Horizon (1964–…): Season 49, Episode 6 - Defeating the Superbugs - full transcript

All around us
there is an invisible world.

The microscopic world of bacteria.

Some of these
bacteria are going rogue,

becoming superbugs that we
can't control.

They're probably smarter than I am.

They're able to adjust fire much
quicker than me

so they're able to develop
resistance a whole lot faster

than I can develop an antibiotic.

Antibiotics are one of the miracles
of modern medicine

and scientists now worry
that superbugs are emerging

which are becoming totally resistant
to these drugs.



That's the scary day, that's the day
when for some unlucky person

their day has come, right,
that the drugs no longer work.

But researchers are engaged in
a fight-back against the superbugs.

Bacteria have
been on the earth for billion years,

humans have been on the earth a few
hundred thousand years.

Right so, they have the accumulated
smarts of eons of generations.

What we do have, as humans,
is we have brains.

The rise of bacteria resistant to
antibiotics

is being seen as a major
public health threat.

So scientists are devising new
and sophisticated ways

to try to defeat the superbugs.

Professor Hazel Barton is
tracking down

one of humanity's greatest
treasures.

To find it she has to venture



to one of the most untouched
places on earth,

hundreds of metres underground.

It's finding a hole, nobody
knows where it goes

and you kind of push and shove
your way through,

and it's
spectacular and it's beautiful

and you're the first person to see it
and you leave the first footprints.

And so you get kind of a man
in the moon feeling to be in there.

She's hunting for something that we
all take for granted.

In these caves are tiny microbes
crucial to our survival.

Where you want to go is where you
can spot bedrock

and it's kind of dry
but near enough the water that

that organic material
can leach in.

And so somewhere like here,
and you can see, this is one here.

These little dots of white
here are the colonies of microbes.

So those are what we go in for
and those are what we go after.

These tiny microbes
are incredibly precious

because they can produce life-saving
drugs we all rely on.

Antibiotics.

Professor Barton is going to the
ends of the earth

because here she can find new
antibiotics.

We need new ones, because the ones
we have are starting to fail.

The last thing you want to do is go
to the clinic, give someone

this drug that's gonna save
their life, and it's not working.

Scientists like Professor Barton
are going to such extreme lengths

because finding new antibiotics
is fast becoming

the most critical concern.

Antibiotics are one of the miracles
of modern medicine.

Since the discovery
of penicillin in 1928,

they have
revolutionized our lives.

They have stopped simple cuts

developing into life-threatening
infections,

saved millions from diseases
like cholera,

diphtheria and tuberculosis.

Antibiotics are so valuable
because they stop and destroy

the bacteria that cause
these life-threatening diseases.

But over the last decade
scientists have witnessed outbreaks

around the world where antibiotics
we have relied on in the past

have stopped working.

These outbreaks have been
caused by new types of bacteria.

Bacteria that can sweep straight
through our antibiotics,

and carry on growing.

These are the superbugs.

And we are becoming
powerless against them.

But by studying these outbreaks,

scientists are hoping to
defeat them.

The Brooke Army Medical Centre
in Texas.

Just a few years ago, this renowned
military hospital

unexpectedly found itself
at the frontline

of the war against superbugs.

It started in 2006 when
Master Sergeant Dan Robles

was just four months into
his deployment to Iraq.

His unit was on a routine patrol,
searching for a weapons cache.

It was about 2.00 in the afternoon,
Baghdad time.

It looked like business as usual,
cars driving back and forth,

people on the side of the streets.

It was quiet.

And there was just a big
flash of light,

it sounded like I had my
head in a bell

and someone was pounding on it
real hard.

There was smoke everywhere.

The patrol had been hit by an IED

which tore into his side
of the vehicle.

Sitting there in the Humvee after
the explosion, I looked down

and I saw that one part of my leg,
my calf muscle,

through the pants of my uniform.

And I didn't want to
look down after that.

He sustained terrible injuries,

and ultimately the combat medics
were unable to save his legs.

Within days, he was back
on home soil at the Brooke
Army Medical Centre,

but he was about to face an even
tougher battle.

His wounds were infected and the
usual antibiotics weren't working.

So they called in the Chief
of the Infectious Disease Service,

Colonel Clint Murray.

You're not necessarily
sure who the enemy is

when you walk in to
see your patient.

I think it's very similar to what
we do in combat,

is we try to figure out what we're
doing who are we fighting?

Why are we fighting them?

Colonel Murray discovered that his
patient had brought back from Iraq

three of the toughest
superbugs to beat.

The first thing to do was protect
the other patients

and control the outbreak.

So what we do is
we try to isolate all our patients,

put them in their private rooms
and before we go in

and out of those rooms,
we put on gowns and gloves

to really prevent the bacteria
from getting on us

so when we get to the
next patient's room

we're not taking the
bacteria with us.

Everyone does this,

so you'll actually see pictures
of Presidents putting this stuff on

before they've gone into
some soldier's room in the past.

It's just what you do.

Now he turned his attention to
treating the infection,

but his usual arsenal of antibiotics
just wouldn't work.

The number of antimicrobial agents
we had were limited to treat them.

So in contrast to giving them
the standard antibiotic

we give anyone that has a wound,
we'd have to sort of

what we call is a bigger gun,
but a more powerful antibiotic.

But these powerful
antibiotics carry a risk.

They're not just toxic to bacteria,
they can be toxic to people too.

I do remember Dr Murray
explaining my situation to me,

and I was like, "OK, let's do it,
whatever we've got to do."

Like most doctors, Colonel Murray
has rarely used these antibiotics

because of the damaging
side effects.

It had started to shut down my
kidneys, I went into renal failure.

And so he comes back and says,
"We've got to stop the antibiotics."

Based upon that, I really figured
out, OK so here are the bacteria

and here's how we're helping you,
but here's how we're hurting you.

I knew it was going to be
a long fight

when it started doing more
damage than good.

They had to keep changing
the antibiotics

as each one became too toxic.

And this time it had
shut down my immune system.

That was probably the most
scary thing ever,

out of my whole ordeal.

No white blood cells,
no immune system.

I had to wear a mask,
I was in isolation.

Any cold, any...you know,
the simple cold could have killed me

because I had nothing to
fight it off.

Dan Robles is living a normal life
back with his family,

but six years after the attack
he still comes here

to check on his ongoing struggle
with the superbugs.

Looking back over the two
battles for his life,

his fight with the superbugs
was the toughest.

When I was hurt, at least
I knew that there was a chance

that I could survive,
and that things were in place

to take care of me and fix me
and make me better.

But as far as
losing your immune system,

there was nothing that any
doctor in the hospital could do

to keep me from getting the simple
cold that could potentially kill me.

That was the scariest.

And it was scary because my family
was right there with me.

And I was more worried about them
watching something like that happen

than me coming back from
Iraq in a box.

The Brooke Army Medical Centre
experienced what happens

when a superbug enters a hospital.

Often the only choice for doctors
is to use antibiotics

which themselves can be harmful.

The antibiotics that I could use
ten years ago

are almost completely
ineffective now

for some of the bacteria we have.

And often times we are resorting

to that last-ditch effort of
antibiotics.

If we don't fix this issue,

we're eventually not going to
have antibiotics.

The reason scientists are concerned
is that over the last ten years,

antibiotic resistance has been
growing across the world,

which has forced scientists to
devise new strategies to combat it.

Dr Ruth McNerney is at the forefront
of the battle against tuberculosis,

a disease caused by bacteria
we thought we'd confined to history.

In the 18th-19th century,

tuberculosis was the biggest
killer, full stop.

I mean, not just in
infectious diseases.

In the middle of the 19th century,
life expectancy was just 41.

In this time before antibiotics,

diseases like TB spread through
the crowded and cramped streets.

It transmits very easily
through the air

so it's very hard
to avoid getting TB,

you don't know you've been exposed,

you don't have to do anything to
catch TB, except continue breathing.

It would just affect everyone.
Young and old.

One of the great
achievements of modern medicine

was the defeat of this disease
with a cocktail of antibiotics.

Today, over 8 million people
live in London

without giving a thought to TB.

But our crowded cities are still
the perfect playground for bacteria.

We pour into the city every day,
we pour down the tube,

on to buses, out round the streets.

If someone had infectious TB,

and they were coughing out
the tiny droplets

then it would be very easy
to infect so many people.

It would spread very, very easily.

Now if we can imagine that we didn't
have the antibiotics to treat TB,

well, we'd be in big trouble
because that's the only way

we can stop TB spreading.

But the fear now
is that our achievement

in controlling this disease is
being threatened.

Dr McNerney is seeing a rise
in cases of antibiotic-resistant TB.

We're now seeing the emergence of
strains of TB

that are resistant to the drugs.

And that's becoming quite
a serious problem.

One of the issues is that we don't
know how much drug resistance

there is because it's
actually quite difficult to measure.

For now, the resistant strains
showing up in the UK

can still be treated by a small
number of antibiotics.

But outside the UK, Dr McNerney has
seen a new strain of TB emerge

that is resistant to all of
the antibiotics we have to treat it.

It could arrive tomorrow on an
aeroplane. It might already be here.

We don't know.
We just have to be on our guard.

We just can't afford to let this
genie out of the bag.

Scientists are now trying
to understand

exactly how superbugs
have gained resistance,

and, ultimately, how
we can defeat them.

Here at Harvard University,

scientists are investigating why
some of our antibiotics are failing.

It's an experiment that happens
in Professor Roy Kishony's lab.

Here they are deliberately trying
to create superbugs.

This is a new device we've
developed - we call it
the morbidostat.

Using the morbidostat, they are
going to produce a highly resistant
version

of a harmless strain of a bacteria
we all have in our gut.

E. coli.

At the beginning you have
bacteria just growing

happily in the tubes, they have
enough food, they are growing fast.

They start by trying to
kill the E. coli

by dripping in a low
concentration of antibiotic.

But as the millions of bacteria have
been multiplying in the tubes,

some, by chance,
will have developed mutations

that allow them to be resistant
to the antibiotic.

This mutant would start replicating
faster than everyone else,

ultimately it would
take over on the whole population.

So now they try to kill this new
mutant strain.

They up the strength
of the antibiotic.

Again, most of them die.

But a new mutation appears,

that can survive the even
stronger antibiotic.

And then we see another step,
now they can grow

in even higher drug concentrations,

so we keep iterating this process
over and over and over.

This experiment shows that bacteria
become resistant

by being exposed to low levels of
the very thing we use to protect us,

antibiotics.

Now the team have created a new
experiment to find out exactly

what is happening in these mutant
bacteria to allow them be resistant.

It starts with what is in effect
a giant Petri dish.

We're setting an experiment
really for the first time

in which we're going to let
bacteria swim against

an ever-increasing concentration of
an antibiotic, and see what happens.

The jelly contains
food for the bacteria to grow,

but each slab is infused
with an increasing concentration

of antibiotic, which should act
as a barrier, killing the bacteria.

First slab is no drug,

then about the amount needed to
kill the bacteria,

then ten times more, 100 times more,
and 1,000 times more.

The experiment begins with
a tiny drop of E. coli.

They're certainly going to spread
when there is no drug but

we want to see can they actually go
to the place where there
is an antibiotic?

A time-lapse camera captures
the spread of the bacteria.

As the experiment begins,
it's easy for the bacteria to grow

in the first section,
with no antibiotic.

Where there is no drug,
it's very easy for them,

there's food but no stress.

Then they hit the boundary where
the drug concentration increases.

At the barrier where the
antibiotic starts

at the first concentration,
the spread is halted.

They get stuck there for a while,

they try to go into this area
because there is food,

but every time they try to go
into it they get killed by the drug.

But that doesn't last long.

Very soon, a mutant appears that can
break through the barrier.

Whole new colonies grow that can
live happily

in this concentration of antibiotic.

And it doesn't stop there,
this happens again and again,

even up to 1,000 times
concentration.

At the end of the experiment we are
the maximal level of solubility

of the drug, we just cannot add more
drug, it doesn't dissolve anymore.

This carefully controlled epidemic

all happens in the space
of just one week.

The team is beginning to pick apart
these mutant bacteria

to see exactly how this is happening
in the presence of antibiotics,

by peering inside the bacteria,
at their genes.

What actually happen under the hood,

when we open and look at the genomes
of this bacteria.

We can do it now, we can sequence
a whole genome of these bacteria

and see what are the exact
changes that happen.

Typically, what genes changed and
allowed them to mutate in such a way

it can grow in this higher drug
concentration.

This is evolution in action.

Over millions of divisions,
the bacteria's DNA changes.

Evolution happens here
fairly fast,

in basically two weeks of experiment

we see a very dramatic increase
in drug resistance,

1,000-fold increase
in drug resistance.

So, yes, you might want to say
evolution is happening

in front of our eyes,
as we speak.

Used properly, antibiotics can kill
bacteria and save lives,

but as these experiments show,

low levels of antibiotics encourage
bacteria to develop resistance.

In the real world too,

our use of antibiotics may actually
be causing more superbugs to emerge.

Superbugs were once rare
and infrequent,

but they are now showing up
across the world's major cities.

Professor Tim Walsh studies these
newly emerging outbreaks,

and there's one region that
concerns him most of all.

The southern Asian continent
suffers from antibiotic resistance

far more than probably any
other area on the planet.

For the last three years he's been
travelling to Southern Asia

to understand why some of the
poorest parts of the planet

are superbug hotspots.

He's on his way to Karachi's
Civil Hospital, in Pakistan.

In both rich and poor countries,

resistant bacteria cause their most
costly and deadly infections

in the places where people are most
vulnerable - hospitals.

The doctors at the hospital
are working with Prof Walsh

to identify and improve
the conditions contributing
to the spread of superbugs.

A lot of times you see them and
they're not washing their hands.

This is one of the reasons
we have so much infection.

I think the infection control
issue here

clearly seems to be very important.

One of the key issues
in places like the Civil Hospital

is sort of overcrowding of the wards
and lack of infection control.

Windows are open
so bacteria can kind of blow into

intensive care units etc,
and there seems to be a lack of

understanding as to the importance
of things like hand-washing

in moving from patient to patient,
or indeed from ward to ward.

The doctors are facing dangerous
infections,

in impossible conditions.

Professor Walsh has found

there are no dedicated
infection control teams,

insufficient bacterial diagnosis,
and no isolation rooms.

Well, the people in Karachi
know about their limitations,

and that's the great thing, they're
very open and honest about them,

they realise they must do
something about it.

But there's another factor at play
that the hospital can't control.

There is an easy availability

of the very thing needed to
create superbugs.

In most parts of Asia,
antibiotics can be purchased

freely from shops without
prescription.

A problem that the
doctors throughout the hospital

are aware of.

From the pharmacy right
outside the hospital

I bought all these antibiotics
and they cost me just 2.50 rupees.

Anyone can go and buy these.

Bought over the counter, antibiotics
are misused and misunderstood,

taken even for things that they
can't cure.

And there are no instructions,
certainly not with these, on usage.

Yeah,
they don't come with a leaflet.

And a lot of people just will go
to the corner shop

and simply buy a whole range of
antibiotics and simply self medicate

and you can see on this one here one
tablet has obviously been sold

to one particular person - just
to take one tablet is just crazy.

You're just exposing
the bacteria to what we call

sub-killing-concentrations of that
antibiotic.

And so you're actually not killing
the bacteria, or indeed

preventing it from growing, and
more or less all we're doing

to the bacteria is saying,

"OK, here's the antibiotic,
become resistant."

It's not just the sale
of antibiotics that's unregulated.

Elsewhere in Asia, outlets from the
industrial-scale manufacture

of antibiotics have
contaminated rivers and streams.

As a result, societies can be
awash with antibiotics,

the perfect conditions
for superbugs.

However, the conditions needed to
create a superbug

are not just happening in Asia,
but right across the world.

Professor Lance Price
is a superbug tracker.

A few years ago, he was called to
investigate a superbug

which helped to reveal how another
use of antibiotics

was driving resistance.

Bacteria are everywhere. They're
a natural part of our environment,

they're a natural part of us,
in fact human beings are sort of

a walking ecosystem, we have
bacteria that live in and on us,

one of the bacteria that I'm
particularly interested in

is Staph aureus.

It's estimated the between 20%
and 30% of humans

are colonised with Staph aureus,

and most of the time it
doesn't pose a problem.

If Staph aureus does cause
an infection, it is usually

straightforward to treat with
an antibiotic called methicillin.

But when it develops resistance to
methicillin

it becomes a superbug we've all
heard of, MRSA.

This is a picture of
methicillin-resistant Staph aureus.

Methicillin-resistant Staph aureus
and regular Staph aureus

don't look
any different in a photo like this,

but when you look at the DNA, you'll
see very distinct differences.

MRSA carries genes that make it
resistant to methicillin,

that's why we call it
methicillin-resistant Staph aureus,
or MRSA.

He uses these genetic
differences as clues

to lead him to the source of the
outbreaks.

We crack these cells open and
we sequence the DNA,

and then we use that to trace the
evolutionary history of these bugs

and determine how and sometimes when

they became resistant to
methicillin.

Three years ago, he discovered
a new strain of MRSA

in 18 different countries,
including the USA and in Europe.

And there was one thing that seemed
to connect them all.

A new strain of MRSA emerged
that we'd never seen before,

and when we started tracking it back
we found out that

most of the people who were getting
it were actually employed in the

livestock industry, so people that
had direct exposure to food animals.

And that set off an
investigation for us.

The genetic trail revealed this
strain of MRSA

had passed into these
people from pigs.

But then they went further.

They tried to follow the genes back
to a time before

the MRSA became resistant.

And what we found
was a big surprise to us,

we found that in fact that this new
strain had started off in people

but it was not MRSA,
it was just Staph aureus, or SA,

it spread to pigs, and that's where
it became resistant to methicillin.

Professor Price had discovered that
this ordinary Staph aureus bacteria

had mutated
while it was in the livestock,

to become potentially deadly.

To him, the reason was obvious,
antibiotics.

The simplest explanation
is that we're using

lots and lots of antibiotics
in food animal production.

Most of the time they're just
being added to animal feed,

so they're being
mixed in giant silos of feed

and given on a routine basis,
just basically with every meal

that animals are getting
a little bit of antibiotics.

Many farmers thought it was
the best way

to keep closely packed animals
healthy

and for them to grow faster,

but Professor Price believes
the superbug he was tracking

was created as a result of this
kind of antibiotic use.

We're raising animals under
the conditions that we know

lead to the spread of bacteria
between people,

and then we add the magic ingredient
which is antibiotics,

which just virtually guarantees
that we're going to have

drug-resistant bacteria.

In 2006, the European Union banned
the use of antibiotics

as growth promoters in animal feed.

But elsewhere in the world, it is
still being used in vast quantities.

In the United States we use 29
million pounds of antibiotics

every year in food animal
production.

I mean, you know, these are the crown
jewels of modern medicine,

they're being
used like cheap production tools.

There is a movement in the US
to change this practice.

Professor Price is working with
farmers who are trying new ways

of keeping animals healthy,

without constant
use of antibiotics in the feed.

Like to come in and see what we're
doing here? I would.

Yeah. Give you some coveralls
and some booties for you.

Removing antibiotics from the feed
means farmers need to take

other measures to avoid
their livestock getting infections.

I have to wear these in a lab
sometimes.

In that case, we're protecting
ourselves from the microbes

rather than the turkeys from us.

But working this way means
farms are less likely

to encourage superbugs to emerge.

Everybody would say,

"There's no way you're going to be
able to grow turkeys without
antibiotics."

So we started trials and learned
from that,

that we needed to give
the birds more space

and really go out of your way
to have the best animal husbandry,

that they don't get stressed.

And now, if we do get a sick flock,
which is rare,

but if we get one and we have
to treat it,

we can use the simplest
antibiotic like a tetracycline,

and it usually works great.

For where it continues, large-scale
use of antibiotics in animal feed

can create the right
environment for superbug emergence.

Bacteria don't wear lapel pins.

They're not confined to any
geographic area,

and so what we do here in the United
States can potentially impact you.

So as we create these
multi-drug-resistant pathogens,

those pathogens can then
spread around the world.

And so you should just be as
concerned as I am

about what we're doing over here.

Wherever a superbug outbreak
occurs in the world,

doctors across the globe
start to worry,

because regardless of where
they first emerge,

a superbug can soon become
a citizen of the world.

We carry about 100 trillion
bacteria in us,

therefore, when we travel the world,
they travel the world.

Any types of resistance that
occurs in one country

can very easily be transported around
the world, almost in real time.

With the rising
levels of air travel,

resistant bacteria have hitched
rides across the globe.

Probably in about the last
15 to 20 years,

we've managed to contaminate
the whole of the planet.

If you go to the north of Norway,
or even down into Australia,

down to Tasmania, you will find
these type of resistances.

Not only are superbugs being found
all over the world,

scientists are finding that
these bacteria

are becoming harder and
harder to treat.

It's this problem that Professor Tim
Walsh grapples with every day.

This a very quick illustration of
how resistance has evolved

over about the last 20 years.

Each white disc on these plates
contains a different antibiotic.

A clear circle indicates
the antibiotic is working

and killing the bacteria.

This E. coli from
India about 20 years ago

is fully sensitive to
the series of antibiotics

which we would use to treat E. coli
infections.

12 years ago, the E. coli had
started to become resistant

to some of the antibiotics,

but the newest strain has shown
unprecedented levels of resistance.

You can see here it's virtually
totally resistant.

The only antibiotic that
shows any activity

against this particular organism,
is this antibiotic here,

which has some issues with toxicity,

and it's at the moment about
40, 50 years old.

We're starting to have a
bit of a renaissance with it,

because clearly you can
see that we have nothing left.

We are beginning to see this
level of resistance appear

all over the world.

Bacteria that only respond to a few
rarely used antibiotics.

And the trouble is,

these antibiotics of last resort can
often be toxic themselves.

Scientists believe there is
an urgent need

to re-stock our arsenal
with new antibiotics.

It's a hunt that has taken Professor
Hazel Barton across the globe.

I get to travel the world,
I get to see amazing things,

so I just love it!

You might think that new antibiotics
were created in a lab,

or discovered
deep in the rainforest,

but actually most of them
have been found in the dirt.

Almost all of the antibiotics
that we use now

have come from soil micro-organisms.

The procedures that we have
in the lab for finding antibiotics

is literally to pull the microbes
out of this dirt and grow them.

More than three-quarters
of the antibiotics we regularly use

in hospitals today were
taken from microbes in the soil.

And the trouble is, we've been
doing that for 50 years

and we keep finding the same things.

And the best microbes for producing
antibiotics are bacteria themselves.

To find new antibiotics, Professor
Barton has to hunt down new bacteria

in some of the most
untouched places on Earth.

Hundreds of metres underground.

Oh, it's slippery here.

For bacteria,

these caves are one of the toughest
places in the world to survive.

Between where we're standing right
now and the surface,

there's about 1,000 feet of rock.

So for anything that's
happening on the surface,

all that energy from plants
and animals, for that to come here,

it has to get through all that rock,
and it can't do that very easily.

So we end up with a very
starved environment,

where there's hardly any
energy available.

These caves may look peaceful
and still,

but they are, in fact,
a battlefield.

With so few resources available,

bacteria must fight each
other to survive.

They become either much more
careful of their resources

in defending them,

or they get a lot more aggressive in
stealing someone else's resources.

They do this by producing
an arsenal of chemical weapons.

Professor Barton has been collecting
these weapons

in the hope they might be used
as antibiotics.

Last year, she captured
one type of bacteria

that produced over 38 different
bacteria-killing chemicals.

To put that in perspective,

there's only about 40 antimicrobial
drugs in the clinic right now.

So one bug from this cave
was able to make

almost as many as we have available
to us in the clinic.

Not all of those are going
to be useful as medicines,

but the potential becomes huge.

I mean, we've pulled out
4,000 microbes,

so it's almost like a chemical
universe

and we are kind of playing
on the edges of it

with antimicrobial
compounds and there's this huge vast

unknown space that we've yet to kind
of explore to see what's out there.

The work of scientists
like Professor Barton

is becoming increasingly important,
as any new antibiotic discovery

will enable us to retain our hold
over the superbugs.

But eventually, bacteria will always
find a way to become resistant

to even the new antibiotics.

If we are going to finally overcome
the problem of resistance

we are going to need a whole
new approach.

On the face of it, this seems
an unlikely place to discover

a new strategy for fighting
superbugs.

It's a sewage works
in Buckinghamshire.

But microbiologist Dr David Harper
believes the answer

may be found here.

He's hoping to exploit the weapons
technology of a creature

that has developed its own way to
fight bacteria.

Bacteria have been on the Earth
for billions of years.

That's why they're so tricky.

But there's something else that's
been on the Earth

for billions of years.

And it knows how to deal with
bacteria.

That's what I'm here to collect.

Good to see you. And you, David.
Let's go and get some good ones.

Raw sewage is the perfect breeding
ground for bacteria.

But that also makes it
the ideal home

for the ultimate bacterial predator.

He wants to enlist that predator to
fight for us in the superbug war.

In there, although we can't see it,
there's a war going on.

There are billions of bacteria
struggling for existence,

and tens of billions
of bacteriophages.

Viruses that only and specifically
affect and kill bacteria.

And they are fighting in there,
as we speak.

Just like humans, bacteria can be
infected and killed by viruses.

Bacteriophages are the most common
and diverse predators on Earth.

There are 10,000 billion,
billion, billion,

bacteriophages on the planet.

We haven't actually counted,
that is an estimate.

Dr Harper wants to get these
bacterial viruses

fighting on our side
in the superbug war.

"Bacteriophage" literally means
"bacteria eater".

They work by landing on the
bacteria,

injecting in their own DNA,

then reproducing themselves
inside the bacteria until it bursts.

Back in his company's lab,

Dr Harper is attempting to harness
the power

of these bacterial predators.

It's a tricky business.

To kill disease-causing bacteria,

you need the particular phage
which attacks that bacteria species.

We go and collect the sewage,
we bring it back here,

we put the sewage into a culture
of the target bacterial species.

There are lots of different
phages in there,

I said there were billions -
there are. Maybe thousands,

maybe hundreds, will hit that
particular species.

In a few cases, you might have a
species where only a few will hit it,

but still, if they're there,
they will bind,

they will kill, they will multiply

and you can pick them
and grow them.

Using viruses to kill bacteria

sounds like an attractive
idea in principle,

but in practice, working with live
organisms has proven difficult.

But Dr Harper is drawn to this
field of research

because phages offer one significant
advantage over antibiotics.

Antibiotics can't change.

If the bacteria generate resistance,
that's it,

you need a new antibiotic.

With phages,
the bacteria are their lunch.

If they can't multiply, they die out.
If they can, they grow.

So when the bacteria change,
a few phages will be in there,

which can grow in the new ones.

That mutation is then preferred,
those phages will multiply

and come to dominate.

The bacteria will change again,
a few of those will be able to grow,

they grow again, they amplify,
they come to dominate.

It's an arms race.

Tapping into this arms race
would hand us a key advantage

because the bacteriophages
are able to evolve.

If we are able to enlist them
to fight for us,

they will keep fighting for us,
even as the bacteria change.

They are in many ways a perfect
drug, in many ways they aren't.

One of the most telling things
against bacteriophages as drugs

is that nobody has yet developed one.

Dr Harper's company have seen
some early successes

and are now planning a trial
to treat lung infections

often affecting
cystic fibrosis sufferers.

We hope that the results in cystic
fibrosis will be convincing.

We hope to move on to
the large clinical trials

of hundreds of patients,
which will underpin

progressing this to market
to improve people's lives,
to save people's lives.

There's a long way still to go,
but we're working on it.

Right now, phage medicines are
still in the very early stages

but new developments
in understanding exactly how

bacteria become deadly are giving
hope that there could be

another way to outsmart them.

Princeton University in New Jersey.

Here, a team are taking
a radically new approach,

one that has led
to an unexpected breakthrough

in the fight against
deadly bacteria.

Professor Bonnie Bassler has spent
her career

getting in to their world.

I love bacteria.
I think most of the things

they do on this earth are fantastic
and essential,

but bacteria have features, bells
and whistles, different processes,

that they are, that they have for
fighting in their own environments.

And when those get
unleashed in a human or in an animal

or in a plant, it can kill us.

With antibiotics,
we have been attacking bacteria,

forcing them to evolve resistance.

But Professor Bassler thinks that we
may not have to be so aggressive.

Instead of just smashing
them to smithereens

like we've done with traditional
antibiotics, if we could learn enough

of their secrets, and get them
to spill their guts a little bit

and tell us how they work,
we could just get them to behave.

And do behaviour modification
instead of killing them.

Compared to us,
bacteria are so incredibly small

that on their own, they shouldn't
be able to hurt us at all.

If one or a few bacteria release

their mostly deadly arsenal of
toxins, they have no effect.

I mean, this is not a David
and Goliath, this is like

way beyond that, so the question is,

how can these bacteria have us
on our knees,

right, how can it
be that they can actually kill us?

Bacteria don't attempt to
attack us on their own,

they wait until there are enough
of them and then act all at once.

You can think of the bacteria, each
individual bacterium as a soldier,

and so you have these masses of
soldiers, but it's only useful

when somebody says "charge",
right, so the question is

what's the information that tells the
bacteria now is the time to attack?

If we could find a way to stop
the bacteria attacking together,

they wouldn't be able to harm us.

But understanding how
they co-ordinate their attack

is incredibly difficult

because bacteria
are hidden from sight.

But there is a type of bacteria
that you can see,

and they have a rather unusual
relationship.

The Hawaiian bob-tailed squid
is a master of disguise.

In the day, it
disappears into the sea bed,

but when it comes out to feed
at night, it's even more ingenious.

At night, this is like the stealth
bomber of the ocean,

it likes to cloak itself
in an invisible device.

If it were to just swim around,

the starlight or moonlight would
hit its back

and it would cast a shadow
on the sea floor here

and then predators
that could see that shadow

could calculate its
trajectory, and eat it.

To eliminate their shadow,

these squid project
light down onto the sea floor.

So by matching how much starlight
or moonlight hits its back

with how much light comes
out of its body, there's no shadow.

So it's a fantastic sleight of hand,
sleight of tentacle,

if you will, it's a fantastic
anti-predation device

because it makes
it invisible at night.

And this incredible invisibility
cloak is created by bacteria.

There's a bacterium that
lives in the body of the squid,

the bacterium's name is Vibrio
ficheri, and it makes light,

so the squid gives the
bacterium a home,

the bacterium gives the squid light,

and the squid uses the light
to protect itself from predators.

But just as a single dangerous
bacteria would not be enough

to make us sick, a single glowing
bacteria would never produce

enough light to help the squid.

For the bacteria to be useful,
there must be lots of them.

So the bacteria wait
until there are enough of them,

and only then, all start
glowing at exactly the same time.

When this was initially discovered,

the idea that bacteria could do
something as a group was revelatory.

The bacteria were working together,

but the question was,
how were they doing it?

The beauty of these marine bacteria
is that they glow in the dark,

so they could experiment
to see what exactly caused them

to start making light.

They discovered the bacteria were
producing a chemical messenger -

they were talking to each other.

As they grow and divide,

they all make
and release these molecules.

When there's more cells,
the molecule outside the cells

increases in proportion
to cell number.

And when the molecule hits
a certain amount,

the bacteria have receptors on their
surfaces, they detect that the

molecule is there and then they all
change their behaviour in unison.

Using these molecules,
the bacteria were able to detect

when other bacteria
were around them.

And by communicating with each
other, the bacteria were able to

achieve something they could never
achieve as individuals.

This behaviour is called
quorum sensing.

Sometimes, the way I think of it,
is if you want to move a piano

from over there, to over there, you
don't try to do that yourself,

you get all your friends, everybody
grabs and you say,

"One, two, three, lift."

And then you can carry out this task
as a co-ordinated synchronous group

that you couldn't do,
if you were just acting on your own.

Once they'd discovered the glowing
bacteria could talk to each other

using chemicals, Professor Bassler
began to wonder if this was the way

dangerous bacteria were
coordinating their attack.

And so I thought, "Well, I wonder
if anybody else makes this molecule."

So I just collected every bacterium
I could get my hands on.

And every bacterium
I tried that with, it worked.

And there was this moment,
I still get goose pimples with that,

there's this moment where I thought,

"Holy cow,
they're talking between species,

"they all make this molecule."

It looked like all bacteria could
communicate using these molecules.

This had incredible implications.

If she could interrupt
these conversations,

she could get the bacteria
to stop their group behaviour.

We know what these molecules are,
at least some of them,

these quorum-sensing molecules,
so we've made antagonists, right,

molecules that look kind of like the
real things,

but they jam the receptors.

And so if you add those,
it's like static, you know,

you add these anti-quorum-sensing
molecules, the bacteria can't hear.

Professor Bassler had found a way

to stop the glow-in-the-dark
bacteria from talking.

Could she do the same with
dangerous bacteria

and prevent them
from launching their attacks?

We started this work with
Vibrio haveri and Vibrio ficheri,

these beautiful bio-luminescent
bacteria,

but they have a nasty cousin,
Vibrio cholera.

Those two bacteria make this
beautiful light, this guy kills you.

Although completely eradicated
in the UK,

the cholera bacteria is responsible
for over 100,000 deaths

in the developing world every year.

So we transferred what we learned

from the glow-in-the-dark
bacterium to this bacterium.

Professor Bassler can measure
the level of a protein

that cholera bacteria produce that
makes them deadly.

This is the protein that
cholera makes

that lets it adhere to your
intestine.

It has to make this.
It's step one in the infection

and that makes it virulent.

So then what we did was, we added
our anti-quorum-sensing molecule

at different amounts
to cholera cells,

and if we add more and more
and more of our molecule,

what you can see is,

it makes cholera incapable of making
that virulence protein,

and incapable
of making an infection.

This is just the beginning
for Professor Bassler and her team,

as other researchers around the
world are now investigating

whether this method of silencing
the bacteria

has the potential to work where
antibiotics are failing.

Scientists have entered a new
stage in the battle with superbugs.

It may be that we have
underestimated our enemy.

They're probably smarter than I am.

They're able to adjust fire
much quicker than I can

so they're able to develop
resistance a whole lot faster

than I can develop an antibiotic.

But around the world,
scientists are taking up

this cat and mouse challenge.

It is a game. They're playing their
game and we need to play our game.

We each need to do our best move.

We are understanding bacteria
better than ever before

but maybe we don't have to
triumph over all,

we just have to stay one step ahead.

We don't have to totally win,
that's not the goal.

The goal is simply to find out enough
to be able to do something useful

and then let the next scientist find
out the next thing that's enough

to do something useful.

Subtitles by Red Bee Media Ltd