The Infinite Monkey Cage - Antibiotics

Episode Date: January 22, 2018

Antibiotics Brian Cox and Robin Ince are joined by comedian Chris Addison, Chief Medical Officer, Dame Sally Davies, and Professor Martha Clokie to look at the history and future for antibiotics. Producer: Alexandra Feachem.

In our new podcast, Nature Answers, rural stories from a changing planet, we are traveling with you to Uganda and Ghana to meet the people on the front lines of climate change. We will share stories of how they are thriving using lessons learned from nature. And good news, it is working. Learn more by listening to Nature Answers wherever you get your podcasts. This is the BBC. Hello, I'm Robin Ince. And I'm Brian Cox. Today we are talking about health, which is a lot more interesting to me than it is to Brian because I am a human and therefore may well become ill,

whereas he is a replicant that was made in Switzerland and is only poorly if we have to reboot him when he's just there going, wonderful, wonderful, wonderful, wonderful, wonderful, wonderful. Now, medicine has moved on. Medicine has

moved on a lot in the last hundred years. The best cure for being ill used to be leeches, cutting and newt spit, in which I years. The best cure for being ill used to be leeches, cutting, and newt spit, in which I really mean the best cure for being ill was to kill you, because then you didn't have flu anymore. You were merely dead. This is why homeopathy was relatively

successful, actually, because it did absolutely sod all, and therefore didn't kill you, which was a measure of success. At least you were alive. Sorry, there's going to be letters, aren't there? Well, this water's already been telling me you've been very bad. Ooh, it's got a horrible memory. Today we'll be talking about medicine that works,

in fact, a medicine without which many of us would not be alive today. Antibiotics. How do antibiotics work? What are the consequences of their overuse? And what can we do to fight bacterial infections in the future? To prolong our painful existence and postpone our inevitable demise, we have a panel of distinguished guests, and they are... Well, I'm Dame Sally Davis. I'm the Chief Medical Officer for the UK, so I'm concerned with the health of every one of you in this room and the nation. I advise

the government, and I'm particularly concerned about the increase of infections that don't respond to the treatments. And I'm Martha Clokey. I'm a professor of microbiology at the University of Leicester and my research is on bacteriophages which are viruses that specifically kill bacteria and we'll talk more about them later. And the organism I've been working on for the last decade is a thing called Clostridium difficile. Many of you may not know this bacteria. It's not a particularly sexy bug,

but it's the major cause of infectious diarrhoea in the Western world. But in terms of working with it, it has a particular smell of horse urine. So once you've actually found it, you know that you've got it in the lab. And when you look at the colonies on a plate they are a particular show trues color so it's being pragmatic it's it's it's not a good bug to get but it's you can work with it sick green if yeah it's right and i'm uh chris addison i'm an actor and comedian and director and I love being introduced lower down the bill than diarrhoea and urine. LAUGHTER Find my rightful place at last.

And the disease that interests me most is Kuru, which was a disease of the Papua New Guinean people. Still is. Is it still? So you can tell me. So as I understand it, it was called the laughing sickness, was it not? So it was because one of the symptoms of Kuru is this sort of spasmodic, uncontrollable laughter. It's like the dead Riggins audience.

And there's no explanation for it, but they're laughing anyway. So... Can I just say, this is the longest quick introduction of all the guests we've ever had. It's meant to be, hello, my name's Dr McNaught, I am from the University of Rotherham, and my favourite disease is... But instead it's just broken out. I'm enjoying it.

I mean, it's certainly more avant-garde than the previous versions. It's not live, that's the main thing, because we'd be crashing the shipping forecast by now. But I think we all just think in podcasts these days, which are rambly and unfocused. And that's very much how I think of you as well, Robin. Yeah, exactly. Your favourite disease? It's Kuru.

My favourite disease, which is an extraordinary way of putting it, is Kuru, the laughing sickness which was caused by cannibalism. Cannibalismum? That's cannibalising your mother. I thought it was cannibalising the Muppets. Cannibalismumumum. That's cannibalismumum. It was caused...

LAUGHTER..by the religious beliefs of the Papua New Guinean people who believed that eating the departed would help free their souls and they would especially give the food, as it were, to mothers and children. It's the brain. It's the brain, isn't it, that they eat? It's the prion. And this is our panel, and all we have time for today.

Now, because of the way this has been set up, I don't think we should go to question one. I want to preamble before that. Martha, you said that you worked with a not particularly sexy bacteria. How do we define the sexier bacteria? Well, I would say sexier ones are generally more heard of. So everyone knows about MRSA and everyone knows about maybe salmonella, E. coli,

but Clostridium is just the sort of... People don't sort of think about it as much as they should. You could take gonorrhoea. For what? What's that going to cure me off if you sound like one of the more maverick homeopaths don't pollute it more to just have the whole gonorrhea that'll get rid of your headache you'll have something else to think about i just thought it's it's an interesting one you want a sexy one it's transmitted through sex it's on the rise and we now have patients dying across the world because there's no treatment for, it's on the rise, and we now have patients dying across the world

because there's no treatment for them. You sort of said that like it's an achievement. Well, it is the bug, isn't it? Yes, well done, gonorrhoea. Full marks to you. So, Sally, to start, could you tell us how an antibiotic works? So, antibiotics only work against bacteria, and they work by killing. They're absorbed through the bacterial wall into the inside,

and they poison it by interacting with the metabolism. Each antibiotic family works in a different way. But it's very interesting that survival of the fittest, it's quite easy over time for the bacteria to have a mutation and become resistant. And it's also a big group of the bacteria have two cell walls. They're called the gram-negative ones. So it's actually very difficult to get the antibiotic in

to kill it in the first place. So we need to get high levels in the blood or the tissue where the infection is so that they can get into the bugs. If they're absorbed, they then interrupt the metabolism and then it can't duplicate, it can't replicate, have children and it dies off. So they're essentially poisons.

Absolutely, of many sorts. So, Martha, what is the difference between a virus and a bacteria? Why for instance antibiotics will only work against bacteria? Yes that's right well a bacteria is a living organism like all it needs is a source of food and a source of carbon and it lives it lives within us it lives on the food that we digest they have their own metabolism they just replicate and grow whereas a virus needs a host so a virus is not living essentially until it's infecting something else so a virus is a very simple thing it just has a genetic code generally we can have dna or rna or both and then it has a

capsid has something to keep it safe from the outside environment, but it's an inert particle unless it's infecting something else. So I study viruses that kill bacteria. So everything has its own specific viruses that infect us. So humans do, dogs do, cats do, and bacteria have their own set. And we get very interested in all these viruses that are everywhere that are infecting those bacteria. But actually the most interesting thing about them is when they're infecting those bacteria and causing disease.

So a virus will go into a cell and turn it into a viral factory. So when a virus enters a bacteria, it goes in, and about half an hour later, 100 viruses will be released. So it goes in and it says to that bacteria, no, you're not a bacteria anymore, you're a viral-making machine. Chris, we both did a head-to-head turnout. She did, it was really sweet. That was five minutes of proper Radio 4 programme.

I didn't think we were going to get there. That was all kind of serious with a little light touch as well. Brilliant. Now, Chris, your father was a doctor. How did it go wrong for you? Yeah, my dad was a doctor. And so we grew up in a scrupulously clean house. There was a huge amount of attention paid to health and cleanliness. That's nonsense. There are no doctors like that.

I've never met anybody filthier than doctors in general. I think rather than teaching us, it's doctors you should actually be worrying about, Sally. Those are the people who need to know about bacteria and filth, and not in hospitals so much as in their own socks... LAUGHTER ..and other accoutrements. Yeah, my dad was a doctor.

So your dad's going to enjoy... Oh, yet again, Chris has gone on the radio to remind us all that we live in squalor. No, they don't live in squalor, but equally, doctors... There are no more cavalier people about health than doctors, in my experience. They're the worst at going to doctors themselves. And usually, it's, I've broken my leg.

Really? Well, have an aspirin and lie down for a while. That's generally what you get off a parental doctor. So, not hypochondriacs? Because I suppose, in one sense, you think of doctors as being aware of all the possible diseases you can get and therefore being worried that they've got them, but your father was not one of them. I think they just go, well, we're all screwed, aren't we?

We might as well just eat that toast that's been on the floor the last three days. We fight in a losing battle. Sally, we're going to talk primarily about antibiotics today and what we can do to make them more effective. Could you paint a picture of the world before antibiotics, which most of us don't remember, but it's not too long ago, I suppose the 1930s, 40s and 50s. Definitely the first half of last century and before. More people died of infection in the First World War and probably the second, than of actually injury.

And we reckon that antibiotics have added an average of 20 years to people's lives. So they have really changed. One of the first patients that had penicillin was in the States, and it was a seven-year-old, and she had a scratch on her cheek, her whole mouth swelled up, and it intruded on her breathing, and she was about to die when they tried it,

and six days later she walked out a pretty little girl again. So it's absolutely changed the picture of disease, and we've done a lot of modelling, as have the World Bank, and we can see that if we go on the way we are doing and we can talk about how the problem is getting worse and actually how we have an empty pipeline of new antibiotics, we know that by 2050 we'll have 10 million people a year dying of drug-resistant infections.

That's more than die of cancer at the moment around the world, significantly more. We know that it will take an extra 28 million people into poverty because they will be paying either for extra treatments that don't work or they'll be losing the wage earners of the families so people will die younger it it is a post-antibiotic era is a possibility, and we have to take lots of action to stop it happening, and it would be horrid and people would be shocked. So it's really possible that in our lifetimes

that fear of a scratch that would have been present in 1900, 1850, may return. Yes. We're not just talking about less developed countries here, we're talking about countries like the UK and the USA, Western Europe, that that fear could return. It could. After all, we know that probably about 5,000 people

die each year in England of drug-resistant infections already. We know that 60,000 babies every year in India die of drug-resistant infections in the first few weeks of life. So it's already here. It's just going to get much worse. Why? Why? Well, it is a natural response of the genetic code of those bacteria that when they meet antibiotics, if they mutate and find that they have a survival advantage, they will. And then they pass that genetic mutation not only to their children, but they have very clever ways of passing it horizontally so you can pass the advantageous mutation

which protects you against an antibiotic to your brothers, sisters, cousin's uncle's aunts and they can then pass it down to all their progeny so it's very easy to see how survival of the fittest you lose your good bugs and you are left with the resistant ones and i think historically alexander fleming noticed this problem didn't't he? He mentioned it initially on discovery of penicillin, that overuse and casual prescription may be a problem. He did in his Nobel Prize acceptance speech that you and I looked at the original speech in the Royal Society Library.

He talked about how resistance would happen and people would die as a result. It's very moving. So, Martha, this is a case, then, of... There's the old line by the physicist Richard Feynman, which was, the imagination of nature is far greater than the imagination of man. And what we're seeing...

I mean, I presume, for instance, some people will say that evolution can't be observed. You see creationists and intelligent design proponents who say evolution can't be observed. And then when they are very poorly, due to drug resistance, you can say, I've got some terrible news for you. two one you're very ill and two we've just seen evolution in action i mean this is absolutely yeah this is kind of what's what's what is occurring here no absolutely i mean bacteria are very good at um becoming resistant to anything that if you if you

give a bacteria any compound any antibiotic any pressure it'll it'll find a way to to grow without it it'll just get way to grow without it. It'll just get around it. They're very, very good at evolving. And you can see that when antibiotics, new antibiotics are brought onto the market, just within a few years, there's resistance found to all of them as they've come along.

So certainly antibiotics haven't been used in a careful way to minimise resistance. So, Chris, in terms of your background, where you are being brought up in a medical household, I mean, one in a terrible state, as we know, but how has that affected the way that you... I mean, when you hear things like this, when you see, of course, there's a lot of also, you know, pseudoscience out there,

have you grown up with a healthy level of scepticism about us being able to understand the nature of human beings, the nature of the medical world? Well, I think my dad was always very... Like a lot of doctors and medical professionals, he's very rude about the medical profession and its place in science. He goes, listen, we tried a thing, it worked, and so we're doing it again.

And that is fundamentally the science of medicine. It's all just guesswork that's worked out. You're on your own, kid. And that's the most interesting part to me, because we all, non-scientists, I think, have the sense of this big thing, this big, abstract thing, science, that has the power to solve everything,

and all you have to do is push the right buttons and the right answer will ping out the other end. And in fact, medicine is basically... He was saying, you know, it's a few hundred years, mostly the last hundred years of people really trying something or noticing something by accident. That worked, let's just, we'll put that in the book then. And because of that, you come out feeling,

oh, there's no system. There is, that doesn't exist. It isn't digital, it's analogue. It has changed since your father's time. Well, he is... He's still with us, I'm pleased to say, as of the beginning of this recording. So...

I think they've changed. Unfortunately, the antibiotics he's been taking haven't really been working out. Yeah, but he was always... Equally about antibiotics, he was always very, don't just go and get the antibiotics. That's not a good solution for you and it's not a good solution for everyone in general.

Well, it is a fairly common misconception, isn't it, that if you get a cold or you get the flu, you go to your GP and demand antibiotics. That is a problem, is it one of the central problems, actually, that we want this drug because we think it cures everything? Yes. Far too many people think that if they have an infection of any sort, they need antibiotics. And there's some quite interesting behavioural work

which shows that many people feel validated that they're truly sick and therefore they can take time off work if they've got an antibiotic. So we've been trying all sorts of behavioural things, like in the North West they did a lovely study where they used prescription pads, which started with, you do have an infection, you are ill, but actually you don't need an antibiotic. And then it described what was going on

and how long it was likely to last and go home and have some paracetamol and a hot drink and take some rest and nature will run its course and you'll get better. And that sort of thing actually does help reduce prescribing. There's also a sense, though, now I feel like people go to the doctor and go, give me this thing that I've heard of and because I've heard that it does the job and so any attempt by you to sway me or to to to tell me that there is a better option available to me is some nefarious plot by you or the deep state

or you know there's something about a suspicion of doctoral authority now that people have that I think marries into the need to get the thing that you want. And we picked that up with some public research. So our latest campaign in the autumn was actually not doctors on television saying, you don't need antibiotics. it was antibiotics dancing and singing, saying, look after us or we won't be here when you need us. Oh, because I thought that was a fever dream. The Californian raisins have let themselves go.

I feel so much better, ironically, without antibiotics. This has really worked for me. Thank you. Martha, so your research is based... You're looking at a potential alternative for the standard antibiotics, as you mentioned, which is phages. Yes. Could you describe what that possibility is? Sure.

So if you have a think, first of all, about what an antibiotic is, it's not just something that we buy from the chemists it's a it's an antibiotic is something generally they've come from they're made by bacteria or fungi and they're part of bacterial bacterial warfare so if you go into you can take permian soil defrost it and you can find antibiotic resistance tens of thousands of years ago so it's something that's always been there bacteria endlessly competing for space and resources and trying to knock each other out so we've capitalized on that and use these defenses so that is one natural enemy of bacteria which is other bacteria and fungi but another natural enemy of bacteria are the viruses so as i said the viruses bacteria have got their completely

own sets of viruses that just target them and they're really specific within the species so if you have an e coli infection you'd have viruses that just infect that, and they're really specific within the species. So if you have an E. coli infection, you'd have viruses that just infect that. Or if you have a Clostridium infection, there'll be another set of viruses. So each different type of bacteria has got its own set. So the fact is, nature has already done it. Ever since the 3.9 billion years that bacteria have existed, they've had their own viral enemies. So by studying these, we can find whole sets of new tools in the way these viruses target and kill their bacteria well this has got i mean

i was reading the the bacteria news weekly i think and it's an incredible incredible story though that this is this idea is older than antibiotics and why was it antibiotics became that this is what can be and and phage is it's been a long time of kind of just being left in a lot of medical cultures. Yeah, absolutely. So the discovery of bacteriophages was 101 years ago. So last year we had a series of parties throughout the world to celebrate this.

How many people came to the party? Not very many. Oh, no, we've all got diarrhoea. Who makes this punch? Sorry. It wasn't sexy punch at all. Sorry. It's a surprising number. We had around 300 or more people at the Pasteur Institute,

I think 400 people. But actually, they were discovered 101 years ago by a French-Canadian, but actually an Englishman discovered them two years independently before that, but in sort of typical English style. He wrote it up beautifully in The Lancet, and he didn't have enough funding to continue with his research. So he wrote a very nice thing saying, I've shown you what I've discovered, and I really hope it's useful to you. So he published that, and then it was more or less ignored.

He went off and fought in the war. And meanwhile, this French-Canadian Durell he discovered them independently in the Pasteur Institute and he's sort of often seemed to be the sort of forefather of bacteriophage research because he then took them further so this was in 1917 he found them 1919 he did his first clinical trial so he immediately developed them he looked at salmonella and chickens and then he did a study quite early on looking at shigella diarrhea infection in children and he showed that the virus has worked really well but he was a bit of a maverick character and he fell out very badly with the director of the Pasteur Institute and was a

little bit sidelined but then he trained a young Georgian scientist so often people think about phages and they think oh it's something that happened vaguely east vaguely Russia Georgia and that was because there was a young Georgian that trained in the Pasteur Institute and he was called George Eliyava and he went back to Georgia and set up this institute in the in 1927 there. He then had a slightly unfortunate ending. He was executed by Stalin for being an enemy of the people. But he also had fallen in love with the girlfriend of the chief of the secret police and joined Stalin.

So, anyway, Darrell, therefore, fled Georgia at this point. This is better than Peaky Blinders. Please commission this for 9 o'clock Sunday night. You've got to direct this. Yeah, I'm taking copious notes. The phage research did carry on. So they carried on working on different phages for all sorts of things in Georgia and in Russia.

And actually, in the heyday, they were producing... So in the 60s and 70s, they were producing tons, a couple of tons of phages were produced every year in Georgia and disseminated throughout the whole of the USSR for skin disorders, intestinal disorders, and all sorts of other bacterial diseases, both of humans and animals. So they were used a lot in those places. And also in the Pasteur Institute, they carried on using phages until about the 70s. So they have got this long history of use in certain places. But I think this is part of... So we've talked about all your questions. Why didn't phages take on?

They have this complicated backstory. And then antibiotics just seem so much simpler. You have one compound. You can purify your antibiotics. So you've got one thing. You can make it easy to produce. You can make a standard dose response so that you can check exactly how they kill bacteria.

They're less specific. So they're easier. All the logistics of making them and using them seemed easier. So at that point, most research on therapeutics and phages in apart from these pockets i've mentioned that the therapeutic angle more or less stopped and people used antibiotics it would just seem as unnecessary and and but the problem from a physician's perspective is that you have to know precisely what it is that you're able to treat because strain the bug and the strain of the bug it's very and you can have lots of strains of any one bug,

whereas an antibiotic will kill all the strains of that bug, plus some other bugs if you're lucky. And you take it as a tablet. It's very easy, synthesised. So it's much easier and cheaper to use antibiotics. So I'm rather excited about phage. But, I mean, I imagine drinking cocktails of phage oh what E. coli have I got in my gut today right I'm going to need a phage for each of those

different strains. What the Georgians do the way they use phages is they have very complicated mixtures so they'll have about they'll have a mixture of phages that treat skin diseases and in that mixture there'll be viruses that target the six different main bacteria that live on skin, and then within that they'll endlessly be looking for new viruses, so they'll find the most effective ones within that, so they'll have six viruses for each of the six bacteria, so they have these very, very complicated soups that they give people.

So if you go to Georgia and you go to the pharmacies there that are linked with this institute, you see people snaking around the corner, and they're all getting their general, essentially like their general antibiotic. But from a regulatory standpoint, in the West, it's very complicated and expensive to manufacture. And, of course, resistance happens as well. So the phage are not immune to the mutational changes, are they, and escape of the bacteria.

But if you can get... I prefer cocktail to soup. If you can get the right cocktail... Who does it? Depends on the time of day. Depends on this, yes. Cocktail, then soup, then your main course, dinner, brandy, home. Well, there we are. I prefer the cocktail. And if you can get the right cocktail, it could be very useful.

But there are other approaches too. If you're looking at gut disorders, there are people developing probiotics and things like that that are beginning to look quite hopeful at kind of outgrowing the pathogenic, the ill health bugs in your gut and things. You mentioned that, by the way, you said that they search for new phages. So how would you, because it's a mystery,

so how would you go about finding a disease that attacks a bacteria? Where do you find these things? So phage biologists hang around in fairly unsavoury environments. To find, wherever you find bacterial high numbers you will find viruses associated with it so as i say all viruses bacteria have got their own sets of viruses or phages um so a very good source and many uh therapeutic phages come from sewage so we can so did you did you know this before you chose this line of work no i used to study ocean bacteria.

Sampling was so much nicer. No, it's basically sewage and sputum. Well, I mean, there are sewage pipes at the beach. You could combine both of those things. But funnily enough, I have done. Which beach is it? No, don't answer. If you see her surfing, walk away from the top.

Walk away from the top. Walk away from the top. Most British beaches are pretty good for phages. They really are. And actually, that was one of my breakthroughs, my Clostridium work. So I spent about two years, when I started my own research group about ten years ago, I thought, right, I'll try to find new viruses that target Clostridium difficile,

because there was only two in the literature, and I just sort of had that arrogance of, you know, new position. No-one else has done it right. I will find viruses. So I screened patient diarrhoea samples for two years. It was really unpleasant. Hundreds of samples. Not a virus in sight. So then I went back... What was your favourite sample?

Oh, yeah, I trained my research technician. That's abuse. That's technically abuse. He was my favourite. This is the conversation of the party, isn't it? Yeah, yeah. What was your favourite? Yes, bring your own. And we do mean booze, we don't mean anything else. Yeah, it was not good sampling.

So then I went back to the marine environment where I'd sampled a lot before. And because you find Clostridium difficile, you can find it in the environment. You can find it in rivers and in soils and estuaries. So we think of it as being a gut, bad pathogenic bacteria, but it also lives in the wild. When I went into the wild, that's where I could find my viruses. So by actually going into a sort of more natural state where you have viruses and bacteria interacting,

I was able to isolate lots of viruses from that environment. Sally, how do we search for new antibiotics is it entirely synthetic now or do we still look in in the wild for them? No we look in the wild there's been some really nice research recently looking at how to culture soil to find different bacteria from the ones we've found before and that's looking quite helpful we found a big carrot shaped one and i was at a very exciting presentation of a research group in germany that is looking at insects because insects of course survive against bacteria and they have innate antibacterials and they're finding really interesting compounds and once you them, you can work out what they are, you can then look at their efficacy, and then you can synthesise them.

So we often look in nature, or generally look in nature, and then you can start to synthesise anything you're interested in. So there are different approaches now. But it's proving awfully difficult. Because you read that little research spend is directed in this area, certainly compared to cancer, for example. And the way you've described a possible future is that it seems that maybe there should be more research activity in this area. Would that be it? If we don't find new antibiotics, we will see the end of modern medicine. So cancer comes in here.

If you have cancer, your immune system's not working well. But, you know, we use antibiotics to cover most modern medicine. Yeah. Replacement hips, cesarean sections. You can replace hips with antibiotics. Don't they just crumble? They're quite small. To prevent infections after the operation, yes. So they're a critical part of virtually every medical procedure.

And the world thought we'd got antibiotics, we'd cracked it. There was a surgeon general a few decades ago in the early 80s who said, we can close the book on infections. And this lack of recognition that mutations would keep going. So we had to keep the pipeline going. We lost a lot of the research in universities. You are very special for what you do, Martha, and we need to rebuild that.

And the drug companies stopped investing, in part because they didn't think we needed it and in part because, actually actually we pay peanuts for antibiotics, so they didn't see a nice healthy profit in it. So yes, we don't spend enough, we don't train enough people, we really have to start from the beginning. If you're working at full capacity, if you've got all of the funding that you needed and were able in the shortest possible time to set up what you needed to do that what is the sort of the the time the the time period between uh between strains becoming resistant and finding an alternative so in other words you know if if your if your phages become um become useless because they have been they've been worked around by the bacteria.

What do you think the average cycle is? How long is the lead time before you can find something that replaces it? In general, there's a 10 to 15 at least year from finding something to it being used as a product. One of the nice things about phages is that you don't necessarily have to start right from the very beginning again because phages and bacteria are instantly fighting each other so the phage will find a way

to kill the bacteria and the bacteria become resistant and that phage, you can then just keep growing them together and that phage will then get around it. Or you can go back into the environment and find a phage that's already got around it. So you don't necessarily have to start right from that very beginning again. There was a lovely moment today where every now and again

Brian will see a statistic and he will just question it. And there was a statistic I think we got from you and Brian went, I don't believe that. And he gets out his pocket calculator, or Jim Al-Khalili as we call him. And the statistic was, it was brilliant, that if you put all the phages end to end, which I presume would be a tricky manoeuvre anyway, but it would be 200 million light years?

Is that right? Yes, that's right. There's an estimated 10 to the 31 bacteria phages on Earth. So it's very hard to imagine this number of... No, I didn't believe it, because it sounds ridiculous, doesn't it? If you got all the phages on Earth now and lined them up, it would be 200 million light years long. I thought, that's nonsense.

And that would make it even harder to find the right one. Yeah. But I did a little calculation. Yeah, it seems right, which is quite astonishing. Oh, well, if Brian says so, then that's fine. No, no, because it says so, then that's fine. It just sounds... Chapeau. My big question to you about the phages and antibiotics,

phages versus antibiotics, is if you get to a point where phages are available to the general population to take for much of the same reasons that we would take antibiotics, will we be able to have alcohol with them? the same reasons that we would take antibiotics, will we be able to have alcohol with them? APPLAUSE And... Everybody wants to know.

We don't care about resistance, but why can't I have the chardonnay for 12? No, I'm afraid alcohol will kill most vagers. Oh, my God. What a sad ending to the show. So we asked the audience question as well, and we always find out what they think. This is... Today we asked them,

if you are feeling a bit under the weather, what is your favourite remedy? And they include the complete box set of Wonders Of The Universe. Especially... Brian, well done for getting this in. Especially the one where Brian plays with the sand. Not near that beach again.

Have you got that? Jim Alka-Seltzer. That's what he says. I usually undo some buttons. Most of my feelings of creeping malaise are caused by trying to force myself into clothes I'm too some buttons. Most of my feelings of creeping malaise are caused by trying to force myself into clothes I'm too fat for. What have you got there, Chris? I've got...

From Katie McDonagh, I've got... I just get on with it. I'm a woman. A certain 90s pop synth band, because then things can only get better. Thank you, Joanna. There it is. It goes on to say, biology, when it goes wrong, only ends life. Oh, I remind myself, it is biology causing the problem, not physics. Biology, when it goes wrong, only ends life.

Physics, when it goes wrong, could be the end of the universe. Yes. Oh, that was a great... Yes! Yes! There was a microbiologist. Yeah, that's nailed, Brian. Physics doesn't... He's dastardly killing physics. Physics can't go wrong, though, can it?

It's the study of the laws of nature. How can the laws of nature go wrong? They are the laws of nature. Somebody's got an idea for the next episode. It's like falling off a roof and blaming gravity. Ridiculous. That's fair enough.

I constantly say damn you Newton when things fall on the floor. Do you? Yeah. It's illogical. It's nonsense. Well, of course it is. But that's how jokes work, Brian. Is it? See, if we go over an hour on a recording, Brian's empathy and sentient circuit start to go and he no longer can manage to pass the test

that makes you believe he would help people. Oh, no, the robotic side is coming out. Physics is kind. Physics is good. Humans are messy. Well, thank you very much. Thank you to our panel, Dame Sally Davis, Chris Addison and Martha Clokey. Next week, you'll have to listen to the show in your bedroom, very loudly, with your dad downstairs saying,

will you turn that science down? Because we are doing a show all about the teenage brain and we're going to ask what it is, why it is, why Morrissey still has one. Oh, why won't people leave me alone? Just want to stay in bed. Another niche impression. Niche impressions. Always the niche impressions.

Always the niche. Anyway, thank you very much. I'm Robin Ince. And I'm Brian Cunst. That's what... They'll never know. They'll never know he left early. Thank you very much for listening.

Bye-bye. APPLAUSE No, they'll never know he left early. Thanks very much for listening. Bye-bye. In the Infinite Monkey Cage. Without you shouting. In the Infinite Monkey Cage. Turned out nice again. Well, Adam Rutherford, that was a marvellous episode of The Infinite Monkey Cage, wasn't it? It was, Hannah Fry.

Not necessarily the best ones, because I think the best ones are the ones that you were on. I like the ones that you were on. Yes, but if you enjoyed those episodes of The Infinite Monkey Cage that I, Adam Rutherford, and you, Hannah Fry, were on, it turns out... Hello. ..that we've got a whole eight series worth of just us.

Yes, we do. The Curious Cases of Rutherford and Fry, our very own science podcast in which we investigate your questions. Questions like, does Kate Bush have a secret sonic weapon that she's trying to use to kill all of humanity? We did answer that question. What about, what would happen to Hannah if we threw her into a black hole? a secret sonic weapon that she's trying to use to kill all of humanity? We did answer that question.

What about what would happen to Hannah if we threw her into a black hole? Specifically me. I wasn't particularly happy about that episode. That's The Curious Cases of Rutherford and Fry, which you can download from... Your podcast providers. In our new podcast, Nature Answers, rural stories from a changing planet,

we are traveling with you to Uganda and Ghana to meet the people on the front lines of climate change. We will share stories of how they are thriving using lessons learned from nature. And good news, it is working. Learn more by listening to Nature Answers wherever you get your podcasts. you