Antibiotics

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Speaker 8 This is the BBC.

Speaker 4 Hello, I'm Robin Ace. And I'm Brian Cox.

Speaker 9 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, wonderful, woof.

Speaker 9 Now, medicine has moved on.

Speaker 9 Medicine has moved on a lot in the last hundred years.

Speaker 9 The best cure for being ill used to be leeches, cutting, and newt spit, in which we really mean the best cure for being ill was to kill you, because then you didn't have flu anymore.

Speaker 9 You were merely dead.

Speaker 10 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.

Speaker 11 At least you were alive.

Speaker 10 Sorry, there's going to be letters, aren't there?

Speaker 4 Well,

Speaker 9 this water's already been telling me you've been very bad. Oh, it's got a horrible memory.

Speaker 9 Today, we'll be talking about medicine that works, in fact, a medicine without which many of us would not be alive today: antibiotics.

Speaker 10 How do antibiotics work? What are the consequences of their overuse? And what can we do to fight bacterial infections in the future?

Speaker 9 To prolong our painful existence and postpone our inevitable demise, we have a panel of distinguished guests, and they are.

Speaker 8 Well, I'm Dame Sally Davis. I'm the chief medical officer for the UK.

Speaker 8 So I'm concerned with the health of every one of you in this room and the nation. I advise the government.

Speaker 8 And I'm particularly concerned about the increase of infections that don't respond to the treatments.

Speaker 12 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.

Speaker 12 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.

Speaker 12 It's not a particularly sexy bug, but it's the major cause of infectious diarrhea in the Western world. But in terms of working with it, it has a particular smell of horse urine.

Speaker 12 It's like when you actually find it, you know that you've got it in the lab.

Speaker 12 And when you look at the colonies on a plate, they are a particular chautreuse colour. So it's being pragmatic.

Speaker 12 It's not a good bug to get, but it's you can work with it.

Speaker 10 Sick green, if you

Speaker 10 think it is right.

Speaker 11 There you are.

Speaker 11 I'm uh Chris Addison. Uh I'm uh an actor and comedian and director, and I love being introduced lower down the bill than diarrhoea and urea.

Speaker 7 Find my rightful place at last.

Speaker 11 And the the disease that interests me most uh is uh is Kuru,

Speaker 11 which uh was a disease of the Papua New Guinean people.

Speaker 11 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

Speaker 11 one of the symptoms of kuru is this sort of spasmodic, uncontrollable laughter. It's like the dead riggins' audience.

Speaker 7 And

Speaker 9 there's no explanation for it, but they're laughing anyway.

Speaker 7 So,

Speaker 9 can I just say this is the longest quick introduction of all the guests we've ever had?

Speaker 7 It's meant to be, hello, my name's Dr. Va.

Speaker 9 I am from the University of Rotherham and my favourite disease is. But in a sense, it's just broken out.
I'm enjoying it. I mean, it's certainly more avant-garde than the previous version.

Speaker 7 It's not live.

Speaker 11 That's the main thing, because we'd be crashing the shipping forecast by now.

Speaker 11 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.

Speaker 7 Yeah.

Speaker 9 your favourite disease.

Speaker 4 It's kuru.

Speaker 11 My favourite disease, my favourite disease, which is an extraordinary way of putting it, is kuru, the laughing sickness, which was caused by cannibalismumum. Cannibalismum?

Speaker 11 That's cannibalizing your mother.

Speaker 9 I thought it was cannibalising the Muppets. Cannibalismum.

Speaker 7 Cannibalism.

Speaker 11 It was caused

Speaker 11 by the religious beliefs of the Papua New Guinean people who believed that eating the departed would help free their souls and they would

Speaker 11 especially give

Speaker 11 the food, as it were, to mothers and children. So it was particularly

Speaker 11 that they eat.

Speaker 12 The prions.

Speaker 7 And this is our panel, and all we have time for today.

Speaker 9 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.

Speaker 9 How do we we define the sexier bacteria?

Speaker 10 Well

Speaker 12 I would say sexier ones are generally more heard of. So everyone knows about MRSA and everyone knows about maybe salmonella E.
coli, but Plostridium is just a sort of just

Speaker 12 people don't sort of think about it as much as they should.

Speaker 8 You could take gonorrhea.

Speaker 7 For what?

Speaker 9 What's that going to cure me of? If you save one of the more maverick homeopaths, don't know how to want to just have the whole gonorrhea. That'll get rid of your headache.

Speaker 1 You'd have something else to think about.

Speaker 8 I just thought it's an interesting one. You want a sexy one.

Speaker 7 It's transmitted through sex.

Speaker 8 It's on the rise. And we now have patients dying across the world because there's no treatment for them.

Speaker 11 It's becoming more.

Speaker 11 You sort of said that like it's an achievement, Sally.

Speaker 8 Well, it is the bug, isn't it?

Speaker 7 Yes, well done, gonorrhea. Full marks of you.

Speaker 10 So, Sally, to start, could you tell us how an antibiotic works?

Speaker 8 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.

Speaker 8 Each antibiotic family works in a different way,

Speaker 8 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

Speaker 8 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.

Speaker 8 So

Speaker 8 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.

Speaker 8 And then it can't duplicate, it can't replicate, have children, and it dies off.

Speaker 10 So they're essentially poisons.

Speaker 8 Absolutely, of many sorts.

Speaker 9 So, Martha, what is the difference between a virus and a bacteria? Why, for instance, antibiotics will only work against bacteria?

Speaker 12 Yes, that's right. Well, a bacteria is a living organism.
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.

Speaker 12 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.

Speaker 12 So a virus is a very simple thing. It just has a genetic code.
Generally, it can have DNA or RNA or both. And then it has a capsid has something to keep it safe from the outside environment.

Speaker 12 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.

Speaker 12 So humans do, dogs do, cats do, and bacteria have their own set.

Speaker 12 And we get very interested in all these viruses that are everywhere that are infecting those bacteria.

Speaker 12 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.

Speaker 12 So when a virus enters a bacteria, it goes in, and about half an hour later, 100 viruses will be released.

Speaker 12 So it goes in and it says to that bacteria, No, you're not a bacteria anymore, you're a viral-making machine.

Speaker 11 Chris,

Speaker 10 we both did a head turnout exactly.

Speaker 9 By the way, well done, everyone.

Speaker 9 That was five minutes of proper Radio 4 programme.

Speaker 7 I didn't think we were going to get there.

Speaker 4 That was all kind of serious, but a little light touch as well. Brilliant.

Speaker 9 Now, Chris,

Speaker 9 your father was a doctor.

Speaker 1 How did it go wrong for you?

Speaker 11 Yeah, my dad was a doctor.

Speaker 11 And so we grew up in a scrupulously clean house. There was a huge amount of attention paid to health and cleanliness.

Speaker 10 That's nonsense.

Speaker 11 There are no doctors like that. I've never met anybody filthier than doctors in general.

Speaker 11 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.

Speaker 11 And not in hospitals so much as in their own socks

Speaker 11 and other accoutrements. Yeah, my dad was a doctor.

Speaker 9 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.

Speaker 11 Well, they don't live in squalor, but

Speaker 11 equally, doctors, there are no more cavalier people about health than doctors in my experience.

Speaker 11 They're the worst at going to doctors themselves.

Speaker 11 And usually it's, I've broken my leg, really? Well, have an aspirin and lie down for a while.

Speaker 11 That's generally what you get off a parental doctor.

Speaker 10 So they're 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

Speaker 10 got them, but you're

Speaker 7 just

Speaker 11 I think they just go, well, we're all screwed, aren't we?

Speaker 11 We might as well just eat that toast that's been on the floor the last three days.

Speaker 10 We're fighting a losing battle. Sally, we're going to talk primarily about antibiotics today and what we can do to make them more effective.

Speaker 10 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

Speaker 10 1930s, 40s, and 50s?

Speaker 8 Definitely, the first half of last century and before. More people died of infection in the

Speaker 8 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.

Speaker 8 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.

Speaker 8 And she was about to die when they tried it, and you know, six days later, she walked out a pretty little girl again. So it's absolutely changed the picture of disease.

Speaker 8 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 ten million people a year dying of drug-resistant infections.

Speaker 8 That's more than die of cancer at the moment around the world, significantly more.

Speaker 8 We know that it'll take an extra twenty-eight 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.

Speaker 8 So people will die younger. It it is a ver 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.

Speaker 10 So so it's really possible. possible that in our lifetimes that that fear of a scratch that would have been present in nineteen hundred eighteen fifty may return.

Speaker 10 So countries like the not we're not just talking about you know uh less developed countries here, we're talking about countries like the UK and the USA, Western Europe, that that fear could return.

Speaker 8 It could. After all, we know that probably about five thousand people die each year in England of drug-resistant infections already.

Speaker 8 We know that sixty thousand 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.

Speaker 10 Why?

Speaker 8 Why? Well, it is a natural response of the genetic code

Speaker 8 of those bacteria that when they meet antibiotics, if they mutate and find that they have a survival advantage, they will.

Speaker 8 And then they pass that genetic mutation not only to their children, but they have very clever ways of passing it horizontally.

Speaker 8 So you can pass the advantageous mutation, which protects you against an antibiotic, to your brothers, sisters, cousins, uncles, aunts, and they can then pass it down to all their progeny.

Speaker 8 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.

Speaker 10 And I think historically, Alexander Fleming noticed this problem, didn't he? He mentioned it initially on discovery of penicillin, that overuse and casual prescription may be.

Speaker 8 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.

Speaker 10 It's very moving.

Speaker 9 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.

Speaker 9 And what we're seeing, I mean, I presume, for instance, some people will say that evolution can't be observed.

Speaker 9 You see creationists and intelligent design proponents who say evolution can't be observed.

Speaker 9 And then, when they are very poorly due to drug resistance, you can say, I've got some terrible news for you. And so, one, you're very ill, and two, we've just seen evolution in action.

Speaker 9 I mean, this is absolutely yeah. This is kind of what's what's what is occurring here.

Speaker 12 No, absolutely.

Speaker 12 I mean, bacteria are very good at becoming resistant to anything that you if you if you give a bacteria any compound, any antibiotic, any pressure, it'll it'll find a way to grow without it.

Speaker 12 It'll just get around it. They're very, very good at evolving.

Speaker 12 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,

Speaker 12 certainly, antibiotics haven't been used in a careful way to minimise resistance.

Speaker 9 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 do you, 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

Speaker 9 a healthy level of scepticism about us being able to understand

Speaker 9 the nature of human beings, the nature of the medical world?

Speaker 11 Well, I think my dad was always very,

Speaker 11 like a lot of doctors and medical professionals, he's very rude about the medical profession and its place in science. In that he goes, listen,

Speaker 11 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.

Speaker 11 And that's the most interesting part to me was that 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 their right answer will ping out the other end.

Speaker 11 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.

Speaker 11 That worked, let's just, we'll put that in the book then.

Speaker 11 And because of that, you come up feeling, oh, there's no system.

Speaker 11 That doesn't exist.

Speaker 7 It isn't digital, it's analog.

Speaker 8 It's your father's Well, he is

Speaker 7 he is still he is still with us, I'm pleased to say, as of the beginning of this recording.

Speaker 7 So

Speaker 7 his name won't change yet.

Speaker 7 Unfortunately,

Speaker 7 the antibiotics he's been taking haven't really been working out.

Speaker 11 But he was always very equally about antibiotics, he was always very, don't just go and get the antibiotics.

Speaker 11 That's not a good, it's not a good solution for you, and it's not a good solution for everyone in general.

Speaker 10 Well, and 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

Speaker 10 a problem, isn't it? One of the central problems, actually, that we want this drug because we think it cures everything.

Speaker 8 Yes. Far too many people

Speaker 8 think that if they have an infection of any sort, they need antibiotics.

Speaker 8 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.

Speaker 8 So, we've been trying all sorts of behavioral things, like in the northwest, they did a lovely study where they used prescription pads, which started with you do have an infection, you are ill,

Speaker 8 but actually, you don't need an antibiotic. And then it described what was going on and how long it was likely to last.

Speaker 8 Go home and you know, 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.

Speaker 11 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,

Speaker 11 and because I've heard that it does the job, and so any attempt by you to sway me or to

Speaker 11 to tell me that there is a a better option available to me is some nefarious plot by you or the deep state, or I, you know, there's something about

Speaker 11 a suspicion of doctorial authority now that people have that I think marries into the need to get your, you know, get the thing that you want.

Speaker 8 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,

Speaker 8 saying, Look after us, or we won't be here when you need us.

Speaker 11 Oh, because I I thought that was a fever dream.

Speaker 9 The Californian raisins have let themselves go.

Speaker 11 I feel so much better, ironically, without antibiotics. This has really worked for me.

Speaker 7 Thank you.

Speaker 10 So,

Speaker 10 your research

Speaker 10 is based. Well, you're looking at a potential alternative for the standard antibiotics, as you mentioned, which is phages.
So, could you describe what that possibility is?

Speaker 12 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.

Speaker 12 An antibiotic is something generally they've come from, they're made by bacteria or fungi, and they're part of bacterial-bacterial warfare.

Speaker 12 So, if you go into, you can take Permian soil, defrost it, and you can find antibiotic resistance tens of thousands of years ago.

Speaker 12 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 used these defenses.

Speaker 12 So, that is one natural enemy of bacteria, which is other bacteria and fungi. But another natural enemy of bacteria are the viruses.

Speaker 12 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.

Speaker 12 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.

Speaker 12 So, the fact is,

Speaker 12 nature's already done it. So, ever since the 3.9 billion years that bacteria have existed, they've had their own viral enemies.

Speaker 12 So, by studying these, we can find new whole sets of new tools on the way these viruses target and kill their bacteria.

Speaker 9 Well, this has got-I mean, I was reading the Bacteria News Weekly thing, and there's an incredible, incredible story, though, that this is this idea is older than antibiotics.

Speaker 7 Absolutely.

Speaker 9 And why was it antibiotics became that this is what can be, and phages, it's been a long time of kind of just being left in a lot of medical culture.

Speaker 12 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.

Speaker 7 How many people came to the party?

Speaker 7 Not very many. Oh no, we've all got diarrhea.

Speaker 7 Who mixed this punch? Sorry. It wasn't sexy punch at all.

Speaker 7 Sorry. It's a surprising number.

Speaker 12 We had around 300 or more people at the Pastor Institute, I think 400 people.

Speaker 12 But actually,

Speaker 12 they were discovered 101 years ago by a French Canadian. But actually, an Englishman discovered them two years independently before that, but in a sort of typical English style.

Speaker 12 He wrote it up beautifully in the Lancet, but

Speaker 12 he didn't have enough funding to continue with his research.

Speaker 12 So he wrote a very nice thing saying,

Speaker 12 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

Speaker 12 meanwhile, this French Canadian, Félix Durrell, he discovered them independently in the Pasteur Institute.

Speaker 12 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.
In 1919, he did his first clinical trial.

Speaker 12 So he immediately developed them. He looked at salmonella in chickens.
And then he did a study quite early on looking at Shigella, diarrhea, factor diarrhea, infection in children.

Speaker 12 And he showed that the viruses 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.

Speaker 12 But then he trained a young Georgian scientist. So often people think about phages and they think something that happened vaguely East, vaguely Russia, Georgia.

Speaker 12 And that was because there was a young Georgian that chained trained in the Plastor Institute. And he was called George Elijah.

Speaker 12 And he went back to Georgia and set up this institute in the uh in 1927 there. He then had a slightly unfortunate ending.

Speaker 12 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

Speaker 12 to Stalin. So, anyway, he, so Durrell, therefore, fled Georgia at this point.

Speaker 7 This is better than Peaky Blinders. This is.

Speaker 9 Please commission this when I'm not.

Speaker 7 You've got to be on late nights.

Speaker 7 You've got to direct this, yes. Yeah, I'm taking copious notes.

Speaker 12 But phage research

Speaker 12 did carry on. So they carried on working on different phages for all sorts of things in Georgia and in Russia.
And actually, until in the heyday, they were producers.

Speaker 12 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,

Speaker 12 intestinal disorders, on all sorts of other bacterial diseases, both of humans and animals.

Speaker 12 So they were used a lot in those places. And also in the Pasteur Institute, they carried on using phages until about the 70s.

Speaker 12 So they have got this long history of use in certain places. But I think this is part of so we've talked about

Speaker 12 so all your question to why didn't phages take on take on? They have this complicated backstory. And then antibiotics just seem so much simpler.

Speaker 12 You have you have one compound,

Speaker 12 or you can purify your antibiotics, so you've got one thing, you can make it in a it's easy to produce, you can make a standard dosed responses so you can check exactly how they kill bacteria.

Speaker 12 They're less specific. So they're easy to sort of all the logistics of making them and easy in and using them seemed easier.

Speaker 12 So at that point, most research on therapeutics and phages, apart from these pockets I've mentioned, the therapeutic angle more or less stopped, and people used antibiotics.

Speaker 12 They were just seen as unnecessary.

Speaker 10 And but the problem from a

Speaker 10 physician's perspective is that you have to know precisely what it is that you're aiming to treat.

Speaker 8 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.

Speaker 8 So, and you take it as a tablet, it's very easy, synthesized. So, it's much easier and cheaper to use antibiotics.
So, I'm rather excited about phage.

Speaker 8 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.

Speaker 12 What the Georgians do, the way they use phages, is they have very complicated mixtures. So, they'll have about

Speaker 12 a mixture of 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.

Speaker 12 And then within that, they'll endlessly be looking for new viruses, so they'll find that the most effective ones within that. So they'll have six viruses for each of the six bacteria.

Speaker 12 So they have these very, very complicated soups that they give people.

Speaker 12 So if you go to Georgia and you go to the pharmacies there that are linked with the with this institute, you see people snaking around the the corner, and they're all getting their general they're just essentially like their general antibiotic.

Speaker 12 But from a regulatory standpoint in the West, it's very complicated and expensive to manufacture.

Speaker 7 Of course, because

Speaker 8 it 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.

Speaker 7 If you can get the right cocktail. Who does it?

Speaker 10 Depends on the time of day.

Speaker 7 Depends on this, yes. Cocktail, then soup, then your main course, dinner, brandy, home.

Speaker 8 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.

Speaker 8 If you're looking at gut disorders, there are people developing probiotics and things like that, that are beginning to look quite hopeful at

Speaker 8 kind of outgrowing the pathogenic, the ill-health bugs in your gut and things.

Speaker 10 Yeah, you mentioned that, by the way, you said that they search for new phages. So, how would you, because it's a a mystery to how would you go about finding a disease that attacks a bacteria?

Speaker 10 Where do you find these things?

Speaker 12 So, phage biologists hang around in fairly unsavoury environments

Speaker 12 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.

Speaker 12 So, a very good source, and many therapeutic phages come from sewage.

Speaker 7 So, body, we're going to say that.

Speaker 11 Did you know this before you chose this line of work?

Speaker 12 No, I used to study ocean bacteria. Sampling was so much nicer.

Speaker 12 It's basically sewage and sputum.

Speaker 11 I mean, there are sewage pipes at the beach.

Speaker 7 You could combine both of those things.

Speaker 10 But funnily enough, I have done.

Speaker 7 She's a particular dungeon.

Speaker 7 If you see her surfing, walk away from the top.

Speaker 7 Way from the top.

Speaker 11 Most British beaches are pretty good for phages. Well,

Speaker 12 they really are. And actually, that was one of my breakthroughs of my Clostridian work.
So I spent about two years when I started my own research group about 10 years ago.

Speaker 12 I thought, right, I'll try to find new viruses that target Clostridium difficile, because there were only two in the literature. And I just sort of had that arrogance of a

Speaker 12 new position.

Speaker 12 No one else has done it right. I will find viruses.
So I screened patient diarrheal samples for two years. It was really unpleasant.
Hundreds of samples. Not a virus in sight.

Speaker 12 So then I went back.

Speaker 7 What was your favourite sample?

Speaker 10 Oh,

Speaker 10 yeah.

Speaker 12 I trained my research technician.

Speaker 7 Well, that's abuse. That's technically abuse.

Speaker 7 This is the

Speaker 9 conversation of the party, isn't it?

Speaker 7 Yes, bring your own. And we do mean booze, we don't mean anything else.

Speaker 12 Yeah, it was not good sampling. So then I went back to the marine environment where I'd sampled a lot before.

Speaker 12 And I, and I, and because you find Clostridium difficile, just you can find it in the environment. You can find it in rivers and in soils and estuaries.

Speaker 12 So we think of it as being a gut, bad, pathogenic bacteria, but it also lives in the wild. When I went into into the wild, I could that's where I could find my viruses.

Speaker 12 So by actually going into 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.

Speaker 10 Sally, how do we um search for new antibiotics? I is it entirely synthetic now, or do we still look in in in the wild for them?

Speaker 8 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.

Speaker 7 They found a big carrot-shaped one and they found a turnip-shaped one.

Speaker 8 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.

Speaker 8 And once you find them, you can work out what they are, you can then look at their efficacy, and then you can synthesize them. So we often look in nature, or generally look in nature,

Speaker 8 and then you can start to synthesize anything you're interested in. So, there are different approaches now, but it's proving awfully difficult.

Speaker 10 Because

Speaker 10 you read that

Speaker 10 little research spend is directed in this area, certainly compared to cancer, for example.

Speaker 10 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 a

Speaker 8 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.

Speaker 8 But, you know, we use antibiotics to cover most modern medicine, replacement hips, cesarean sections.

Speaker 7 You can replace hips with antibiotics.

Speaker 7 Don't they just

Speaker 8 prevent infections after the operation, yes?

Speaker 7 So they're a critical part of virtually every medical procedure.

Speaker 8 And

Speaker 8 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.

Speaker 8 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,

Speaker 8 Martha, and we need to rebuild that.

Speaker 8 And the drug companies stopped investing, in part because didn't think we needed it, and in part because actually we pay peanuts for antibiotics, so they didn't see a nice, healthy profit in it.

Speaker 8 So, yes, we don't spend enough, we don't train enough people, we really have to start from the beginning.

Speaker 11 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 time the time period

Speaker 11 between

Speaker 11 strains becoming resistant and finding an alternative.

Speaker 11 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 by the bacteria, what's the what do you think the average cycle is b you know, in terms how long is the lead time before you can find something that replaces it?

Speaker 12 In in general, there's there's a fairly there's a ten to ten to fifteen at least year from finding something to it being u uh used as a product.

Speaker 12 And one of the nice things about phages is that you don't

Speaker 12 necessarily have to start right from the very beginning again, because phages and bacteria are instantly fighting each other.

Speaker 12 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.

Speaker 12 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.

Speaker 9 Right. This is well, there was a lovely moment today where every now and again Brian will see a statistic and he will just question it.

Speaker 9 And there was a 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

Speaker 9 the statistic was, it was brilliant, that if you put all the phages end-to-end, which I presume would be a tricky maneuver anyway, but it would be 200 million light-years.

Speaker 12 Is that right?

Speaker 12 Yeah,

Speaker 12 yes, that's right. There's

Speaker 12 an estimated 10 to the 31 bacteriophages on Earth. So it's very hard to imagine this number.

Speaker 10 Yeah, no, I people. I didn't believe it because it sounds ridiculous, doesn't it? If you've got all the phages on Earth now and lined them up, it would be 200 million light years long.

Speaker 10 I thought that's nonsense.

Speaker 11 And that would make it even harder to find the right one.

Speaker 10 But if I did a little calculator, yeah,

Speaker 10 it seems right,

Speaker 7 which is quite astonishing number. Well, if Brian says so, then that's fine.

Speaker 7 It just sounds cheap.

Speaker 11 My big question to you about the phages and

Speaker 11 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?

Speaker 7 That is what everybody wants to know.

Speaker 7 We don't care about resistance, but why can't I have the Chardonnay for 12?

Speaker 12 No, I'm afraid alcohol will kill most most pages.

Speaker 9 What a sad ending to the show.

Speaker 9 So we asked the audience a 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 favorite remedy?

Speaker 9 And they include the complete box set of wonders of the universe, especially.

Speaker 9 Brian, well done for getting this in.

Speaker 9 Especially the one where Brian plays with the sand.

Speaker 4 Yes. Not near that beach again.

Speaker 7 Woo.

Speaker 10 Have you got there? Jim Alkiseltzer.

Speaker 7 That's what he says.

Speaker 9 I usually undo some buttons. Most of my feelings of creeping malaise are caused by trying to force myself into clothes I'm too fat for.

Speaker 7 What have you got there, Chris?

Speaker 11 I've got

Speaker 11 from Katie McDonough, I've got, I just get on with it. I'm a woman.

Speaker 9 A certain 90s pop synth band, because then things can only get better.

Speaker 7 Thank you.

Speaker 10 It goes on to say, biology, when it goes wrong, only ends life.

Speaker 9 Oh, I remind myself it is biology causing the problem, not physics.

Speaker 10 Biology, when it goes wrong, only ends life. Physics, when it goes wrong, could be the end of the universe.

Speaker 7 With

Speaker 7 a great yes!

Speaker 9 There was a microbiologist.

Speaker 7 Yeah, that's nailed Brian. Physics Physics doesn't...

Speaker 9 I mean, he's dastardly killing physics.

Speaker 10 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?

Speaker 7 They are the laws of nature. Somebody's going to be able to do it.
I love it for the next episode. Is it what you say?

Speaker 10 It's like falling off a roof and blaming gravity.

Speaker 7 Isn't it? It's just.

Speaker 10 I try to. Ridiculous.
Well, that's fair enough.

Speaker 11 I constantly say, damn you, Newton, when things fall on the floor.

Speaker 10 Do you? Yeah. Well, it's illogical.
It's nonsense. Well, of course it is, but that's how jokes work, Brian.

Speaker 7 Physics?

Speaker 9 See, if we go over an hour on a recording, Brian's empathy and sentient circuits start to go, and he no longer can manage to pass the test that makes you believe he would help people.

Speaker 9 Well, no, the robotic side is coming out. Physics is kind, physics is good.

Speaker 9 Humans are messy.

Speaker 4 Well, thank you very much.

Speaker 9 Thank you to our panel, Dame Sally Davis, Chris Addison, and Martha Klokey.

Speaker 9 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?

Speaker 9 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.

Speaker 7 Oh, why won't people leave me alone?

Speaker 4 I just want to stay in bed.

Speaker 9 Another niche impression, niche impressions. Always the niche impressions.
Always the niche. Anyway, thank you very much.
I'm Robin Inst and I'm Brian Cox.

Speaker 7 That's what

Speaker 9 they'll never know. They'll never know he left early.
Thank you very much for listening. Bye-bye.

Speaker 5 Well, Adam Rutherford, that was a marvellous episode of the Infinite Monkey Cage, wasn't it?

Speaker 16 It was, Hannah Fry.

Speaker 16 Not necessarily the best ones, because I think the best ones are the ones that you were on.

Speaker 5 I like the ones that you were on.

Speaker 15 Yes.

Speaker 13 But if you enjoyed those episodes of The Infinite Monkey Cage that I, Adam Rutherford, and you, Hannah Fry, were on, it turns out

Speaker 16 that we've got a whole eight series worth of just us.

Speaker 15 We do.

Speaker 17 The Curious Cases of Rutherford and Fry,

Speaker 5 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?

Speaker 13 We did answer that question.

Speaker 16 What about what would happen to Hannah if we threw her into a black hole? Specifically me.

Speaker 17 I wasn't particularly happy about that episode.

Speaker 16 That's the curious cases of Rutherford and Fry, which you can download from your podcast providers.

Speaker 14 Hello, I'm Greg Jenner, host of You're Dead to Me, the comedy podcast from the BBC that takes history seriously.

Speaker 14 Each week, I'm joined by a comedian and an expert historian to learn and laugh about the past.

Speaker 14 In our all-new season, we cover unique areas of history that your school lessons may have missed, from getting ready in the Renaissance era to the Kellogg Brothers.

Speaker 14 Listen to You're Dead to Me Now, wherever you get your podcasts.