Michael Mosley vs The Superbugs


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Michael Mosley vs The Superbugs

Michael Mosley looks at what can be done to combat resistance to antibiotics by create a clone of himself in agar and growing on it bacteria taken from all over his body.


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For more than 70 years,

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we've waged war against bacterial infections

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using antibiotics.

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But it's a war we're now losing.

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Drug-resistant superbugs...

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..are spreading.

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To find out what we're up against,

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I'm donating my body to an extraordinary experiment.

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We are going to unleash bacterial hell on a clone of my body.

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Woohoo!

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We're hoping this experiment - which is novel and rather spooky -

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will give us a whole new insight into the way that bacteria

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fight back against antibiotics.

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-That is absolutely revolting.

-It's fabulous!

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I'll search high and low for radical solutions...

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Die, bacteria, die!

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..to stop the spread of the superbugs.

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When I remove the bandage, we should see quite a difference.

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Oh, yeah!

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Is it too late to prevent antibiotic Armageddon?

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Me and my body are about to find out.

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Hello.

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-Good to see you upright.

-Well, it's nice to be upright.

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-Come and have a seat.

-Thank you.

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Hi there.

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A month ago, 57-year-old John Shelton was fighting

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for his life against a sudden bacterial infection.

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HE EXHALES LOUDLY

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-Good.

-When I arrived here, they opened me up, there was a big mass.

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It was very, very infected,

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and the bacteria were already working their merry havoc,

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trashing my body, shutting down my lungs,

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shutting down my kidneys, shutting down everything, pretty much.

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-You don't remember anything?

-Not a thing.

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His lung had almost completely filled up with bacteria,

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or infection, and he wasn't able to oxygenate his blood.

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Bacteria called staph aureus caused the infection.

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They were eventually stopped by a concoction of antibiotics,

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but for a while it was touch and go.

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-HE INHALES AND EXHALES

-Brilliant.

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-EMOTIONAL:

-When they thought he'd had a brain haemorrhage -

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sorry -

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that was not a great moment.

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You know, just one day at a time, really, and you do place your faith

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in the fact there's going to be another antibiotic to come up.

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It's interesting that, you know, there is a lot of technology here,

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there is obviously a fantastic staff

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but, in the end, it's kind of antibiotics versus bacteria.

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That's it. Simple as that.

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There is no doubt in my mind that, without antibiotics,

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I would not be here.

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Before the 1940s, up to a third of deaths were caused

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by bacterial infection.

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A simple cut could kill you.

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Then came antibiotics - drugs able to kill bacteria.

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The first was penicillin,

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discovered by Alexander Fleming in 1928.

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More followed.

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But then, the pipeline dried up.

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No totally new antibiotics

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have been found for more than 30 years.

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And more and more bacteria are becoming resistant

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to our dwindling stock...

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..including superbugs,

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which threaten to send modern medicine back to the Dark Ages.

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Around 700,000 people die every year because of drug-resistant

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strains of infections like E. coli

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and TB, but that figure could soar to around 10 million a year

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by the middle of this century if urgent action isn't taken.

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Increasing numbers of people are finding that antibiotics are

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no longer working.

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People like Slawa.

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Slawa's foot is so infected with E. coli.

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It could lead to her whole leg being amputated.

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Be warned, this glimpse into a post-antibiotic world

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is gruesome.

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So, if you are squeamish, look away now.

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'If we do nothing,

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'modern medicine in all its finery will become much more hazardous.'

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Cancer therapy, immunotherapy...

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I mean, just simple infections like meningitis.

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All of these things become more hazardous.

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So anti-microbial resistance is the biggest single issue

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which is affecting modern medicine at the moment.

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In 2015, 34 million prescriptions

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were issued for antibiotics in the UK alone.

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Have we created superbugs by popping too many of these pills?

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I want to find out exactly what antibiotics do and why

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bacteria are resisting them.

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Time for an unusual experiment.

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So I have done a lot of strange things in my time,

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and a lot of self experiments, but nothing quite like this.

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Now, I'm in pretty good health and I only take antibiotics

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when I absolutely have to, but I am going to explore what

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a powerful antibiotic does to my body

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by making my bacteria visible.

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If you'd like to know, I have not washed for two days.

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-Great.

-All right! Yeah, that's...

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When I start doing these things, I always think,

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"Oh, it sounds like a good idea,"

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and when I actually get there, I start to wonder if it really is.

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THEY LAUGH

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Artist Mellissa Fisher specialises in creating

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living biological sculptures.

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HE LAUGHS

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-Oooh!

-Right in between your toes.

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With Professor Mark Clements of Lincoln University,

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she is leading a team to make

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a living bacterial sculpture out of me.

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So, that's the...the right here.

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Step one - collect material from all over my body

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using cotton-wool swabs.

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On the skin, you've got over 1,000 different types of bacteria.

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And each person is unique.

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All different parts of the body will have slightly different

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micro flora, depending on whether it's a moist area,

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whether it's a dry area, oily area...

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By moist, I'm thinking armpits, probably.

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Yeah, the very moist areas...

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The armpit and the groin are particularly good.

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-OK. I might do my own groin.

-Yes. Yeah, yeah, yeah.

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Next, I'm wrapped in plaster to create a mould of me...

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Woo!

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..and given a full body wax in the process.

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YELLS: Ow!

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Do you want your hair back?

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THEY LAUGH

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Our home for this experiment is Imperial College in London.

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It's right on that edge, there.

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Here, our team of scientists and sculptors turn my body mould

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into possibly the world's largest Petri dish by filling it

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with a nutrient-rich jelly called agar.

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Good morning, gang. Good morning.

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After 12 hours, the agar jelly has set.

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It is like Tutankhamen's tomb, isn't it?

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All right, so nice and gently, up and out.

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There's two parts to this experiment,

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which is why my rather spooky clone is split in half.

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-The foot's out.

-Woohoo!

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That is wonderfully weird.

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On one side, we want to grow bacteria from all over my skin

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to see what's living on me.

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It kind of looks like me, I must admit that.

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A slightly bald version of me, but...

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THEY CHUCKLE Wow.

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On the other side, we've added a broad-spectrum antibiotic used

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in hospitals against a wide range of infections.

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But before we even get the chance to add my bacteria,

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something else has snuck in.

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What's the green stuff?

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-Does this suggest the presence of bacteria already, then?

-It does.

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On this side, where we don't have any antibiotics,

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-then there has been some growth of bacteria.

-Right.

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So even given the tiniest opportunity,

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the bacteria have got stuck in.

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They do, they do. Yes, yep, yep. They're everywhere.

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We don't know where these green bacteria have come from.

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But you can see that the antibiotic embedded on the left-hand side

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have so far stopped the invader from growing.

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Time to add bacteria collected from my body.

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These are all the swabs we've taken of your body.

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We're going to start with the bottom of the feet, so number 20.

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We want to make visible the invisible microbes -

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mainly bacteria - that live on a healthy human.

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So we're adding each of my samples to the corresponding

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part of my clone.

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Let's see what they make of their new home.

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OK, we can do this.

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Our giant Petri dish is sealed into an airtight case.

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It really does feel like they're taking my body and embalming it.

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Whoa!

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-Oop, the foot's gone.

-Oh, no!

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Despite a couple of rather nasty foot injuries...

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..Microbial Michael is now ready for our experiment to start.

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Which microbes will thrive and where?

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I would expect, within the next few days,

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we'll start seeing them emerge on that side.

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The question is, will they be able to overcome the antibiotics

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and start growing on this side?

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The truth is, we have absolutely

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no idea what is going to happen next, because this sort of thing

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has never been done on this sort of scale before.

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We simply have to wait to find out.

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Time for a road trip.

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I want to dig deeper into the roots of the crisis.

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So why are more and more bacteria becoming resistant?

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Is it simply that we're overdoing the antibiotics,

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or is it more complicated than that?

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I recently read about a fascinating discovery made here,

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in New Mexico, which changed the way I think about antibiotic resistance.

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Now, this is the spot. Gorgeous, isn't it?

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Unfortunately, what I am looking for is not here, on the surface.

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It is deep underground.

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And I say unfortunately because I am pretty claustrophobic.

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My guide is Dr Hazel Barton.

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-Hey-ho. Hello.

-Hi, Michael, how are you doing?

-Glad to see you.

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Hazel's a microbiologist who searches for new species

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of bacteria living deep under Carlsbad National Park,

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in a vast network of caves.

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-Thank you. What's the longest you've been down here for?

-Eight days.

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-Eight days? Cool. Journey to the centre of the earth.

-Yeah.

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So we're getting off the tourist trail here.

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Blimey. It gets narrower, doesn't it?

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-It's quite big in here.

-Yeah. It's cool.

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It was in 2012 in a cave much deeper than I'm able to go that

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Hazel's team made their breakthrough discovery.

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So the kind of areas that we sample look quite a bit like this.

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Hazel took a bunch of bacterial samples from the cave and

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sent them off to a lab for analysis.

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The results shocked everyone.

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So I sent him just 100, right?

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He started testing them, and he's like,

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"You're not going to believe this,

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"but they are resistant to everything."

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-Blimey.

-Everything that's used...

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So these were bacteria you found on a wall in a cave.

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Much more remote than this,

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-much further away.

-That had not seen humans for...

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We know humans had never been in there because we know...

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we had the exploration records,

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so there was no impact on it.

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And they were resistant to practically every antibiotic

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-that's used in the clinic.

-Wow.

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That is both incredibly exciting and incredibly scary.

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Nobody had ever thought that you would find resistant bacteria

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down in the bottom of a bloody cave.

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They'd had no interaction with humans,

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but the bacteria Hazel found in the cave were resistant to

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a huge array of antibiotics we use in modern medicine.

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This resistance had clearly evolved over millions of years

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without us having anything to do with it.

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Why?

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Well, it makes sense when you think of antibiotics

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not as man-made but the by-product of war between microbes.

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They make chemical weapons to destroy their enemies and

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steal their resources...

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..weapons we have learnt to exploit as antibiotics.

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The bacteria living deep in the cave have had millions of years to

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evolve weapons that can target and destroy even their toughest rivals.

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The battle for scarce resources like nutrients and energy is

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particularly brutal down here, in the caves.

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It's really starved down here. There's no resources.

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It's probably one of the most starved environments on Earth

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because, if you think about it, any energy needs to come in through

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the rock, and so there's a big competition for nutrients.

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The fewer the resources, the more intensely the microbes battle,

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and that creates resistance because the bacteria under

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attack don't just lie back and die.

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When billions of bacterial cells are bombarded,

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all it takes is for one cell to mutate its DNA...

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..in such a way that the antibiotic can no longer kill it.

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This ability to resist then spreads...fast.

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So developing resistance to antibiotics is an entirely

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natural process, which the bacteria

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of Carlsbad have taken to the extreme.

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-So, a fierce competition going around us all the time.

-Uh-huh.

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Microbes producing antibiotics,

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but this is all happening millions of years before Fleming and

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his friends at Oxford actually developed penicillin.

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Right. And that's what we discovered down here that kind of blew

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everybody's mind, is the thought that resistance and that antibiotic

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battle is because we've been using antibiotics,

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but it can't be down here cos these guys have never seen

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the antibiotics that Fleming, everyone has made since.

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But if resistance to antibiotics arises naturally,

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what does that mean for us?

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Let's see if Microbial Michael has any answers.

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Bloody hell. That is grotesque.

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We've left him alone for a few days,

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and the bacteria swabbed from my body have run riot.

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I'm hoping immunologist Dr Sheena Cruickshank

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from Manchester University

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can help me make sense of what's happening.

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Michael, meet Michael.

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That is so weird.

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-I just think it's so exciting to be able to see...

-It is both exciting

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and really, really disgusting, I have to say.

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There's something, as well, about seeing me down there, effectively

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covered with this stuff.

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I think you should be looking at this as showing you the

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amazing life that is living on you.

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We're starting on the right-hand side,

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where there's no added antibiotic.

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That means these different-coloured bacteria should be part of my

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normal skin flora.

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Look at this amazing white, blue...

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OK, I thought white, blue meant there was nothing growing there,

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but there is something?

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No, that's actually growing over the blue,

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and that's really exciting

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-because it suggests that perhaps it is battling with the blue.

-OK.

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It's competing with it.

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And I think that's Staphylococcus epidermidis,

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and that's a really common skin bacteria.

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And we actually know that some bacteria make anti-bacterials,

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so they compete with each other and they kill other bacteria.

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So, perhaps that's what's happening here.

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So we're kind of seeing warfare in action between the bacteria.

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Absolutely.

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What this side of this experiment is showing us very colourfully is

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how bacteria in a healthy body keep each other in check as they

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battle for space and nutrients.

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Because most bacteria living on us are harmless or beneficial,

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in a balanced ecosystem, they leave limited room

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for the bad bugs - the pathogens.

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Behind the scenes, our team is identifying exactly what's grown

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using DNA analysis.

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And they found something potentially nasty up my nose.

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This is really interesting.

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If you look around your nose there, around your nostril,

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there is Staphylococcus aureus growing there.

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That is the sort of orangey...

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-They call it the golden staph, don't they?

-Yeah.

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A lot of people - about a third of people -

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have Staphylococcus aureus in their nostrils.

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It's quite, quite normal.

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But a lot of people associate it with being a pathogen.

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In the right circumstances, it's fine.

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In the wrong, it can be deadly.

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If our immune system takes a hit, some species amongst our bacteria

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can get out of control and do serious harm.

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That's what then relatives of the golden staph aureus in my nose did

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to patient John Shelton,

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overrunning his body's defences and very nearly killing him.

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On this side of the experiment,

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my bacteria are keeping each other in check, just as I'd expect.

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But on the other side, it's a different story.

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So we are coming across to the side which was actually enriched

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-with antibiotics, wasn't it?

-Mm-hm.

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Peer past the fog of condensation caused by

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so much microbial activity,

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and our time-lapse cameras reveal that even on the side which

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is heavily impregnated with broad-spectrum antibiotics,

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there are still bacteria growing.

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Though, admittedly, there are a lot less of them.

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Here, just here, at the top of the head, you can see,

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there's actually quite a few clear zones.

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So that suggests that certainly the antibiotic is doing its job

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in areas, and it's certainly been controlling in this area

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the blue, which was kind of taking over everything.

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One of the things that is very striking to me

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-is that on the other side, there's competition going on...

-Mm-hm.

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..which suggests that wiping out all your bacteria is

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a bad idea because actually you do want sort of good bacteria,

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if you like, to kind of compete with the pathogens and stop them

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-encroaching.

-Absolutely.

0:21:330:21:35

What this demonstrates very clearly is you shouldn't take

0:21:380:21:41

a broad-spectrum antibiotic unless you really need to.

0:21:410:21:45

As the caves of New Mexico showed us,

0:21:510:21:54

the more bacteria are attacked, the more they will resist.

0:21:540:21:58

But there is also an unfortunate fact - that broad-spectrum

0:22:040:22:07

antibiotics carpet bomb friend and foe indiscriminately.

0:22:070:22:11

There is a lot of collateral damage amongst the benign

0:22:130:22:16

and beneficial species.

0:22:160:22:18

This accelerates resistance because surviving pathogens now have

0:22:240:22:28

less competition for resources,

0:22:280:22:30

and they can colonise the whole battlefield.

0:22:300:22:34

If one of these survivors is resistant to multiple drugs

0:22:370:22:41

and potentially harmful, it's a superbug.

0:22:410:22:43

The bad news for me is the team have found two growing on my clone.

0:22:460:22:51

One that is particularly interesting is an organism called

0:22:510:22:54

Enterococcus faecium.

0:22:540:22:56

And this is an entirely normal part of our gut flora.

0:22:560:23:00

But if it gets into the wrong parts of the body,

0:23:000:23:02

or if the person has a compromised immune system,

0:23:020:23:06

it can cause really serious invasive infections.

0:23:060:23:09

And because it's inherently resistant to antibiotics,

0:23:090:23:12

it's very, very hard to treat.

0:23:120:23:13

The team has also found Pseudomonas growing through the antibiotic.

0:23:160:23:20

It's not part of my skin flora, but a travelling pathogen

0:23:230:23:26

that can cause infection and pneumonia

0:23:260:23:28

if it gets inside our bodies...

0:23:280:23:30

..say, through an open wound.

0:23:320:23:34

Microbial Michael has shown me superbugs on my skin.

0:23:370:23:41

But what about inside me, where some really important stuff happens?

0:23:450:23:50

I've sent off a very personal sample to be analysed.

0:23:520:23:57

So, we've received our poo sample from Michael.

0:23:590:24:03

And we want to have a look to determine if he's got any

0:24:030:24:06

resistant bacteria.

0:24:060:24:07

When you think about antibiotics,

0:24:090:24:10

most of these us will take these

0:24:100:24:12

orally, and also we'll take it

0:24:120:24:14

with a drink of water,

0:24:140:24:15

so therefore, the antibiotics will hit the gut first.

0:24:150:24:18

Our guts and intestines are home to at least 1,000 different

0:24:210:24:24

species of bacteria.

0:24:240:24:25

But now there's new research about what can happen to them when

0:24:280:24:32

we take antibiotics.

0:24:320:24:33

The striking thing about

0:24:350:24:38

a healthy person who takes an antibiotic

0:24:380:24:40

is that, in all likelihood,

0:24:400:24:43

they will get resistant bacteria

0:24:430:24:46

in their tummies - in their colon, actually -

0:24:460:24:49

after about seven days.

0:24:490:24:52

And with some antibiotics,

0:24:520:24:53

these resistant bugs last in their tummies for up to a year.

0:24:530:24:59

That sounds like another compelling reason not to take antibiotics

0:25:010:25:05

unless you really have to.

0:25:050:25:07

I'm hoping my gut doesn't contain resistant bacteria.

0:25:080:25:12

Right, so you had my poo samples. What did you find?

0:25:120:25:15

-So...

-'Lindsay has tried growing my gut bacteria

0:25:150:25:19

'on plates containing four clinically important antibiotics.'

0:25:190:25:23

-Presumably, these plates should be clear of bacteria.

-Yeah.

0:25:230:25:27

If you had susceptible bacteria, then they should be clear,

0:25:270:25:29

but as you can see, there's multiple colonies on each of

0:25:290:25:32

the plates, which would suggest they are resistant to that antibiotic.

0:25:320:25:35

That does surprise me.

0:25:350:25:36

I haven't had that many antibiotics in my life.

0:25:360:25:38

Well, I was going to ask,

0:25:380:25:39

when was the last time you had a course of antibiotics?

0:25:390:25:41

Probably about four years ago.

0:25:410:25:43

Yeah, OK, so that's quite a long time ago,

0:25:430:25:45

but maybe does correlate with some of the data that we've shown.

0:25:450:25:49

That's a nasty surprise. I've got bacteria growing inside me

0:25:490:25:52

which are resistant to all four antibiotics -

0:25:520:25:55

one of which I've never even taken.

0:25:550:25:58

I know the name, but I think I would know if I'd had it.

0:25:580:26:01

Yeah, you would probably know if you had vancomycin.

0:26:010:26:04

It's a last-resort antibiotic,

0:26:040:26:05

-so this is what you get if you're really ill.

-OK.

0:26:050:26:08

That is really quite worrying, I must admit.

0:26:080:26:11

And what is really quite striking is the fact that the main

0:26:110:26:15

culprit in terms of having antibiotic resistant genes

0:26:150:26:18

is E. coli.

0:26:180:26:19

Blimey. I have E. coli in my gut which is resistant to everything.

0:26:190:26:23

-Yes.

-Blimey. That's bad news!

0:26:230:26:25

OK. That's not what I was hoping to hear.

0:26:250:26:28

There are lots of different strains of E. coli. A few are very nasty.

0:26:320:26:36

We don't know what strain I've got,

0:26:380:26:41

but we do know it is very resistant.

0:26:410:26:44

Now, that was an unpleasant surprise.

0:26:450:26:47

It's one thing to talk about antibiotic resistance,

0:26:470:26:50

but to discover that I've got these E. coli,

0:26:500:26:53

and they are resistant to all sorts of antibiotics is,

0:26:530:26:56

I must admit, worrying.

0:26:560:26:57

I'm not really worried by the fact it's E. coli.

0:26:590:27:03

It's the resistance bit.

0:27:030:27:05

Why?

0:27:050:27:06

Well, once resistance emerges in one species of bacteria,

0:27:060:27:10

it can spread to other species.

0:27:100:27:12

It's all to do with the way they exchange genes,

0:27:120:27:15

as Sheena can explain.

0:27:150:27:18

We get all our DNA from our parents, - so you get half from your mum,

0:27:180:27:21

half from your dad. That's your lot. You don't get any more.

0:27:210:27:25

You might see that chap down the corridor who never catches

0:27:250:27:28

a cold and think, "Oh, I'd love to be able to steal that ability."

0:27:280:27:31

But we can't.

0:27:310:27:33

But imagine you could.

0:27:330:27:34

Imagine you could steal DNA and swap DNA just as easily as you swap your

0:27:340:27:39

e-mail or your telephone number. And basically, bacteria can do that.

0:27:390:27:44

It's called horizontal gene transfer,

0:27:440:27:46

and this is the way antibiotic resistance can spread.

0:27:460:27:50

Using this trick,

0:27:550:27:56

different species of bacteria share genetic information...

0:27:560:27:59

..including the ability to resist a specific antibiotic.

0:28:020:28:05

The bacteria don't even have to be touching because they can also

0:28:090:28:13

pick up bits of genetic information left in the environment around them.

0:28:130:28:17

That means the E. coli inside me could, theoretically,

0:28:220:28:25

share its genes with other species...

0:28:250:28:27

..and turn my gut into a factory of resistant bacteria.

0:28:280:28:32

And we have plenty of evidence that really does happen.

0:28:360:28:40

Resistance is spreading from microbe to microbe.

0:28:400:28:43

Wherever antibiotics are used intensively, such as hospitals,

0:28:450:28:49

more resistant bacteria emerge.

0:28:490:28:52

They share their genes. They multiply.

0:28:520:28:54

This explains how superbugs like MRSA and E. coli can resist

0:28:560:29:01

so many different drugs.

0:29:010:29:02

And they don't stay confined inside our hospitals...

0:29:040:29:07

..because, like us, bacteria can travel.

0:29:080:29:11

And people aren't the only source of resistant bacteria.

0:29:130:29:17

Globally, half of all antibiotics are given to animals.

0:29:170:29:21

COW LOWS

0:29:210:29:23

In countries like America and China,

0:29:230:29:25

they are even widely used as growth promoters.

0:29:250:29:28

COW LOWS

0:29:280:29:30

Animals and humans alike pump out more and more resistant bacteria.

0:29:320:29:37

But how far is the wave of resistance spreading?

0:29:390:29:42

In Cornwall,

0:29:490:29:50

a pioneering new study has found evidence that resistant bacteria are

0:29:500:29:55

travelling through our waterways, out to sea, and then back again,

0:29:550:30:00

into humans.

0:30:000:30:01

Hi. I'm going to talk to you about the Beach Bums survey.

0:30:020:30:07

We recruited 300 people to our survey -

0:30:070:30:11

surfers and people who don't surf, as well -

0:30:110:30:16

and asked them to collect swabs of their faecal material.

0:30:160:30:20

You take the swab, send it back to us in the post,

0:30:200:30:23

and then we test it for the presence of resistant bacteria.

0:30:230:30:26

What we found is that a greater proportion of surfers have

0:30:270:30:31

resistant bacteria in their guts compared to people who don't surf.

0:30:310:30:35

We think that, if you swallow a lot of seawater,

0:30:390:30:42

that some of the bacteria that are present in the seawater

0:30:420:30:45

survive and go on to live inside...inside your gut.

0:30:450:30:48

If resistant bacteria can make it out to sea and then into surfers,

0:30:520:30:56

I could have picked up the resistant E. coli in my gut from, well,

0:30:560:31:00

just about anywhere.

0:31:000:31:01

The good news is that in the UK and some other countries,

0:31:080:31:11

antibiotic use in farming has started to come down.

0:31:110:31:15

But there's no putting the genie back in the bottle.

0:31:200:31:23

Resistant bugs are in our bodies and all around us.

0:31:250:31:28

There isn't any doubt that we have been complacent

0:31:310:31:35

and we have walked into this huge problem.

0:31:350:31:39

But humans have been between a rock and a hard place here.

0:31:400:31:44

They want to use antibiotics, but as soon as they use them,

0:31:440:31:47

resistance arises.

0:31:470:31:49

Because they are life-saving, if you stop using antibiotics, people die.

0:31:490:31:55

MONITOR SIGNALS FLATLINE

0:31:570:31:59

At the end of the day,

0:31:590:32:01

we need new antibiotics.

0:32:010:32:03

Trouble is, modern medicine hasn't found

0:32:070:32:10

a totally new type of antibiotic in more than 30 years.

0:32:100:32:13

Each new drug involves a long and complex process of chemical

0:32:160:32:19

engineering and testing.

0:32:190:32:21

They are certainly difficult to make from scratch.

0:32:240:32:28

Instead, scientists have relied on finding new microbes,

0:32:280:32:31

growing them and then trying to identify and extract any

0:32:310:32:34

chemicals with potential antibiotic properties.

0:32:340:32:37

One problem is that many microbes simply won't grow using

0:32:430:32:46

traditional lab techniques.

0:32:460:32:48

And without being able to grow them,

0:32:480:32:50

we will struggle to develop new antibiotics.

0:32:500:32:53

Time to search out some novel solutions.

0:33:000:33:03

Here in Boston, I've come to meet a maverick microbiologist who,

0:33:050:33:09

I'm told, has developed a whole new way of growing bacteria

0:33:090:33:13

and, in the process, discovered possibly the first new class

0:33:130:33:16

of antibiotics in decades.

0:33:160:33:18

Dr Slava Epstein has promised to show me his secret.

0:33:200:33:24

Do you see a suitable spot somewhere around here?

0:33:260:33:28

We can find a suitable spot just about anywhere on the planet.

0:33:280:33:34

So, the first thing that happens, we collect soil.

0:33:340:33:37

We collect soil.

0:33:370:33:39

We don't have to have too much of it

0:33:390:33:41

because every gram of soil is

0:33:410:33:44

easily a billion or 10 billion cells.

0:33:440:33:46

But what we're going to do with the cells in the lab is going to

0:33:460:33:50

be very different.

0:33:500:33:51

Two thirds of our most important antibiotics were originally found

0:33:520:33:56

in microbes living in soil, a well which looked like it had run dry.

0:33:560:34:02

But now, Slava has thrown out the 130-year-old Petri dish and

0:34:020:34:07

replaced it with a device that, to my eyes, looks equally low-tech -

0:34:070:34:11

a plastic tray into which his assistant adds a diluted

0:34:110:34:15

solution of the soil sample.

0:34:150:34:18

In this vial, there is about 100 cells.

0:34:180:34:20

-100 cells down from a few billion?

-Yes.

-And these are all bacteria?

0:34:200:34:23

These are all bacteria.

0:34:230:34:24

It is starting from this point that things are going to be different

0:34:240:34:27

because we are not going to put them into a Petri dish.

0:34:270:34:29

Instead, we are preparing this device.

0:34:290:34:33

-It is just a collection of wells with a porous bottom.

-OK.

0:34:330:34:37

So, I have to say, this doesn't look that radical.

0:34:390:34:42

Not being a microbiologist,

0:34:420:34:44

I probably don't understand why it is so different.

0:34:440:34:47

It is radical because

0:34:470:34:49

-have I ever mentioned any word nutrient?

-No.

0:34:490:34:53

-Because there is none.

-OK.

-We don't need them.

0:34:530:34:56

Unlike the Petri dish, we do not.

0:34:560:34:58

We do not want to create artificial conditions.

0:34:580:35:01

-Now that will go into the soil...

-OK.

0:35:030:35:06

-..from which these cells came from.

-Ah!

0:35:060:35:10

-That is clever.

-So inside... Thank you.

0:35:100:35:14

-Inside...

-I get it at last.

-..chemically...

-OK, yeah.

0:35:140:35:18

..it will not be different from the outside.

0:35:180:35:20

So if the cells can grow in nature...

0:35:210:35:23

-You are returning them to their normal environment...

-Yes.

0:35:230:35:25

..rather than sticking them in agar.

0:35:250:35:27

-They should be able to grow inside.

-Ah!

0:35:270:35:29

By putting the bacteria back into the soil they came from,

0:35:310:35:35

Slava is encouraging them to grow just like they would in the wild.

0:35:350:35:39

Compared to using agar jelly,

0:35:390:35:42

the results are astounding.

0:35:420:35:44

The difference in colony count between the two methods

0:35:440:35:46

-is 30,000%.

-Wow.

0:35:460:35:49

You can grow 30,000% more cells if you do it this way than if

0:35:490:35:54

you do it the conventional way.

0:35:540:35:56

That's correct.

0:35:560:35:57

This technique means they can grow bacteria that would normally

0:35:580:36:01

be missed, and they have created versions of the device to

0:36:010:36:05

look for novel bacteria in all sorts of environments,

0:36:050:36:08

including the human mouth.

0:36:080:36:11

-Very neat.

-It's also very simple.

0:36:110:36:14

You can really build this device in your garage.

0:36:140:36:19

What excites me about Slava's discovery is it means

0:36:200:36:23

there's clearly a whole world of microbes out there,

0:36:230:36:27

just waiting to be found.

0:36:270:36:29

Imagine you are an ancient Greek looking up at the sky.

0:36:320:36:34

You'd only see a tiny handful of the stars and planets that are

0:36:340:36:38

actually out there.

0:36:380:36:39

In some ways, we are a bit like that ancient Greek when it comes to

0:36:390:36:43

the microbial world.

0:36:430:36:44

There is a vast galaxy of tiny creatures,

0:36:440:36:48

and we are currently only aware of a very small proportion of them.

0:36:480:36:52

We need to start looking for new antibiotics much further

0:37:000:37:03

afield than the soil under our feet.

0:37:030:37:05

Some scientists think seabeds could be rich in antibacterial potential.

0:37:080:37:13

Easier pickings are washing up on our shores with evidence

0:37:160:37:20

clips of seaweed contain microbial agents effective against MRSA.

0:37:200:37:24

And deep in the caves under New Mexico, Hazel Barton's team

0:37:270:37:31

has discovered that millions of years of intense bacterial

0:37:310:37:34

warfare has produced chemicals we may be able to use.

0:37:340:37:39

One of the organisms that we found

0:37:400:37:43

made 38 novel antimicrobial compounds,

0:37:430:37:46

-of which three were new antibiotics.

-Hm.

0:37:460:37:49

So the potential is that people turn their attention to these

0:37:490:37:52

extreme environments - like caves, like the deep ocean, like,

0:37:520:37:55

you know, the Arctic - we are going to have this explosion

0:37:550:37:58

in new compounds over the next ten, 15 years.

0:37:580:38:02

The hunt for antibiotics is not just in extreme environments

0:38:070:38:11

but anywhere that's home to novel microbes.

0:38:110:38:14

Professor Matt Hutchings has found what could be

0:38:150:38:18

a novel antibiotic in...

0:38:180:38:21

an ant farm.

0:38:210:38:22

It's an amazing system.

0:38:250:38:26

They've been using antibiotics for 50 to 60 million years.

0:38:260:38:29

The secret Matt's team has unlocked is in the relationship

0:38:320:38:36

between these leaf-cutter ants and their food source.

0:38:360:38:39

The fungus is the only food for this whole ant colony.

0:38:400:38:43

And if they smell any foreign fungi that might cause disease in there,

0:38:430:38:47

they cut it out, they carry it over to this part,

0:38:470:38:50

which is the waste dump, which is usually outside the nest.

0:38:500:38:53

They rub their bodies against it and then they dig it back into

0:38:530:38:56

the ground.

0:38:560:38:57

The really interesting thing for us is the reason they rub their bodies

0:38:570:39:00

against it is because their bodies are covered in

0:39:000:39:02

antibiotic-producing bacteria that the ants can use to defend

0:39:020:39:05

their fungus against disease.

0:39:050:39:07

Matt's lab has extracted a couple of experimental new antibiotics

0:39:110:39:15

from the bacteria on the ants.

0:39:150:39:17

They haven't yet been tested on humans.

0:39:210:39:24

So, time for part two of our experiment, using my body -

0:39:280:39:32

well, bits of my body - to test out some of these novel drugs.

0:39:320:39:36

We are creating a biohazard and infecting different parts of

0:39:400:39:43

me with three of the most common multi-drug-resistant superbugs -

0:39:430:39:48

MRSA, salmonella and Pseudomonas.

0:39:480:39:53

Where should I put it, then?

0:39:530:39:54

-On the fingers.

-On the fingers, in there? OK.

0:39:540:39:56

Then, we'll try to cure them.

0:39:560:39:58

First, I want to see if ant antibiotic can tackle

0:40:010:40:05

an infection of MRSA...

0:40:050:40:06

..on my face.

0:40:100:40:11

MRSA can cause skin infections.

0:40:150:40:17

If it gets inside us and attacks our lungs,

0:40:180:40:21

it can be particularly dangerous.

0:40:210:40:23

We've given my face a few days for the bacteria to take hold.

0:40:250:40:28

So, this is the ant antibiotic, and it is genuinely new and

0:40:320:40:37

really rather exciting because, as you can see, it is really working,

0:40:370:40:41

because that white disc on my forehead there,

0:40:410:40:43

there's a zone of death around it which suggests

0:40:430:40:46

that it really is killing

0:40:460:40:47

all those bacteria.

0:40:470:40:49

So the good news is, it's new and it's working.

0:40:490:40:52

The bad news is it's probably ten, 15, 20 years away.

0:40:520:40:57

Why so long?

0:40:590:41:00

Well, finding an antibiotic in nature is just the first stage in

0:41:000:41:04

an expensive and very complicated process.

0:41:040:41:08

To discover a new antibiotic, I mean,

0:41:090:41:11

you have to go from the early stage of discovery -

0:41:110:41:13

so isolate bacteria from a place like a leaf-cutter ant nest -

0:41:130:41:16

get those bacteria growing on a plate,

0:41:160:41:18

solve the chemical structure of that antibiotic - which is not trivial -

0:41:180:41:22

and then, of course, you have to get a drug company interested

0:41:220:41:25

because they're the only people with enough money

0:41:250:41:27

to get things through clinical trials.

0:41:270:41:29

The reality is, less than 1% are actually suitable candidates

0:41:290:41:33

and make it through to actually get them to the stage where they're

0:41:330:41:37

approved as safe to use in humans.

0:41:370:41:38

So it can take 15, 20 years and cost, well,

0:41:400:41:43

between half and 1 billion.

0:41:430:41:45

A time lag of 15 to 20 years is massive given that around 700,000

0:41:510:41:57

people already die annually because of antibiotic-resistant bacteria.

0:41:570:42:02

So what are we going to do until new drugs emerge?

0:42:060:42:09

For starters, surely we could use our existing stock more carefully.

0:42:120:42:16

Half of all hospital prescriptions are for broad-spectrum antibiotics.

0:42:180:42:22

And given everything I've learnt, that can't be a good idea.

0:42:250:42:28

Why do doctors continue to use broad-spectrum antibiotics?

0:42:290:42:32

It strikes me as like carpet bombing everything and you'd be better off

0:42:320:42:36

if you were a bit more targeted.

0:42:360:42:37

Well, as a doctor, you're confronted with a dilemma.

0:42:370:42:39

When you see a new patient,

0:42:390:42:41

you don't necessarily have the diagnosis in front of you.

0:42:410:42:43

-So you want to save the patient...

-Mm-hm.

0:42:430:42:45

..and you want to cover all the eventualities.

0:42:450:42:48

And hence, you use a broad-spectrum antibiotic.

0:42:480:42:50

-Right, because you don't know what it is you're trying to hit.

-Exactly.

0:42:500:42:53

To use targeted narrow-spectrum antibiotics, doctors need to

0:42:570:43:01

be able to quickly diagnose the specific infection in a patient.

0:43:010:43:05

For some bugs, like the ones that cause tuberculosis,

0:43:070:43:10

that means taking samples, growing the bacteria

0:43:100:43:14

and sequencing its DNA -

0:43:140:43:16

a process that can take up to ten weeks.

0:43:160:43:19

But Tim's part of a team working on

0:43:220:43:24

a prototype gadget that could massively speed up DNA sequencing.

0:43:240:43:28

So, you see the patient and they spit into your pot.

0:43:300:43:33

Yep. And the DNA from your phlegm goes on there.

0:43:330:43:37

-OK.

-You close it.

0:43:370:43:40

-And then it... This sequences it?

-That sequences it.

-Bloody hell.

0:43:400:43:44

-Now...

-That is really, really impressive, I have to say.

0:43:440:43:47

That is impressive.

0:43:470:43:48

So, how quickly would you then be able to make a diagnosis?

0:43:480:43:52

-The sequencing of the genome will take less than an hour.

-Yeah.

0:43:520:43:56

The analysis takes about two minutes.

0:43:560:43:58

MICHAEL LAUGHS OK, right.

0:43:580:44:00

-OK. Two minutes as opposed to ten weeks?

-Yes.

0:44:000:44:04

Right, that is really crunching it, isn't it?

0:44:040:44:06

And this, presumably, isn't just for TB.

0:44:060:44:10

No. It's of great use for TB, but it can be used for any bacterium.

0:44:100:44:14

If you're able to get a diagnosis within minutes of seeing your

0:44:150:44:19

patient, it enables you to give the correct narrow-spectrum

0:44:190:44:21

antibiotic that targets just those bacteria that are causing the

0:44:210:44:24

illness and nothing else,

0:44:240:44:26

so it's precision bombing rather than carpet bombing.

0:44:260:44:29

If trials in clinics over the next couple of years are successful,

0:44:300:44:33

this device could extend the life of antibiotics by slowing

0:44:330:44:37

the pace of resistance.

0:44:370:44:39

But what if we could also stop some bugs from resisting altogether?

0:44:430:44:47

Some commonly prescribed antibiotics work by getting into

0:44:510:44:54

bacterial cells, and when they hit a lethal dose,

0:44:540:44:57

this causes the bacteria to rupture -

0:44:570:45:01

something they have evolved ways to resist.

0:45:010:45:03

Dr Jess Blair is part of a team from Birmingham University

0:45:120:45:16

with a plan to stop the bacteria fighting back.

0:45:160:45:20

She is going to try and explain the principle behind her approach

0:45:200:45:23

using a bucket as a bacterial cell.

0:45:230:45:27

OK, so you've got a watering can here full of antibiotic.

0:45:270:45:30

If you start pouring that into our bacterial cell, what we hope,

0:45:300:45:33

then, is that this will kill off the bacterial cell.

0:45:330:45:36

So, for argument's sake, let's say our level at which the

0:45:360:45:38

antibiotic becomes toxic is here.

0:45:380:45:41

So you need to keep pouring.

0:45:410:45:43

However, bacteria have a nifty trick.

0:45:440:45:47

In their membranes, they have pumps called efflux pumps.

0:45:480:45:52

So I'm pouring in antibiotics,

0:45:520:45:53

and the bacteria are just pumping them out.

0:45:530:45:56

Pumping them straight back out again.

0:45:560:45:57

So now it's not looking quite so good.

0:45:570:46:00

-Sorry, I'm getting your feet wet.

-Yep.

0:46:000:46:02

It's going to become a bit more difficult for you to get

0:46:020:46:05

the antibiotic towards our line at which it's going to become toxic.

0:46:050:46:08

Right.

0:46:080:46:09

And what happens when they become really antibiotic resistant

0:46:090:46:12

is they make more and more of these pumps.

0:46:120:46:14

OK, that's a very neat trick. So, what can you do about it?

0:46:140:46:17

Well, in my pocket,

0:46:170:46:19

I've got a cable tie to sort of demonstrate this.

0:46:190:46:22

So, we have inhibited the efflux pump.

0:46:240:46:26

-So you're able to keep pouring the antibiotic in...

-There we go!

0:46:260:46:28

..and we're about to reach the level

0:46:280:46:30

which is going to kill our bacterial cell.

0:46:300:46:32

Die, bacteria, die!

0:46:320:46:33

There we go. OK. So that's the theory.

0:46:330:46:36

I mean, how close are we to it in practice?

0:46:360:46:39

When I say we, I mean you, of course.

0:46:390:46:41

Well, people have been able to find molecules that do this.

0:46:410:46:44

The problem is there's no molecules at the moment which are able

0:46:440:46:47

to both inhibit efflux pumps but also are OK to be given to a person.

0:46:470:46:51

Most of the ones that we currently have are toxic to people.

0:46:510:46:54

Because she can't test her inhibitor chemical on a living human being,

0:47:020:47:07

Jess is going to test it instead on a salmonella infection in my hand.

0:47:070:47:12

While she does that,

0:47:160:47:17

Dr Andy Edwards and I are trying out another experimental chemical

0:47:170:47:22

on my other hand, which we have infected with MRSA.

0:47:220:47:25

Andy wants to show me what he calls an antibiotic amplifier.

0:47:270:47:31

It's designed to stop this superbug from resisting

0:47:310:47:34

an existing antibiotic called ciprofloxacin.

0:47:340:47:37

So, what ciprofloxacin does is to break up bacterial DNA.

0:47:390:47:43

It smashes it into lots of small pieces.

0:47:430:47:45

And MRSA is really good at then sticking that back together

0:47:450:47:48

and surviving.

0:47:480:47:49

So what we want to do with our antibiotic amplifier is

0:47:490:47:51

prevent the bacterium from sticking the DNA back together again.

0:47:510:47:55

MRSA has a very bad reputation, doesn't it?

0:47:550:47:57

It has a bad reputation for a good reason.

0:47:570:47:59

So, MRSA causes lots of lots of surgical-site infections and

0:47:590:48:03

other skin infections, particularly in hospitals.

0:48:030:48:05

And once it gets into the blood, it is very, very serious.

0:48:050:48:08

It can attach to your heart, bones and joints.

0:48:080:48:10

So you're going to try and make this non-resistant again,

0:48:120:48:15

reverse it if you like.

0:48:150:48:16

That's right, that's right. We're trying to outsmart the bug.

0:48:160:48:20

Andy's antibiotic amplifier and Jess's pump inhibitor are

0:48:230:48:27

amongst a number of so-called resistance breakers currently

0:48:270:48:30

in development.

0:48:300:48:31

The results from our test certainly suggest they could have

0:48:330:48:36

a promising future.

0:48:360:48:38

Though, the first one is easier to make out on

0:48:380:48:40

a Petri dish than on my agar hand.

0:48:400:48:43

This is the pump inhibitor,

0:48:450:48:47

the one that stops the bacteria pumping out the antibiotics.

0:48:470:48:51

And this one is working rather well.

0:48:510:48:53

You've got the salmonella infection here,

0:48:530:48:57

and it is resistant to the antibiotic

0:48:570:48:59

which is in the rest of the plate.

0:48:590:49:01

But here, in the middle,

0:49:010:49:03

that bit there is working because the area around it is clear.

0:49:030:49:07

So that's promising. That's good.

0:49:070:49:09

Next, the hand that was infected with MRSA.

0:49:130:49:16

What's encouraging is the area that I painted

0:49:180:49:21

on the back of the hand, here,

0:49:210:49:23

which was a mixture of the amplifier

0:49:230:49:26

and the antibiotic, that is clean.

0:49:260:49:29

So that would suggest the amplifier is doing what it should do,

0:49:290:49:32

which is preventing bacteria from reforming their DNA,

0:49:320:49:38

and therefore, the bacteria are being killed.

0:49:380:49:40

That one I give high marks to. That one worked.

0:49:400:49:44

That's encouraging results from one experimental antibiotic

0:49:470:49:51

and two resistance-breakers.

0:49:510:49:52

But none of these cures will be ready to use on you or me

0:49:550:49:58

any time soon.

0:49:580:50:00

BELL CHIMES

0:50:010:50:03

The final thing I want to look at is something which will kill

0:50:030:50:07

bacteria but which isn't actually an antibiotic.

0:50:070:50:10

This is where I normally come.

0:50:120:50:14

At Oxford University, microbiologist

0:50:140:50:17

Dr Alex Betts is investigating

0:50:170:50:19

viruses which naturally attack bacteria.

0:50:190:50:22

Mind your feet, cos we are looking for...something, actually,

0:50:220:50:26

a lot like that. Perfect.

0:50:260:50:28

Alex is one of a handful of scientists in the UK working

0:50:310:50:35

with bacterial phages.

0:50:350:50:37

All right, here we go. Oh, look at that. Isn't that disgusting?

0:50:390:50:43

This is a fresh goose poo, and from these,

0:50:430:50:46

I can isolate the bacteria and the viruses that are inside

0:50:460:50:50

the digestive tract of geese.

0:50:500:50:52

And that I can take back to the lab, and it should be a treasure

0:50:520:50:55

trove of things that could potentially treat disease in humans.

0:50:550:50:59

Lovely.

0:51:010:51:02

I want to see if Alex's viruses can cure me.

0:51:030:51:06

-Here we go.

-Oh, wow.

-I have a gift for you, my lovely face.

0:51:080:51:11

For the scientist who has everything.

0:51:110:51:12

-It's quite weird, isn't it?

-Look at that nose!

0:51:120:51:14

LAUGHING: Thank you(!)

0:51:140:51:16

What we're going to do now is test a type of virus Alex

0:51:190:51:23

has acquired from a sewage farm against a superbug - Pseudomonas.

0:51:230:51:28

This bug causes septicaemia and pneumonia.

0:51:290:51:32

In short, it's very nasty.

0:51:320:51:35

It's a powerhouse of antibiotic resistance. It's a real problem.

0:51:350:51:38

And it's been isolated from food,

0:51:380:51:42

soil, drinking water,

0:51:420:51:43

even really extreme environments like aviation fuel.

0:51:430:51:46

This thing can grow on pretty much anything. So it's...

0:51:460:51:48

-It's a good test, basically.

-Very much so.

0:51:480:51:51

If we can beat this, then we are in a good position.

0:51:510:51:53

-So these are billions of viruses, is that right?

-Yes, indeed.

0:51:550:51:58

These are viruses that infect and kill bacteria,

0:51:580:52:01

just as part of their natural life cycles.

0:52:010:52:04

It's not something we've engineered in the lab.

0:52:040:52:07

These images were taken with a hugely powerful microscope.

0:52:080:52:13

You can see the tiny viruses known as phages clamped on to

0:52:130:52:17

a single bacterial cell.

0:52:170:52:20

Phages are parasites for bacteria.

0:52:200:52:23

They inject their genetic material into a cell,

0:52:250:52:27

forcing it to produce a huge number of new phages.

0:52:270:52:30

These then burst out of the cell, destroying it.

0:52:320:52:35

Research into phages is just getting started in the UK.

0:52:400:52:43

BELLS CHIME

0:52:450:52:47

But in Eastern Europe, they've been experimenting with

0:52:470:52:50

viruses therapeutically for almost a century.

0:52:500:52:53

And in the Polish city of Wroclaw,

0:52:550:52:57

there's a specialist clinic that's achieving really impressive results

0:52:570:53:01

in treating people with antibiotic-resistant infections.

0:53:010:53:04

THEY SPEAK POLISH

0:53:070:53:08

Remember the gruesome wound in Slawa's foot?

0:53:100:53:14

Her E. coli infection is so bad and so untreatable,

0:53:140:53:18

there's a serious risk she will have to have it amputated.

0:53:180:53:21

Now she's hoping phages can save it.

0:53:210:53:24

Through our experimental phage therapy,

0:53:240:53:27

we want to protect her against amputation.

0:53:270:53:29

I'm going to apply

0:53:310:53:33

phage preparation into the wound.

0:53:330:53:35

And I show you how I do it.

0:53:350:53:37

This is a phage preparation against E. coli.

0:53:370:53:40

The doctors hope to get Slawa's infection under control

0:53:420:53:46

and then perform an operation to save the foot.

0:53:460:53:49

Look away for a minute if you're squeamish.

0:53:490:53:52

The patient will have surgery, which aim is to cut

0:53:560:54:01

this dead tissue,

0:54:010:54:03

but we apply phages before to decrease a lot of bacteria.

0:54:030:54:08

After surgery, Slawa will receive combination therapy using

0:54:320:54:36

phages and targeted antibiotics.

0:54:360:54:38

SHE LAUGHS

0:54:520:54:54

It will be months before Slawa knows if the therapy is working.

0:54:540:54:57

Fingers crossed.

0:54:570:54:58

In the meantime, let's see how my virus treatment is getting on.

0:55:010:55:04

-Here we go.

-OK.

0:55:050:55:07

Now, it doesn't look obviously different.

0:55:070:55:09

So, under white lights, the bacteria aren't particularly visible,

0:55:090:55:12

cos they have kind of a similar colour to the agar,

0:55:120:55:14

but there is this neat trick.

0:55:140:55:16

They produce a molecule that fluoresces very intensely

0:55:160:55:18

under UV light.

0:55:180:55:19

-Look at that.

-Yeah!

0:55:210:55:23

-And hopefully, when I remove the bandage...

-Yeah.

0:55:230:55:26

-..we should see quite a difference.

-Oh, yeah!

0:55:260:55:29

That is very, very striking, isn't it?

0:55:300:55:32

-And that is because the bacteria were unable to grow in there.

-Right.

0:55:320:55:35

-It's really done the business, hasn't it?

-It has done, yeah.

0:55:350:55:38

The viruses are natural parasites.

0:55:380:55:39

They haven't evolved to completely obliterate their hosts,

0:55:390:55:44

but what you will get is, hopefully,

0:55:440:55:45

in the context of therapy where you're treating

0:55:450:55:48

a patient with an immune system,

0:55:480:55:49

that you'll push the bacteria far enough

0:55:490:55:52

the patient's immune system can take care of whatever's left.

0:55:520:55:54

There have been no clinical trials in the UK yet.

0:55:560:55:59

But I'm hoping that one day phages will make

0:56:010:56:04

a significant contribution to frontline medicine.

0:56:040:56:08

They're not going to replace antibiotics,

0:56:080:56:09

but there are certain roles that they can fulfil that would

0:56:090:56:12

ease the pressure on our existing therapeutics,

0:56:120:56:14

buy us some time to develop new antimicrobials,

0:56:140:56:16

and it can certainly be used alongside antibiotics.

0:56:160:56:19

Phages are going to have to step up and take a role.

0:56:190:56:22

So what have I learnt about antibiotic resistance?

0:56:300:56:33

Well, the biggest lesson is that bacteria will never stop

0:56:360:56:40

evolving ways to fight back...

0:56:400:56:41

..which means we need a multi-pronged response,

0:56:430:56:47

including, of course, new, better-targeted antibiotics.

0:56:470:56:52

It's going to take serious resources to turn things around and prevent

0:56:520:56:57

the projected death toll.

0:56:570:57:00

If ten million people a year are going to die by 2050,

0:57:000:57:02

that's not that far away

0:57:020:57:04

if you consider that it takes 20 or 25 years

0:57:040:57:06

to get a new drug to market.

0:57:060:57:07

And you don't just need one new antibiotic -

0:57:070:57:09

you need a whole generation of new antibiotics,

0:57:090:57:11

so it's going to cost tens of billions of dollars, basically.

0:57:110:57:13

And the reality is that,

0:57:130:57:14

if you spend 1 billion getting an antibiotic to the clinic,

0:57:140:57:17

you probably won't make your money back.

0:57:170:57:19

So it's not great business.

0:57:190:57:20

That money has got to come from somewhere and, presumably,

0:57:210:57:25

it's going to be at a government level.

0:57:250:57:27

Last year, the United Nations passed a resolution,

0:57:290:57:32

unanimously signed by 193 countries,

0:57:320:57:36

saying that all countries

0:57:360:57:38

should get together and take action,

0:57:380:57:41

so I do detect movement forwards,

0:57:410:57:44

but these things are slow.

0:57:440:57:47

If we fail to act, we risk plunging medicine back into the Dark Ages.

0:57:500:57:54

But I'm encouraged by the fact there's a vast world of

0:57:560:57:59

microbes out there, packed with potential allies as well as

0:57:590:58:03

enemies - a world which we are only just beginning to explore.

0:58:030:58:08

I'm actually feeling more confident than I was at the beginning of

0:58:110:58:15

this film that we will find ways to combat the threat of

0:58:150:58:17

antibiotic resistance.

0:58:170:58:19

I can only hope that when we develop new weapons, we will treat them

0:58:190:58:23

with greater care and respect than we have in the past.

0:58:230:58:27

For 70 years we've waged war against harmful bacteria using antibiotics. But bacteria are fighting back and today more and more bacterial infections are becoming resistant to antibiotics. Drug-resistant superbugs are spreading; not just MRSA - also TB, pneumonia, e-coli. In Britain, hundreds are already dying of these infections - mainly the very young or the frail and elderly. But experts warn that unless we crack the problem, by 2050 we'll be facing a massive health crisis with over 10 million people dying of resistant bacterial infection worldwide every year.

Michael Mosley goes in search of the causes of this crisis and new solutions to overcome it. Have we caused the resistant superbug crisis by overusing antibiotics?

At the heart of the film is an unprecedented experiment using "Microbial Michael", a life-sized living bacterial clone of Michael Mosley. Using microbes taken from all over his body and grown on his clone we set out to find out what happens when we take a powerful broad spectrum antibiotic. What are the effects of the antibiotic on our bacteria - both beneficial bacteria and potentially harmful bugs we have on our bodies?

Michael discovers to his surprise that growing on his clone are bugs that have acquired resistance to antibiotics - and that some of them could even turn nasty if his immune system were ever to become compromised. It's worrying news.

But how do bacteria acquire resistance to antibiotics? In New Mexico, Michael discovers that deep down in a hard-to-access cave system are bacteria able to resist nearly every antibiotic we use in modern medicine. Yet they have never - in millennia - had any interaction with humans or our medicines. How can this have happened?

It makes sense when we learn that antibiotics are not man-made; rather they're chemical weapons made by one species of bacteria to target and destroy other kinds of rival bacteria. And in order to survive, the target bacteria have had to evolve resistance; it's a natural process that's been going on for millions of years - long before the discovery of penicillin.

What does this mean for us, and for our dependence on antibiotics - are we off the hook? The answer is a firm no - because although the development of resistance is a natural process, nonetheless our overuse of antibiotics in medicine and farming massively accelerates the process. So we need to use our existing antibiotics more carefully, and we desperately need new antibiotics.

In a trip that will take us to the US, to Poland and to research labs around the UK we'll meet the 'resistance hunters' - scientists who are trying to find new ways of beating resistant superbugs. And in a finale to the Microbial Michael experiment, some of his bacterial clone's body parts - his face and his hands - are infected with superbugs. Can any of the new treatments get rid of them?