0:00:04 > 0:00:06For more than 70 years,
0:00:06 > 0:00:08we've waged war against bacterial infections
0:00:08 > 0:00:10using antibiotics.
0:00:12 > 0:00:14But it's a war we're now losing.
0:00:17 > 0:00:19Drug-resistant superbugs...
0:00:21 > 0:00:22..are spreading.
0:00:24 > 0:00:26To find out what we're up against,
0:00:26 > 0:00:29I'm donating my body to an extraordinary experiment.
0:00:32 > 0:00:37We are going to unleash bacterial hell on a clone of my body.
0:00:37 > 0:00:38Woohoo!
0:00:38 > 0:00:42We're hoping this experiment - which is novel and rather spooky -
0:00:42 > 0:00:45will give us a whole new insight into the way that bacteria
0:00:45 > 0:00:47fight back against antibiotics.
0:00:50 > 0:00:54- That is absolutely revolting. - It's fabulous!
0:00:57 > 0:01:01I'll search high and low for radical solutions...
0:01:01 > 0:01:03Die, bacteria, die!
0:01:03 > 0:01:06..to stop the spread of the superbugs.
0:01:07 > 0:01:11When I remove the bandage, we should see quite a difference.
0:01:11 > 0:01:13Oh, yeah!
0:01:13 > 0:01:16Is it too late to prevent antibiotic Armageddon?
0:01:18 > 0:01:21Me and my body are about to find out.
0:01:30 > 0:01:31Hello.
0:01:31 > 0:01:33- Good to see you upright. - Well, it's nice to be upright.
0:01:33 > 0:01:35- Come and have a seat.- Thank you.
0:01:35 > 0:01:36Hi there.
0:01:36 > 0:01:40A month ago, 57-year-old John Shelton was fighting
0:01:40 > 0:01:43for his life against a sudden bacterial infection.
0:01:43 > 0:01:45HE EXHALES LOUDLY
0:01:45 > 0:01:48- Good.- When I arrived here, they opened me up, there was a big mass.
0:01:48 > 0:01:50It was very, very infected,
0:01:50 > 0:01:53and the bacteria were already working their merry havoc,
0:01:53 > 0:01:55trashing my body, shutting down my lungs,
0:01:55 > 0:01:58shutting down my kidneys, shutting down everything, pretty much.
0:01:58 > 0:02:01- You don't remember anything? - Not a thing.
0:02:01 > 0:02:04His lung had almost completely filled up with bacteria,
0:02:04 > 0:02:08or infection, and he wasn't able to oxygenate his blood.
0:02:10 > 0:02:14Bacteria called staph aureus caused the infection.
0:02:14 > 0:02:18They were eventually stopped by a concoction of antibiotics,
0:02:18 > 0:02:20but for a while it was touch and go.
0:02:20 > 0:02:22- HE INHALES AND EXHALES - Brilliant.
0:02:22 > 0:02:25- EMOTIONAL:- When they thought he'd had a brain haemorrhage -
0:02:25 > 0:02:27sorry -
0:02:27 > 0:02:29that was not a great moment.
0:02:29 > 0:02:32You know, just one day at a time, really, and you do place your faith
0:02:32 > 0:02:35in the fact there's going to be another antibiotic to come up.
0:02:35 > 0:02:38It's interesting that, you know, there is a lot of technology here,
0:02:38 > 0:02:40there is obviously a fantastic staff
0:02:40 > 0:02:44but, in the end, it's kind of antibiotics versus bacteria.
0:02:44 > 0:02:46That's it. Simple as that.
0:02:46 > 0:02:48There is no doubt in my mind that, without antibiotics,
0:02:48 > 0:02:49I would not be here.
0:02:54 > 0:02:57Before the 1940s, up to a third of deaths were caused
0:02:57 > 0:02:59by bacterial infection.
0:03:01 > 0:03:03A simple cut could kill you.
0:03:06 > 0:03:09Then came antibiotics - drugs able to kill bacteria.
0:03:11 > 0:03:12The first was penicillin,
0:03:12 > 0:03:15discovered by Alexander Fleming in 1928.
0:03:18 > 0:03:20More followed.
0:03:20 > 0:03:22But then, the pipeline dried up.
0:03:24 > 0:03:26No totally new antibiotics
0:03:26 > 0:03:28have been found for more than 30 years.
0:03:29 > 0:03:32And more and more bacteria are becoming resistant
0:03:32 > 0:03:33to our dwindling stock...
0:03:36 > 0:03:38..including superbugs,
0:03:38 > 0:03:41which threaten to send modern medicine back to the Dark Ages.
0:03:44 > 0:03:48Around 700,000 people die every year because of drug-resistant
0:03:48 > 0:03:50strains of infections like E. coli
0:03:50 > 0:03:54and TB, but that figure could soar to around 10 million a year
0:03:54 > 0:03:57by the middle of this century if urgent action isn't taken.
0:03:59 > 0:04:02Increasing numbers of people are finding that antibiotics are
0:04:02 > 0:04:03no longer working.
0:04:05 > 0:04:06People like Slawa.
0:04:28 > 0:04:31Slawa's foot is so infected with E. coli.
0:04:31 > 0:04:33It could lead to her whole leg being amputated.
0:04:36 > 0:04:39Be warned, this glimpse into a post-antibiotic world
0:04:39 > 0:04:40is gruesome.
0:04:40 > 0:04:42So, if you are squeamish, look away now.
0:04:56 > 0:04:58'If we do nothing,
0:04:58 > 0:05:03'modern medicine in all its finery will become much more hazardous.'
0:05:04 > 0:05:08Cancer therapy, immunotherapy...
0:05:08 > 0:05:11I mean, just simple infections like meningitis.
0:05:11 > 0:05:14All of these things become more hazardous.
0:05:15 > 0:05:19So anti-microbial resistance is the biggest single issue
0:05:19 > 0:05:23which is affecting modern medicine at the moment.
0:05:26 > 0:05:29In 2015, 34 million prescriptions
0:05:29 > 0:05:32were issued for antibiotics in the UK alone.
0:05:35 > 0:05:39Have we created superbugs by popping too many of these pills?
0:05:46 > 0:05:49I want to find out exactly what antibiotics do and why
0:05:49 > 0:05:51bacteria are resisting them.
0:05:54 > 0:05:56Time for an unusual experiment.
0:05:58 > 0:06:03So I have done a lot of strange things in my time,
0:06:03 > 0:06:07and a lot of self experiments, but nothing quite like this.
0:06:11 > 0:06:14Now, I'm in pretty good health and I only take antibiotics
0:06:14 > 0:06:18when I absolutely have to, but I am going to explore what
0:06:18 > 0:06:21a powerful antibiotic does to my body
0:06:21 > 0:06:25by making my bacteria visible.
0:06:25 > 0:06:27If you'd like to know, I have not washed for two days.
0:06:27 > 0:06:28- Great.- All right! Yeah, that's...
0:06:28 > 0:06:30When I start doing these things, I always think,
0:06:30 > 0:06:32"Oh, it sounds like a good idea,"
0:06:32 > 0:06:34and when I actually get there, I start to wonder if it really is.
0:06:34 > 0:06:36THEY LAUGH
0:06:36 > 0:06:39Artist Mellissa Fisher specialises in creating
0:06:39 > 0:06:42living biological sculptures.
0:06:42 > 0:06:44HE LAUGHS
0:06:44 > 0:06:46- Oooh!- Right in between your toes.
0:06:46 > 0:06:48With Professor Mark Clements of Lincoln University,
0:06:48 > 0:06:50she is leading a team to make
0:06:50 > 0:06:53a living bacterial sculpture out of me.
0:06:55 > 0:06:58So, that's the...the right here.
0:06:58 > 0:07:01Step one - collect material from all over my body
0:07:01 > 0:07:03using cotton-wool swabs.
0:07:07 > 0:07:11On the skin, you've got over 1,000 different types of bacteria.
0:07:11 > 0:07:13And each person is unique.
0:07:13 > 0:07:16All different parts of the body will have slightly different
0:07:16 > 0:07:20micro flora, depending on whether it's a moist area,
0:07:20 > 0:07:23whether it's a dry area, oily area...
0:07:23 > 0:07:25By moist, I'm thinking armpits, probably.
0:07:25 > 0:07:27Yeah, the very moist areas...
0:07:27 > 0:07:29The armpit and the groin are particularly good.
0:07:29 > 0:07:32- OK. I might do my own groin. - Yes. Yeah, yeah, yeah.
0:07:37 > 0:07:39Next, I'm wrapped in plaster to create a mould of me...
0:07:42 > 0:07:44Woo!
0:07:44 > 0:07:47..and given a full body wax in the process.
0:07:47 > 0:07:49YELLS: Ow!
0:07:49 > 0:07:51Do you want your hair back?
0:07:51 > 0:07:53THEY LAUGH
0:08:00 > 0:08:04Our home for this experiment is Imperial College in London.
0:08:04 > 0:08:06It's right on that edge, there.
0:08:06 > 0:08:10Here, our team of scientists and sculptors turn my body mould
0:08:10 > 0:08:14into possibly the world's largest Petri dish by filling it
0:08:14 > 0:08:17with a nutrient-rich jelly called agar.
0:08:20 > 0:08:21Good morning, gang. Good morning.
0:08:21 > 0:08:25After 12 hours, the agar jelly has set.
0:08:25 > 0:08:28It is like Tutankhamen's tomb, isn't it?
0:08:28 > 0:08:31All right, so nice and gently, up and out.
0:08:31 > 0:08:34There's two parts to this experiment,
0:08:34 > 0:08:37which is why my rather spooky clone is split in half.
0:08:37 > 0:08:40- The foot's out.- Woohoo!
0:08:40 > 0:08:42That is wonderfully weird.
0:08:42 > 0:08:45On one side, we want to grow bacteria from all over my skin
0:08:45 > 0:08:47to see what's living on me.
0:08:47 > 0:08:51It kind of looks like me, I must admit that.
0:08:51 > 0:08:52A slightly bald version of me, but...
0:08:52 > 0:08:55THEY CHUCKLE Wow.
0:08:56 > 0:09:00On the other side, we've added a broad-spectrum antibiotic used
0:09:00 > 0:09:03in hospitals against a wide range of infections.
0:09:04 > 0:09:08But before we even get the chance to add my bacteria,
0:09:08 > 0:09:10something else has snuck in.
0:09:10 > 0:09:12What's the green stuff?
0:09:12 > 0:09:16- Does this suggest the presence of bacteria already, then?- It does.
0:09:16 > 0:09:19On this side, where we don't have any antibiotics,
0:09:19 > 0:09:22- then there has been some growth of bacteria.- Right.
0:09:22 > 0:09:24So even given the tiniest opportunity,
0:09:24 > 0:09:26the bacteria have got stuck in.
0:09:26 > 0:09:28They do, they do. Yes, yep, yep. They're everywhere.
0:09:31 > 0:09:34We don't know where these green bacteria have come from.
0:09:35 > 0:09:39But you can see that the antibiotic embedded on the left-hand side
0:09:39 > 0:09:42have so far stopped the invader from growing.
0:09:45 > 0:09:48Time to add bacteria collected from my body.
0:09:49 > 0:09:52These are all the swabs we've taken of your body.
0:09:52 > 0:09:55We're going to start with the bottom of the feet, so number 20.
0:09:57 > 0:10:00We want to make visible the invisible microbes -
0:10:00 > 0:10:02mainly bacteria - that live on a healthy human.
0:10:03 > 0:10:06So we're adding each of my samples to the corresponding
0:10:06 > 0:10:09part of my clone.
0:10:09 > 0:10:12Let's see what they make of their new home.
0:10:14 > 0:10:16OK, we can do this.
0:10:16 > 0:10:20Our giant Petri dish is sealed into an airtight case.
0:10:20 > 0:10:24It really does feel like they're taking my body and embalming it.
0:10:24 > 0:10:26Whoa!
0:10:26 > 0:10:29- Oop, the foot's gone.- Oh, no!
0:10:31 > 0:10:34Despite a couple of rather nasty foot injuries...
0:10:36 > 0:10:40..Microbial Michael is now ready for our experiment to start.
0:10:40 > 0:10:42Which microbes will thrive and where?
0:10:45 > 0:10:47I would expect, within the next few days,
0:10:47 > 0:10:51we'll start seeing them emerge on that side.
0:10:51 > 0:10:55The question is, will they be able to overcome the antibiotics
0:10:55 > 0:10:57and start growing on this side?
0:11:00 > 0:11:02The truth is, we have absolutely
0:11:02 > 0:11:06no idea what is going to happen next, because this sort of thing
0:11:06 > 0:11:10has never been done on this sort of scale before.
0:11:10 > 0:11:12We simply have to wait to find out.
0:11:21 > 0:11:23Time for a road trip.
0:11:25 > 0:11:28I want to dig deeper into the roots of the crisis.
0:11:32 > 0:11:36So why are more and more bacteria becoming resistant?
0:11:36 > 0:11:40Is it simply that we're overdoing the antibiotics,
0:11:40 > 0:11:42or is it more complicated than that?
0:11:44 > 0:11:47I recently read about a fascinating discovery made here,
0:11:47 > 0:11:52in New Mexico, which changed the way I think about antibiotic resistance.
0:11:53 > 0:11:57Now, this is the spot. Gorgeous, isn't it?
0:11:57 > 0:12:00Unfortunately, what I am looking for is not here, on the surface.
0:12:00 > 0:12:02It is deep underground.
0:12:02 > 0:12:05And I say unfortunately because I am pretty claustrophobic.
0:12:08 > 0:12:10My guide is Dr Hazel Barton.
0:12:10 > 0:12:14- Hey-ho. Hello.- Hi, Michael, how are you doing?- Glad to see you.
0:12:14 > 0:12:17Hazel's a microbiologist who searches for new species
0:12:17 > 0:12:21of bacteria living deep under Carlsbad National Park,
0:12:21 > 0:12:23in a vast network of caves.
0:12:23 > 0:12:28- Thank you. What's the longest you've been down here for?- Eight days.
0:12:28 > 0:12:33- Eight days? Cool. Journey to the centre of the earth.- Yeah.
0:12:33 > 0:12:36So we're getting off the tourist trail here.
0:12:36 > 0:12:39Blimey. It gets narrower, doesn't it?
0:12:40 > 0:12:44- It's quite big in here. - Yeah. It's cool.
0:12:44 > 0:12:49It was in 2012 in a cave much deeper than I'm able to go that
0:12:49 > 0:12:53Hazel's team made their breakthrough discovery.
0:12:53 > 0:12:58So the kind of areas that we sample look quite a bit like this.
0:13:00 > 0:13:03Hazel took a bunch of bacterial samples from the cave and
0:13:03 > 0:13:05sent them off to a lab for analysis.
0:13:07 > 0:13:09The results shocked everyone.
0:13:09 > 0:13:11So I sent him just 100, right?
0:13:11 > 0:13:12He started testing them, and he's like,
0:13:12 > 0:13:14"You're not going to believe this,
0:13:14 > 0:13:16"but they are resistant to everything."
0:13:16 > 0:13:17- Blimey.- Everything that's used...
0:13:17 > 0:13:20So these were bacteria you found on a wall in a cave.
0:13:20 > 0:13:22Much more remote than this,
0:13:22 > 0:13:25- much further away. - That had not seen humans for...
0:13:25 > 0:13:27We know humans had never been in there because we know...
0:13:27 > 0:13:29we had the exploration records,
0:13:29 > 0:13:31so there was no impact on it.
0:13:31 > 0:13:34And they were resistant to practically every antibiotic
0:13:34 > 0:13:36- that's used in the clinic.- Wow.
0:13:36 > 0:13:39That is both incredibly exciting and incredibly scary.
0:13:39 > 0:13:43Nobody had ever thought that you would find resistant bacteria
0:13:43 > 0:13:45down in the bottom of a bloody cave.
0:13:47 > 0:13:50They'd had no interaction with humans,
0:13:50 > 0:13:53but the bacteria Hazel found in the cave were resistant to
0:13:53 > 0:13:57a huge array of antibiotics we use in modern medicine.
0:14:00 > 0:14:04This resistance had clearly evolved over millions of years
0:14:04 > 0:14:06without us having anything to do with it.
0:14:08 > 0:14:10Why?
0:14:13 > 0:14:15Well, it makes sense when you think of antibiotics
0:14:15 > 0:14:19not as man-made but the by-product of war between microbes.
0:14:23 > 0:14:26They make chemical weapons to destroy their enemies and
0:14:26 > 0:14:27steal their resources...
0:14:31 > 0:14:34..weapons we have learnt to exploit as antibiotics.
0:14:37 > 0:14:41The bacteria living deep in the cave have had millions of years to
0:14:41 > 0:14:46evolve weapons that can target and destroy even their toughest rivals.
0:14:49 > 0:14:54The battle for scarce resources like nutrients and energy is
0:14:54 > 0:14:57particularly brutal down here, in the caves.
0:14:59 > 0:15:03It's really starved down here. There's no resources.
0:15:03 > 0:15:06It's probably one of the most starved environments on Earth
0:15:06 > 0:15:10because, if you think about it, any energy needs to come in through
0:15:10 > 0:15:15the rock, and so there's a big competition for nutrients.
0:15:15 > 0:15:19The fewer the resources, the more intensely the microbes battle,
0:15:19 > 0:15:23and that creates resistance because the bacteria under
0:15:23 > 0:15:25attack don't just lie back and die.
0:15:28 > 0:15:31When billions of bacterial cells are bombarded,
0:15:31 > 0:15:35all it takes is for one cell to mutate its DNA...
0:15:37 > 0:15:41..in such a way that the antibiotic can no longer kill it.
0:15:44 > 0:15:48This ability to resist then spreads...fast.
0:15:50 > 0:15:53So developing resistance to antibiotics is an entirely
0:15:53 > 0:15:56natural process, which the bacteria
0:15:56 > 0:15:59of Carlsbad have taken to the extreme.
0:16:02 > 0:16:05- So, a fierce competition going around us all the time.- Uh-huh.
0:16:05 > 0:16:07Microbes producing antibiotics,
0:16:07 > 0:16:11but this is all happening millions of years before Fleming and
0:16:11 > 0:16:13his friends at Oxford actually developed penicillin.
0:16:13 > 0:16:16Right. And that's what we discovered down here that kind of blew
0:16:16 > 0:16:20everybody's mind, is the thought that resistance and that antibiotic
0:16:20 > 0:16:23battle is because we've been using antibiotics,
0:16:23 > 0:16:26but it can't be down here cos these guys have never seen
0:16:26 > 0:16:30the antibiotics that Fleming, everyone has made since.
0:16:33 > 0:16:36But if resistance to antibiotics arises naturally,
0:16:36 > 0:16:38what does that mean for us?
0:16:47 > 0:16:50Let's see if Microbial Michael has any answers.
0:17:02 > 0:17:04Bloody hell. That is grotesque.
0:17:09 > 0:17:11We've left him alone for a few days,
0:17:11 > 0:17:15and the bacteria swabbed from my body have run riot.
0:17:19 > 0:17:21I'm hoping immunologist Dr Sheena Cruickshank
0:17:21 > 0:17:23from Manchester University
0:17:23 > 0:17:26can help me make sense of what's happening.
0:17:30 > 0:17:32Michael, meet Michael.
0:17:32 > 0:17:33That is so weird.
0:17:35 > 0:17:38- I just think it's so exciting to be able to see...- It is both exciting
0:17:38 > 0:17:41and really, really disgusting, I have to say.
0:17:41 > 0:17:44There's something, as well, about seeing me down there, effectively
0:17:44 > 0:17:45covered with this stuff.
0:17:45 > 0:17:49I think you should be looking at this as showing you the
0:17:49 > 0:17:52amazing life that is living on you.
0:17:52 > 0:17:55We're starting on the right-hand side,
0:17:55 > 0:17:57where there's no added antibiotic.
0:17:58 > 0:18:01That means these different-coloured bacteria should be part of my
0:18:01 > 0:18:03normal skin flora.
0:18:03 > 0:18:05Look at this amazing white, blue...
0:18:05 > 0:18:08OK, I thought white, blue meant there was nothing growing there,
0:18:08 > 0:18:09but there is something?
0:18:09 > 0:18:11No, that's actually growing over the blue,
0:18:11 > 0:18:13and that's really exciting
0:18:13 > 0:18:17- because it suggests that perhaps it is battling with the blue.- OK.
0:18:17 > 0:18:19It's competing with it.
0:18:19 > 0:18:22And I think that's Staphylococcus epidermidis,
0:18:22 > 0:18:24and that's a really common skin bacteria.
0:18:24 > 0:18:27And we actually know that some bacteria make anti-bacterials,
0:18:27 > 0:18:30so they compete with each other and they kill other bacteria.
0:18:30 > 0:18:32So, perhaps that's what's happening here.
0:18:32 > 0:18:35So we're kind of seeing warfare in action between the bacteria.
0:18:35 > 0:18:36Absolutely.
0:18:37 > 0:18:41What this side of this experiment is showing us very colourfully is
0:18:41 > 0:18:45how bacteria in a healthy body keep each other in check as they
0:18:45 > 0:18:47battle for space and nutrients.
0:18:49 > 0:18:52Because most bacteria living on us are harmless or beneficial,
0:18:52 > 0:18:55in a balanced ecosystem, they leave limited room
0:18:55 > 0:18:58for the bad bugs - the pathogens.
0:19:00 > 0:19:04Behind the scenes, our team is identifying exactly what's grown
0:19:04 > 0:19:07using DNA analysis.
0:19:07 > 0:19:11And they found something potentially nasty up my nose.
0:19:13 > 0:19:14This is really interesting.
0:19:14 > 0:19:17If you look around your nose there, around your nostril,
0:19:17 > 0:19:20there is Staphylococcus aureus growing there.
0:19:20 > 0:19:22That is the sort of orangey...
0:19:22 > 0:19:24- They call it the golden staph, don't they?- Yeah.
0:19:24 > 0:19:26A lot of people - about a third of people -
0:19:26 > 0:19:28have Staphylococcus aureus in their nostrils.
0:19:28 > 0:19:30It's quite, quite normal.
0:19:30 > 0:19:34But a lot of people associate it with being a pathogen.
0:19:34 > 0:19:36In the right circumstances, it's fine.
0:19:36 > 0:19:38In the wrong, it can be deadly.
0:19:41 > 0:19:45If our immune system takes a hit, some species amongst our bacteria
0:19:45 > 0:19:48can get out of control and do serious harm.
0:19:51 > 0:19:55That's what then relatives of the golden staph aureus in my nose did
0:19:55 > 0:19:57to patient John Shelton,
0:19:57 > 0:20:01overrunning his body's defences and very nearly killing him.
0:20:05 > 0:20:07On this side of the experiment,
0:20:07 > 0:20:11my bacteria are keeping each other in check, just as I'd expect.
0:20:19 > 0:20:23But on the other side, it's a different story.
0:20:23 > 0:20:27So we are coming across to the side which was actually enriched
0:20:27 > 0:20:29- with antibiotics, wasn't it?- Mm-hm.
0:20:30 > 0:20:34Peer past the fog of condensation caused by
0:20:34 > 0:20:36so much microbial activity,
0:20:36 > 0:20:40and our time-lapse cameras reveal that even on the side which
0:20:40 > 0:20:44is heavily impregnated with broad-spectrum antibiotics,
0:20:44 > 0:20:46there are still bacteria growing.
0:20:49 > 0:20:52Though, admittedly, there are a lot less of them.
0:20:58 > 0:21:02Here, just here, at the top of the head, you can see,
0:21:02 > 0:21:05there's actually quite a few clear zones.
0:21:05 > 0:21:08So that suggests that certainly the antibiotic is doing its job
0:21:08 > 0:21:12in areas, and it's certainly been controlling in this area
0:21:12 > 0:21:16the blue, which was kind of taking over everything.
0:21:17 > 0:21:19One of the things that is very striking to me
0:21:19 > 0:21:22- is that on the other side, there's competition going on...- Mm-hm.
0:21:22 > 0:21:26..which suggests that wiping out all your bacteria is
0:21:26 > 0:21:30a bad idea because actually you do want sort of good bacteria,
0:21:30 > 0:21:33if you like, to kind of compete with the pathogens and stop them
0:21:33 > 0:21:35- encroaching.- Absolutely.
0:21:38 > 0:21:41What this demonstrates very clearly is you shouldn't take
0:21:41 > 0:21:45a broad-spectrum antibiotic unless you really need to.
0:21:51 > 0:21:54As the caves of New Mexico showed us,
0:21:54 > 0:21:58the more bacteria are attacked, the more they will resist.
0:22:04 > 0:22:07But there is also an unfortunate fact - that broad-spectrum
0:22:07 > 0:22:11antibiotics carpet bomb friend and foe indiscriminately.
0:22:13 > 0:22:16There is a lot of collateral damage amongst the benign
0:22:16 > 0:22:18and beneficial species.
0:22:24 > 0:22:28This accelerates resistance because surviving pathogens now have
0:22:28 > 0:22:30less competition for resources,
0:22:30 > 0:22:34and they can colonise the whole battlefield.
0:22:37 > 0:22:41If one of these survivors is resistant to multiple drugs
0:22:41 > 0:22:43and potentially harmful, it's a superbug.
0:22:46 > 0:22:51The bad news for me is the team have found two growing on my clone.
0:22:51 > 0:22:54One that is particularly interesting is an organism called
0:22:54 > 0:22:56Enterococcus faecium.
0:22:56 > 0:23:00And this is an entirely normal part of our gut flora.
0:23:00 > 0:23:02But if it gets into the wrong parts of the body,
0:23:02 > 0:23:06or if the person has a compromised immune system,
0:23:06 > 0:23:09it can cause really serious invasive infections.
0:23:09 > 0:23:12And because it's inherently resistant to antibiotics,
0:23:12 > 0:23:13it's very, very hard to treat.
0:23:16 > 0:23:20The team has also found Pseudomonas growing through the antibiotic.
0:23:23 > 0:23:26It's not part of my skin flora, but a travelling pathogen
0:23:26 > 0:23:28that can cause infection and pneumonia
0:23:28 > 0:23:30if it gets inside our bodies...
0:23:32 > 0:23:34..say, through an open wound.
0:23:37 > 0:23:41Microbial Michael has shown me superbugs on my skin.
0:23:45 > 0:23:50But what about inside me, where some really important stuff happens?
0:23:52 > 0:23:57I've sent off a very personal sample to be analysed.
0:23:59 > 0:24:03So, we've received our poo sample from Michael.
0:24:03 > 0:24:06And we want to have a look to determine if he's got any
0:24:06 > 0:24:07resistant bacteria.
0:24:09 > 0:24:10When you think about antibiotics,
0:24:10 > 0:24:12most of these us will take these
0:24:12 > 0:24:14orally, and also we'll take it
0:24:14 > 0:24:15with a drink of water,
0:24:15 > 0:24:18so therefore, the antibiotics will hit the gut first.
0:24:21 > 0:24:24Our guts and intestines are home to at least 1,000 different
0:24:24 > 0:24:25species of bacteria.
0:24:28 > 0:24:32But now there's new research about what can happen to them when
0:24:32 > 0:24:33we take antibiotics.
0:24:35 > 0:24:38The striking thing about
0:24:38 > 0:24:40a healthy person who takes an antibiotic
0:24:40 > 0:24:43is that, in all likelihood,
0:24:43 > 0:24:46they will get resistant bacteria
0:24:46 > 0:24:49in their tummies - in their colon, actually -
0:24:49 > 0:24:52after about seven days.
0:24:52 > 0:24:53And with some antibiotics,
0:24:53 > 0:24:59these resistant bugs last in their tummies for up to a year.
0:25:01 > 0:25:05That sounds like another compelling reason not to take antibiotics
0:25:05 > 0:25:07unless you really have to.
0:25:08 > 0:25:12I'm hoping my gut doesn't contain resistant bacteria.
0:25:12 > 0:25:15Right, so you had my poo samples. What did you find?
0:25:15 > 0:25:19- So...- 'Lindsay has tried growing my gut bacteria
0:25:19 > 0:25:23'on plates containing four clinically important antibiotics.'
0:25:23 > 0:25:27- Presumably, these plates should be clear of bacteria.- Yeah.
0:25:27 > 0:25:29If you had susceptible bacteria, then they should be clear,
0:25:29 > 0:25:32but as you can see, there's multiple colonies on each of
0:25:32 > 0:25:35the plates, which would suggest they are resistant to that antibiotic.
0:25:35 > 0:25:36That does surprise me.
0:25:36 > 0:25:38I haven't had that many antibiotics in my life.
0:25:38 > 0:25:39Well, I was going to ask,
0:25:39 > 0:25:41when was the last time you had a course of antibiotics?
0:25:41 > 0:25:43Probably about four years ago.
0:25:43 > 0:25:45Yeah, OK, so that's quite a long time ago,
0:25:45 > 0:25:49but maybe does correlate with some of the data that we've shown.
0:25:49 > 0:25:52That's a nasty surprise. I've got bacteria growing inside me
0:25:52 > 0:25:55which are resistant to all four antibiotics -
0:25:55 > 0:25:58one of which I've never even taken.
0:25:58 > 0:26:01I know the name, but I think I would know if I'd had it.
0:26:01 > 0:26:04Yeah, you would probably know if you had vancomycin.
0:26:04 > 0:26:05It's a last-resort antibiotic,
0:26:05 > 0:26:08- so this is what you get if you're really ill.- OK.
0:26:08 > 0:26:11That is really quite worrying, I must admit.
0:26:11 > 0:26:15And what is really quite striking is the fact that the main
0:26:15 > 0:26:18culprit in terms of having antibiotic resistant genes
0:26:18 > 0:26:19is E. coli.
0:26:19 > 0:26:23Blimey. I have E. coli in my gut which is resistant to everything.
0:26:23 > 0:26:25- Yes.- Blimey. That's bad news!
0:26:25 > 0:26:28OK. That's not what I was hoping to hear.
0:26:32 > 0:26:36There are lots of different strains of E. coli. A few are very nasty.
0:26:38 > 0:26:41We don't know what strain I've got,
0:26:41 > 0:26:44but we do know it is very resistant.
0:26:45 > 0:26:47Now, that was an unpleasant surprise.
0:26:47 > 0:26:50It's one thing to talk about antibiotic resistance,
0:26:50 > 0:26:53but to discover that I've got these E. coli,
0:26:53 > 0:26:56and they are resistant to all sorts of antibiotics is,
0:26:56 > 0:26:57I must admit, worrying.
0:26:59 > 0:27:03I'm not really worried by the fact it's E. coli.
0:27:03 > 0:27:05It's the resistance bit.
0:27:05 > 0:27:06Why?
0:27:06 > 0:27:10Well, once resistance emerges in one species of bacteria,
0:27:10 > 0:27:12it can spread to other species.
0:27:12 > 0:27:15It's all to do with the way they exchange genes,
0:27:15 > 0:27:18as Sheena can explain.
0:27:18 > 0:27:21We get all our DNA from our parents, - so you get half from your mum,
0:27:21 > 0:27:25half from your dad. That's your lot. You don't get any more.
0:27:25 > 0:27:28You might see that chap down the corridor who never catches
0:27:28 > 0:27:31a cold and think, "Oh, I'd love to be able to steal that ability."
0:27:31 > 0:27:33But we can't.
0:27:33 > 0:27:34But imagine you could.
0:27:34 > 0:27:39Imagine you could steal DNA and swap DNA just as easily as you swap your
0:27:39 > 0:27:44e-mail or your telephone number. And basically, bacteria can do that.
0:27:44 > 0:27:46It's called horizontal gene transfer,
0:27:46 > 0:27:50and this is the way antibiotic resistance can spread.
0:27:55 > 0:27:56Using this trick,
0:27:56 > 0:27:59different species of bacteria share genetic information...
0:28:02 > 0:28:05..including the ability to resist a specific antibiotic.
0:28:09 > 0:28:13The bacteria don't even have to be touching because they can also
0:28:13 > 0:28:17pick up bits of genetic information left in the environment around them.
0:28:22 > 0:28:25That means the E. coli inside me could, theoretically,
0:28:25 > 0:28:27share its genes with other species...
0:28:28 > 0:28:32..and turn my gut into a factory of resistant bacteria.
0:28:36 > 0:28:40And we have plenty of evidence that really does happen.
0:28:40 > 0:28:43Resistance is spreading from microbe to microbe.
0:28:45 > 0:28:49Wherever antibiotics are used intensively, such as hospitals,
0:28:49 > 0:28:52more resistant bacteria emerge.
0:28:52 > 0:28:54They share their genes. They multiply.
0:28:56 > 0:29:01This explains how superbugs like MRSA and E. coli can resist
0:29:01 > 0:29:02so many different drugs.
0:29:04 > 0:29:07And they don't stay confined inside our hospitals...
0:29:08 > 0:29:11..because, like us, bacteria can travel.
0:29:13 > 0:29:17And people aren't the only source of resistant bacteria.
0:29:17 > 0:29:21Globally, half of all antibiotics are given to animals.
0:29:21 > 0:29:23COW LOWS
0:29:23 > 0:29:25In countries like America and China,
0:29:25 > 0:29:28they are even widely used as growth promoters.
0:29:28 > 0:29:30COW LOWS
0:29:32 > 0:29:37Animals and humans alike pump out more and more resistant bacteria.
0:29:39 > 0:29:42But how far is the wave of resistance spreading?
0:29:49 > 0:29:50In Cornwall,
0:29:50 > 0:29:55a pioneering new study has found evidence that resistant bacteria are
0:29:55 > 0:30:00travelling through our waterways, out to sea, and then back again,
0:30:00 > 0:30:01into humans.
0:30:02 > 0:30:07Hi. I'm going to talk to you about the Beach Bums survey.
0:30:07 > 0:30:11We recruited 300 people to our survey -
0:30:11 > 0:30:16surfers and people who don't surf, as well -
0:30:16 > 0:30:20and asked them to collect swabs of their faecal material.
0:30:20 > 0:30:23You take the swab, send it back to us in the post,
0:30:23 > 0:30:26and then we test it for the presence of resistant bacteria.
0:30:27 > 0:30:31What we found is that a greater proportion of surfers have
0:30:31 > 0:30:35resistant bacteria in their guts compared to people who don't surf.
0:30:39 > 0:30:42We think that, if you swallow a lot of seawater,
0:30:42 > 0:30:45that some of the bacteria that are present in the seawater
0:30:45 > 0:30:48survive and go on to live inside...inside your gut.
0:30:52 > 0:30:56If resistant bacteria can make it out to sea and then into surfers,
0:30:56 > 0:31:00I could have picked up the resistant E. coli in my gut from, well,
0:31:00 > 0:31:01just about anywhere.
0:31:08 > 0:31:11The good news is that in the UK and some other countries,
0:31:11 > 0:31:15antibiotic use in farming has started to come down.
0:31:20 > 0:31:23But there's no putting the genie back in the bottle.
0:31:25 > 0:31:28Resistant bugs are in our bodies and all around us.
0:31:31 > 0:31:35There isn't any doubt that we have been complacent
0:31:35 > 0:31:39and we have walked into this huge problem.
0:31:40 > 0:31:44But humans have been between a rock and a hard place here.
0:31:44 > 0:31:47They want to use antibiotics, but as soon as they use them,
0:31:47 > 0:31:49resistance arises.
0:31:49 > 0:31:55Because they are life-saving, if you stop using antibiotics, people die.
0:31:57 > 0:31:59MONITOR SIGNALS FLATLINE
0:31:59 > 0:32:01At the end of the day,
0:32:01 > 0:32:03we need new antibiotics.
0:32:07 > 0:32:10Trouble is, modern medicine hasn't found
0:32:10 > 0:32:13a totally new type of antibiotic in more than 30 years.
0:32:16 > 0:32:19Each new drug involves a long and complex process of chemical
0:32:19 > 0:32:21engineering and testing.
0:32:24 > 0:32:28They are certainly difficult to make from scratch.
0:32:28 > 0:32:31Instead, scientists have relied on finding new microbes,
0:32:31 > 0:32:34growing them and then trying to identify and extract any
0:32:34 > 0:32:37chemicals with potential antibiotic properties.
0:32:43 > 0:32:46One problem is that many microbes simply won't grow using
0:32:46 > 0:32:48traditional lab techniques.
0:32:48 > 0:32:50And without being able to grow them,
0:32:50 > 0:32:53we will struggle to develop new antibiotics.
0:33:00 > 0:33:03Time to search out some novel solutions.
0:33:05 > 0:33:09Here in Boston, I've come to meet a maverick microbiologist who,
0:33:09 > 0:33:13I'm told, has developed a whole new way of growing bacteria
0:33:13 > 0:33:16and, in the process, discovered possibly the first new class
0:33:16 > 0:33:18of antibiotics in decades.
0:33:20 > 0:33:24Dr Slava Epstein has promised to show me his secret.
0:33:26 > 0:33:28Do you see a suitable spot somewhere around here?
0:33:28 > 0:33:34We can find a suitable spot just about anywhere on the planet.
0:33:34 > 0:33:37So, the first thing that happens, we collect soil.
0:33:37 > 0:33:39We collect soil.
0:33:39 > 0:33:41We don't have to have too much of it
0:33:41 > 0:33:44because every gram of soil is
0:33:44 > 0:33:46easily a billion or 10 billion cells.
0:33:46 > 0:33:50But what we're going to do with the cells in the lab is going to
0:33:50 > 0:33:51be very different.
0:33:52 > 0:33:56Two thirds of our most important antibiotics were originally found
0:33:56 > 0:34:02in microbes living in soil, a well which looked like it had run dry.
0:34:02 > 0:34:07But now, Slava has thrown out the 130-year-old Petri dish and
0:34:07 > 0:34:11replaced it with a device that, to my eyes, looks equally low-tech -
0:34:11 > 0:34:15a plastic tray into which his assistant adds a diluted
0:34:15 > 0:34:18solution of the soil sample.
0:34:18 > 0:34:20In this vial, there is about 100 cells.
0:34:20 > 0:34:23- 100 cells down from a few billion? - Yes.- And these are all bacteria?
0:34:23 > 0:34:24These are all bacteria.
0:34:24 > 0:34:27It is starting from this point that things are going to be different
0:34:27 > 0:34:29because we are not going to put them into a Petri dish.
0:34:29 > 0:34:33Instead, we are preparing this device.
0:34:33 > 0:34:37- It is just a collection of wells with a porous bottom.- OK.
0:34:39 > 0:34:42So, I have to say, this doesn't look that radical.
0:34:42 > 0:34:44Not being a microbiologist,
0:34:44 > 0:34:47I probably don't understand why it is so different.
0:34:47 > 0:34:49It is radical because
0:34:49 > 0:34:53- have I ever mentioned any word nutrient?- No.
0:34:53 > 0:34:56- Because there is none.- OK. - We don't need them.
0:34:56 > 0:34:58Unlike the Petri dish, we do not.
0:34:58 > 0:35:01We do not want to create artificial conditions.
0:35:03 > 0:35:06- Now that will go into the soil... - OK.
0:35:06 > 0:35:10- ..from which these cells came from.- Ah!
0:35:10 > 0:35:14- That is clever.- So inside... Thank you.
0:35:14 > 0:35:18- Inside...- I get it at last. - ..chemically...- OK, yeah.
0:35:18 > 0:35:20..it will not be different from the outside.
0:35:21 > 0:35:23So if the cells can grow in nature...
0:35:23 > 0:35:25- You are returning them to their normal environment...- Yes.
0:35:25 > 0:35:27..rather than sticking them in agar.
0:35:27 > 0:35:29- They should be able to grow inside. - Ah!
0:35:31 > 0:35:35By putting the bacteria back into the soil they came from,
0:35:35 > 0:35:39Slava is encouraging them to grow just like they would in the wild.
0:35:39 > 0:35:42Compared to using agar jelly,
0:35:42 > 0:35:44the results are astounding.
0:35:44 > 0:35:46The difference in colony count between the two methods
0:35:46 > 0:35:49- is 30,000%.- Wow.
0:35:49 > 0:35:54You can grow 30,000% more cells if you do it this way than if
0:35:54 > 0:35:56you do it the conventional way.
0:35:56 > 0:35:57That's correct.
0:35:58 > 0:36:01This technique means they can grow bacteria that would normally
0:36:01 > 0:36:05be missed, and they have created versions of the device to
0:36:05 > 0:36:08look for novel bacteria in all sorts of environments,
0:36:08 > 0:36:11including the human mouth.
0:36:11 > 0:36:14- Very neat.- It's also very simple.
0:36:14 > 0:36:19You can really build this device in your garage.
0:36:20 > 0:36:23What excites me about Slava's discovery is it means
0:36:23 > 0:36:27there's clearly a whole world of microbes out there,
0:36:27 > 0:36:29just waiting to be found.
0:36:32 > 0:36:34Imagine you are an ancient Greek looking up at the sky.
0:36:34 > 0:36:38You'd only see a tiny handful of the stars and planets that are
0:36:38 > 0:36:39actually out there.
0:36:39 > 0:36:43In some ways, we are a bit like that ancient Greek when it comes to
0:36:43 > 0:36:44the microbial world.
0:36:44 > 0:36:48There is a vast galaxy of tiny creatures,
0:36:48 > 0:36:52and we are currently only aware of a very small proportion of them.
0:37:00 > 0:37:03We need to start looking for new antibiotics much further
0:37:03 > 0:37:05afield than the soil under our feet.
0:37:08 > 0:37:13Some scientists think seabeds could be rich in antibacterial potential.
0:37:16 > 0:37:20Easier pickings are washing up on our shores with evidence
0:37:20 > 0:37:24clips of seaweed contain microbial agents effective against MRSA.
0:37:27 > 0:37:31And deep in the caves under New Mexico, Hazel Barton's team
0:37:31 > 0:37:34has discovered that millions of years of intense bacterial
0:37:34 > 0:37:39warfare has produced chemicals we may be able to use.
0:37:40 > 0:37:43One of the organisms that we found
0:37:43 > 0:37:46made 38 novel antimicrobial compounds,
0:37:46 > 0:37:49- of which three were new antibiotics. - Hm.
0:37:49 > 0:37:52So the potential is that people turn their attention to these
0:37:52 > 0:37:55extreme environments - like caves, like the deep ocean, like,
0:37:55 > 0:37:58you know, the Arctic - we are going to have this explosion
0:37:58 > 0:38:02in new compounds over the next ten, 15 years.
0:38:07 > 0:38:11The hunt for antibiotics is not just in extreme environments
0:38:11 > 0:38:14but anywhere that's home to novel microbes.
0:38:15 > 0:38:18Professor Matt Hutchings has found what could be
0:38:18 > 0:38:21a novel antibiotic in...
0:38:21 > 0:38:22an ant farm.
0:38:25 > 0:38:26It's an amazing system.
0:38:26 > 0:38:29They've been using antibiotics for 50 to 60 million years.
0:38:32 > 0:38:36The secret Matt's team has unlocked is in the relationship
0:38:36 > 0:38:39between these leaf-cutter ants and their food source.
0:38:40 > 0:38:43The fungus is the only food for this whole ant colony.
0:38:43 > 0:38:47And if they smell any foreign fungi that might cause disease in there,
0:38:47 > 0:38:50they cut it out, they carry it over to this part,
0:38:50 > 0:38:53which is the waste dump, which is usually outside the nest.
0:38:53 > 0:38:56They rub their bodies against it and then they dig it back into
0:38:56 > 0:38:57the ground.
0:38:57 > 0:39:00The really interesting thing for us is the reason they rub their bodies
0:39:00 > 0:39:02against it is because their bodies are covered in
0:39:02 > 0:39:05antibiotic-producing bacteria that the ants can use to defend
0:39:05 > 0:39:07their fungus against disease.
0:39:11 > 0:39:15Matt's lab has extracted a couple of experimental new antibiotics
0:39:15 > 0:39:17from the bacteria on the ants.
0:39:21 > 0:39:24They haven't yet been tested on humans.
0:39:28 > 0:39:32So, time for part two of our experiment, using my body -
0:39:32 > 0:39:36well, bits of my body - to test out some of these novel drugs.
0:39:40 > 0:39:43We are creating a biohazard and infecting different parts of
0:39:43 > 0:39:48me with three of the most common multi-drug-resistant superbugs -
0:39:48 > 0:39:53MRSA, salmonella and Pseudomonas.
0:39:53 > 0:39:54Where should I put it, then?
0:39:54 > 0:39:56- On the fingers.- On the fingers, in there? OK.
0:39:56 > 0:39:58Then, we'll try to cure them.
0:40:01 > 0:40:05First, I want to see if ant antibiotic can tackle
0:40:05 > 0:40:06an infection of MRSA...
0:40:10 > 0:40:11..on my face.
0:40:15 > 0:40:17MRSA can cause skin infections.
0:40:18 > 0:40:21If it gets inside us and attacks our lungs,
0:40:21 > 0:40:23it can be particularly dangerous.
0:40:25 > 0:40:28We've given my face a few days for the bacteria to take hold.
0:40:32 > 0:40:37So, this is the ant antibiotic, and it is genuinely new and
0:40:37 > 0:40:41really rather exciting because, as you can see, it is really working,
0:40:41 > 0:40:43because that white disc on my forehead there,
0:40:43 > 0:40:46there's a zone of death around it which suggests
0:40:46 > 0:40:47that it really is killing
0:40:47 > 0:40:49all those bacteria.
0:40:49 > 0:40:52So the good news is, it's new and it's working.
0:40:52 > 0:40:57The bad news is it's probably ten, 15, 20 years away.
0:40:59 > 0:41:00Why so long?
0:41:00 > 0:41:04Well, finding an antibiotic in nature is just the first stage in
0:41:04 > 0:41:08an expensive and very complicated process.
0:41:09 > 0:41:11To discover a new antibiotic, I mean,
0:41:11 > 0:41:13you have to go from the early stage of discovery -
0:41:13 > 0:41:16so isolate bacteria from a place like a leaf-cutter ant nest -
0:41:16 > 0:41:18get those bacteria growing on a plate,
0:41:18 > 0:41:22solve the chemical structure of that antibiotic - which is not trivial -
0:41:22 > 0:41:25and then, of course, you have to get a drug company interested
0:41:25 > 0:41:27because they're the only people with enough money
0:41:27 > 0:41:29to get things through clinical trials.
0:41:29 > 0:41:33The reality is, less than 1% are actually suitable candidates
0:41:33 > 0:41:37and make it through to actually get them to the stage where they're
0:41:37 > 0:41:38approved as safe to use in humans.
0:41:40 > 0:41:43So it can take 15, 20 years and cost, well,
0:41:43 > 0:41:45between half and 1 billion.
0:41:51 > 0:41:57A time lag of 15 to 20 years is massive given that around 700,000
0:41:57 > 0:42:02people already die annually because of antibiotic-resistant bacteria.
0:42:06 > 0:42:09So what are we going to do until new drugs emerge?
0:42:12 > 0:42:16For starters, surely we could use our existing stock more carefully.
0:42:18 > 0:42:22Half of all hospital prescriptions are for broad-spectrum antibiotics.
0:42:25 > 0:42:28And given everything I've learnt, that can't be a good idea.
0:42:29 > 0:42:32Why do doctors continue to use broad-spectrum antibiotics?
0:42:32 > 0:42:36It strikes me as like carpet bombing everything and you'd be better off
0:42:36 > 0:42:37if you were a bit more targeted.
0:42:37 > 0:42:39Well, as a doctor, you're confronted with a dilemma.
0:42:39 > 0:42:41When you see a new patient,
0:42:41 > 0:42:43you don't necessarily have the diagnosis in front of you.
0:42:43 > 0:42:45- So you want to save the patient... - Mm-hm.
0:42:45 > 0:42:48..and you want to cover all the eventualities.
0:42:48 > 0:42:50And hence, you use a broad-spectrum antibiotic.
0:42:50 > 0:42:53- Right, because you don't know what it is you're trying to hit.- Exactly.
0:42:57 > 0:43:01To use targeted narrow-spectrum antibiotics, doctors need to
0:43:01 > 0:43:05be able to quickly diagnose the specific infection in a patient.
0:43:07 > 0:43:10For some bugs, like the ones that cause tuberculosis,
0:43:10 > 0:43:14that means taking samples, growing the bacteria
0:43:14 > 0:43:16and sequencing its DNA -
0:43:16 > 0:43:19a process that can take up to ten weeks.
0:43:22 > 0:43:24But Tim's part of a team working on
0:43:24 > 0:43:28a prototype gadget that could massively speed up DNA sequencing.
0:43:30 > 0:43:33So, you see the patient and they spit into your pot.
0:43:33 > 0:43:37Yep. And the DNA from your phlegm goes on there.
0:43:37 > 0:43:40- OK.- You close it.
0:43:40 > 0:43:44- And then it... This sequences it? - That sequences it.- Bloody hell.
0:43:44 > 0:43:47- Now...- That is really, really impressive, I have to say.
0:43:47 > 0:43:48That is impressive.
0:43:48 > 0:43:52So, how quickly would you then be able to make a diagnosis?
0:43:52 > 0:43:56- The sequencing of the genome will take less than an hour.- Yeah.
0:43:56 > 0:43:58The analysis takes about two minutes.
0:43:58 > 0:44:00MICHAEL LAUGHS OK, right.
0:44:00 > 0:44:04- OK. Two minutes as opposed to ten weeks?- Yes.
0:44:04 > 0:44:06Right, that is really crunching it, isn't it?
0:44:06 > 0:44:10And this, presumably, isn't just for TB.
0:44:10 > 0:44:14No. It's of great use for TB, but it can be used for any bacterium.
0:44:15 > 0:44:19If you're able to get a diagnosis within minutes of seeing your
0:44:19 > 0:44:21patient, it enables you to give the correct narrow-spectrum
0:44:21 > 0:44:24antibiotic that targets just those bacteria that are causing the
0:44:24 > 0:44:26illness and nothing else,
0:44:26 > 0:44:29so it's precision bombing rather than carpet bombing.
0:44:30 > 0:44:33If trials in clinics over the next couple of years are successful,
0:44:33 > 0:44:37this device could extend the life of antibiotics by slowing
0:44:37 > 0:44:39the pace of resistance.
0:44:43 > 0:44:47But what if we could also stop some bugs from resisting altogether?
0:44:51 > 0:44:54Some commonly prescribed antibiotics work by getting into
0:44:54 > 0:44:57bacterial cells, and when they hit a lethal dose,
0:44:57 > 0:45:01this causes the bacteria to rupture -
0:45:01 > 0:45:03something they have evolved ways to resist.
0:45:12 > 0:45:16Dr Jess Blair is part of a team from Birmingham University
0:45:16 > 0:45:20with a plan to stop the bacteria fighting back.
0:45:20 > 0:45:23She is going to try and explain the principle behind her approach
0:45:23 > 0:45:27using a bucket as a bacterial cell.
0:45:27 > 0:45:30OK, so you've got a watering can here full of antibiotic.
0:45:30 > 0:45:33If you start pouring that into our bacterial cell, what we hope,
0:45:33 > 0:45:36then, is that this will kill off the bacterial cell.
0:45:36 > 0:45:38So, for argument's sake, let's say our level at which the
0:45:38 > 0:45:41antibiotic becomes toxic is here.
0:45:41 > 0:45:43So you need to keep pouring.
0:45:44 > 0:45:47However, bacteria have a nifty trick.
0:45:48 > 0:45:52In their membranes, they have pumps called efflux pumps.
0:45:52 > 0:45:53So I'm pouring in antibiotics,
0:45:53 > 0:45:56and the bacteria are just pumping them out.
0:45:56 > 0:45:57Pumping them straight back out again.
0:45:57 > 0:46:00So now it's not looking quite so good.
0:46:00 > 0:46:02- Sorry, I'm getting your feet wet. - Yep.
0:46:02 > 0:46:05It's going to become a bit more difficult for you to get
0:46:05 > 0:46:08the antibiotic towards our line at which it's going to become toxic.
0:46:08 > 0:46:09Right.
0:46:09 > 0:46:12And what happens when they become really antibiotic resistant
0:46:12 > 0:46:14is they make more and more of these pumps.
0:46:14 > 0:46:17OK, that's a very neat trick. So, what can you do about it?
0:46:17 > 0:46:19Well, in my pocket,
0:46:19 > 0:46:22I've got a cable tie to sort of demonstrate this.
0:46:24 > 0:46:26So, we have inhibited the efflux pump.
0:46:26 > 0:46:28- So you're able to keep pouring the antibiotic in...- There we go!
0:46:28 > 0:46:30..and we're about to reach the level
0:46:30 > 0:46:32which is going to kill our bacterial cell.
0:46:32 > 0:46:33Die, bacteria, die!
0:46:33 > 0:46:36There we go. OK. So that's the theory.
0:46:36 > 0:46:39I mean, how close are we to it in practice?
0:46:39 > 0:46:41When I say we, I mean you, of course.
0:46:41 > 0:46:44Well, people have been able to find molecules that do this.
0:46:44 > 0:46:47The problem is there's no molecules at the moment which are able
0:46:47 > 0:46:51to both inhibit efflux pumps but also are OK to be given to a person.
0:46:51 > 0:46:54Most of the ones that we currently have are toxic to people.
0:47:02 > 0:47:07Because she can't test her inhibitor chemical on a living human being,
0:47:07 > 0:47:12Jess is going to test it instead on a salmonella infection in my hand.
0:47:16 > 0:47:17While she does that,
0:47:17 > 0:47:22Dr Andy Edwards and I are trying out another experimental chemical
0:47:22 > 0:47:25on my other hand, which we have infected with MRSA.
0:47:27 > 0:47:31Andy wants to show me what he calls an antibiotic amplifier.
0:47:31 > 0:47:34It's designed to stop this superbug from resisting
0:47:34 > 0:47:37an existing antibiotic called ciprofloxacin.
0:47:39 > 0:47:43So, what ciprofloxacin does is to break up bacterial DNA.
0:47:43 > 0:47:45It smashes it into lots of small pieces.
0:47:45 > 0:47:48And MRSA is really good at then sticking that back together
0:47:48 > 0:47:49and surviving.
0:47:49 > 0:47:51So what we want to do with our antibiotic amplifier is
0:47:51 > 0:47:55prevent the bacterium from sticking the DNA back together again.
0:47:55 > 0:47:57MRSA has a very bad reputation, doesn't it?
0:47:57 > 0:47:59It has a bad reputation for a good reason.
0:47:59 > 0:48:03So, MRSA causes lots of lots of surgical-site infections and
0:48:03 > 0:48:05other skin infections, particularly in hospitals.
0:48:05 > 0:48:08And once it gets into the blood, it is very, very serious.
0:48:08 > 0:48:10It can attach to your heart, bones and joints.
0:48:12 > 0:48:15So you're going to try and make this non-resistant again,
0:48:15 > 0:48:16reverse it if you like.
0:48:16 > 0:48:20That's right, that's right. We're trying to outsmart the bug.
0:48:23 > 0:48:27Andy's antibiotic amplifier and Jess's pump inhibitor are
0:48:27 > 0:48:30amongst a number of so-called resistance breakers currently
0:48:30 > 0:48:31in development.
0:48:33 > 0:48:36The results from our test certainly suggest they could have
0:48:36 > 0:48:38a promising future.
0:48:38 > 0:48:40Though, the first one is easier to make out on
0:48:40 > 0:48:43a Petri dish than on my agar hand.
0:48:45 > 0:48:47This is the pump inhibitor,
0:48:47 > 0:48:51the one that stops the bacteria pumping out the antibiotics.
0:48:51 > 0:48:53And this one is working rather well.
0:48:53 > 0:48:57You've got the salmonella infection here,
0:48:57 > 0:48:59and it is resistant to the antibiotic
0:48:59 > 0:49:01which is in the rest of the plate.
0:49:01 > 0:49:03But here, in the middle,
0:49:03 > 0:49:07that bit there is working because the area around it is clear.
0:49:07 > 0:49:09So that's promising. That's good.
0:49:13 > 0:49:16Next, the hand that was infected with MRSA.
0:49:18 > 0:49:21What's encouraging is the area that I painted
0:49:21 > 0:49:23on the back of the hand, here,
0:49:23 > 0:49:26which was a mixture of the amplifier
0:49:26 > 0:49:29and the antibiotic, that is clean.
0:49:29 > 0:49:32So that would suggest the amplifier is doing what it should do,
0:49:32 > 0:49:38which is preventing bacteria from reforming their DNA,
0:49:38 > 0:49:40and therefore, the bacteria are being killed.
0:49:40 > 0:49:44That one I give high marks to. That one worked.
0:49:47 > 0:49:51That's encouraging results from one experimental antibiotic
0:49:51 > 0:49:52and two resistance-breakers.
0:49:55 > 0:49:58But none of these cures will be ready to use on you or me
0:49:58 > 0:50:00any time soon.
0:50:01 > 0:50:03BELL CHIMES
0:50:03 > 0:50:07The final thing I want to look at is something which will kill
0:50:07 > 0:50:10bacteria but which isn't actually an antibiotic.
0:50:12 > 0:50:14This is where I normally come.
0:50:14 > 0:50:17At Oxford University, microbiologist
0:50:17 > 0:50:19Dr Alex Betts is investigating
0:50:19 > 0:50:22viruses which naturally attack bacteria.
0:50:22 > 0:50:26Mind your feet, cos we are looking for...something, actually,
0:50:26 > 0:50:28a lot like that. Perfect.
0:50:31 > 0:50:35Alex is one of a handful of scientists in the UK working
0:50:35 > 0:50:37with bacterial phages.
0:50:39 > 0:50:43All right, here we go. Oh, look at that. Isn't that disgusting?
0:50:43 > 0:50:46This is a fresh goose poo, and from these,
0:50:46 > 0:50:50I can isolate the bacteria and the viruses that are inside
0:50:50 > 0:50:52the digestive tract of geese.
0:50:52 > 0:50:55And that I can take back to the lab, and it should be a treasure
0:50:55 > 0:50:59trove of things that could potentially treat disease in humans.
0:51:01 > 0:51:02Lovely.
0:51:03 > 0:51:06I want to see if Alex's viruses can cure me.
0:51:08 > 0:51:11- Here we go.- Oh, wow.- I have a gift for you, my lovely face.
0:51:11 > 0:51:12For the scientist who has everything.
0:51:12 > 0:51:14- It's quite weird, isn't it? - Look at that nose!
0:51:14 > 0:51:16LAUGHING: Thank you(!)
0:51:19 > 0:51:23What we're going to do now is test a type of virus Alex
0:51:23 > 0:51:28has acquired from a sewage farm against a superbug - Pseudomonas.
0:51:29 > 0:51:32This bug causes septicaemia and pneumonia.
0:51:32 > 0:51:35In short, it's very nasty.
0:51:35 > 0:51:38It's a powerhouse of antibiotic resistance. It's a real problem.
0:51:38 > 0:51:42And it's been isolated from food,
0:51:42 > 0:51:43soil, drinking water,
0:51:43 > 0:51:46even really extreme environments like aviation fuel.
0:51:46 > 0:51:48This thing can grow on pretty much anything. So it's...
0:51:48 > 0:51:51- It's a good test, basically. - Very much so.
0:51:51 > 0:51:53If we can beat this, then we are in a good position.
0:51:55 > 0:51:58- So these are billions of viruses, is that right?- Yes, indeed.
0:51:58 > 0:52:01These are viruses that infect and kill bacteria,
0:52:01 > 0:52:04just as part of their natural life cycles.
0:52:04 > 0:52:07It's not something we've engineered in the lab.
0:52:08 > 0:52:13These images were taken with a hugely powerful microscope.
0:52:13 > 0:52:17You can see the tiny viruses known as phages clamped on to
0:52:17 > 0:52:20a single bacterial cell.
0:52:20 > 0:52:23Phages are parasites for bacteria.
0:52:25 > 0:52:27They inject their genetic material into a cell,
0:52:27 > 0:52:30forcing it to produce a huge number of new phages.
0:52:32 > 0:52:35These then burst out of the cell, destroying it.
0:52:40 > 0:52:43Research into phages is just getting started in the UK.
0:52:45 > 0:52:47BELLS CHIME
0:52:47 > 0:52:50But in Eastern Europe, they've been experimenting with
0:52:50 > 0:52:53viruses therapeutically for almost a century.
0:52:55 > 0:52:57And in the Polish city of Wroclaw,
0:52:57 > 0:53:01there's a specialist clinic that's achieving really impressive results
0:53:01 > 0:53:04in treating people with antibiotic-resistant infections.
0:53:07 > 0:53:08THEY SPEAK POLISH
0:53:10 > 0:53:14Remember the gruesome wound in Slawa's foot?
0:53:14 > 0:53:18Her E. coli infection is so bad and so untreatable,
0:53:18 > 0:53:21there's a serious risk she will have to have it amputated.
0:53:21 > 0:53:24Now she's hoping phages can save it.
0:53:24 > 0:53:27Through our experimental phage therapy,
0:53:27 > 0:53:29we want to protect her against amputation.
0:53:31 > 0:53:33I'm going to apply
0:53:33 > 0:53:35phage preparation into the wound.
0:53:35 > 0:53:37And I show you how I do it.
0:53:37 > 0:53:40This is a phage preparation against E. coli.
0:53:42 > 0:53:46The doctors hope to get Slawa's infection under control
0:53:46 > 0:53:49and then perform an operation to save the foot.
0:53:49 > 0:53:52Look away for a minute if you're squeamish.
0:53:56 > 0:54:01The patient will have surgery, which aim is to cut
0:54:01 > 0:54:03this dead tissue,
0:54:03 > 0:54:08but we apply phages before to decrease a lot of bacteria.
0:54:32 > 0:54:36After surgery, Slawa will receive combination therapy using
0:54:36 > 0:54:38phages and targeted antibiotics.
0:54:52 > 0:54:54SHE LAUGHS
0:54:54 > 0:54:57It will be months before Slawa knows if the therapy is working.
0:54:57 > 0:54:58Fingers crossed.
0:55:01 > 0:55:04In the meantime, let's see how my virus treatment is getting on.
0:55:05 > 0:55:07- Here we go.- OK.
0:55:07 > 0:55:09Now, it doesn't look obviously different.
0:55:09 > 0:55:12So, under white lights, the bacteria aren't particularly visible,
0:55:12 > 0:55:14cos they have kind of a similar colour to the agar,
0:55:14 > 0:55:16but there is this neat trick.
0:55:16 > 0:55:18They produce a molecule that fluoresces very intensely
0:55:18 > 0:55:19under UV light.
0:55:21 > 0:55:23- Look at that.- Yeah!
0:55:23 > 0:55:26- And hopefully, when I remove the bandage...- Yeah.
0:55:26 > 0:55:29- ..we should see quite a difference. - Oh, yeah!
0:55:30 > 0:55:32That is very, very striking, isn't it?
0:55:32 > 0:55:35- And that is because the bacteria were unable to grow in there.- Right.
0:55:35 > 0:55:38- It's really done the business, hasn't it?- It has done, yeah.
0:55:38 > 0:55:39The viruses are natural parasites.
0:55:39 > 0:55:44They haven't evolved to completely obliterate their hosts,
0:55:44 > 0:55:45but what you will get is, hopefully,
0:55:45 > 0:55:48in the context of therapy where you're treating
0:55:48 > 0:55:49a patient with an immune system,
0:55:49 > 0:55:52that you'll push the bacteria far enough
0:55:52 > 0:55:54the patient's immune system can take care of whatever's left.
0:55:56 > 0:55:59There have been no clinical trials in the UK yet.
0:56:01 > 0:56:04But I'm hoping that one day phages will make
0:56:04 > 0:56:08a significant contribution to frontline medicine.
0:56:08 > 0:56:09They're not going to replace antibiotics,
0:56:09 > 0:56:12but there are certain roles that they can fulfil that would
0:56:12 > 0:56:14ease the pressure on our existing therapeutics,
0:56:14 > 0:56:16buy us some time to develop new antimicrobials,
0:56:16 > 0:56:19and it can certainly be used alongside antibiotics.
0:56:19 > 0:56:22Phages are going to have to step up and take a role.
0:56:30 > 0:56:33So what have I learnt about antibiotic resistance?
0:56:36 > 0:56:40Well, the biggest lesson is that bacteria will never stop
0:56:40 > 0:56:41evolving ways to fight back...
0:56:43 > 0:56:47..which means we need a multi-pronged response,
0:56:47 > 0:56:52including, of course, new, better-targeted antibiotics.
0:56:52 > 0:56:57It's going to take serious resources to turn things around and prevent
0:56:57 > 0:57:00the projected death toll.
0:57:00 > 0:57:02If ten million people a year are going to die by 2050,
0:57:02 > 0:57:04that's not that far away
0:57:04 > 0:57:06if you consider that it takes 20 or 25 years
0:57:06 > 0:57:07to get a new drug to market.
0:57:07 > 0:57:09And you don't just need one new antibiotic -
0:57:09 > 0:57:11you need a whole generation of new antibiotics,
0:57:11 > 0:57:13so it's going to cost tens of billions of dollars, basically.
0:57:13 > 0:57:14And the reality is that,
0:57:14 > 0:57:17if you spend 1 billion getting an antibiotic to the clinic,
0:57:17 > 0:57:19you probably won't make your money back.
0:57:19 > 0:57:20So it's not great business.
0:57:21 > 0:57:25That money has got to come from somewhere and, presumably,
0:57:25 > 0:57:27it's going to be at a government level.
0:57:29 > 0:57:32Last year, the United Nations passed a resolution,
0:57:32 > 0:57:36unanimously signed by 193 countries,
0:57:36 > 0:57:38saying that all countries
0:57:38 > 0:57:41should get together and take action,
0:57:41 > 0:57:44so I do detect movement forwards,
0:57:44 > 0:57:47but these things are slow.
0:57:50 > 0:57:54If we fail to act, we risk plunging medicine back into the Dark Ages.
0:57:56 > 0:57:59But I'm encouraged by the fact there's a vast world of
0:57:59 > 0:58:03microbes out there, packed with potential allies as well as
0:58:03 > 0:58:08enemies - a world which we are only just beginning to explore.
0:58:11 > 0:58:15I'm actually feeling more confident than I was at the beginning of
0:58:15 > 0:58:17this film that we will find ways to combat the threat of
0:58:17 > 0:58:19antibiotic resistance.
0:58:19 > 0:58:23I can only hope that when we develop new weapons, we will treat them
0:58:23 > 0:58:27with greater care and respect than we have in the past.