed loop system, is an algorithm which in the system that's been developed at the University of Cambridge is hosted as an app on a mobile phone. That receives information from the glucose sensor and calculates the right amount of insulin to be delivered by the pump. It does this automatically adjusting the levels every sort of 10 to 12 minutes and allows the person with diabetes to continue without having to do those adjustments manually.

Chris - Apart from superior convenience - not having to prick your finger, test your blood and so on - is it better to have a system continuously taking these measurements and topping up insulin? Is that because it's more similar to what your body would do itself? Does that translate into better health?

Charlotte - Yeah, exactly. It allows you to get more what we call physiological replacement of insulin and we've shown, and other groups internationally as well, that close loop systems allow people to get better glucose control than with a pump on its own or injections, and also can reduce the risk of dangerous hypoglycemia as well. So there's both biological benefits, but also psychological and burden benefits for somebody living with type 1 diabetes.

Chris - Is this the only show in town or are you working on version 2.0 which doesn't have any external features? How are you going to take this forward?

Charlotte - At the moment, the systems that are commercially available to people with type one diabetes still require people to count their carbohydrates and manually tell the insulin pump how much they're eating and therefore how much insulin to deliver. With the newer ultra rapid insulins that have been developed we are seeing at the moment whether those are quick enough to get rid of the need for people to interact with it. So, actually, people could literally just wear the devices and forget about it until the devices need changing. That would truly reduce the burden of type 1 diabetes management. There are also lots of other areas of research within this including smart insulins, which are designed to turn on when they're needed (when glucose levels are high) and turn off when they're not. I think these are quite far behind where we are with diabetes technologies such as closed loop. But I think these are certainly something to look out for in the future.

Chris - I wonder what Leonard would've made of this a hundred years ago, Kersten.

Kersten - I think, well, I think he would've been delighted. I just wanted to say to Charlotte, I actually have type 1 diabetes myself. In fact, as you've been speaking there I've just been doing a quick blood glucose check. I'm fitted with one of these cyborg devices. That's how the kids like to think of it as Dad being a cyborg - one of these implants. I just swipe my phone on it. I thought your work there on the artificial pancreas is so exciting. As somebody with type 1 diabetes, I'm really gonna be watching this with eager anticipation, and as somebody who's just written a book about the history of insulin I'm thinking, "oh my goodness, I better get in touch with my publishers and beg them to publish a second edition", so I can write another chapter to cover the research you've been doing! I just wanted to say thanks very much for all you're doing there and I look forward to it. Got big hopes. Fingers crossed.

Chris - Thank you very much Kersten and thanks also Charlotte. That's Charlotte Boughton and Kersten Hall. And you can get Kersten's book that's out from the 13th of January, appropriately enough for the anniversary; the centenary. It's called 'Insulin - The Crooked Timber: A History From Thick Brown Muck to Wall Street Gold.'

Film camera

40:40 - 'The Green Planet' Filming Secrets

We uproot the behind-the-scenes features of the new David Attenborough show 'The Green Planet'

'The Green Planet' Filming Secrets
Mike Gunton, BBC

 

Chris Smith delves into the behind-the-scenes features of the new David Attenborough show 'The Green Planet' with producer Mike Gunton... 

Chris - Would you call yourself green fingered? While many of us dabble with a bit of gardening, or tend to the odd house plant, we often don't consider how plants behave. Well, the new BBC documentary, 'The Green Planet', presented by Sir David Attenborough, is looking at just that. I can tell already it's going to be a hit. Mike Gunton is the executive producer of "The Green Planet." He's here to give us an insight into the fascinating plant species that we live alongside and, also, the fascinating stories behind the filming of this new series. Mike, how do you go about putting all this together because, presumably, before you put a camera in front of a plant or even a script in front of Sir David Attenborough, there must be massive amounts of work that go on behind the scenes to work out what you are actually going to document.

Mike - Absolutely right. It's a combination of two things: one is the research to find the stories. In this particular case, with trying to take an audience into the world of plants which, of course, live in this kind of parallel universe in a different timeframe, we also had to spend an enormous amount of time thinking about how we're going to do that technically. Time lapse is a way of doing that - seeing plants in their timeframe. We've done time lapse for many years to try and get something that feels more like a 'Planet Earth'. That's what we were trying to do: a 'Planet Earth' for plants, if you like. It meant we had to think of some new technology to allow us to do that, to immerse the audience in this extraordinary world. So, yes, probably about a year of scientific research to find the stories and about the same amount of time going alongside, trying to find and develop new pieces of tech to allow the audience to come on this extraordinary journey.

Chris - There's about 400,000 plant species on earth - I learned that from a plant scientist who's actually trying to document every cell in every plant species on earth, and she said, "it's a big project" and now I understand why. But how did you choose the plants you were going to look at? Did you have some kind of insight into what sort of stories you were going to tell and what was the new technology that you had to invent.

Mike - Funnily enough, in the same way as you go about choosing stories for 'Planet Earth', where it's all about the animals, you are looking for stories that the audience can connect with; that are dramatic, that tell you something remarkable about the lives of these living things. So it was trying to find stories where there was an intrinsic drama and often that comes with conflict. Conflict in the animal world is paralleled in the plant world; plants competing with each other for light, for nutrients, for mates, or for sex, and we look for those kind of stories and also stories where the plants themselves were very active. When we put our time lapse cameras on them and speed up time and enter their world, you start to see this dynamism in action and what the technology was trying to do was, rather than just reveal this in a kind of tableau, just as locked off shot, the idea was the camera would move through the world as if you were following animals and taking different perspectives. If you had, for example, two plants competing with each other or fighting with each other or one attacking the other, rather than just seeing it in one shot, the camera can take the perspective of the attacker, it can take the perspective of the attackee, the one that's being subjected to the attack, and then also see it from a wider perspective and sometimes even see it from effectively an onlooker's perspective: some of the other plants. The way you do that - and it's all a bit secret the technology - but it's using robotic motion control cameras. Effectively, the cameras remember where they were throughout the playing out of the story so they can take time lapse image 1 of plant A and then they move round to a different position to take a shot of plant B, but then they go back to where they were to position plant A to take the next shot. As you can imagine, the engineering challenge of that to be so precise was immense. Anyway, we've done it, and when you see it, it almost feels like an unreal, almost a magical perspective because you, the viewer, and the camera, are moving in our time, but what's going on inside the frame, which is the plant world, is going on in their time, in time lapse. It's quite the interesting mind game when you watch it.

Chris - Well, you mentioned time. There's a clip of a plant that you documented that took a very long time to open. The rafflesia - did you really spend five years on that?

Mike - No. The backstory of that is five years. We filmed the bud growing over a considerable length of time but the bit that we spent most of our time on was watching the flower open and this remarkable seduction that goes on where the flower attracts Carrion flies effectively.

Chris - Because it smells like death, doesn't it? It smells gross. Apparently it's one of the worst smells you can encounter.

Mike - And you can tell David's enjoying himself with the relish with which he tells all that because there is a sort of theatre about this because they're unseeable other than through the camera and our technology. When you do see it, it is like going to the theatre and seeing some magic show being performed, but the difference being it's real and it's true. And it's all the more remarkable for that. That's one of my favourite stories: it's the biggest fly in the world. It's a remarkable thing. 

Chris - You were commenting on a brush with cacti as well. Because that's one of the things you cover in the series?

Mike - One of the things about this series that has been fun for me as a filmmaker (I've been doing this for about 30 years and started way back in the late eighties with my first film with David Attenborough when I was in my twenties) and the fun of that was taking David all over the world and doing these remarkable demos where he'd climb into this and climb up that and, of course, you know, he's now in his nineties and it's harder to do that. But he and we were very keen to try and redo that, revisit that in this series. And so we have taken him not all over the world, but to much of the world and he's got out there and done stuff and, as ever, game for all sorts of remarkable things, including: there's this extraordinary cactus called a Teddy-bear cholla - in back light it looks a bit like a Teddy bear's ears, it slightly looks like it's fur, but those are really nasty spines, very powerful defensive spines. David being David said, "well, I can demonstrate that by shoving my hand into one of these things and showing how vicious they are," but of course he has to do it with a welding glove, with a Kevlar lining to it, which we thought nothing could get through. And so he gamely shoves his hand into this thing to show you, and then, "Ah!" pulls his hand back because these spikes are so vicious they even managed to go through this glove. Being the tropper he is he carries on and delivers his story about how effective it is.

Chris - One of the things which has increasingly come up in recent years has been the conflict between us as humans, our use of the planet, our use of the world, and the animal species that you've been documenting. Are you also showing those conflicts here in 'The Green Planet?'

Mike - Absolutely. There's two things that I think we want to get out of this: one is that it is a wonderful, extraordinary, magical world full of fascinating science, fascinating biology. But, also, how important plants are and how we are all a bit plant blind: we take them for granted. They will do a lot of the heavy lifting for us in trying to recover, both in terms of biodiversity, but also in terms of carbon capture and all those kinds of things. And they'll do it without us having to do much! Leave them alone and they'll do it. Part of the story really is to say: not only be amazed and wonder in these things but treasure them and realise that, just because they don't run around, doesn't mean they're not important and, also, that they're not vulnerable. Lose them at our peril. If we don't look after them, that will be a fundamental problem for us in the future. So that message, I tell it in stories, but that message, hopefully will come over loud and clear.

Chris - And before you go: stand out moment for the viewers to look out for?

Mike - It's like trying to choose your favourite child, isn't it? I've done this for 30 years and I don't think I've ever been more astounded by the stories that we've discovered and told. I think in the the opening program, when you see that moment when the tree falls and suddenly the forest floor, which has been quiet for tens of tens of years, bursts into life and all these plants start doing their thing to try and race to the light using different technologies. And you see it in this... it's almost godlike, looking down on a battlefield, seeing all these different things fighting and trying to win. I think that's pretty remarkable and that sort of dynamism is, I think, throughout the series and I think you get a sense that these are extraordinary living things that are doing stuff just out of our sensory world but, nevertheless, still utterly remarkable.

Chris - Thank you very much to Mike Gunton who makes a very powerful case for why we should all tune in and watch 'The Green Planet', which is the David Attenborough's new BBC documentary series that starts on Sunday 7:00 PM on BBC one. You can also find that on BBC Iplayer.

 

  

Hedgehog outdoors

50:40 - Hedgehogs harbouring superbugs

A battle between bacteria and fungi on the skin of Hedgehogs may be how MRSA developed

Hedgehogs harbouring superbugs
Mark Holmes, University of Cambridge

Chris Smith interviews Mark Holmes about his team’s discovery of the prickly origin story of the MRSA superbug...

Chris - This week, there's been a surprising finding that hedgehogs might be the origin of one form of the antibiotic resistant bacterial superbug MRSA (which stands for Methicillin-resistant Staphylococcus aureus). New research, which has been published in the journal ‘Nature’ this week, has found that a microbial war going on on the skins of our prickly hedgehog friends is probably where MRSA came from in the first place. Here is Cambridge University vet and immunologist Mark Holmes, who's one of the team who made the discovery. How did you link MRSA and hedgehogs in the first place? It's not an intuitive leap.

Mark - No, it isn't. About 10 years ago, we discovered this new strain of MRSA in dairy cows and at the time we assumed that antibiotic use in treating cows might have selected for this, but we looked more widely to see where this type of MRSA was and we found quite a bit of it in wildlife - in fact, scattered throughout Europe. Then we almost stumbled upon the fact that hedgehogs seem to have lots of this MRSA. We started off with a survey in Sweden and in Denmark and it turns out that around 50 or 60% of hedgehogs have this MRSA.

Chris - Someone just swabbing hedgehogs for the fun of it? How did this come to light? It doesn't seem an intuitive thing to do.

Mark - No. There's always the aspect, I think, of most scientists being a bit curious and a bit stamp collector-y. When we found it in farm animals our initial thought was: "Where are the farm animals getting MRSA?" The obvious place they'd get it from is people, but we still swab wildlife to see, because actually one of the other aspects of our research is what makes a bacteria particularly want to live on a particular host. Particularly something like Staphyloccocus aureus - we find it in many species of animals, but we don't necessarily find the same strains on the same species.

Chris - Why have they got it at all?

Mark - About 60 years ago, researchers in New Zealand had made an observation that there's a particular fungus, a skin disease, on hedgehogs. When you've got hedgehogs with this skin disease, you tended to be able to detect penicillin resistant bacteria. So when we made our observation and read those papers in the dark history of microbiology, we put two and two together and wondered if this is what was selecting for the MRSA on hedgehogs, and there followed a lot of work where we sampled lots of hedgehogs, we looked for fungus on hedgehogs, we sampled the MRSA, we sequenced those bacteria, and are able to show pretty well without much doubt that the hedgehog MRSAs firstly existed all that time ago. The ones we find in people are closely related to the ones we see in the hedgehogs, and they are similarly geographically distanced. Particularly, one of our sample sets is from Denmark and they're all on one of the islands. All the people and all the hedgehogs have one strain of the MRSA, and on another island in a different part of Denmark, again, the hedgehogs and the people share very similar strains of the MRSA, but two geographical strains are clearly distinguishable.

Chris - To make this clear then - some hedgehogs get fungal skin infections and that fungus is doing something that enriches for the presence of the Staphylococcus and specifically the Staphylococcus that happens to be resistant to, you say, from New Zealand penicillin, but that's going to include methicillin, isn't it? MRSA? So, it's the presence of the fungus carried by the hedgehog that then selects for resistant bacteria on those hedgehogs.

Mark - Yes - And it won't come as a surprise to many listeners who'll remember that Alexander Fleming discovered penicillin because he had a fungus growing on a plate of bacteria. So we'd known for a long time that fungi are a good source of antibiotics, things that kill the bacteria, and the fungus produces this antibiotic in order to outcompete for the food resources on the skin of the hedgehog.

Chris - And the genetic know-how for how their particular MRSA does what it does, that's then shared with strains that then cause superbug infections in hospital? That's basically how we have got those things: they already existed, but our use of antibiotics in hospital has enriched the genetic sharing of the know-how among strains that infect humans?

Mark - Yes. I mean, it's probably true of almost every type of antibiotic resistance: they're actually evolved in nature. It was selected a long time ago. So these resistant genes are scattered about, throughout nature and throughout the environment. However, what we do as people is we use vastly more antibiotic than ever a fungus secretes. Many of these antibiotics end up in the environment, and what's happening with human use of antibiotics is that we've upped the anti as far as selection pressure. The amount of antibiotics that bugs are exposed to is much more than it would be in nature. They come across it more frequently at higher concentrations because of the medical and veterinary use of antibiotics.

Chris - Mark, thank you very much indeed for sharing that discovery with us. That's Mark Holmes, he just published that in the journal 'Nature.'

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