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Chapter 1: What is antibiotic resistance and why is it a growing concern?
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Autoliitto auttaa. Mökillä, tien päällä, lofoteilla. Autoliitto auttaa. Jäätölö sulaa. Nuolaisen ennen kuin tipahtaa. Jos mutkia matkassa, Autoliitto auttaa. Missä ja milloin vain.
Liity plus jäseneksi autoliitto.fi Tapahtuipa kerran, että pessimisti, optimisti ja saletisti grillasivat. Ja niinhän siinä kävi, että saletisti onnistui.
Saletisti onnistuu
What does snow leopard poo have to do with the biggest challenge facing modern medicine? According to some scientists, we're about to meet potentially quite a lot. The connection is our ability to harness the tiniest, most plentiful, almost living things on the planet, bacteriophages. Before we go back to the zoo, I think we need a little more on these tiny phages. What are they?
Well, they're viruses. And if I were to look at some with an electron microscope, I'd see a curious menagerie of structures. Imagine the six legs of an insect with something a bit like a bolt screwed on the top of it. Or angular squids. These are bacteria killers.
The word phage means to eat or consume in Greek, and bacteriophages are picky predators, infecting and attacking specific strains of bacteria, often unpleasant bacteria like E. coli or MRSA. You can think of them as our enemy's enemy, the friendly viruses.
They have the potential to be our superpower in the battle being fought in every hospital in every country on earth against antibiotic-resistant bacterial infections. There is nothing else that's scalable. We need antibiotics for everything we do in medicine. So it's a problem that desperately needs to be addressed before we're just returned to the dark ages.
We've known about phages for more than 100 years, yet there are no licensed products available in the UK. There is, however, a buzz about phages right now. Only last year, the UK Health Security Agency said, phage therapy truly has the potential to transform the way we treat bacterial infections. So what's stopping us? How close are we to using phages?
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Chapter 2: What are bacteriophages and how do they work?
Can you point them out to me? Yeah, of course. So over on the right here, we've got Kira, who's our younger one. And then on the left-hand side here, we've got Josie Mum, who is 17. They are a pretty pair. Thank you. All right, we're heading into the giraffe enclosure. Man with a bucket. Oh, bucket of poop. We have got a range in here, I believe.
We've got a bit of Kira and a bit of Josie, because there are some smaller and larger ones in here. Martha, bacteriophages are everywhere, but why is there particular diversity interest in poo? Most of the abundance of our guts and the guts of animals is bacteria. What most people don't know is that those bacteria are being manipulated by bacteriophages. in different animals.
The phages and bacteria have evolved with time. They've gone over their own sort of micro battles, as it were. So we can specifically see if there are phages associated with different animals that have got good features that might be useful for us in different ways. So phages are everywhere, but particularly wherever the bacteria they attack are found.
Sewage water has proven a good source, but so are all animals' gut microbiomes. And Martha and her team say no one has systematically phage hunted from zoo animal poo. So these are unexplored territories, which is a more romantic way to describe a couple of olive-sized giraffe poos in my sample pot. ready for testing in the lab at Leicester University.
My name is Faisal Patel. I work as the biobank lead, helping organise and obtain as many phages as possible using the collection of poo that we've got in-house.
As a special treat, the team have allowed me to put on lab coat and gloves and I'm going to process some poo.
On the white rack to your left, correct, there's some liquid there. You're going to open that tube. You're going to aim for 20 mil.
And now if you just get another wooden spatula and mash up basically, you're just going to... You can see lots of bits of grass that it's been eating. I'm so pleased this is a vegetarian animal.
So that will go, we call it the ferris wheel of poo. So we're going to take it onto there and tomorrow we'll spin it down and actually start processing and testing it tomorrow.
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Chapter 3: Why is there renewed interest in phage therapy?
Yes, big stomach and always hurting. Eating anything, it's just hurting every time, all the time. So you're in the middle of the treatment? Yes, and I already feel it much better. I just told her it's the first time for years that I'm hungry.
Oh, wow.
Because I didn't know what it means anymore. How does that feel? I'm normal. Really thankful. I'm not saying this place is a cure-all, but the research that has been published on phage therapies here supports Anya's testimony. Phage therapy can have remarkable consequences, and yet the rest of the world had abandoned these viruses mid-century in favour of antibiotics. Or so I thought.
Back to my early morning train ride. I know that Paris played a part in Eliava's story. Now, we are currently gliding through the outskirts of this great city, and when I get there, the first place I'm heading for is somewhere where Eliava worked and discovered phages, to see if I can find out more. Where are we going? Right here. I'm at the world-famous Pasteur Institute in Paris.
Yes, that's Louis Pasteur of pasteurisation fame. This was the place for phage research, and it still is a hub, which is why Professor Laurent de Barbier is showing me around a refrigerated lab. Yeah, I nearly took my coat off and then thought, no. Can I just get you to describe the smell in here, Laurent?
Well, it doesn't smell anything for me.
LAUGHTER
I mean, what it's meaning is the medium that we use for growing bacteria.
So Laurent has got a big plastic box off the top shelf and in it are hundreds of little glass vials.
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Chapter 4: How are scientists collecting bacteriophages from animal waste?
Back in 2019, I was lucky enough to travel to Tbilisi in Georgia, and I went to the Eliyava Institute, named after George Eliyava. He first worked with phages here, though, right?
Yes, he was at Institut Pasteur in the 1920s, like many Russian microbiologists, actually, who had their training here in Paris. Derelle has already discovered phage. And Derelle, this is the other crucial thing, has already started experimenting with phage therapy.
And Ilyava actually meets Derelle here in Paris and later on actually invites him over to visit and help him set up the kind of major phage production facilities in Georgia.
As clinical trials developed, antibiotics produced more impressive results. But fringe phage therapies persisted. Klaas shows me a graph from Pasteur Records showing a steady stream of cases from the 1950s right through to the 90s of phage medicines produced for French citizens fighting particularly nasty bacterial infections.
They did it on a no-cost basis. They were just charging the hospital for as much as it cost the technician to produce the phage. The Pasteur Institute experienced a financial crisis like many other scientific and public health institutes in the 1990s, and as a result, the therapy service gets cut.
For just a few years, the phage pipeline in France dried up, which, as Laurent de Barbier explains to me, meant that all the regulation to start using them again needed to start from the beginning.
There was probably a delay of maybe 10 years, maximum 20 years, between the time where we drop it and the time where we realised maybe we need it.
It feels like... phage therapy is always happening soon but not now and it's been soon but not now for a while how soon
How soon? Well, it's never soon enough for the patients. I understand that. I've been in contact with some of them. They are always in a situation that is, I would say, desperate. When you read this letter that you received, could you help me on the treatment?
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Chapter 5: What challenges do phage therapies face in clinical settings?
They test if phages can actually affect the strains that patients have and then they go on and use them. But what we're hoping to do is actually ask questions like, How do we make sure that those phages don't immediately drive resistance like antimicrobial resistance? How can we learn from those mistakes of the past?
With these big standardised collections, we can make sure by the time we get to do the clinical trials that are really needed to make phages mainstream, we're going to use phages that have got the highest chance of actually working. OK. What about synthetic phages? Are there extra safety issues there if we're genetically engineering them? Well, there are. And I think...
We're of the strong opinion, yes, it's going to be great to engineer phages. Andy's brilliant at engineering phages. He's got a big team of people doing it. But the thing is, again, you need to know what you're engineering. Okay, so Andy, you see with the ecosystem developing, it's going to be natural phages first and then synthetic phages as a later stage?
Yeah, I think so. I think it's going to be really important that we understand the biology of the huge diversity of phages that are natural phages to start with. So there's a lot of fundamental biology to come, I think, first. and then build upon that for the engineered phages.
Yeah, I mean, nature's been doing this for 3.9 billion years. I always think it's funny that humans think we can come along, we can do it better. It's a great comfort to know that as the powers of antibiotics wane, that harmful bacteria can, just like us, get a viral infection. And that harnessing the power of those useful viruses is nothing new.
What is new is a suite of tools, fast genetic sequencing and artificial intelligence algorithms to help us match the best cocktail of phages to fight the infection. Human trials that fit our stringent modern safety standards are just starting in the UK. And who knows, maybe in a decade, every pharmacy will have a phage fridge full of friendly viruses ready to help sick patients.
Let's party!
Let's party!
Seuraavaksi potilas 2934.
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